life before covid 19 and after covid 19 essay

COVID-19: Where we’ve been, where we are, and where we’re going

One of the hardest things to deal with in this type of crisis is being able to go the distance. Moderna CEO Stéphane Bancel

Where we're going

Living with covid-19, people & organizations, sustainable, inclusive growth, related collection.

The Next Normal: Emerging stronger from the coronavirus pandemic

Three Years Later: How the Pandemic Changed Us

From routines to deep losses, the global health crisis altered lives of staff and faculty

Since her father’s death from COVID-19 in 2021, Alexy Hernandez’s days have become emotional minefields. Any small thing can be a gut punch, reminding her of what’s lost.

Perhaps it’s a football highlight, since she and her father, Josue, shared a love of the sport. Coffee has become complicated since her dad always got a kick out of pictures she sent of the creative designs left in her latte foam.

Or maybe it will simply be the small pieces of her daily routine — getting into work in the morning, coming home at night — experiences that warranted a quick text to her dad, who always wrote back with love and encouragement.

“He was my best friend, my biggest supporter, my biggest cheerleader,” said Hernandez, 28, a clinical research coordinator with the Department of Population Health Sciences . “I am who I am because of him.”

The pandemic changed the way most of us lived. We learned how to work remotely or gained new appreciation for human connection. And, for the loved ones of the roughly 1 million Americans who died from the virus, life will forever feel incomplete.

While the worst of the pandemic may be behind us, its effects linger. According to a Gallup poll , 53 percent of U.S. adults don’t expect their life to ever be the same as it was before the pandemic.

“We all felt this,” said Rachel Kranton, the James B. Duke Professor of Economics who, early in the pandemic, contributed to Project ROUSE , an independent Duke faculty research study that looked at how staff and faculty at Duke coped with changes to life, work, and well-being.

Project ROUSE showed that the pandemic had profound effects on everyone, including that, during the pandemic’s first year, roughly 40 percent of nearly 5,000 study respondents were at risk of moderate or severe depression.

As the pandemic’s difficult early days fade, Kranton said that other changes will likely endure, such as a willingness to connect in new ways, reassess careers, or build lives with more flexibility.

“I think there’s probably a new normal, and I think that new normal includes both good things and bad things,” Kranton said.

Hernandez’s life won’t be the same after her father’s death, but she is moving forward.

She’s learned not to stress about trivial things and thinks often about how she can make her father proud. Nothing, she said, can be taken for granted.

“Losing my dad has completely changed how I view and interact with the world and has given me more clarity on what I value,” said Hernandez, who has worked at Duke for four years.

We asked staff and faculty to share how the pandemic changed their lives, and here’s what some colleagues shared.

‘I’ve learned from students’

“It’s a new normal. You’ve got to deal with what you’ve got to deal with. Teaching markets and management, I’ve tried to move on and try to keep things fun. I like to make my courses interactive. So whether that’s changing materials or adding new things to a class, I’ve had to adapt. A lot of new stuff I’ve learned from students, whether it’s using polls, or Kahoot, or other activities. You’ve got to keep things fresh. The world is changing, you’ve got to change with it.”

George Grody, 64, Lecturing Fellow of Markets & Management, Trinity College of Arts and Sciences

Value of Life

“I appreciate more than ever before, not only the value of life, but a strong appreciation for others in the respiratory field and healthcare. I have been a respiratory therapist 33 years, and I’ve worked at Duke 35 years. Many have come and some have gone from this world. It’s devastating when you’ve worked so hard on patients, and they don’t make it out. Nothing can replace the value of life and what it means. Life is so important, and each and every day that you work with your patients is important. This all taught me a lot about what it means to really care for your patients, and it taught me a great deal of humility in caring for those who needed me.”

Pamela Bowman, 63, recently retired Respiratory Care Practitioner, Duke Regional Hospital

Out of the Quiet

“Though it’s crazy to say, my life started to flourish during the pandemic in more ways than one. I went back to school at the beginning of the pandemic at Durham Technical Community College to study business. I got in the best shape of my life by focusing on clean eating, and I lost 35 pounds. I started earning more money by taking a job at Duke. The pandemic was a time for me to quiet down the noise around me. Personally, I was able to shut out the world, decide what I really wanted out of life, and for myself, and start making those things happen. Ever since things started getting back to how they were pre-pandemic, those progressions I’ve made slowly started to derail. I gained back the 35 pounds I lost once the world started to open up again, and it’s just been harder to do everything I was doing to better myself every day. I went into a bit of a depression, but now I’m finally coming out of it. I’m back down 20 pounds. I’m learning how to cope with things and get back to being able to do those things that progressed for me and made me happy, even though I’m not able to get the same quietness I once had.”

Sadie Horton, 27, Staff Assistant, Academic Support, Fuqua School of Business

Cherish Loved Ones

“My mom, Johnnie Mae Snipes, was put on hospice on Jan. 11, 2021, and she passed away on January 20, 2021, at age 83. Me and my sisters were holding her hand, and, needless to say, we lost the strongest woman we ever knew. Our queen was gone. My mother had six daughters, 17 grandchildren, 44 great grandchildren and seven great, great grandchildren. My mother passed away from dementia and COVID. The past few years have taught me to never take anything for granted and to cherish your loved ones. It also has showed me how the world can change in one day. But one thing I know for sure that will never change is God is still in charge.”

Clara Bailey, 58, Staff Assistant, Department of Medicine, Oncology

‘I don’t go anywhere without my mask’

“When Dr. Anthony Fauci came out and said we need to wear masks in public, I did it. I’m claustrophobic, so when I first started wearing the cloth masks, I would have panic and anxiety attacks, particularly at the grocery store. Over time, I got used to it, and I started feeling safer by wearing my mask. Now, I don't think I will ever go into another crowded event without a mask. As a woman, we have our purses. We don’t go anywhere without our purses. Now, I don’t go anywhere without my mask. Since wearing my mask, I haven't caught a cold, let alone anything else. It's a piece of cloth, no big deal.”

Sandy Ouellette, 62, Access Specialist, Consultation & Referral Center

Rethinking What’s Most Important

“During the pandemic, my wife got a new job in Virginia, and because I’ve been working remote since March 2020, it made it easy to move with her because, in the past, somebody would have had to quit their job, find a new job, and do all kinds of stuff. Personally, the pandemic has made me rethink what’s most important in life, such as making sure to set aside time for family and friends. Now, I get to spend more time with my wife. We can do house projects, take our dogs out and explore. Now that our parents are getting older, we try to take advantage of any time we can spend with them. The pandemic made spending time with people who are important to you a little extra important because they’re what helped me get through.”

Christopher Morgenstern, 39, Administrative Manager, Cardiology

‘180-degrees different’

“My wedding, honeymoon, and bachelorette party were all canceled due to COVID, so my husband, Brent Durden, and I got married in our backyard with just our parents. We were going to wait several years to start a family so we could travel but decided to seize the day during quarantine after buying a house. Now, we have a beautiful 18-month-old daughter, Eliana. As tragic as the losses we experienced as a country and community have been through this pandemic, my entire world is 180-degrees different than it was before COVID, and it makes me so grateful to have the family that I do.”

Tricia Smar, 36, Education and Training Coordinator, Duke Trauma Center

‘I’m fulfilling my bucket list’

“I have terminal prostate cancer. I live one day at a time. They gave me 18 months to live about six years ago. During the pandemic, I retired to fulfill my bucket list only to find disappointment. I made all sorts of plans, but everything was shut down so my plans were shot. I returned to work. I have a love for nursing and have no regrets coming back to patient care. I missed interacting with people. I missed my coworkers, I missed the patients. Now I travel, and I'm fulfilling my bucket list, but I always look forward to coming back to Duke for both my own care and to care for our patients.”

Doug Buehrle, 68, Clinical Nurse, Apheresis, Duke University Hospital

Savor Small Moments

“I learned to make the best out of a horrific situation. My kids, Derek and Joshua, were 5 and nearly 3 when COVID hit. In the clinical research field, we had to scramble to see which trials could keep going and which ones would have to go on pause. We had to be very flexible to work around each other’s schedules and everyone’s kid’s schedules. But I got to spend a lot more time with my kids than I ever would have if COVID didn't hit, so I'm grateful I was able to do it. We got to spend time going to the park and flying kites since the playgrounds were closed. We went hiking and exploring since the museums were closed. Those were memories I am thankful to have made, and I'm hoping they don't fade.”

Kristin Byrne, 41, Clinical Research Coordinator, Hematology

‘Packed up my car with as much as I could fit into it’

“I graduated from nursing school at George Fox University in Oregon about a month after lockdown happened. I have a grandmother in High Point, so I started applying to hospitals in North Carolina, and Duke turned out to be the best option. In October of 2020, I packed up my car with as much as I could fit into it, and I drove across the country with my dad. I left my family, friends, my church back in Portland, and I’ve had to build an entirely new life here. My first nursing job was working for the medical-surgical float pool at Duke University Hospital, which basically staffed the COVID-19 floors for a while. I was thrown into the thick of it, and I really had to stay on my toes all the time. It was really hard, and it was really a dark period in my life, until I started to get my feet settled. I just started to put myself out there out of my comfort zone, and I started inviting people to do things with me. I found Bright City Church too. Over time, I started to find those little sparks of hope, when you send a patient home instead of the ICU. I’ve learned a lot from my nursing career, and I’ve learned a lot about myself and how to take care of myself.”

Lauren Berky, 25, Clinical Nurse, Internal Staffing Resource Pool

‘More Openness to Change’

“I think COVID has opened the clinical community to change more than ever before. Sharing data has replaced hoarding data. Technology has come so far, and we had a hard time getting people to change the way they think about data. I think COVID opened their minds that we need other ways of dealing with data, particularly that the patient needs to be the centerpiece of everything that we’re doing. Some people have said to me, that five years ago we’d have been laughed at for some of the things we’re trying to do. But now, everybody is at least willing to have the conversation.”

William Edward Hammond, 88, Professor of Biostatistics and Bioinformatics, Family Medicine and Community Health

‘Never take tomorrow for granted’

“I am much more committed to ‘living in the moment,’ appreciating what I have, and looking inward. At home, I find joy with my husband. I walk much more. I cook at home almost all the time. And, maybe most important, I appreciate the beautiful natural environment around our home on Morgan Creek in Chapel Hill, where husband, David, and I began walking nearly every afternoon in January 2021. I’ve learned to never take tomorrow for granted. To appreciate friendships and family and the place where we are, now. To be OK with less ‘running around.’  To not take progress for granted, and to realize that things can get worse.”

Anne Mitchell Whisnant, 55, Director, Graduate Liberal Studies, and Associate Professor of the Practice, Social Science Research Institute

Bittersweet Milestones

“COVID was honestly a bittersweet time. My father-in-law, Mark, the president of North Georgia Technical College, passed away from COVID on September 13, 2020. Then in January 2021, my husband, Andrew, and I found out we were pregnant with our first child, Lilly, after a very long time. We thought we couldn’t have kids, so that was quite the surprise. When she was born on October 21, 2021, the joy of having her was indescribable. She just turned a year old, and I know she’ll never know her grandfather, and he’ll never know her. We want her to be happy and healthy and treat others the best way possible, and we’ll continue to tell her about her Papa when we can. We can’t wish Mark back because he’s not coming back. We’re living in the reality knowing that we can’t change it; it’s something Ecclesiastes calls our lot in life. COVID-19 brought out the worst for so many families, including ours, but it also brought so much good.”

Marissa Ivester, 34, Fellowship Program Coordinator, Office of Pediatrics

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When Life Felt Normal: Your Pre-Pandemic Moments

Readers share memories, images and videos from before the coronavirus became a pandemic, and reflect on what they mean now.

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By Hannah Wise

Our lives have been forever changed by the coronavirus pandemic. Hundreds of thousands of people around the world have died. Millions in the United States alone have lost their jobs.

Though the coronavirus outbreak was declared a pandemic just over a month ago, many of us are already feeling nostalgic for our lives before the virus went global. We asked you to send us photos and videos that captured those moments of normalcy. We received nearly 700 submissions from all over the world — from Wuhan, China, to Paris, Milan to Mumbai, and across the United States.

You shared photos from weddings, funerals, meals with friends, and powerful scenes from crowded places that feel almost unthinkable now.

Nearly every submission expressed a sense of gratitude and appreciation for the time before the pandemic. Many also conveyed worry and a longing to feel a sense of safety and normalcy again.

What follows is a selection of those snapshots. The responses have been edited for clarity and length.

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Life after COVID-19: Making space for growth

In this time of grief, the theory of post-traumatic growth suggests people can emerge from trauma even stronger

Vol. 51, No. 4

In the traditional Japanese art of kintsugi, artisans fill the cracks in broken pottery with gold or silver, transforming damaged pieces into something more beautiful than they were when new. Post-traumatic growth is like kintsugi for the mind.

Developed in the 1990s by psychologists Richard Tedeschi, PhD, and Lawrence Calhoun, PhD, the theory of post-traumatic growth suggests that people can emerge from trauma or adversity having achieved positive personal growth. It’s a comforting idea in the best of times. But it holds particular appeal as we live through a pandemic that’s upending lives for people around the globe.

Growing from trauma isn’t unusual, says Tedeschi, now a professor emeritus at the University of North Carolina Charlotte and chair of the Boulder Crest Institute for Posttraumatic Growth in Bluemont, Virginia. “Studies support the notion that post-traumatic growth is common and universal across cultures,” he says. “We’re talking about a transformation—a challenge to people’s core beliefs that causes them to become different than they were before.”

And the COVID-19 pandemic may have the ingredients to foster such growth. “We’re still in the middle of this situation, and we don’t know yet what might happen—but there will be serious challenges to people’s lives,” Tedeschi says. While those effects may be devastating, it’s possible to emerge from such adversity for the better, he adds. “For some people, this event may be a shock to their core belief system. When that’s the case, it has the potential to result in s­ignificant positive changes.”

Resilience vs. post-traumatic growth

Research across a variety of disasters has shown that there are different trajectories for recovery, says Erika Felix, PhD, a psychologist at the University of California, Santa Barbara, who treats and studies trauma survivors. Some people need time to recover from a trauma before returning to normal functioning. A portion of people experience negative mental health impacts that become chronic, but the majority of people bounce back from a trauma pretty quickly, she says. “Most people will be resilient and return to their previous level of functioning.”

Resilience and post-­traumatic growth are not the same thing, however. In fact, people who bounce back quickly from a setback aren’t the ones likely to experience positive growth, Tedeschi explains. Rather, people who experience post-traumatic growth are those who endure some cognitive and emotional struggle and then emerge changed on the other side.

This experience is measured by Tedeschi and Calhoun’s Post­traumatic Growth Inventory (PTGI) ( Journal of Traumatic Stress , Vol. 9, No. 3, 1996), which evaluates growth in five areas: appreciation of life, relating to others, personal strength, recognizing new possibilities and spiritual change. It’s not necessary or even typical to show change in all five areas, Tedeschi says. But growth in even one or two of those realms “can have a profound effect on a person’s life,” he says.

Some psychologists say the evidence for post-traumatic growth isn’t yet as robust as it could be. For example, Patricia Frazier, PhD, at the University of Minnesota, and colleagues followed undergraduates before and after a trauma. They found that participants’ self-reported perceived growth didn’t align with actual growth as measured by the PTGI. And while actual growth was related to positive coping, perceived growth was not, suggesting the construct may not fully reflect the way people are transformed by trauma ( Psychological Science , Vol. 20, No. 7, 2009).

But other evidence suggests that people do grow from trauma. A 2018 book by Tedeschi and colleagues summarizes more than 700 studies related to post-traumatic growth, including Tedeschi’s own research and work from other scientists (“ Posttraumatic Growth: Theory, Research, and Applications ,” Routledge, 2018). “When you look at how people respond to traumatic events, post-traumatic growth seems to be fairly common,” he says.

Planting the seeds for positive change

Post-traumatic growth isn’t something psychologists can prescribe or create, Tedeschi says. But they can facilitate it. “We see it as a natural tendency that we can watch for and encourage, without trying to make people feel pressured or that they’re failures if they don’t achieve this growth,” Tedeschi explains.

Most evidence-based trauma treatments provide a “manualized approach” to alleviating stress and symptoms such as anxiety, Tedeschi says. The post-traumatic growth framework he uses is an integrated approach that includes elements of cognitive-behavioral therapy, along with other aspects that emphasize personal growth. “It has elements of narrative and existential aspects, too, because traumas often present people with existential questions about what’s important in life.”

One way to help clients see the possibilities for growth is to be an “expert companion” during their struggle, he says. “That’s someone who accompanies their trauma, listens carefully to their story and learns from them about what has happened in their lives. By being that kind of expert, people start to open up and look at the possibilities in their lives more thoroughly.”

Yet post-traumatic growth isn’t something that can be rushed, and it often takes a long time to come to fruition. “As a clinician, you can plant the seeds that may germinate later,” Tedeschi says.

As we emerge from the COVID-19 crisis, clinicians and their clients may have opportunities to help those seeds begin to sprout. “This situation presents a challenge to people’s lives, and some people will be able to emerge from this for the better,” Tedeschi says.

One doesn’t necessarily need to experience trauma and existential struggle to learn from this crisis, however. For many people, the pandemic is shining a light on the things that are most important. “We might be making more time for things we find meaningful, simplifying our lives and making time for being connected in our relationships,” Felix says. “A stressor like this makes all of us think: What does this slowdown mean for our lives? We might be fundamentally changed in some ways that are beneficial.”

The Posttraumatic Growth Workbook Tedeschi, R.G., & Moore, B.A. New Harbinger Publications, 2016

The Posttraumatic Growth Inventory: A Revision Integrating Existential and Spiritual Change Tedeschi R.G., et al., Journal of Traumatic Stress , 2017

Do Levels of Posttraumatic Growth Vary by Type of Traumatic Event Experienced? An Analysis of the Nurses’ Health Study II Lowe, S.R., et al., Psychological Trauma , 2020

Resiliency and Posttraumatic Growth Despotes, A.M., et al. In Wilson, L.C. (Ed.)The Wiley Handbook of the Psychology of Mass Shootings, John Wiley & Sons, 2017

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Greater Good Science Center • Magazine • In Action • In Education

How Life Could Get Better (or Worse) After COVID

How do pandemics change our societies? It is tempting to believe that there will not be a single sector of society untouched by the COVID-19 pandemic . However, a quick look at previous pandemics in the 20th century reveals that such negative forecasts may be vastly exaggerated.

Prior pandemics have corresponded to changes in architecture and urban planning, and a greater awareness of public health . Yet the psychological and societal effects of the Spanish flu, the worst pandemic of the 20th century, were later perceived as less dramatic than anticipated, perhaps because it originated in the shadow of WWI. Austrian psychoanalyst Sigmund Freud described Spanish flu as a “ Nebenschauplatz ”—a sideshow in his life of that time, even though he eventually lost one of his daughters to the disease. Neither do we recall much more recent pandemics: the Asian flu of 1957 and the Hong Kong flu from 1968.

Imagining and planning for the future can be a powerful coping mechanism to gain some sense of control in an increasingly unpredictable pandemic life. Over the past year, some experts proclaimed that the world after COVID would be a completely different place , with changed values and a new map of international relations. The opinions of oracles who were not downplaying the virus were mostly negative . Societal unrest and the rise of totalitarian regimes, stunted child social development, mental health crises, exacerbated inequality, and the worst economic recession since the Great Depression were just a few worries discussed by pundits and on the news.

Other predictions were brighter—the disruptive force of the pandemic would provide an opportunity to reshape the world for the better, some said. To complement the voices of journalists, pundits, and policymakers, one of us (Igor Grossmann) embarked on a quest to gather opinions from the world’s leading scholars on behavioral and social science, founding the World after COVID project.

The World after COVID project is a multimedia collection of expert visions for the post-pandemic world, including scientists’ hopes, worries, and recommendations. In a series of 57 interviews, we invited scientists, along with futurists, to reflect on the positive and negative societal or psychological change that might occur after the pandemic, and the type of wisdom we need right now. Our team used a range of methodological techniques to quantify general sentiment, along with common and unique themes in scientists’ responses.

The results of this interview series were surprising, both in terms of the variability and ambivalence in expert predictions. Though the pandemic has and will continue to create adverse effects for many aspects of our society, the experts observed, there are also opportunities for positive change, if we are deliberate about learning from this experience.

Three opportunities after COVID-19

Scientists’ opinions about positive consequences were highly diverse. As the graph shows, we identified 20 distinct themes in their predictions. These predictions ranged from better care for elders, to improved critical thinking about misinformation, to greater appreciation of nature. But the three most common categories concerned social and societal issues.

1. Solidarity. Experts predicted that the shared struggles and experiences that we face due to the pandemic could foster solidarity and bring us closer together, both within our communities and globally. As clinical psychologist Katie A. McLaughlin from Harvard University pointed out, the pandemic could be “an opportunity for us to become more committed to supporting and helping one another.”

Similarly, sociologist Monika Ardelt from the University of Florida noted the possibility that “we realize these kinds of global events can only be solved if we work together as a world community.” Social identities—such as group memberships, nationality, or those that form in response to significant events such as pandemics or natural disasters—play an important role in fostering collective action. The shared experience of the pandemic could help foster a more global, inclusive identity that could promote international solidarity.

2. Structural and political changes. Early in the pandemic, experts also believed that we might also see proactive efforts and societal will to bring about structural and political changes toward a more just and diversity-inclusive society. Experts observed that the pandemic had exposed inequalities and injustices in our societies and hoped that their visibility might encourage societies to address them.

Philosopher Valerie Tiberius from the University of Minnesota suggested that the pandemic might bring about an “increased awareness of our vulnerability and mutual dependence.”

Fellow of the Royal Institute for International Affairs in the U.K. Anand Menon proposed that the pandemic might lead to growing awareness of economic inequality, which could lead to “greater sustained public and political attention paid to that issue.” Cultural psychologist Ayse Uskul from Kent University in the U.K. shared this sentiment and predicted that this awareness “will motivate us to pick up a stronger fight against the unfair distribution of resources and rights not just where we live, but much more globally.”

3. Renewed social connections. Finally, the most common positive consequence discussed was that we might see an increased awareness of the importance of our social connections. The pandemic has limited our ability to connect face to face with friends and families, and it has highlighted just how vulnerable some of our family members and neighbors might be. Greater Good Science Center founding director and UC Berkeley professor Dacher Keltner suggested that the pandemic might teach us “how absolutely sacred our best relationships are” and that the value of these relationships would be much higher in the post-pandemic world. Past president of the Society of Evolution and Human Behavior Douglas Kenrick echoed this sentiment by predicting that “tighter family relationships would be the most positive outcome of this [pandemic].”

Similarly, Jennifer Lerner—professor of decision-making from Harvard University—discussed how the pandemic had led people to “learn who their neighbors are, even though they didn’t know their neighbors before, because we’ve discovered that we need them.” These kinds of social relationships have been tied to a range of benefits, such as increased well-being and health , and could provide lasting benefits to individuals.

Post-pandemic risks

How about predictions for negative consequences of the pandemic? Again, opinions were variable, with more than half of the themes were mentioned by less than 10% of our interviewees. Only two predictions were mentioned by at least ten experts: the potential for political unrest and increased prejudice or racism. These predictions highlight a tension in expert predictions: Whereas some scholars viewed the future bright and “diversity-inclusive,” others fear the rise in racism and prejudice. Before we discuss this tension, let us examine what exactly scholars meant by these two worries.

1. Increased prejudice or racism. Many experts discussed how the conditions brought about by the pandemic could lead us to focus on our in-group and become more dismissive of those outside our circles. Incheol Choi, professor of cultural and positive psychology from Seoul National University, discussed that his main area of concern was that “stereotypes, prejudices against other group members might arise.” Lisa Feldman Barrett, fellow of the American Academy of Arts & Sciences and the Royal Society of Canada, echoed this sentiment, noting that previous epidemics saw “people become more entrenched in their in-group and out-group beliefs.”

2. Political unrest. Similarly, many experts discussed how a greater focus on our in-groups might also exacerbate existing political divisions. Past president of the Society for Philosophy and Psychology Paul Bloom discussed how a greater dismissiveness toward out-groups was visible both within countries and internationally, where “countries are blaming other countries and not working together enough.” Dilip Jeste, past president of the American Psychiatric Association, discussed his concerns that the tendency to view both candidates and supporters as winners and losers in elections could mean that the “political polarization that we are observing today in the U.S. and the world will only increase.”

These predictions were not surprising— pundits and other public figures have been discussing these topics, too. However, as we analyzed and compared predictions for positive and negative consequences, we found something unexpected.

The yin and yang of COVID’s effects

Almost half of the interviewees spontaneously mentioned that the same change could be a force for good and for bad . In other words, they were dialectical , recognizing the multidetermined nature of predictions and acknowledging that context matters—context that determines who may be the winners and losers in the years to come. For example, experts predicted that we may see greater acceptance of digital technologies at home and at work. But besides the benefits of this—flexible work schedules, reduced commutes—they also mentioned likely costs, such as missing social information in virtual communication and disadvantages for people who cannot afford high-speed internet or digital devices.

Share Your Perspective

Curious about the world after COVID? So are we, and we'd love your opinion about possible changes ahead. Fill out this short survey to offer your perspective on the hopes and worries of a post-pandemic world.

Amid this complexity, experts weighed in on what type of wisdom we need to help bring about more positive changes ahead. Not only do we need the will to sustain political and structural change, many argued, but also a certain set of psychological strategies promoting sound judgment: perspective taking, critical thinking, recognizing the limits of our knowledge, and sympathy and compassion.

In other words, experts’ recommended wisdom focuses on meta-cognition, which underlies successful emotion regulation, mindfulness, and wiser judgment about complex social issues. The good news is that these psychological strategies are malleable and trainable ; one way we can cultivate wisdom and perspective, for example, is by adopting a third-person, observer perspective on our challenges.

On the surface, the “it depends” attitude of many experts about the world after COVID may be dissatisfying. However, as research on forecasting shows, such a dialectical attitude is exactly what distinguishes more accurate forecasters from the rest of the population. Forecasting is hard and predictions are often uncertain and likely wrong. In fact, despite some hopes for the future, it is equally possible that the change after the pandemic will not even be noticeable. Not because changes will not happen, but because people quickly adjust to their immediate circumstances.

The future will tell whether and how the current pandemic has altered our societies. In the meantime, the World after COVID project provides a time-stamped window into experts’ apartments and their minds. As we embrace another pandemic spring, these insights can serve as a reminder that the pandemic may lead not only to worries but also to hopes for the years ahead.

About the Authors

Igor Grossmann

Igor Grossmann, Ph.D. , studies people and cultures, sometimes together, and often across time. He is an associate professor of psychology at the University of Waterloo, where he directs the Wisdom and Culture Lab.

Oliver Twardus

Oliver Twardus is the lab manager for the Wisdom and Culture lab and an aspiring researcher. He will be starting his master’s in neuroscience and applied cognitive science in September 2021.

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Read these 12 moving essays about life during coronavirus

Artists, novelists, critics, and essayists are writing the first draft of history.

by Alissa Wilkinson

The world is grappling with an invisible, deadly enemy, trying to understand how to live with the threat posed by a virus . For some writers, the only way forward is to put pen to paper, trying to conceptualize and document what it feels like to continue living as countries are under lockdown and regular life seems to have ground to a halt.

So as the coronavirus pandemic has stretched around the world, it’s sparked a crop of diary entries and essays that describe how life has changed. Novelists, critics, artists, and journalists have put words to the feelings many are experiencing. The result is a first draft of how we’ll someday remember this time, filled with uncertainty and pain and fear as well as small moments of hope and humanity.

• The Vox guide to navigating the coronavirus crisis

At the New York Review of Books, Ali Bhutto writes that in Karachi, Pakistan, the government-imposed curfew due to the virus is “eerily reminiscent of past military clampdowns”:

Beneath the quiet calm lies a sense that society has been unhinged and that the usual rules no longer apply. Small groups of pedestrians look on from the shadows, like an audience watching a spectacle slowly unfolding. People pause on street corners and in the shade of trees, under the watchful gaze of the paramilitary forces and the police.

His essay concludes with the sobering note that “in the minds of many, Covid-19 is just another life-threatening hazard in a city that stumbles from one crisis to another.”

Writing from Chattanooga, novelist Jamie Quatro documents the mixed ways her neighbors have been responding to the threat, and the frustration of conflicting direction, or no direction at all, from local, state, and federal leaders:

Whiplash, trying to keep up with who’s ordering what. We’re already experiencing enough chaos without this back-and-forth. Why didn’t the federal government issue a nationwide shelter-in-place at the get-go, the way other countries did? What happens when one state’s shelter-in-place ends, while others continue? Do states still under quarantine close their borders? We are still one nation, not fifty individual countries. Right?

• A syllabus for the end of the world

Award-winning photojournalist Alessio Mamo, quarantined with his partner Marta in Sicily after she tested positive for the virus, accompanies his photographs in the Guardian of their confinement with a reflection on being confined :

The doctors asked me to take a second test, but again I tested negative. Perhaps I’m immune? The days dragged on in my apartment, in black and white, like my photos. Sometimes we tried to smile, imagining that I was asymptomatic, because I was the virus. Our smiles seemed to bring good news. My mother left hospital, but I won’t be able to see her for weeks. Marta started breathing well again, and so did I. I would have liked to photograph my country in the midst of this emergency, the battles that the doctors wage on the frontline, the hospitals pushed to their limits, Italy on its knees fighting an invisible enemy. That enemy, a day in March, knocked on my door instead.

In the New York Times Magazine, deputy editor Jessica Lustig writes with devastating clarity about her family’s life in Brooklyn while her husband battled the virus, weeks before most people began taking the threat seriously:

At the door of the clinic, we stand looking out at two older women chatting outside the doorway, oblivious. Do I wave them away? Call out that they should get far away, go home, wash their hands, stay inside? Instead we just stand there, awkwardly, until they move on. Only then do we step outside to begin the long three-block walk home. I point out the early magnolia, the forsythia. T says he is cold. The untrimmed hairs on his neck, under his beard, are white. The few people walking past us on the sidewalk don’t know that we are visitors from the future. A vision, a premonition, a walking visitation. This will be them: Either T, in the mask, or — if they’re lucky — me, tending to him.

Essayist Leslie Jamison writes in the New York Review of Books about being shut away alone in her New York City apartment with her 2-year-old daughter since she became sick:

The virus. Its sinewy, intimate name. What does it feel like in my body today? Shivering under blankets. A hot itch behind the eyes. Three sweatshirts in the middle of the day. My daughter trying to pull another blanket over my body with her tiny arms. An ache in the muscles that somehow makes it hard to lie still. This loss of taste has become a kind of sensory quarantine. It’s as if the quarantine keeps inching closer and closer to my insides. First I lost the touch of other bodies; then I lost the air; now I’ve lost the taste of bananas. Nothing about any of these losses is particularly unique. I’ve made a schedule so I won’t go insane with the toddler. Five days ago, I wrote Walk/Adventure! on it, next to a cut-out illustration of a tiger—as if we’d see tigers on our walks. It was good to keep possibility alive.

At Literary Hub, novelist Heidi Pitlor writes about the elastic nature of time during her family’s quarantine in Massachusetts:

During a shutdown, the things that mark our days—commuting to work, sending our kids to school, having a drink with friends—vanish and time takes on a flat, seamless quality. Without some self-imposed structure, it’s easy to feel a little untethered. A friend recently posted on Facebook: “For those who have lost track, today is Blursday the fortyteenth of Maprilay.” ... Giving shape to time is especially important now, when the future is so shapeless. We do not know whether the virus will continue to rage for weeks or months or, lord help us, on and off for years. We do not know when we will feel safe again. And so many of us, minus those who are gifted at compartmentalization or denial, remain largely captive to fear. We may stay this way if we do not create at least the illusion of movement in our lives, our long days spent with ourselves or partners or families.

• What day is it today?

Novelist Lauren Groff writes at the New York Review of Books about trying to escape the prison of her fears while sequestered at home in Gainesville, Florida:

Some people have imaginations sparked only by what they can see; I blame this blinkered empiricism for the parks overwhelmed with people, the bars, until a few nights ago, thickly thronged. My imagination is the opposite. I fear everything invisible to me. From the enclosure of my house, I am afraid of the suffering that isn’t present before me, the people running out of money and food or drowning in the fluid in their lungs, the deaths of health-care workers now growing ill while performing their duties. I fear the federal government, which the right wing has so—intentionally—weakened that not only is it insufficient to help its people, it is actively standing in help’s way. I fear we won’t sufficiently punish the right. I fear leaving the house and spreading the disease. I fear what this time of fear is doing to my children, their imaginations, and their souls.

At ArtForum , Berlin-based critic and writer Kristian Vistrup Madsen reflects on martinis, melancholia, and Finnish artist Jaakko Pallasvuo’s 2018 graphic novel Retreat , in which three young people exile themselves in the woods:

In melancholia, the shape of what is ending, and its temporality, is sprawling and incomprehensible. The ambivalence makes it hard to bear. The world of Retreat is rendered in lush pink and purple watercolors, which dissolve into wild and messy abstractions. In apocalypse, the divisions established in genesis bleed back out. My own Corona-retreat is similarly soft, color-field like, each day a blurred succession of quarantinis, YouTube–yoga, and televized press conferences. As restrictions mount, so does abstraction. For now, I’m still rooting for love to save the world.

At the Paris Review , Matt Levin writes about reading Virginia Woolf’s novel The Waves during quarantine:

A retreat, a quarantine, a sickness—they simultaneously distort and clarify, curtail and expand. It is an ideal state in which to read literature with a reputation for difficulty and inaccessibility, those hermetic books shorn of the handholds of conventional plot or characterization or description. A novel like Virginia Woolf’s The Waves is perfect for the state of interiority induced by quarantine—a story of three men and three women, meeting after the death of a mutual friend, told entirely in the overlapping internal monologues of the six, interspersed only with sections of pure, achingly beautiful descriptions of the natural world, a day’s procession and recession of light and waves. The novel is, in my mind’s eye, a perfectly spherical object. It is translucent and shimmering and infinitely fragile, prone to shatter at the slightest disturbance. It is not a book that can be read in snatches on the subway—it demands total absorption. Though it revels in a stark emotional nakedness, the book remains aloof, remote in its own deep self-absorption.

• Vox is starting a book club. Come read with us!

In an essay for the Financial Times, novelist Arundhati Roy writes with anger about Indian Prime Minister Narendra Modi’s anemic response to the threat, but also offers a glimmer of hope for the future:

Historically, pandemics have forced humans to break with the past and imagine their world anew. This one is no different. It is a portal, a gateway between one world and the next. We can choose to walk through it, dragging the carcasses of our prejudice and hatred, our avarice, our data banks and dead ideas, our dead rivers and smoky skies behind us. Or we can walk through lightly, with little luggage, ready to imagine another world. And ready to fight for it.

From Boston, Nora Caplan-Bricker writes in The Point about the strange contraction of space under quarantine, in which a friend in Beirut is as close as the one around the corner in the same city:

It’s a nice illusion—nice to feel like we’re in it together, even if my real world has shrunk to one person, my husband, who sits with his laptop in the other room. It’s nice in the same way as reading those essays that reframe social distancing as solidarity. “We must begin to see the negative space as clearly as the positive, to know what we don’t do is also brilliant and full of love,” the poet Anne Boyer wrote on March 10th, the day that Massachusetts declared a state of emergency. If you squint, you could almost make sense of this quarantine as an effort to flatten, along with the curve, the distinctions we make between our bonds with others. Right now, I care for my neighbor in the same way I demonstrate love for my mother: in all instances, I stay away. And in moments this month, I have loved strangers with an intensity that is new to me. On March 14th, the Saturday night after the end of life as we knew it, I went out with my dog and found the street silent: no lines for restaurants, no children on bicycles, no couples strolling with little cups of ice cream. It had taken the combined will of thousands of people to deliver such a sudden and complete emptiness. I felt so grateful, and so bereft.

And on his own website, musician and artist David Byrne writes about rediscovering the value of working for collective good , saying that “what is happening now is an opportunity to learn how to change our behavior”:

In emergencies, citizens can suddenly cooperate and collaborate. Change can happen. We’re going to need to work together as the effects of climate change ramp up. In order for capitalism to survive in any form, we will have to be a little more socialist. Here is an opportunity for us to see things differently — to see that we really are all connected — and adjust our behavior accordingly. Are we willing to do this? Is this moment an opportunity to see how truly interdependent we all are? To live in a world that is different and better than the one we live in now? We might be too far down the road to test every asymptomatic person, but a change in our mindsets, in how we view our neighbors, could lay the groundwork for the collective action we’ll need to deal with other global crises. The time to see how connected we all are is now.

The portrait these writers paint of a world under quarantine is multifaceted. Our worlds have contracted to the confines of our homes, and yet in some ways we’re more connected than ever to one another. We feel fear and boredom, anger and gratitude, frustration and strange peace. Uncertainty drives us to find metaphors and images that will let us wrap our minds around what is happening.

Yet there’s no single “what” that is happening. Everyone is contending with the pandemic and its effects from different places and in different ways. Reading others’ experiences — even the most frightening ones — can help alleviate the loneliness and dread, a little, and remind us that what we’re going through is both unique and shared by all.

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Life before COVID-19: how was the World actually performing?

• Published: 11 January 2021
• Volume 55 , pages 1871–1888, ( 2021 )

Cite this article

• Salvatore F. Pileggi   ORCID: orcid.org/0000-0001-9722-2205 1 , 2  

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The COVID-19 pandemic has suddenly and deeply changed our lives in a way comparable with the most traumatic events in history, such as a World war. With millions of people infected around the World and already thousands of deaths, there is still a great uncertainty on the actual evolution of the crisis, as well as on the possible post-crisis scenarios, which depend on a number of key variables and factors (e.g. a treatment, a vaccine or some kind of immunity). Despite the optimism enforced by the positive results recently achieved to produce a vaccine, uncertainty is probably still somehow the predominant feeling. From a more philosophical perspective, the COVID-19 drama is also a kind of stress-test for our global system and, probably, an opportunity to reconsider some aspects underpinning it, as well as its sustainability. In this article we focus on the pre-crisis situation by combining a number of selected global indicators that are likely to represent measures of different aspects of life. How was the World actually performing? We have defined 6 macro-categories and inferred their relevance from different sources. Results show that economic-oriented priorities correspond to positive performances, while all other distributions point to a negative performance. Additionally, balanced and economy-focused distributions of weights propose an optimistic interpretation of performance regardless of the absolute score.

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1 Introduction

The unpredictable and overwhelming COVID-19 pandemic has completely and radically changed our lives and lifestyle in a way comparable with the most traumatic events in history, such as a World war. With millions of people infected around the World and already thousands of deaths (Dong et al. 2020 ), there is still a great uncertainty on the actual evolving of the crisis, as well as on the possible post-crisis scenarios, which depend on a number of key variables and factors (e.g. a treatment Felsenstein et al. 2020 , a vaccine Le et al. 2020 or some kind of immunity Weitz et al. 2020 ). Despite the optimism enforced by the positive results recently achieved to produce a vaccine, uncertainty is probably still somehow the predominant feeling (Chater 2020 ).

The whole scientific community is currently committed to face the challenging situation and to provide solutions and mitigation plans as a response to the complex dynamics at different levels. Indeed, the actual impact of COVID-19 on the different aspects of life (e.g. socio-economic Bashir et al. 2020 , environmental Collivignarelli et al. 2020 and psycological Fofana et al. 2020 ) is still not completely clear. Even relatively obvious or largely predictable macro-effects, such as a huge economic recession, present great elements of uncertainty at the moment (Altig et al. 2020 ). Additionally, a large number of studies have been conducted to explore the role of different factors [e.g. temperature Jamil et al. 2020 and air pollution  Fattorini and Regoli ( 2020 )].

From a more philosophical perspective, the COVID-19 drama is also a kind of stress-test for our system and, probably, an opportunity to reconsider some aspects underpinning it, as well as its sustainability (Naidoo and Fisher 2020 ). However, in order to re-design the World and our lives accordingly, we should first of all fully understand them. We definitely recognise the importance of cultural factors, opinions, personal values and beliefs. At the same time, we believe that it would be valuable to understand global performance in a data-driven and relatively systematic way.

In this article we focus on the pre-crisis situation by combining a number of selected global indicators to represent macro-categories that are likely to represent measures of different aspects of life: how was the World actually performing before pandemic?

We believe that answering the previously stated research question by adopting a relatively unbiased and customizable analysis framework can first of all (1) contribute to have a concise understanding of global development evolution and its priorities in the pre-pandemic period; additionally, it should (2) facilitate a better holistic understanding of the post-pandemic scenario; last but not least, (3) a similar approach can be adopted to estimate and analyse more specific aspects (e.g. global or country resilience to pandemic).

Previous work and background This paper is based on the method proposed in Pileggi ( 2020 ) which adopts a Multi-Criteria Decision Analysis (MCDA) philosophy (Ishizaka and Nemery 2013 ; Velasquez and Hester 2013 ). That paper focuses on the method in itself, which is explained in detail and applied to a number of examples using real data. This work is conceptually different and addresses the result, as the method previously defined has been applied to concretely measure global performance from heterogeneous criteria with emphasis on sustainable development (Hopwood et al. 2005 ). The idea of indices in such an area (e.g. Bravo 2014 ; Shaker 2018 ; Barrera-Roldán and Saldıvar-Valdés 2002 ) is a well consolidated concept. Furthermore, many studies explicitely focus on underlying correlations (e.g. Shaker 2018 , 2015 ).

As discussed later on in the paper, the original method has been slightly modified for this concrete application: on one side, the definition of the categories and their relation with numerical indicators has been simplified (see Sect.  3.1 ); on the other side, some extension has been provided in the weighting phase to better model the trade-offs existing among the different aspects considered (see Sect.  4.1 ). Last but not least, the interpretation of computations has been better formalised (see Sect.  5 ).

Structure of the paper This introductory part is followed by a detailed description of the research methodology. Each of the three phases identified in the methodological section is object of one of the core sections which deal, respectively, with the selection of criteria (Sect.  3 ), the weighting of such criteria (Sect.  4 ) and the performance analysis based on the resulting computations (Sect.  5 ). The paper finishes with a typical conclusions and future work section.

2 Methodology and approach

The methodology adopted in this study is summarised in concept in Fig.  1 . The target system is modelled by selecting a number of categorised indicators, which are global indicators in this study. The model also assumes weights and semantics associated with indicators and it’s the input for the computational method (Pileggi 2020 ). Interpretations are based on both qualitative and quantitative metrics. The three main seamless phases are briefly discussed in this section both with key design decisions, possible biases and uncertainties.

Method in concept. The target system is modelled by a number of categorised indicators and by the weights and the semantics associated. Such a model is the input for the computational method. Results are analysed by adopting qualitative and quantitative metrics

Criteria selection: macro-categories and representative indicators The normal approach (adopted also in previous work (Pileggi 2020 ) as well as by many reputable studies and publications, such as Our World in Data ) is to group the different indicators in classes which represent, therefore, an abstracted categorization of the considered indicators. It is very useful, especially considering the great availability of data, dependencies and the need to consider multiple aspects together.

In the context of this work, we have defined a number of categories of interest, each one represented by one single indicator that should be chosen to effectively characterise the target category. In terms of model (Fig.  1 ), given M categories and N indicators, we are assuming \(N=M\) and cardinality 1:1. Such a simplification allows an easier weighting and modelling within the method adopted (Pileggi 2020 ). We are assuming the definition of categories and the selection of representative indicators as an intrinsic bias, which is referred to as selection bias . Additionally, as the different indicators are expressed by different units and scales which don’t necessarily reflect their relevance in the resulting system or model, we assume a second kind of bias called numerical bias . The latter will be further discussed in Sect.  3.1 .

Weighting Weighting the target categories or indicators is a critical step. Indeed, while indicators themselves may be considered objective measures, their weighting should reflect the different relevance/importance of the various criteria in the context of the considered system or model. Weights may be estimated in different ways. For instance, they may reflect the opinions within a given group or community, normally elicited by surveys or interviews. Alternatively, weights may be inferred by capturing input parameters by the users of tools that adopt the method (Pileggi 2020 ). Either ways, to be relevant, the weighting should be based on a significant number of samples. Moreover, in general, survey/interview defines a static approach as it is based on a concrete selection of indicators. Changing indicators implies the need to re-estimate weights. Such a process is very demanding and definitely it is not agile.

In this study we have adopted a more pragmatic and, at the same time, flexible approach to establish weights that are inferred by analysing reports on global priorities, issues or challenges. Although, due to the different intent and extent of the selected reports, it is not possible to define a systematic method to infer weights, this approach assures weighting according to different foci and perspectives. As proposed later on in the paper, the analysis of different reports leads to weight configurations that may vary very much from each other.

Last but not least, unlike in the original method, in this work we assume finite resource for weighting to better model the trade-offs raising in a limited resource world (see Sect.  4 ).

Computation and analysis The final step is the computation of the results based on the input as defined in the two previous phases. The computational method should support the systematic combination of heterogeneous indicators and associated semantics, measure uncertainty and biases, as well as provide a framework for the interpretation of results. Results based on the application of the original method (Pileggi 2020 ) with the modifications previously explained are discussed in Sect.  5 .

3 Categories and indicators

The very first logical step of the study assumes the definition of macro-categories and the consequent selection of representative indicators. Such a step is described in the following subsection, while Sect.  3.2 deals with numerical bias and its minimization.

3.1 Categories

Inspired by Our World in Data , we have defined our own marco-categories (summary in Table  1 ) reflecting different aspects of life as follows:

Environment/sustainability Several indicators might represent this macro-category as either global environmental measures (e.g. temperature anomaly or CO2 emissions) or indicators in sub-categories (e.g. energy) potentially express the performance trend. In the context of this work, we consider temperature anomaly (Morice et al. 2012 ; Ritchie and Roser 2017 ) as a representative indicator which we want, evidently, to decrease.

Health/demographic change Life expectancy (Temperature 2020 ; Riley 2005 ; Zijdeman and Ribeira da Silva 2005 ; Max Roser and Ritchie 2013 ) has been selected to represent this macro-category. Indeed, an increasing life expectancy reflects, normally, an improved healthcare, as well as it implies population increasing. In terms of wished trend, we want life expectancy to increase, although an higher population may have negative implications in terms of global sustainability.

Economy It is represented by the classic GDP per capita (World Development Indicators, Roser 2013b ), as more sophisticated indicators (e.g. Economic Complexity Index Hausmann et al. 2014 ) are normally understood at a country level and might be not very indicative if considered globally. The GDP represents somehow an economical model that assumes never ending growing. The impact of the COVID-19 pandemic on global economy is expected to be much more consistent than in recent crisis (Kotz 2009 ) and to be comparable with the second World war.

Poverty/inequality We consider that the number of people living in extreme poverty (Roser and Ortiz-Ospina 2013 ; Ravallion 2015 ) is the ideal measure to properly integrate economic indicators that express a generic increasing well-being by introducing the concept of inequality. Although we recognise an intrinsic interdependency, we prefer to keep this category separated from the previous one as we want to be able to differentiate ideas and concerns related to the economic growth in itself from the others that explicitly address poverty and inequality.

Human rights/freedom By considering democracy as one of the most relevant achievements of all times, we believe that the number of people living in democracy (Roser 2013a ) may be an effective representative for human rights and, more in general, freedom. Indeed, we consider democracy as a condition necessary (although not always sufficient) to create a socio-political environment in which individual freedom and human rights are likely to be fully respected.

Violence/instability The selection of a single indicator to express violence and instability in general terms is not easy. Looking at recent happenings, we consider that measures related to terrorism (Ritchie et al. 2013 ) may be a very reasonable choice. From one side, it’s not always easy to understand terrorism and classify terrorist attacks according to the same criteria worldwide. However, a clear definition for terrorism and a number of unanimously recognised principles currently exist (Ritchie et al. 2013 ). Terrorism is normally generated by situations of war or local conflict and it definitely causes uncertainty, violence and instability.

All indicators selected are based on objective measures, while others that result from perceptions or opinions (e.g. happiness Frey and Stutzer 2012 ) have not been included.

For the numerical analysis proposed in the paper, we are considering recent years and, more concretely, the time range 2000–2015. Unfortunately, it is not possible to include in the study later years as the indicator measuring people currently living in democracy is available only up to 2015. As per previous explanations, we consider such an indicator as very relevant for the extent and the intent of this research, so we prefer to keep it and reduce the target time range. Additionally, the indicator on people living in extreme poverty is measured at a different granularity of all others, which are available by year. We have indeed adopted approximations considering the available values for the years 2002, 2005, 2008, 2010, 2011, 2012, 2013 and 2015.

In terms of wished trends (Table  1 ), we want the temperature anomaly, people living in poverty and deaths caused by terrorism to decrease, while an increasing trend is wanted for life expectancy, people living in democracy and GDP. The actual trends in the considered time range is shown in Fig.  2 on the left. In the same figure, the contribution to global performance by considering the wished trends (Pileggi 2020 ) is shown on the right. According to this view, positive trends in the chart contributes positively to global performance. Likewise, negative trends have a negative impact on the performance.

Looking at the data reported, health/demographics, economy, poverty/inequality and freedom/human rights are positively performing. On the other side, environment/sustainability and violence/instability present strongly negative performance.

Selected indicators expressed as the percentage of variation with respect to the initial state (left). The contribution of the different indicators to performance as the function of the associated wished trend is reported on the right

3.2 Dealing with numerical bias

At a more theoretical level, the definition of a restricted number of meaningful categories in the extent and intent of the current study can be considered a kind of bias in itself. It’s somehow inherent in study design.

At a practical level, it is almost impossible to provide a numerically balanced set of indicators. Indeed, indicators are normally very heterogeneous, adopts their own units of measure and may present very different numerical variations. In general, the variation of a given indicator is not comparable in terms of relevance with the variation of another indicators. Therefore, numerical proportions are not semantically relevant for the purpose of the considered study, meaning that numerical variations are not necessarily proportional with the relevance in the system or model.

We have represented all indicators uniformly as the percentage variation with respect to the initial state. As shown in Fig.  2 , for the considered set of indicators, the variation of deaths by terrorism is numerically much more relevant than any other. Also the temperature anomaly presents a strong pattern in this sense. However, it is not numerically comparable with the previous. As both indicators contribute potentially in a negative way on global performance, the resulting indicator framework is strongly biased (numerically) in this case and may affect the fairness of the computation.

The numerical differences among the considered indicators imply the need to deal with different scales when computing the different aspects together. In order to minimise numerical biases, we adopt the mechanism described in Pileggi ( 2020 ) in addition to weighting. A detailed description of such an adaptive mechanism is out of the scope of the paper. An example of the numerical bias using and not using the mechanism is reported in Fig.  3 .

Visualization of numerical bias by considering a linear combination of the different criteria by adopting the reference computational method (Pileggi 2020 ) (left). Such numerical bias can be reduced by applying adaptive tuning as per reference method (Pileggi 2020 ) (right)

4 Weighting

Once target criteria are defined, the weighting stage may result extremely subjective. The most natural way to weight criteria is probably by survey, as it is relatively simple to map weights into an opinion-based survey. In such a way, opinions from a generic public as well as opinions within defined communities may be captured and converted in a corresponding set of weights.

However, capturing people’s opinions in a meaningful way requires a large number of samples. Therefore, we have preferred to adopt a completely different and more pragmatic approach that aims to infer weights from the analysis of popular reports (e.g. from United Nations Footnote 1 and Global Economic Forum Footnote 2 ). On one side, the simplified approach adopted in the selection phase allows to weight categories rather than single indicators. It makes the mapping much easier. On the other side, the interpretation of certain kind of report may be subjective.

In the following subsections, we first describe an extension to the reference method to better model existing trade-offs and, then, we discuss the inference of weight sets from different sources of information.

4.1 Finite-resource assumption to model trade-offs

The original method (Pileggi 2020 ) doesn’t assume specific constraints for weights: the different indicators are weighted independently within a minimum value \(W_{min}\) and a maximum value \(W_{max}\) . Thus, any indicator i is associated with the corresponding weight \(W_{min} \leqslant w_i \leqslant W_{max}\) , for instance in a range [0,10].

That independent weighting intrinsically assumes an infinite resource model. For instance, it is possible to associate the maximum weight with all indicators ( \(w_i=W_{max},\forall i\) ). It doesn’t force decisions which should model the trade-offs existing among the different aspects of life. In order to model such trade-offs in a more effective way, we introduce a constraint for the overall weighting value, \(W_{tot}=\sum _{i=1}^{n}{w_i} \leq nk\) , where n is the number of considered criteria and k is a value between \(W_{min}\) and \(W_{max}\) . In the context of this work we are using six different criteria ( \(n=6\) ) and weighting in the range [1,10] ( \(1 \leq w_i \leq 10, \forall {i}\) ) rather than [0,10] as we want all criteria to contribute to overall performance. We consider \(k=5\) , which implies \(W_{tot}=30\) .

4.2 Weighting based on report analysis

In this sub-section we propose different weightings based on the analysis of different sources of information. As previously explained, probably such an inference cannot be completely objective. In order to minimise the impact of interpretations and biases in the analysis, for each case considered, the criteria and conclusions are explained and briefly discussed. Additionally, we have restricted the analysis to sources of information that allow a relative easy mapping. We have excluded those sources that potentially provide very good insight but are objectively hard to be converted in a clear weight set to the target criteria.

A summary of the weights produced by analysing the different reports is proposed in Fig.  4 . Each case is separately analysed and explained in the remaining part of this sub-section.

Weighting based on the analysis of different sources. Each weights set is compared with an homogeneous distribution of the resources—i.e. Neutral Weighting

Weighting based on the analysis of UN Global Issues The UN Global Issues report proposes 22 different global issues. Each issue in the report can be associated to no-one, one or more than one of the categories identified in this study.

According to our analysis, the category Environment/Sustainability is associated with 5 issues from the report (Atomic Energy, Climate Change, Food, Water), Health/Demography with 5 issues (Africa, Ageing, AIDS, Health, Population), Economy with no issue directly, Poverty/Inequality with 6 issues (Africa, Children, Decolonization, Ending Poverty, Food, Water), Human Rights/Freedom with 6 issues (Africa, Democracy, Gender Equality, Human Rights, International Law and Justice, Refugees) and Violence/Instability with 2 issues (Africa, Peace&Security). Resulting weights are reported in Table  2 . As previously discussed, the minimum weight assumed is 1.

Weighting based on the analysis of WEF 10 biggest global challenges (2016) The WEF 10 biggest global challenges [8] is a report with a much more economic focus. The criteria to map the 10 challenges in the report into weights are the same as in the previous case.

From our analysis, Environment/Sustainability is directly related to 2 challenges (Food Security, Climate Change), Health/Demographics to 1 challenge (Healthcare), Economy to 5 challenges (Inclusive Growth, Unemployment, Financial Crisis, Global Trade, Investment Strategy), Poverty/Inequality to 2 challenges (Food Security, Inclusive Growth), Human Rights/Freedom to 1 challenge (Gender Equality) and Violence/Instability to no challenge. The resulting weighing is reported in Table  3 .

Weighting based on the analysis of 10 most important global issues from The Borgen Project The Borgen Project, a nonprofit organization that is addressing poverty and hunger, has provided a list of 10 most important global issues [5].

According to our analysis of such a source, Environment/Sustainability is directly associated with 3 of the 10 issues (Climate Change, Pollution), Health/Demographics with 4 (Pollution, Security and Wellbeing, Malnourishment and Hunger, Substance Abuse), Economy with 1 (Unemployment), Poverty/Inequality with 3 (Lack of Education, Malnourishment and Hunger, Security and Wellbeing), Human Rights/Freedom with 1 (Government Corruption) and Violence/Instability with 3 (Violence, Security and Wellbeing, Terrorism). The resulting weights are reported in Table  4 .

Weighting based on the analysis of Global Shapers Survey 2017 Global Shapers Survey 2017 by WEF reflects opinion of millennials. Business Insider Australia has recently provided a list of the 10 most critical problems in the World according to millennials based on the Global Shapers Survey. In order to assure uniformity and consistency with previous cases, we have considered the list of problems provided but not the relevance associated with each of them.

According to our analysis, Environment/Sustainability matches with 2 problems (Food and water security, Climate change/Destruction of nature), Health/Demographics with 1 (Safety/Security/Wellbeing), Economy with 1 (Lack of economic opportunity and unemployment), Poverty/Inequality with 4 (Lack of education, Food and water security, Poverty, Inequality), Human Rights/Freedom with 1 (Government accountability and transparency/Corruption) and Violence/Instability with 3 (Safety/Security/Wellbeing, Religious conflicts, Large scale conflict/Wars ). Weights are reported in Table  5 .

5 Performance analysis

Performance analysis is based on two main metrics as follows:

Score This is the primary metric for analysis and it is based uniquely on the absolute performance according to computations (Pileggi 2020 ): positive scores are associated with positive performance, as well as negative scores correspond to negative performance.

Interpretation It is a relative metric defined by comparing the score of a given computation with the corresponding neutral computation, which assumes fair weighting (Pileggi 2020 ). In qualitative terms, scores higher than neutral computation correspond to an optimistic interpretation, while lower scores are associated with a pessimistic interpretation.

The two metrics as defined are completely independent as all qualitative combinations of the two metrics (positive/optimistic, positive/pessimistic, negative/optimistic and negative/pessimistic) are possible.

Looking at the analysis framework more holistically, two additional analysis factors may be considered:

Uncertainty In the context of this study, rather than a proper uncertainty, such a metric defines higher and lower bounds based on the potential weighting variance. Such an estimation provides a more consistent support for analysis in context.

Numerical bias Even though it is limited by the method adopted, numerical bias directly affects the absolute result. It is expressed by the neutral computation and can play a relevant role not only in the analysis phase but also when selecting criteria, as it can drive the selection of balanced set of indicators.

Computations for the different weight sets are presented in Fig.  5 , while a qualitative summary of results is presented in Table  6 .

Looking at Fig.  5 , the score associated with the different weight sets is represented by the blue line. Such a score is compared with the corresponding neutral computations in the charts on the left, while it is represented both with extreme computations in the charts on the right.

Weights from the analysis of UN Global Issues propose a relatively balanced distribution with a priority on Poverty/Inequality, Human Rights/Freedom, Health/Demographics and Environment/Sustainability. Additionally, there is a relative low priority for Violence/Instability and no economical focus. The resulting computation shows contrasting results, including a negative performance but also an optimistic interpretation. The weight set resulting from the analysis of the 10 biggest global challenges by WEF presents a much more economic oriented focus with a significant attention also for Environment/Sustainability and Poverty/Inequality. Human Rights/Freedom is still considered a kind of priority, while there is no explicit attention for Violence/Instability. Such a distribution of weights result in a very positive understanding of global performance. By focusing explicitly on addressing poverty, the weights from The Borgen Project proposes an interesting case study. The priority is clearly on 3 criteria, Health/Demographics, Poverty/Inequality and Violence/Instability. The computations associated show a clear negative trend in terms of either performance and interpretation (pessimistic). The analysis based on opinions of Millennials proposes a much more radical distribution with a clear priority on Poverty/Inequality and a significant attention on Environment/Sustainability and Violence/Instability. Final results are very similar to the ones related to the previous case (negative/pessimistic).

Average weights are reported in the last chart in Fig.  4 . As shown, the different case studies considered seem to balance each other. The average case proposes however a priority on Poverty/Inequality. Computations for the average case point out negative performance and optimistic interpretation (Fig. 6 ).

Computations based on the different weight sets. On the left, computed results assuming a given weights set are compared with the corresponding assuming homogeneous weighting ( Neutral Weighting ). On the right, results are considered looking at the extreme possible computations

Computation based on average weights. On the left, the computed result adopting average weighs is compared with the corresponding assuming homogeneous weighting ( Neutral Weighting ). On the right, that same result is considered looking at the extreme possible computations

As expected, the priorities defined by the different weight sets play a key role in the final assessment of performance from a quantitative perspective. However, as shown, it’s the contextual interpretation of such metrics that is considered the final assessment. We believe that the research framework proposed can be simple and effective to assess holistically the post-pandemic scenario, as well as to properly assess and reflect mindset and priorities changes behind the numerical estimations or measures.

Looking at possible interpretations of the results, we would like to remark that the method adopted works in terms of dynamic trend rather than of static snapshot, according to a philosophy of continuous evolution of the World. Such an approach is reflected in the computation of metrics. Therefore, a positive score in a given time-frame should be understood like the World is becoming a better place rather than the World is a good place (Pileggi 2020 ).

6 Conclusions and future work

By adopting a MCDA-based method, we considered 6 different macro-categories to measure global performance. The method provides a relatively fair analysis framework which allows the systematic combination of heterogeneous criteria. The weights associated with the different criteria play a key role in terms of final result. We have adopted a model that assumes finite resource in order to empathize the trade-offs existing among the different aspects considered.

In order to assess global performance and, more in general, global development trends, we have considered four different case studies with a very different focus. Results show that economic-oriented priorities correspond to positive performances, while all other distributions point to a negative performance. Additionally, balanced and economy-focused distributions of weights propose an optimistic interpretation of performance regardless of the absolute score.

Future work is expected to be developed in different directions. In line with the current focus, we will aim more fine grained studies at a country level. We will explore further secondary data sources to infer priorities accordingly (e.g. World Values Survey — http://www.worldvaluessurvey.org/ ). We will also propose and analyse in context additional case studies with a more community-oriented focus to be established by survey (e.g. Danowski and Park 2020 ).

The results obtained contribute to provide a concise understanding in context of the global development evolution and its underpinning priorities in the pre-pandemic period. We believe that such a dynamic snapshot can be useful to facilitate a better holistic understanding of the post-pandemic scenario that will be object of our future research. Indeed, we expect a significant mindset change triggered by the pandemic that will probably have an impact in setting priorities for a sustainable development. Last but not least, we will adopt a similar approach to estimate and analyse more specific aspects (e.g. global or country resilience to pandemic).

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Pileggi, S.F. Life before COVID-19: how was the World actually performing?. Qual Quant 55 , 1871–1888 (2021). https://doi.org/10.1007/s11135-020-01091-6

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Human Life Before and After COVID-19 Pandemics Research Paper

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Introduction

Human life: before and during covid-19, post covid-19, works cited.

The ongoing coronavirus disease of 2019 (COVID-19) can be studied as one of the most dangerous diseases in the recent times. This condition has led to unprecedented problems that have shaken all aspects of human life. Before the onset of this disease, many economies were performing optimally and capable of meeting the demands of the targeted citizens. Unfortunately, the condition forced governments to implement lockdown measures to reduce its spread. The imposed initiatives have affected human life and the global economy negatively by creating money problems, triggering unprecedented job cuts, and compelling companies to downsize.

COVID-19 is a pulmonary infection that has claimed thousands of life in different parts of the world. Experts have agreed that the disease was reported for the first time towards the end of 2019 in Wuhan, China. The forces of globalization and international transport are believed to have led to the spread of COVID-19 across the globe. By March 2020, this condition had already been recorded in most of the countries in different continents (Sikder et al. 328). The mysterious nature and complexity of COVID-19 forced governments to institute a wide range of measures that would minimize human contact and travel.

Some of the implemented strategies included washing hands with soaps, carrying and using hand sanitizers, and keeping social distance. Communities and regions would rely on the power of lockdown measures to achieve better results within a short period. Nonetheless, many people continued to contract the virus with some of them losing their lives (Lebleu). Within the last twelve months, international health organizations, pharmaceutical companies, and world health organization (WHO) have been working hard to get an effective vaccine and support the anticipated economic recovery.

Economic growth depends on the inputs the government provides and the measures different people put in place. Before COVID-19, many countries were performing optimally and engaging in international trade (“Coronavirus World Map”). Most of the people were able to get better jobs and earn competitive salaries. Most of the companies and industries were able to achieve their goals due to the processes of globalization. International trade was also undisturbed for many decades. Such forces were making it possible for some of the emerging economies to compete with giant ones (Sikder et al. 329). For example, China and Brazil were capable of producing additional goods and meeting the increasing demand in the global market.

These scenarios reveal that many people were leading better lives in most of the successful countries. For instance, unemployment rates had reduced significantly in both the developing and the developed world. The changing social and cultural dynamics were allowing people to travel across the globe and search for new job opportunities. Such trends were capable of transforming the experiences and lives of many citizens (Lebleu). Most of the implemented fiscal policies and economic stimulus packages had the potential to improve performance.

Unfortunately, the emergence of this pulmonary disease led to sweeping social, economic, and cultural changes across the globe. First, the imposed transportation measures and curfews worsened the situation for many people. Those who had travelled to other countries were unable to go back to their regions (Lebleu). Some were compelled to stay at home for over two months. Such developments affected the gains that had been recorded within the past two decades. Second, the lockdown measures meant that most of the people were unable to work or open their businesses. Such individuals could not earn any form of income, thereby being forced to exhaust their savings.

Third, most of governments were keen to introduce additional measures that could reduce the spread of COVID-19. For instance, individuals who were found to have the disease after testing were quarantined or hospitalized. The idea of contact tracing was also considered to identify people who could be having the condition. Consequently, millions of people across the globe were forced to isolate or engage in self-quarantine (see Fig. 1). Those who had travelled to countries with reported cases had to quarantine themselves. Such measures were capable of supporting the fight against the COVID-19 (Petersen et al. 234). However, the consequences were felt across the globe since many people lost their jobs or were unable to earn a living.

Fourth, the instituted measures proved to be more catastrophic and damaging to small businesses enterprises. Over the decades, such investments had been promoted due to their capabilities in addressing poverty and empowering more people to transform their lives. The lockdown measures compelled most of these entities to close for good. This trend meant that their owners would be unable to earn a living or pursue their social and economic goals (Kebede et al. e0233744). Those who lacked adequate savings were affected the most by these measures. Similarly, companies operating in different sectors had to downsize and reduce the number of workers to minimize infections.

While the outlined measures were critical to deal with this disease, many experts acknowledged that they were harmful to the lives and experiences of many individuals. Such initiatives led to numerous challenges associated with job losses and poor economic performance. The decision to close schools and other social functions indefinitely affected many people negatively (Petersen et al. 234). Some of the individuals who contracted the virus were forced to use their savings for medication purposes. These issues explain why life has changed significantly in different parts of the world. Without proper mechanisms and strategies to mitigate the disease, chances are high that more individuals will continue to experience similar challenges and be unable to achieve their maximum potential.

Currently, the impacts of COVID-19 are being experienced in both the developed and developing countries. However, Europe and America were some of the continents that suffered due to this disease. Some experts indicated that certain parameters were capable of describing such trends, including population size, age, and travel history (*). Fortunately, most of the nations in the African and Asian continents were not affected the most by this condition. Nonetheless, the implemented strategies were observed to trigger numerous challenges that would change the world forever.

Post COVID-19 is a hypothetical period or era that is expected after human beings succeeded in treating and getting rid of this disease. In such a scenario, scholars believe that most of the countries will continue to feel the impacts of this condition in different ways (Petersen et al. 236). For instance, those who lost their jobs in the developing world might be hit the hardest since businesses and industries might take long to recover. The predicted reliance on modern technologies means that individuals born from the 1980s would be able to use such innovations to complete their jobs (“Coronavirus World Map”). Older people will encounter additional challenges since they have been relying on traditional methods of production.

Governments in the underdeveloped world will be unable to provide adequate stimulus packages and financial resources to support emerging businesses. Such regions lack proper mechanisms and contingency plans to deal with the shocks of this pandemic. This reality means that most of the affected firms will be unable to hire more people and provide high-quality support to the targeted clients (“Coronavirus World Map”). The race to get a vaccine is an initiative that is expected to consume financial resources. More countries will also be compelled to incur huge expenses to acquire immunizations for their citizens. These priority areas would indicate that the recovery process might take longer that many people would expect.

Those who have lost their loved ones and jobs will find it hard to restore their life experiences. Governments might be unable to implement proper mechanisms and initiatives that can help more people to transform their situations (Petersen et al. 235). This knowledge should encourage policymakers and experts to consider some of the best ways to address the predicted challenges. Companies, institutions, and government agencies should also transform their models in such a way that they help mitigate the predicted predicaments in the anticipated post-COVID-19 world.

The ongoing COVID-19 has led to numerous challenges that have transformed human life in different ways. Most of the affected people have lost their jobs, thereby being unable to provide for their children and relatives. The instituted measures have worsened the condition for small-small businesses and workers. The move to find a vaccine for this disease means that governments will exhaust most of their resources, thereby making the process of recovery unpredictable. The developing world is expected to encounter numerous challenges due to the absence of proper contingency plans to deal with pandemics.

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Kebede, Yohannes, et al. “Knowledge, Perceptions and Preventive Practices towards COVID-19 Early in the Outbreak among Jimma University Medical Center Visitors, Southwest Ethiopia. PLoS ONE , vol. 15, no. 5, 2020, p. e0233744.

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Petersen, Eskild, et al. “COVID-19-We Urgently Need to Start Developing an Exit Strategy.” International Journal of Infectious Diseases, vol. 96, no. 1, 2020, pp. 233-239.

Sikder, Mukut, et al. “The Consequential Impact of the Covid-19 Pandemic on Global Emerging Economy.” American Journal of Economics, vol. 10, no. 6, 2020, pp. 325-331.

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Life before COVID-19: how was the World actually performing?

Affiliations.

• 1 School of Information, Systems and Modelling (ISM), University of Technology Sydney, Sydney, Australia.
• 2 Centre on Persuasive Systems for Wise Adaptive Living (PERSWADE), University of Technology Sydney, Sydney, Australia.
• PMID: 33456074
• PMCID: PMC7799424
• DOI: 10.1007/s11135-020-01091-6

The COVID-19 pandemic has suddenly and deeply changed our lives in a way comparable with the most traumatic events in history, such as a World war. With millions of people infected around the World and already thousands of deaths, there is still a great uncertainty on the actual evolution of the crisis, as well as on the possible post-crisis scenarios, which depend on a number of key variables and factors (e.g. a treatment, a vaccine or some kind of immunity). Despite the optimism enforced by the positive results recently achieved to produce a vaccine, uncertainty is probably still somehow the predominant feeling. From a more philosophical perspective, the COVID-19 drama is also a kind of stress-test for our global system and, probably, an opportunity to reconsider some aspects underpinning it, as well as its sustainability. In this article we focus on the pre-crisis situation by combining a number of selected global indicators that are likely to represent measures of different aspects of life. How was the World actually performing? We have defined 6 macro-categories and inferred their relevance from different sources. Results show that economic-oriented priorities correspond to positive performances, while all other distributions point to a negative performance. Additionally, balanced and economy-focused distributions of weights propose an optimistic interpretation of performance regardless of the absolute score.

Keywords: Global indicators; Multi-criteria decision analysis; Sustainability.

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Making visible the invisible: Supporting long COVID patients and the people caring for them

Assistant Professor, Faculty of Health Sciences; Senior Scientist, Pacific Institute on Pathogens, Pandemics and Society, Simon Fraser University

Assistant Professor, Faculty of Health Sciences, Simon Fraser University

Master's Student in Communication, Research Assistant for Pacific Institute on Pathogens, Pandemics and Society, Simon Fraser University

Academic Researcher, Director of Knowledge Mobilization, Pacific Institute on Pathogens, Pandemics and Society, Simon Fraser University

Disclosure statement

Kaylee Byers collaborates with and receives funding from the Post-COVID Interdisciplinary Care Network (PC-ICCN). "The MyGuide: Long COVID" is a resource created by the PC-ICCN. The work mentioned in this study is also funded in part by Michael Smith Health Research BC.

Kayli Jamieson collaborates with and receives funding from the B.C. Post-COVID Interdisciplinary Care Network (PC-ICCN). "The MyGuide: Long COVID" is a resource created by the PC-ICCN. The work mentioned in this study is also funded in part by Michael Smith Health Research BC. She also is a patient advisor for Long COVID The Answers.

Rackeb Tesfaye collaborates and receives funding from the PC-ICCN.

Julia Smith does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.

Simon Fraser University provides funding as a member of The Conversation CA.

Simon Fraser University provides funding as a member of The Conversation CA-FR.

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We are living through a mass-disabling event : Over 200 million people worldwide have long COVID . In Canada, one in nine people have experienced long COVID symptoms, and this is likely an underestimate.

Occurring weeks to months after a COVID-19 infection, this multi-system chronic illness has led to what some have called “ the shadow pandemic .” Although millions are navigating this new illness, four years into the pandemic both patients and their caregivers continue to face challenges accessing the information and care they need.

Most Canadians have had COVID, and at least one in five have been infected more than once . These trends are troubling because evidence suggests that the risk of acquiring long COVID increases with reinfection .

Long COVID is a complex illness that can present with a range of neurological and cardiovascular symptoms, such as post-exertional malaise , heart palpitations, cognitive impairment, fatigue and around 200 other symptoms . Some people with long COVID, often referred to as “longhaulers,” experience other under-researched syndromes, such as myalgic encephalomyelitis (ME) — also known as chronic fatigue syndrome.

With a suite of life-altering impacts, it is unsurprising that longhaulers may also experience impacts to their mental health, financial stability and relationships with others. These experiences are further exacerbated by the fact that there remains no cure for long COVID.

Over the past year, our team at Simon Fraser University has been speaking with long COVID patients, unpaid caregivers — such as family and friends who take on caregiving roles — clinicians and long COVID researchers to better understand patient experiences. In a new report , we documented a number of challenges patients and their caregivers face as well as recommendations to reduce these barriers.

Holistic approaches to care

Because symptoms and experiences vary, there is no single approach to care that will support all longhaulers. In British Columbia, post-COVID recovery clinics have been instrumental in creating specialized regional spaces for long COVID care.

These clinics have blended physician care, allied health care — such as physiotherapy and occupational therapy — and patient support groups. The closure of in-person clinics in transition to an online care system , in combination with long wait times, has meant that some patients have difficulty accessing these clinics.

Longhaulers have emphasized the value of specialized clinics and the need for holistic approaches that encompass allied health care to address the multifaceted impacts of long COVID on patients’ lives. Caregivers in particular expressed a need for mental health supports due to additional strains on their ability to work, their relationships and other responsibilities.

Holistic approaches are being embraced by some groups such as the Clinical Post COVID Society in the United Kingdom which brings together a “ diverse multidisciplinary clinical leadership team to reflect the varied expertise needed to care for patients with long COVID .” This example may serve as a helpful model for mobilizing these approaches in Canada.

Information

Access to information about long COVID remains a significant challenge. While longhaulers obtain information from health-care providers ( which can vary and be contradictory ), many are unable to meet with a doctor.

In B.C., approximately one in five people don’t have a family doctor . As a result, many are left to search for information themselves, wading through websites and articles while trying to discern what to trust. This can be especially challenging for people experiencing brain fog and fatigue, or those limited in time and resources due to caregiving, work or other demands on their time.

Patients, caregivers, clinicians and researchers suggest that the federal government create a national long COVID information platform providing details about symptoms, symptom management, a database of health-care practitioners providing long COVID care, and updates on recent research.

This could be modelled off the Post-COVID MyGuide, produced by the Post-COVID Interdisciplinary Clinical Care Network in B.C. . And while such resources are critical to supporting longhaulers, they are only useful if people access them. Therefore, more investment is needed to raise awareness of these platforms, evaluate their usefulness and explore ways to scale them for national use.

Another key outcome for improving care is refocusing preventive efforts to reduce reinfection risk for longhaulers, and future long COVID cases. Prevention measures might include campaigns promoting wearing respirators, regular vaccinations, increasing paid sick days or improving air filtration and ventilation indoors.

Preventing long COVID also involves taking these precautions in the absence of visible illness , as some early estimates suggested that 59 per cent of transmission occurs without symptoms .

Our team put these prevention measures into practice in April when we hosted a hybrid long COVID event with Pulitzer-prize winning journalist Ed Yong and a panel of patients, caregivers, clinicians and researchers. The event included safety measures such as mandatory masking in KN95/N95 respirators, rapid testing of participants and MERV-13 air filters .

Both during and since this event we have received numerous messages from longhaulers speaking to how the event and the safety measures in place were meaningful to them and made them feel seen. In order to do this, collectively (researchers, clinicians, policymakers and the public) can take many steps to create safe spaces as a baseline to reduce transmission risks.

As we continue to grapple with the enduring legacies of the COVID-19 pandemic, we must recognize that many communities have been disproportionately affected by SARS-CoV-2. To address these differential impacts, patients and caregivers advocate for continued investments in patient-centred research and care to create initiatives that resonate and are relevant for those most affected.

To further amplify these stories and raise awareness, our team is developing a long COVID “Day in the Life” photo exhibit in partnership with the Museum of Vancouver, where long COVID patients can share their stories and photos. Activities like this are one more step to making visible the experiences of people with an invisible illness.

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• Describing the effect of COVID-19 on sexual and healthcare-seeking behaviours of men who have sex with men in three counties in Kenya: a cross-sectional study
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• http://orcid.org/0000-0002-0982-1302 Souradet Y Shaw 1 ,
• Jeffery C S Biegun 2 ,
• Stella Leung 1 ,
• Shajy Isac 3 ,
• Helgar K Musyoki 4 ,
• Mary Mugambi 5 ,
• Japheth Kioko 6 ,
• Janet Musimbi 6 ,
• Kennedy Olango 7 ,
• Samuel Kuria 8 ,
• Martin K Ongaro 9 ,
• Jeffrey Walimbwa 10 ,
• http://orcid.org/0000-0002-7901-0257 Faran Emmanuel 11 ,
• James Blanchard 1 ,
• Michael Pickles 12 ,
• Sharmistha Mishra 13 ,
• Marissa L Becker 11 ,
• http://orcid.org/0000-0002-7673-4671 Lisa Lazarus 1 ,
• Robert Lorway 14 ,
• Parinita Bhattacharjee 6 , 14
• 1 Community Health Sciences , University of Manitoba , Winnipeg , Manitoba , Canada
• 2 Faculty of Arts , University of Manitoba , Winnipeg , Manitoba , Canada
• 3 India Health Action Trust , Delhi , India
• 4 National AIDS and STI Control Programme , Ministry of Health , Nairobi , Kenya
• 5 National Syndemic Disease Control Council , Nairobi , Kenya
• 6 Partners for Health and Development in Africa , Nairobi , Kenya
• 7 Men Against AIDS Youth Group , Kisumu , Kenya
• 8 Mamboleo Peer Empowerment Group , Kiambu , Kenya
• 9 HIV and AIDS People’s Alliance of Kenya , Mombasa , Kenya
• 10 G10 Research Advisory Committee , Nairobi , Kenya
• 11 University of Manitoba , Winnipeg , Manitoba , Canada
• 12 Imperial College London , London , UK
• 13 University of Toronto , Toronto , Ontario , Canada
• 14 Institute for Global Public Health , University of Manitoba , Winnipeg , Manitoba , Canada
• Correspondence to Dr Souradet Y Shaw, Community Health Sciences, University of Manitoba, Winnipeg, Canada; souradet.shaw{at}umanitoba.ca

Background While the COVID-19 pandemic disrupted HIV preventative services in sub-Saharan Africa, little is known about the specific impacts the pandemic has had on men who have sex with men (MSM) in Kenya.

Methods Data were from an HIV self-testing intervention implemented in Kisumu, Mombasa and Kiambu counties in Kenya. Baseline data collection took place from May to July 2019, and endline in August–October 2020, coinciding with the lifting of some COVID-19 mitigation measures. Using endline data, this study characterised the impact the pandemic had on participants’ risk behaviours, experience of violence and behaviours related to HIV. Logistic regression was used to understand factors related to changes in risk behaviours and experiences of violence; adjusted AORs (AORs) and 95% CIs are reported.

Results Median age was 24 years (IQR: 21–27). Most respondents (93.9%) reported no change or a decrease in the number of sexual partners (median number of male sexual partners: 2, IQR: 2–4). Some participants reported an increase in alcohol (10%) and drug (16%) consumption, while 40% and 28% reported decreases in alcohol and drug consumption, respectively. Approximately 3% and 10% reported an increase in violence from intimate partners and police/authorities, respectively. Compared with those with primary education, those with post-secondary education were 60% less likely to report an increase in the number of male sexual partners per week (AOR: 0.4, 95% CI: 0.2 to 0.9), while those who were HIV positive were at twofold the odds of reporting an increase or sustained levels of violence from intimate partners (AOR: 2.0, 95% CI: 1.1 to 4.0).

Conclusion The results of this study demonstrate heterogeneity in participants’ access to preventative HIV and clinical care services in Kenya after the onset of the COVID-19 epidemic. These results indicate the importance of responding to specific needs of MSM and adapting programmes during times of crisis.

• Sexual and Gender Minorities

Data availability statement

Data are available upon reasonable request. These data are confidential considering the fact that MSM are a criminalised population in Kenya and sharing names of sites and individual information may put their life in danger. Aggregate-level de-identified data tables are available and the following designate (Antony Kariri, Information Systems Manager at Partners for Health & Development in Africa: [email protected]) will be able to facilitate access to the data. A formal request needs to be made and a data sharing agreement will be signed before sharing the data.

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See:  https://creativecommons.org/licenses/by/4.0/ .

https://doi.org/10.1136/sextrans-2024-056105

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What is already known on this topic

Few studies have documented the impact of COVID-19 on HIV-related risk and protective behaviours among men who have sex with men in Kenya, although evidence suggests heterogeneity in COVID-19’s impact on behaviours.

What this study adds

The majority of participants reported minimal changes in alcohol and substance use, while behaviours and experiences of violence were linked to education level, place of residence and HIV status.

How this study might affect research, practice or policy

Public health crises impact populations heterogeneously; understanding gaps in care as well as risk behaviours during times of crises can help tailor future interventions.

Introduction

Researchers noted the potential for the COVID-19 pandemic to reverse a decade’s worth of gains made in the response to the HIV epidemic in sub-Saharan Africa. 1 2 Specifically, without adequate supplies of antiretroviral (ARV) therapy, coupled with interruptions to preventative modalities, such as condoms, peer education and HIV testing, increases in HIV mortality and incidence were expected. 1 Fortunately, programmes were able to adapt 3 4 ; for example, Kimani et al showed how programmes started distributing personal protective equipment, while also adapting how clinics were scheduled to meet with physical distancing guidelines. 3 The distributions of both COVID-19 and HIV are shaped by overlapping inequities, 3 5 such as socioeconomic marginalisation, and thus adverse impacts from both infections are shouldered by the most marginalised. Kenya has one of the largest HIV epidemics globally, 6 with key populations, such as men who have sex with men (MSM), prioritised in national HIV responses. 7–10 Same-sex sexual behaviours are criminalised in Kenya, leading to discrimination and limiting access to healthcare, increasing vulnerability of MSM to HIV and the direct and indirect impacts of COVID-19. 3 4 11 12 Peer-driven approaches have been a critical feature of community-based responses to HIV in Nairobi; however, the government of Kenya did not officially recognise peer workers as essential workers during the first wave of COVID-19, and thus workers were not eligible to receive personal protective equipment and training during the pandemic. 4

The first confirmed case of COVID-19 in Kenya was reported on 13 March 2020. 2 As with other countries, the government responded with a series of non-pharmaceutical interventions including curfews, restrictions on movement, and closures of restaurants and bars. 3 13 Some interventions were lifted at the end of June 2020. The pandemic disrupted health services delivery 14 and had a deleterious impact on the socioeconomic security of Kenya’s most vulnerable populations. 4 15 16 Although recent literature has detailed the adaptations MSM and MSM-specific HIV programmes made in response to COVID-19 in Kenya, 4 12 little is known about the specific impacts the pandemic had on MSM, including programmatic-relevant changes in men’s sexual partnership patterns, and healthcare access and utilisation. 17 Using data collected during the COVID-19 pandemic from the second round of serial cross-sectional integrated biological and behavioural assessments (IBBAs), implemented as part of the evaluation of a community-based HIV self-testing (HIVST) project, 18 19 the main objective of our analyses was to characterise the pandemic’s impact on participants’ risk behaviours, experience of violence and behaviours related to the prevention and treatment of HIV infection, including utilisation of HIV-related services. As a secondary analysis, we characterised the places where men met their sexual partners. Finally, factors associated with behaviours and experience of violence were examined. Understanding specific vulnerabilities and gaps in care exacerbated by the COVID-19 pandemic can help inform population-specific responses during times of crises. 5 20

Study setting

The University of Manitoba partnered with MSM-led community-based organisations (CBOs) and Kenya’s National AIDS & STI Control Programme (NASCOP) to design an intervention to promote HIVST in MSM communities in Kisumu, Mombasa and Kiambu counties. 18 These sites were chosen because of high HIV prevalence, with self-reported prevalence among MSM between 13% and 23% in 2017, 7 their large MSM communities 10 and well-established community health infrastructure for MSM. 21 The intervention targeted MSM above 15 years of age and used several delivery mechanisms for HIVST, including distribution through facility and community settings. As part of the evaluation of the HIVST project, serial cross-sectional IBBAs were conducted at baseline and endline, in May–July 2019 and August–October 2020, respectively; analyses are from the endline survey. We followed NASCOP’s guidelines in conducting sexual and reproductive health research with adolescent key populations whereby those 15 years and above are considered mature/emancipated minors. 22 Since HIV testing in Kenya without a guardian is allowed for those 15 years and above, 23 respondents were able to give consent and participate without guardian consent.

Study design and participants

MSM were recruited from physical and virtual sites 18 ; physical sites included locations such as bars, while virtual sites included web-based applications and social network sites. Endline data collection used the same sampling frame as the baseline survey; participants were included if they: (a) identified as male; (b) reported engaging in anal or oral sex with another male in the previous 12 months; and (c) were 15 years of age or above. A multistage cluster sampling approach involving physical and virtual sites was used to recruit 1200 participants (400 in each county); the methodology is described elsewhere. 18 Briefly, a sampling frame was generated using programmatic mapping and size estimation of physical and virtual sites. 10 24 25 Sites were sampled to recruit 200 MSM each from physical and virtual sites in each county. Recruitment involved random sampling of virtual and physical sites; for virtual sites, peer researchers used each selected site to further randomly recruit the predefined number of potential participants who were online when the peer researcher logged into the site. Respondents from both physical and virtual sites provided a list of known MSM contacts, from which a random sample of one contact was selected.

Data collection

Data collection took place in private spaces (eg, CBOs), at a time and location chosen by participants. Individuals were then asked to visit the specified data collection site, where they were invited to provide written informed consent; participants were informed they could choose to participate in all or some elements of the IBBA. Trained researchers administered a face-to-face structured questionnaire in Kiswahili or English, at the participant’s choosing. Participants were offered HIV testing and counselling with a rapid two-test algorithm as per Kenya national guidelines, 26 with on-site reporting of results. For positive results, participants were offered accompaniment to an MSM-focused clinic, or to a government testing and treatment clinic. All participants were provided with condoms, lubricants and information on HIVST. Those who were seronegative were offered HIV pre-exposure prophylaxis (PrEP). Participants were asked to provide a dried blood spot for HIV confirmatory serology, performed at the HIV National Laboratory in Nairobi, using the Bioelisa HIV test kit for screening and if positive, the Murex HIV1-2-O test for confirmation. Completed questionnaires were entered into an electronic database (CSPro, US Census Bureau and ICF International). 19

Measurement and data analysis

IBBAs were co-designed with community members, with the endline containing questions pertaining to the impact of COVID-19. These included questions on partnership patterns, service usage and experience of violence during the months between the onset of COVID-19 and June 2020. Three questions examined impact of COVID-19 on partnership patterns, including changes in the number of male sexual partners per week during the COVID-19 period, the average number of different male sexual partners participants had in a week and what locations they met their male sexual partners. Questions asked about service usage impact, including HIV testing, type of test accessed, whether men received PrEP and whether they received ARV. Finally, men were asked whether their alcohol use, drug consumption and experiences of violence from authorities and their intimate partners changed during the period of COVID-19 restrictions. The following binary outcomes were examined in bivariate and multivariable models: (1) increase in number of male sexual partners per week; (2) increase in alcohol use; (3) increase in substance use; (4) increased or sustained violence from police/authorities; and (5) increased or sustained violence from intimate partners. For the first three outcomes, responses were coded as ‘1’ if respondents answered ‘yes’ to whether number of male sexual partners, alcohol use and substance use had increased since the start of the COVID-19 pandemic in Kenya, respectively. Those answering ‘remained the same’ or ‘no’ were coded ‘0’. For the violence questions, those reporting ‘yes, there was an increase’ or ‘yes, remained the same’ were coded ‘1’, while those answering ‘no’ were coded ‘0’.

Sociodemographic characteristics at endline were described using proportions, means, medians and IQR, where appropriate. These characteristics include age group, county, highest level of education and monthly income; sexual behaviour including whether the participant preferred to meet their partners in physical sites, virtual sites or both, 18 preferred sexual position/role, age at first anal/oral sex with a man, number of different male partners in the past 1 month, receipt of money or gifts in exchange for sex with a man (ever) and condom use at last sex with a male partner. The following variables were used in bivariate and multivariable logistic regression models: age group, county, highest level of education, places where male partners met, sexual position preference, received money/gift in exchange for sex with a man (ever), condom use with last male sexual partner and HIV status. Crude and adjusted ORs (AORs) and their 95% CIs are reported from logistic regression models. Data were analysed with SAS V.9.4 (SAS Institute) and visualised using R (V.4.2.2).

Of the 1239 participants included in the endline survey, 179 were excluded because they answered ‘don’t know’ or ‘N/A’ to at least one of the following questions, prefaced with ‘During the period of COVID-19, ‘was there a change in the number of male sexual partners you had per week?’; ‘On average, how many different male sexual partners did you have in a week?’; ‘Was there a change in your alcohol drinking behaviour in comparison with other months?’ or ‘Did your drug use behaviour change compared with other months?’. Respondents were also excluded if they had missing data on any of the explanatory variables used in this study. A total of 1031 participants were included in the final analytical sample, although some analyses included fewer participants, due to the type of question answered (eg, only those reporting drug use were retained for questions about changes in drug use). Based on the sample of 1031 participants ( table 1 ), median age was 24 years (IQR: 21–27 years), with approximately one-third of participants (n=307, 29.8%) from Kiambu, while 388 (37.6%) and 336 (32.6%) participants were from Kisumu and Mombasa, respectively. Approximately 45% of participants had received post-secondary education. Most participants (68.4%) reported meeting partners at both physical and virtual sites. Approximately half of participants (48%) reported predominantly insertive sex, 62% reported ever receiving money or gifts in exchange for sex with a man, and 66% reported using condoms with their last male sexual partner. HIV prevalence was 19.6%.

• View inline

Selected characteristics, from endline survey, of men who have sex with men enrolled in HIV self-test study in Kisumu, Kiambu and Mombasa counties, Kenya, 2020 (N=1031)

Table 2 displays the impact COVID-19 had on participants. While some participants (6.1%) reported an increase in the period between the onset of the pandemic in Kenya and the endline survey, most experienced no change (50%) or a decrease (43.9%) in weekly number of male sexual partners. Of those reporting an increase in number of partners, the median number of unique partners was 2 (IQR: 2–4; online supplemental figure 1 ). Approximately 10% of participants reported an increase in alcohol, and of those reporting drug use, 16% reported an increase in use. Of those who answered (n=948), 11% (n=114) reported an increase in the amount of violence from police/authorities, while 2% (n=23) reported experiencing violence from this source, but at pre-pandemic levels. Of those participants who reported on their experience of violence from intimate partners (n=1029), 3% (n=34) reported an increase, while 4% (n=39) reported their experience of violence was unchanged from pre-pandemic times. Out of 185 eligible participants, 21.4% (n=40) reported being unable to obtain PrEP; similarly, of 84 eligible participants, only 1 reported being unable to obtain ARV. Out of 511 eligible participants, 20% were no longer able to obtain an HIVST; of 852 participants, 8.1% (n=69) could no longer meet with a peer educator and out of 828 participants, 4.1% (n=34) were unable to visit a drop-in clinic. Online supplemental figure 2 shows the types of HIV testing accessed for those due for an HIV test and were able to get tested. A total of 689 participants were due for an HIV test and received testing, while 201 participants (~20%) who were due for an HIV test reported that they could not get tested. The majority of respondents reported meeting their sexual partners through the internet and social media applications ( online supplemental figure 3 ); of interest is the wide disparity in use of social media and other technologies between sites, with men in Kiambu more likely to report use of WhatsApp and Facebook than the other two sites. Approximately 70% of men in Kiambu reported using Facebook and WhatsApp to connect with male sexual partners; in Kisumu and Mombasa, 33% and 43% reported using Facebook, respectively.

Supplemental material

Change in self-reported risk behaviours, experiences of violence, and use of HIV and other clinical services of men who have sex with men at endline survey, HIV self-test (HIVST) study in Kenya, 2020

Table 3 shows the distribution of participants’ characteristics by the five outcome variables, while online supplemental table 1 shows results from bivariate analyses. In bivariate analyses and relative to those reporting only primary education, participants reporting secondary (OR: 0.5, 95% CI: 0.2 to 0.9) and post-secondary education (OR: 0.4, 95% CI: 0.2 to 0.7) were less likely to report an increase in the number of sexual partners per week. Relative to participants from Kisumu, participants from Kiambu were more likely to report increases in alcohol use (OR: 2.6, 95% CI: 1.6 to 4.3), as were those with post-secondary education (OR: 3.8, 95% CI: 1.3 to 10.6). In adjusted analyses ( table 4 ) and at the p<0.05 level, post-secondary education remained significantly associated with being less likely to report an increase in male sexual partners (AOR: 0.4, 95% CI:0.2 to 0.9), relative to those with primary education. Participants with post-secondary education remained significantly more likely to report an increase in alcohol use (AOR: 3.4, 95% CI: 1.2 to 10.0). Finally, participants living with HIV were twofold more likely (AOR: 2.1, 95% CI: 1.1 to 4.0) to report increased/sustained violence from their intimate partners. In adjusted analyses, the association between virtual sites and increased/sustained violence (from police/authorities and intimate partners) was no longer statistically significant at the p<0.05 level.

Selected characteristics of men who have sex with men enrolled in HIV self-test study in Kisumu, Kiambu and Mombasa counties, by changes in risk behaviours and experiences of violence (Kenya, 2020)

Adjusted ORs (AORs) and 95% CIs from multivariable logistic regression models, association between selected characteristics and reported changes in risk behaviours and experiences of violence of men who have sex with men enrolled in HIV self-test study in Kisumu, Kiambu and Mombasa counties (Kenya, 2020)

The current study demonstrates some participants having increased difficulty accessing preventative HIV and clinical services in Kenya after the arrival of COVID-19. These results align with published literature on the impact of COVID-19. Rao et al , in a multicountry study of MSM, found that perceived access to HIV services was negatively impacted by country-level stringency of COVID-19 measures, suggesting that strategies to ensure continuity of care should be a priority for MSM in public health crises. 27 The authors also found a substantial reduction in access to HIV providers by MSM living with HIV. 27 Similarly, Muhula et al , using a sample of people living with HIV from Kibera settlement, demonstrated a substantial drop in HIV prevention, care and treatment services, including clients starting ARV during the first wave of COVID-19. The same study found an increase in PrEP dispensations, 2 suggesting programmes were able to adapt to COVID-19 in Kenya. It is worth noting that the majority of participants in our study reported little change in their ability to access services during the first wave of the COVID-19 pandemic, suggesting programmes in the three study sites were also able to adapt to the needs of participants, aligning with a recent study from Nairobi. 12

Our study showed that the pandemic resulted in some disruptions to HIV services, with 21.3% of eligible participants unable to access PrEP, while 8.5% of participants found it more difficult to access PrEP. Although 20% of eligible participants reported being unable to access a self-test, with another 16% reporting more difficulty accessing a self-test during this time, our group has demonstrated an overall increase in the use and awareness of HIVST between baseline and endline surveys, 28 suggesting access was not homogeneous overall. We found a portion of participants who reported higher or similar levels of intimate partner or police violence during the first wave COVID-19. However, while previous findings have suggested marginalised and vulnerable populations, particularly women, were more likely to experience higher rates of violence during the beginning of the COVID-19 pandemic, 29 the majority of participants in this study reported decreased experiences with violence. Intimate partner violence has been associated with a greater number of sexual partners in MSM populations, 30 and therefore a decrease in intimate partner violence may be linked to a decreased number of partners during COVID-19. Additionally, many participants in this study reportedly met partners through the internet ( online supplemental figure 3 ), which may explain some participants reporting decreased violence from police and/or authorities, as these ‘meet-ups’ were taking place predominantly online or at home. Further research should explore the context behind experiences of violence during the pandemic to inform tailored support for MSM.

Strengths and limitations

Our study had a number of strengths, including sampling from both physical and virtual sites, biological data on HIV status and the availability of data at the start of the pandemic in Kenya. Our study also had a number of limitations. First, data were collected via face-to-face interviews, and thus subject to social desirability bias, which may have resulted in under-reporting of behaviours. Second, the sampling method included recruitment of a limited number of contacts and may have resulted in selection bias, introducing a higher degree of homogeneity in samples. It should be noted that we have used similar representative sampling techniques across different countries (eg, India, Pakistan, Nigeria and Kenya) and in different contexts (eg, MSM, female sex workers, people who inject drugs). Finally, information on the impact of COVID-19 on participants was collected only at the beginning of the pandemic in Kenya; thus, longer-term impacts are not captured in survey responses; however, we expect that the most acute effects of the pandemic were most likely felt nearer to the start of the pandemic in Kenya.

In conclusion, it is apparent that services accessed by MSM in Kenya, as well as some risk and mitigation behaviours, were impacted by the COVID-19 pandemic. Although HIV programmes, led by community members, adapted to the direct and indirect impacts of the pandemic, heterogeneity in how MSM experienced those impacts exists, and points to the importance of population-specific responses during times of crises to meet protective and preventative healthcare needs.

Ethics statements

Patient consent for publication.

Consent obtained directly from patient(s).

Ethics approval

This study involves human participants and ethics approval was obtained from institutional review boards of the Universities of Nairobi (P557/08/2018) and Manitoba (HS22205). Participants gave informed consent to participate in the study before taking part.

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Supplementary materials

Supplementary data.

This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

• Data supplement 1

X @SouradetS, @mishrash

Contributors SYS, SL, PB and SI conceptualised the paper. SYS, SL and PB designed the plan of analysis. SYS, JCSB, SL, LL, SM and PB wrote the first draft of the paper with edits from SI, MLB, MP, SM, RL, FE and JB. All authors contributed to questionnaire design and interpretation of data and results, and all reviewed the manuscript and provided edits and suggestions. JB and PB conceptualised the larger study method. HM and PB generated the data, and JM, SK, JK, MM, MN and JO managed the data collection process. KO, MKO, MM and JW supported the design of the study and on-site data collection process. SI led questionnaire development and sampling design. SL conducted the data analyses. SYS did the final edit of the manuscript and is the guarantor of the manuscript.

Funding SYS is supported by a Tier 2 Canada Research Chair (950–232822). SM is supported by a Tier 2 Canada Research Chair. RL is supported by a Tier 2 Canada Research Chair. JB is supported by a Tier 1 Canada Research Chair. This study is made possible by the support of Bill & Melinda Gates Foundation (BMGF) under grant OPP11191068.

Disclaimer The views expressed here are those of the authors and do not necessarily reflect the official policy or position of BMGF.

Competing interests None declared.

Provenance and peer review Not commissioned; externally peer reviewed.

Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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• Methodist Debakey Cardiovasc J
• v.17(5); 2021

The Way Ahead: Life After COVID-19

Mouaz h. al-mallah.

1 Houston Methodist DeBakey Heart & Vascular Center, Houston, TX, US

Much has changed in the 2 years since the start of the coronavirus disease 19 (COVID-19) pandemic. The need for social distancing catalyzed the digitization of healthcare delivery and medical education—from telemedicine and virtual conferences to online residency/fellowship interviews. Vaccine development, particularly in the field of mRNA technology, led to widespread availability of safe and effective vaccines. With improved survival from acute infection, the healthcare system is dealing with the ever-growing cohort of patients with lingering symptoms. In addition, social media platforms have fueled a plethora of misinformation campaigns that have adversely affected prevention and control measures. In this review, we examine how COVID-19 has reshaped the healthcare system, and gauge its potential effects on life after the pandemic.

Introduction

In December 2021, after many months of living with the COVID-19 pandemic, the world is still looking for a way out of this healthcare crisis. As of this writing, more than 250 million people globally have been infected with SARS-CoV-2, the virus that causes coronavirus disease 19 (COVID-19), and nearly 5 million individuals lost their lives battling the complications of severe acute respiratory syndromes. 1 Many communities experienced multiple surges of the virus, with changes in normal life and restrictions to daily activities. The intensification of vaccination efforts brought about hope for a possible end to the pandemic. However, the continued emergence of variant strains and vaccine hesitancy have been persistent challenges in the US and globally. In this article, we review the long-term effect of COVID-19 on healthcare systems and envision the future of life after the pandemic ( Figure 1 ).

The long-term effects of the coronavirus disease 19 (COVID-19) pandemic on the healthcare system.

Since the beginning of the pandemic, there have been accelerated efforts to sequence the genetic material of the virus and build effective vaccines that decrease the risk of infection, hospitalization, and mortality. 2 At the time of this writing, more than 10 vaccines have been approved by local healthcare authorities in different parts of the world. 3 The pandemic has also driven innovation in the novel field of messenger ribonucleic acid (mRNA) vaccines. The US Food and Drug Administration (FDA) has approved the use of the Pfizer-BioNTech mRNA vaccine and given emergency use authorization to Moderna. 4 The mRNA vaccines have shown excellent efficacy against many of the strains, including the beta and delta strains.

More recently, booster doses have been approved by the FDA for individuals aged 65 years and older as well as individuals with comorbidities, in long-term care facilities, or at increased risk for COVID-19 exposure and transmission due to occupational or institutional settings. 5 Furthermore, the FDA has also given emergency use authorization for the Pfizer-BioNTech vaccine in individuals aged 12 to 17 years and, as of October 29, in children aged 5 to 11 years.

Although the fast-tracked vaccine production time led some skeptics to hypothesize safety concerns, the rate of adverse events has been very low. One complication that gained significant attention is myocarditis. 6 , 7 , 8 Emerging data have shown that young men are the most commonly affected demographic. Furthermore, the risk was elevated in the setting of a recent COVID-19 illness and after the second dose of the vaccine. 6 , 7 Although the rate of myocarditis is low and the majority of patients recover, the risk of recurrence in patients who developed myocarditis with the first dose or in patients with recent myocarditis is unclear. Similarly, the rate of recurrence after the second or booster doses also is unclear.

Vaccine Mandates

Multiple state and federal governments have issued vaccine mandates, and they have become a highly contested political issue in the United States. The Biden administration issued an executive order on September 9, 2021, requiring all federal employees to vaccinate. 9 Some state and local governments have also followed. 10

Multiple US healthcare systems have also issued COVID-19 vaccine mandates for employees. On March 31, 2021, Houston Methodist became the first healthcare system to mandate the vaccine for employees, and a wave of other healthcare systems followed suit. 11 As of this writing, more than 2,500 hospitals or health systems have followed Houston Methodist and mandated vaccines for their clinical and nonclinical staff. 12

Combating Misinformation

Since the beginning of the pandemic, misinformation has spread throughout the Internet and on social media platforms. 13 People have questioned the existence of the virus, the strain on healthcare systems, and the benefit of masks as well as emphasized the benefits of unproven therapies, many of which were useless and even harmful. 14 Political agendas have also played into the misinformation campaigns. Studies have shown that these misinformation campaigns have had measurable effects on the intent to vaccinate and created widespread fear and panic, ultimately contributing to the reduced number of people willing to vaccinate. 13 , 15 , 16 Tackling this will require concerted efforts by the government and private sector, particularly social media companies, to implement evidence-based communication strategies. 17 Individuals should also assume responsibility in seeking out accurate, evidence-based information for their own consumption.

Telemedicine

As many states and cities implemented measures to reduce transmission, telehealth emerged as the ideal tool to continue patient care while protecting the health of both patients and providers. Many patients preferred this option, especially when hospitals were dealing with record numbers of COVID-19 infections. In 2020, telemedicine was the main means by which ambulatory care was provided, accounting for 10% to 20% of visits when virus transmissibility was low and as high as 80% of visits during the surges. 18

Accordingly, the US Department of Health and Human Services relaxed enforcement of software-based Health Insurance Portability and Accountability Act violations, the Centers for Medicaid and Medicare Services provided waivers for telehealth reimbursements, and, in many instances, commercial insurances provided the same either directly or through mandates provided by local state governments. 19 , 20 The removal of regulatory and reimbursement barriers led to a dramatic increase in the use of telehealth, with some institutions reporting multifold increase in telehealth visits. 21

The pandemic also served as a catalyst for innovation in the software and hardware necessary for telemedicine. 22 For example, important tools were developed to enable secure connections with physicians and allow remote vital sign and weight monitoring. 23 , 24 Unfortunately, not all have equally benefitted from the expanded use of telehealth. Data indicate that minorities and disadvantaged groups often lack access to telehealth-based care. 25 Although the positive response and uptake by physicians and patients indicates the likelihood of telemedicine continuing past the pandemic, it remains to be seen whether the regulatory and reimbursement aspects will continue.

Post Covid-19 Condition

There is a growing body of evidence that some patients have prolonged recovery and/or residual symptoms after acute infection with COVID-19. The World Health Organization has defined this as “post COVID-19 condition.” Common presentation includes shortness of breath, palpitation, anxiety, and depression lingering for several months after acute infection. 26 , 27 Recent data also suggests that post COVID-19 condition might not be limited to somatic symptoms, with studies showing a 7-fold increased risk of developing depression and mental health issues. 28

Although the cause of these symptoms is not clear, one possible link that partly explains the prolonged shortness of breath experienced by some patients is COVID-19–associated myocarditis and the associated microvascular dysfunction. 26 As the pandemic continues and therapeutics improve survival from acute infection, the number of patients reporting post COVID-19 condition is predicted to grow. Several medical centers have already established clinics to better coordinate care and conduct research on the long-term impact and treatment of COVID-19. 29

Collateral Damage

Many patients delayed regular and preventive care during the pandemic due to fear of contracting COVID-19. 30 , 31 Such change in health-seeking behavior also extended to emergency conditions, with studies showing how some patients did not seek care for new onset chest pain. 32 Indirect indicators of this are the reduced rates of cardiovascular testing globally and within the United States 33 , 34 and the increased rate of myocardial infarctions and other emergencies seen on the trailing end of COVID-19–infection surges. 32 There has also been an increase in late complications of myocardial infarction such as ventricular septal rupture, a rare occurrence in the prepandemic reperfusion era and one partly explained by delayed care and ignored early warning signs. 35

Disparities in Healthcare

The pandemic exposed significant disparities in healthcare delivery, particularly among minorities. They were more likely to be affected by misinformation campaigns and less likely to accept research supporting clinical therapies and vaccines. Understanding the disparities and identifying measures to bridge the gap will be an important area of research for policy.

Globally, the pandemic also exposed significant inequities regarding vaccine access. While many developed countries were able to reach vaccination rates as high as 70%, rates in low-to-middle-income countries have remained low. 35 As the delta variant has clearly shown, no one is safe until everyone is safe. To this end, the World Health Organization and the COVAX (COVID-19 Vaccines Global Access) alliance have been a vital source of affordable vaccines. 36

Changes to Medical Education

The pandemic resulted in significant changes to both graduate and continued medical education. Much like patient-physician encounters, postgraduate training programs limited large face-to-face gatherings and transitioned all teaching to online platforms. 37 Residency and fellowship recruitment interviews also shifted to online settings. Lastly, there has been an exponential increase in the number of continued medical education offerings, with many societal meetings and conferences transitioning to online or hybrid formats. 38

The medical community has, for the most part, been very receptive to these changes, and it has afforded unforeseen advantages to trainees. Residency and fellowship applicants no longer need to bear the logistic and financial burden of in-person interviews. More importantly, virtual meetings and conferences have significantly increased audiences and, by extension, enabled the wider dissemination of medical knowledge.

The COVID-19 pandemic has dramatically changed clinical practice, medical education, and research. Beyond the immediate increase in morbidity and mortality, the healthcare system is having to deal with a growing cohort of patients with lingering symptoms. Misinformation, vaccine hesitancy, and vaccine inequity will be continuing challenges to attaining herd immunity. Clinicians, educators, and healthcare administrators will also have to determine how best to leverage the transition to virtual platforms. Lastly, healthcare leaders and policy makers will have to help the country and world chart a course through the end of the pandemic.

• The coronavirus disease 19 (COVID-19) pandemic has dramatically changed clinical practice, medical education, and research.
• It has brought about new challenges for the healthcare system, such as how best to combat misinformation, address the disproportionate impact on minorities and marginalized groups, and treat the ever-growing population of patients with lingering “long COVID” symptoms.
• The pandemic has also catalyzed much needed change in vaccine development, telemedicine, and medical education.
• Addressing these challenges and charting a way forward will require the concerted effort of clinicians, healthcare leaders, and policy makers.

Competing Interests

Dr. Al-Mallah has completed and submitted the Methodist DeBakey Cardiovascular Journal Conflict of Interest Statement and none were reported.

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‘Visionary’ study finds inflammation, evidence of Covid virus years after infection

By Isabella Cueto July 3, 2024

R emember when we thought Covid was a two-week illness? So does Michael Peluso, assistant professor of medicine at the University of California, San Francisco. 

He recalls the rush to study acute Covid infection, and the crush of resulting papers. But Peluso, an HIV researcher, knew what his team excelled at: following people over the long term. 

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So they adapted their HIV research infrastructure to study Covid patients. The LIINC program, short for “Long-term Impact of Infection with Novel Coronavirus,” started in San Francisco at the very beginning of the pandemic. By April 2020, the team was already seeing patients come in with lingering illness and effects of Covid — in those early days still unnamed and unpublicized as long Covid. They planned to follow people’s progress for three months after they were infected with the virus.

By the fall, the investigators had rewritten their plans. Some people’s symptoms were so persistent, Peluso realized they had to follow patients for longer. Research published Wednesday in Science Translational Medicine builds on years of that data. In some cases, the team followed patients up to 900 days, making it one of the longest studies of long Covid (most studies launched in 2021 or 2022, including the NIH-funded RECOVER program).

Investigators found long-lasting immune activation months and even years after infection. And, even more concerning, they report what looked like lingering SARS-CoV-2 virus in participants’ guts. Even those who’d had Covid but no continuing symptoms had different results than those who’d never been infected. 

Related: Listen: Why Long Covid can feel scarier than a gun to the head

The team’s big idea — hypothesizing in early 2020 that, contrary to the popular narrative, Covid would last in the body — was “visionary,” long Covid researcher Ziyad Al-Aly said. “A lot of people don’t think like that.” Al-Aly was not involved with the study, but has published other long-term studies of Covid patients. He is chief of research and development at the VA Saint Louis Healthcare System. 

The research makes use of novel technology developed by the paper’s senior authors, Henry Vanbrocklin, professor in the department of radiology at UCSF, and associate professor of medicine Timothy Henrich. They figured out in the last several years they could use an antibody that bound to HIV’s code protein as a guide to see viral reservoirs. The HIV antibody, labeled with radioactive isotopes, could be tracked with imaging as it moved through the body and migrated to infected tissues. 

There were no antibodies to latch onto early in the coronavirus pandemic. Vanbrocklin instead used a chemical agent, called F-AraG, that binds to activated T cells — immune cells that flood into infected tissues. They injected F-AraG into patients, and into a scan they went. 

Tissues full of activated T cells glowed in the resulting image. Researchers found more glowing sites of immune activation in people who had been infected with Covid than in those who had not, including: the brain stem, spinal cord, cardiopulmonary tissues, bone marrow, upper pharynx, chest lymph nodes, and gut wall. 

In people with long Covid symptoms, like brain fog and fatigue, the study found the gut wall and spinal cord lit up more than in other participants. People with continuing pulmonary symptoms showed greater immune activation in their lungs. Gut biopsies in five participants revealed what appears to be persistent virus, said Peluso, who is part of the LongCovid Research Consortium of the PolyBio Research Foundation (which helped fund the study). 

Related: ‘Concern is real’ about long Covid’s impact on Americans and disability claims, report says

“The data are striking,” said Akiko Iwasaki, a professor of immunobiology and long Covid researcher at Yale University. Iwasaki was not involved in the study but is also part of PolyBio’s long Covid research group. 

Researchers used pre-pandemic scans as a control group, “the cleanest comparison that there is, before anybody on the planet could’ve possibly had this virus,” Peluso said. There were 30 participants in total (24 who’d had Covid, and six controls). Uninfected participants showed some T cell activation, but it showed up in parts of the body that help clear inflammation, like the kidney and liver. In the post-Covid group, immune activation was widespread, even in those who report that they are back to their normal health. 

The data don’t explain what exactly T cells are reacting to. As Iwasaki noted, activated T cells can be responding to persistent SARS-CoV-2 antigens or autoantigens found in people with autoimmune disease. The immune response could also be to antigens coming from other pathogens, like the common Epstein-Barr Virus. This piece requires more study, she said. 

In the gut, the researchers found what they think is RNA that encodes the virus’s signature spike protein. Other studies have found similar pieces of virus in autopsies, or within a couple of months after infection. Peluso’s work suggests the virus may stay in the body much longer — up to years after infection.

The researchers don’t know if what they’re seeing is “fossilized” leftover virus or active, productive virus. But they found double-stranded RNA in the guts of some patients who underwent biopsy. That should technically only be there if a virus is still alive, going through its life cycle, Peluso said. 

Related: Long Covid research gets a big-time funding boost

Scientists and patient advocates have been suspicious for a while of the gut reservoir post-Covid. This new data may add fuel to the idea that SARS-CoV-2 stays in some people’s guts for a long time and could actually be driving long Covid. Or, on the other hand, it could mean our immune response is failing to clear the virus and leaving behind little pieces (which might not be harmful). There are still a lot of questions, Peluso admitted. But the paper undermines the paradigm that declares Covid infection disappears after two weeks, and long Covid is just residual damage. 

The findings also suggest a need for more aggressive evaluation of immunomodulating therapies, and treatments that target leftover virus. 

Most researchers hunting for a long Covid biomarker have turned to the blood or small pieces of tissue as surrogates for what’s happening inside a patient. With the new imaging technique, Peluso and his team can see a full person on their screen — a patient’s phantom figure and gauzy organs covered in splotches of light. “It’s really striking,” he said. “‘Oh, my goodness, this is happening in someone’s spinal cord, or their GI tract, or their heart wall, or their lungs.’” 

For patients like Ezra Spier, a member of the LIINC cohort who’s had imaging done after the period captured in this latest study, the experience was validating. Finally, the life-changing experience of long Covid had become visible. “ I can now see with my own eyes the kind of dysfunction going on throughout my own body,” said Spier, who created a website for long Covid patients to more easily find clinical trials near them. 

Most participants had been infected with a pre-Omicron variant of the virus, and one person had repeat infections throughout the study period. Two participants had been hospitalized during their initial bout of Covid, but neither one received intensive care. A half-dozen patients in the study reported zero long Covid symptoms, but still showed elevated levels of immune activation. 

Related: Could long Covid’s signs of immune dysregulation in the blood lead to a diagnostic test?

The paper does not explain what the sites of infection mean for symptoms, and immune activation in a particular organ doesn’t correspond to symptoms (for example, a gut full of T cells doesn’t necessarily match with GI problems). More studies are needed to figure out what the glowing spots mean for patients’ experience of long Covid. 

And the scans don’t work as a diagnostic. In other words, patients shouldn’t rush to San Francisco (Peluso’s group only accepts study participants from the area). The imaging technique isn’t available to the general public, either. F-AraG is still being studied in this context.

But Peluso and Vanbrocklin said imaging could be a major tool in figuring out long Covid. They’ve expanded their research program to do imaging on about 50 additional patients. They are also scanning people before and after they receive different long Covid clinical trial interventions to see if there’s a change in immune activity.

About the Author Reprints

Isabella cueto.

Chronic Disease Reporter

Isabella Cueto covers the leading causes of death and disability: chronic diseases. Her focus includes autoimmune conditions and diseases of the lungs, kidneys, liver (and more). She writes about intriguing research, the promises and pitfalls of treatment, and what can be done about the burden of disease.

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• Research article
• Open access
• Published: 24 June 2024

Heterologous versus homologous COVID-19 booster vaccinations for adults: systematic review with meta-analysis and trial sequential analysis of randomised clinical trials

• Mark Aninakwah Asante 1   na1 ,
• Martin Ekholm Michelsen 1   na1 ,
• Mithuna Mille Balakumar 1 ,
• Buddheera Kumburegama 1 ,
• Amin Sharifan 2 ,
• Allan Randrup Thomsen 3 ,
• Steven Kwasi Korang 1 , 4 ,
• Christian Gluud 1 , 5 &
• Sonia Menon 1 , 6  

BMC Medicine volume  22 , Article number:  263 ( 2024 ) Cite this article

540 Accesses

15 Altmetric

Metrics details

To combat coronavirus disease 2019 (COVID-19), booster vaccination strategies are important. However, the optimal administration of booster vaccine platforms remains unclear. Herein, we aimed to assess the benefits and harms of three or four heterologous versus homologous booster regimens.

From November 3 2022 to December 21, 2023, we searched five databases for randomised clinical trials (RCT). Reviewers screened, extracted data, and assessed bias risks independently with the Cochrane risk-of-bias 2 tool. We conducted meta-analyses and trial sequential analyses (TSA) on our primary (all-cause mortality; laboratory confirmed symptomatic and severe COVID-19; serious adverse events [SAE]) and secondary outcomes (quality of life [QoL]; adverse events [AE] considered non-serious). We assessed the evidence with the GRADE approach. Subgroup analyses were stratified for trials before and after 2023, three or four boosters, immunocompromised status, follow-up, risk of bias, heterologous booster vaccine platforms, and valency of booster.

We included 29 RCTs with 43 comparisons (12,538 participants). Heterologous booster regimens may not reduce the relative risk (RR) of all-cause mortality (11 trials; RR 0.86; 95% CI 0.33 to 2.26; I 2  0%; very low certainty evidence); laboratory-confirmed symptomatic COVID-19 (14 trials; RR 0.95; 95% CI 0.72 to 1.25; I 2  0%; very low certainty); or severe COVID-19 (10 trials; RR 0.51; 95% CI 0.20 to 1.33; I 2  0%; very low certainty). For safety outcomes, heterologous booster regimens may have no effect on SAE (27 trials; RR 1.15; 95% CI 0.68 to 1.95; I 2 0%; very low certainty) but may raise AE considered non-serious (20 trials; RR 1.19; 95% CI 1.08 to 1.32; I 2 64.4%; very low certainty). No data on QoL was available. Our TSAs showed that the cumulative Z curves did not reach futility for any outcome.

Conclusions

With our current sample sizes, we were not able to infer differences of effects for any outcomes, but heterologous booster regimens seem to cause more non-serious AE. Furthermore, more robust data are instrumental to update this review.

Peer Review reports

Severe respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen that causes coronavirus disease (COVID-19). Despite the official end of the public health emergency declaration on 5 May 2023, SARS-CoV-2 continues to infect people across the world, with vaccination remaining one of the most important protective measures against COVID-19 [ 1 , 2 ].

Between 31 July and 27 August 2023, more than 1.4 million new COVID-19 patients and over 1800 deaths were reported globally underscoring the need for ongoing close monitoring of circulating SARS-CoV-2 variants closely [ 1 ]. Presently, a number of variants are tracked by WHO, including two variants of interest (VOIs) (XBB.1.5 and XBB.1.16) and a number of variants under monitoring (VUMs) [ 1 ]. Significant progress in the handling of the COVID-19 epidemic has already been made as nearly every country has implemented vaccination policies, which has resulted in major reductions in the occurrence of severe disease, hospitalisations, and mortality [ 2 ].

Despite fewer severely diseased and fewer deaths worldwide today, there are concerns about reduced protection because of waning immunity and the appearance of newly emerging variants [ 3 ]. Currently, the Strategic Advisory Group of Experts on Immunisation recommends healthy adults over the age of 18 years are to receive one booster dose after primary vaccine series, whilst individuals with the greater risk of severe disease and death (older adults, pregnant persons, and people with immunocompromised conditions) are recommended an additional booster dose [ 4 ].

Using heterologous vaccine platforms can be an alternative strategy to homologous vaccine platforms to maximise booster vaccine impact in the event of limited supplies. It is unclear whether a heterologous boosting regimen may provide higher vaccine effectiveness than homologous booster vaccines. Two meta-analyses including randomised clinical trials and observational studies suggest that heterologous booster doses have a higher protection against symptomatic COVID-19 and severe COVID-19 compared with or to homologous booster doses [ 5 , 6 ] whilst a ‘living meta-analysis’ also including randomised clinical trials and observational studies does not [ 7 ].

The objective of this systematic review is to compare the vaccine benefits and harms between three or four dose heterologous boosters using different vaccine platforms or intra-platform variations versus homologous booster regimens in randomised trials only to help inform public health policies.

Recognising the needs of COVID-19 vaccine research and the identification of trials on heterologous versus homologous booster regimens as an area of public health interest necessitating evidence synthesis, we performed this specific review of pairwise comparison of heterologous versus homologous boosters in randomised clinical trials. This was performed within the framework of our living systematic review, the methodology of which is thoroughly discussed elsewhere [ 8 ], and the protocol registered in PROSPERO (CRD42020178787). This systematic review was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis [ 9 ] (Additional file: PRISMA checklist ) and the implementation of this review followed the recommended procedures as specified in the Cochrane Handbook of Systematic Reviews of Interventions [ 10 ].

Search strategy and trial inclusion criteria

This updated review follows a two-step approach. As for the first living systematic review, the literature searches were conducted on a biweekly basis, from 3 November 2022 to 21 December 2023 using Medline, Cochrane Central Register of Controlled Trials, Embase, Latin American and Caribbean Health Sciences Literature, and Science Citation Index Expanded to identify newly published trials following the initial search strategy and eligibility criteria (for more ample information on the search strategy and study inclusion, please refer to the protocol (Additional file: Additional search Strategy]). After identifying eligible randomised clinical trials for our original research on the efficacy of all COVID-19 vaccines in relation to all-cause mortality, safety, and vaccine efficacy, we employed a specific search strategy tailored to our present research question (Additional file: Additional search strategy). As a quality control measure, we also conducted a snowball search to identify any potential missed trials [ 11 ]. All randomised clinical trials reporting on a third or fourth heterologous booster vaccine versus either a third or fourth homologous booster vaccine were included. In instances where it was not possible to determine whether the intervention arm used a heterologous or homologous booster vaccine, and no clarification was provided by the authors, the trial was excluded. Also, only full booster doses between both arms were compared, in instances when boosters between both arms only compared half doses to full doses, the trial was excluded. Trials with mixed primary series in the heterologous arm were excluded. Furthermore, trials reporting exclusively on immunogenicity, along with trials comparing different types of heterologous booster vaccines or heterologous third booster to a placebo were also excluded. Trials that included open-label cohorts with no randomisation of the participants were excluded.

Data analysis

The vaccine efficacy outcomes included the primary outcomes, all-cause mortality, prevention of laboratory-confirmed symptomatic COVID-19, severe symptoms associated with COVID-19, and serious adverse events (SAE) [ 8 ]. Whenever participants were noted to have (laboratory-confirmed) COVID-19 symptoms, we classified it as symptomatic COVID-19. Conversely, if participants were hospitalised due to severe COVID-19 symptoms, we defined it as severe COVID-19. Secondary outcomes were health-related quality of life and adverse events (AE) considered not serious [ 8 ]. We used the trial results reported at maximum follow-up for each specific abovementioned outcome and used intention-to-treat data if provided by the trialist.

Data extraction and risk of bias assessment

Two independent authors conducted the screening, data extraction, quality assessment, and GRADE assessment for each eligible trial following the Cochrane risk of bias tool—version 2 and the procedure described in our protocol. If three domains were assigned a ‘some concern’ assessment, then the trial was graded at ‘high risk of bias’. Any discrepancies were resolved by consensus and authors were contacted to clarify uncertainties and provide additional context, including available data stratified by older adults.

Statistical synthesis

We performed meta-analysis using STATA 17 for Windows (StataCorp, College Station, TX, USA, 2021) and analysed data with the meta command for meta-analysis. For the trial sequential analysis (TSA), we used version 0.9.5.10 beta (TSA 2017) [ 12 ]. To quantify the strength of associations between booster vaccines and vaccine efficacy and safety outcomes, we employed relative risk (RR). The risk ratio was computed by dividing the risk observed in the heterologous vaccine regimen group by the risk in the homologous vaccine regimen group, and the 95% confidence intervals (CI) for the risk ratio was used to determine the precision of the estimated associations. With a view to avoiding attributing excessive weight to the control groups in the meta-analysis, we divided both the numerator and the denominator of the control group by the number of intervention groups whenever the same control group was used in a trial to compare different intervention groups. To account for potential heterogeneity amongst the trials, random-effects DerSimonian and Laird models were applied [ 13 , 14 ]. In addition, the fixed-effect meta-analysis (Mantel–Haenszel method) was assessed separately and the most conservative point estimate of the two reported [ 15 , 16 ]. We also post hoc applied Peto’s odds ratio (OR) due to very few outcomes in some comparisons.

Assessment of heterogeneity within and between study groups was conducted using the Cochrane Q test, with a significance level of p  < 0.1 indicating the presence of heterogeneity [ 10 ]. The I 2 statistic, as described by Higgins and Thompson was employed to estimate the percentage of observed between-study variability due to heterogeneity, as opposed to chance [ 17 ]. This statistic ranges from 0 to 100%, with values of 0 to 40% representing moderate heterogeneity, 30 to 60% moderate heterogeneity, 50 to 90% substantial heterogeneity, and 75 to 100% considerable heterogeneity [ 10 ].

Furthermore, we performed a subgroup analysis based on the risk of biases to examine the effect of potential biases on the risk ratio. The variable was categorised as low risk of bias compared to some concerns/high risk of bias, allowing us to discern any differential effects on the overall results. Moreover, we conducted subgroup analyses based on the follow-up time: studies with follow-up periods of 3 months and under were compared to those with follow-up periods of above 3 months. Additionally, we compared vaccine regimens with three doses against those with four doses to explore differences in their risk ratios. As different vaccine booster platforms use distinct mechanisms to elicit immune responses [ 18 ], which may lead to varying efficacy and safety profiles [ 19 ], we also conducted a subgroup analysis to compare differences in risk ratios between boosters with different vaccine platforms, including inactivated, protein-based, viral vectored, and mRNA-based boosters. Furthermore, we investigated the variation in risk ratios for vaccine efficacy outcomes between trials from 2023 and those from 2022, thereby allowing us to consider the potential influence of the predominance of XBB subvariants towards the end of 2022 and 2023. Also, we conducted a subgroup analysis by immunocompromised status as immunocompromised individuals may not have a robust immune response to COVID-19 vaccines compared to those without an immunocompromised condition [ 20 ]. Initially, our plan was to conduct a subgroup analysis by categorising adults into younger and older age groups; however, we were constrained by the absence of disaggregated data. Additionally, as an increase in inoculation interval times may impact vaccine efficacy and possibly safety outcomes [ 21 ], we aimed to investigate the impact of different inoculation interval times on vaccine efficacy and safety outcomes using a 12-week cutoff [ 22 ]. Nevertheless, inconsistent reporting and a lack of interpretable data due to large ranges of inoculation intervals prevented us from conducting these planned subgroup analyses. To capture more recent trials comparing vaccine valency, monovalent vaccine boosters to multivalent vaccine boosters (bivalent and tetravalent vaccine boosters) using heterologous and homologous vaccine boosters, we have also conducted a subgroup analysis. By conducting these subgroup analyses, we aimed to assess the differential effect on risk ratios and their associated heterogeneity.

We conducted the TSAs to control risks of type I and type II errors [ 23 , 24 , 25 ]. To assess publication bias, a visual inspection of the funnel plots was conducted and the Egger statistical test performed when an outcome had at least 10 trials [ 10 ].

Summary of findings and assessment of certainty

We used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) profiler Guideline Development Tool to create the summary of findings tables (GRADEpro GDT https://www.gradepro.org/ ). We created a summary of findings tables including each of the prespecified outcomes (all-cause mortality, vaccine efficacy, serious adverse events, health-related quality of life, and non-serious adverse events) (Table 1 : GRADE assessment). We used the five GRADE considerations (bias risk of the trials, consistency of effect, imprecision, indirectness, and publication bias). We assessed imprecision using trial sequential analysis [ 8 , 26 , 27 ].

Trial characteristics

Out of 29,145 abstracts screened by the initial search, 28,044 were excluded after abstract screening. Following a full-text review of 1,101 studies, 601 were excluded based on our inclusion and exclusion criteria. Ultimately, 500 trials met our criteria for the initial research question, of which 29 trials conducted in Europe, North America, Asia, and Latin America were retained in the final analysis of this specific research question. See the PRISMA flow diagram for more details about reasons for exclusion (Additional file: PRISMA flow chart).

In total, 12,538 participants provided data for our predefined meta-analyses. All participants were adults (≥ 18 years) and all trials included older adults (either ≥ 60 or ≥ 65 years) except for four trials [ 28 , 29 , 30 , 31 ] while five trials exclusively included immunocompromised participants [ 32 , 33 , 34 , 35 , 36 ]. None of the trials included pregnant women. One trial exclusively included healthy older adults (≥ 60 years) [ 37 ]. Most trials assessed a third dose heterologous booster vaccine compared with a third dose homologous booster vaccine [ 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 ] while four trials compared a fourth heterologous booster with a fourth homologous booster [ 47 , 54 , 55 , 56 ]. The included heterologous booster vaccines encompassed viral-vectored, mRNA, protein subunit, or inactivated virus platforms (Table 2 : Trials’ characteristics). Follow-up of participants varied from 7 to 365 days after randomisation for all outcomes. Inoculation intervals between the 2nd and 3rd dose, when reported, ranged from 8 to 43 weeks and 28 to 37 weeks between the 3rd dose and 4th dose (Table 2 : Trials’ characteristics).

Primary outcomes

All-cause mortality.

The 11 trials ( N  = 5883) which reported on all-cause mortality observed one death in an immunocompromised participant in the heterologous group because of a SAE (myocardial infarction) (Fig.  1 ). Five trials (45%) were assessed as having some concerns regarding bias (Additional file: FigS 24) and 5 trials (45%) followed participants 90 days or more (Additional file: FigS 20).

Heterologous versus homologous vaccine booster regimens: all-cause mortality

The meta-analysis suggested that the heterologous booster vaccines may have no effect on reducing all-cause mortality compared with homologous booster vaccines (RR 0.86; 95% CI 0.33 to 2.26; I 2 0.0%; very low certainty evidence), with comparable fixed-model and Peto OR effect estimates (Additional file: Table S3).

The trial sequential analysis (Additional file: FigS1) showed that the cumulative Z -curve did not cross the conventional boundaries after inclusion of eleven trials, nor reached the futility boundaries, indicating a need for more trials. It is very uncertain that subgroup analyses across heterologous booster vaccine platforms (Additional file: FigS12), number of doses (Additional file: FigS17), follow-up time (Additional file: FigS20), risk of bias (Additional file: FigS24), health status (Additional file: FigS27), and trials published before and in 2023 (Additional file: FigS31) have no effect in reducing all-cause mortality.

Laboratory-confirmed symptomatic COVID-19

All trials either used reverse transcription polymerase chain reaction (RT-PCR) or similar laboratory tests for COVID-19 exclusively for those reporting symptoms. Thus, we were only able to report on symptomatic participants of COVID-19 and not all participants with confirmed COVID-19 as stated in our protocol. Fourteen trials ( N  = 5677) reported on symptomatic COVID-19 with 13 trials (Fig.  2 ) assessed as having some concerns for Domain 4 (measurement of the outcome) and one being downgraded to high risk of bias due to three domains being attributed some concerns. Seven trials (50%) followed participants 90 days or more (Additional file: FigS21). The pooled RR suggested that the heterologous booster vaccines may not have effect on risk of confirmed symptomatic COVID-19 compared with homologous booster vaccines (RR 0.95; 95% CI 0.72 to 1.25; I 2 0.0%; very low certainty evidence), which was further supported by estimates from the fixed-effect model and the Peto OR (Additional file: Table S3). The TSA showed that the cumulative Z -curve did not cross the conventional boundaries after inclusion of the fourteen trials, nor reached the futility boundaries, indicating a need for more trials (Additional file: FigS2).

Heterologous versus homologous vaccine booster regimens: laboratory-confirmed symptomatic COVID-19

As authors did not report the methodology of how symptomatic COVID-19 participants were diagnosed, this was reflected by assigning some concerns in Domain 4 (measurement of the outcome), therefore precluding us from performing a subgroup analysis by risk of bias. It is uncertain that subgroup analyses according to heterologous booster vaccine platforms (Additional file: Fig S13), variations in follow-up duration (Additional file: Fig S21), health status (Additional file: Fig S28), by pre-2023 and in 2023 (Additional file: Fig S32), and according to vaccine booster valency (Additional file: Fig S34), have no effect in reducing laboratory-confirmed symptomatic COVID-19 events between the two intervention groups.

Laboratory-confirmed severe COVID-19

Ten trials ( N  = 4494) assessed severe disease associated with laboratory-confirmed COVID-19 (Fig.  3 ), with all trials having some concerns for Domain 4 (measurement of the outcome). Only two participants with severe COVID-19 were reported, which occurred in the homologous booster group. Six trials (60%) followed participants 90 days or more ( Additional file: Fig S22).

Heterologous versus homologous vaccine booster regimens: severe COVID-19 disease

The pooled random-effects model estimates that heterologous booster doses may have no effect on reducing severe COVID-19 symptoms versus homologous booster doses (RR 0.51; 95% CI 0.20 to 1.33; I 2 0.0%; very low certainty), with comparable estimates from the fixed-effect model and Peto OR (Additional file: Table S3). The TSA underscored that the required meta-analytic sample size has not been met, thereby preventing the establishment of conclusive evidence (Additional file: FigS3). Therefore, additional trials are imperative to substantiate the impact of a heterologous vaccine regimen on laboratory-confirmed severe COVID-19 participants.

As trial authors did not report the methodology of how severe COVID participants were diagnosed, all trials measuring this outcome were assessed as having some concerns for Domain 4 (measurement of the outcome), therefore precluding us from performing a subgroup analysis by risk of bias. It is very uncertain that subgroup analyses across heterologous booster vaccine platforms (Additional file: FigS14), variations in follow-up duration (Additional file: FigS22), pre-2023 and in 2023 (Additional file: FigS33), and according to vaccine booster valency (Additional file: FigS35) have any effect in reducing laboratory-confirmed severe COVID-19 between the subgroups.

Serious adverse events

Twenty-seven trials ( N  = 11,384) reported serious adverse events (SAE) when assessing the safety profile of the heterologous versus homologous booster vaccines (Fig.  4 ), of which 13 of trials (48%) were assessed as having one or more concerns across domains of which three trials at high risk of bias. Fourteen trials (52%) followed participants 90 days or longer .

Heterologous versus homologous vaccine booster regimens: serious adverse events

The overall estimates suggest that there may be no difference on the risk for serious adverse events between heterologous booster vaccines versus homologous booster vaccines (RR 1.15; 95% CI 0.68 to 1.95; I 2 0.0%; very low certainty evidence), with comparable estimates from the fixed-effect model and Peto OR (Additional file: Table S3). The TSA reveals that the cumulative number of participants remains suboptimal, indicating the insufficiency of the accrued sample size (Additional file: FigS4). Therefore, additional trials are necessary to ascertain the impact of a heterologous vaccine regimen on serious adverse events. It is very uncertain that subgroup analyses across heterologous booster vaccine platforms (Additional file: FigS15), different doses (Additional file: FigS18), variations in follow-up duration (Additional file: FigS23), risk of bias (Additional file: FigS25), health status (Additional file: FigS29), and according to vaccine booster valency (Additional file: FigS36) may have any effect on SAE between the subgroups.

Secondary outcomes

Quality of life

None of the included trials reported on health-related QoL.

Adverse events considered not serious

Twenty trials ( N  = 10,008) reported on AE considered non-serious when assessing the safety profile for booster vaccines (Fig.  5 ), of which ten trials (50%) were considered as having one or more concerns across domains of which two were at high risks of bias. Follow-up for all trials was less than 90 days.

Heterologous versus homologous vaccine booster regimens: non-serious adverse events

Most common types of AE considered non serious were fatigue, fever, injection site pain, redness, muscle pain, and headache. The overall pooled RR suggested that there may be a higher risk of AE considered non-serious by 21% in the heterologous vaccination group versus the homologous vaccination group (RR 1.19; 95% CI 1.08 to 1.32; I 2 64.4%; very low certainty), with concurring estimates with the fixed-effect model and Peto OR (Additional file: Table S3). The TSA showed that the cumulative Z -curve did not intersect the threshold indicating potential harm nor potential benefit associated with heterologous vaccines after incorporating the 20 trials (Additional file: FigS5).

Subgroup analyses based on different doses (Additional file: Fig S19), risk of bias (Additional file: Fig S26), and health status (Additional file: Fig S30) did not impact the pooled relative risk (RR) or reduce heterogeneity. The lack of difference in effect due to different doses on adverse events (AEs) considered non-serious remains very uncertain across subgroups. Furthermore, the evidence for differential higher risks of non-serious AE with protein-based vaccine boosters, viral-vectored booster platforms, and mRNA vaccine booster platforms remain very uncertain due to an even higher risk of imprecision (RR 1.13; 95% CI 1.00 to 1.29; I 2 : 62.5%), (RR 1.51; 95% CI 1.16 to 1.97; I 2 : 56.2%,) and (RR 1.25; 95% CI 1.00 to 1.56), respectively (Additional file: FigS16).

Publication bias

No asymmetry for all-cause mortality, symptomatic COVID-19, severe COVID-19, and SAE (Additional file: Fig S37-40) were observed in the funnel plots, providing evidence against publication bias, which was further corroborated by Egger’s tests showing no significant evidence of publication bias. For adverse events considered non-serious, despite the presence of slight asymmetry in the funnel plot for the outcome (Additional file: FigS44), the significant result from the Egger’s test ( P : 0.02) suggests evidence of publication bias for non-serious adverse events. It is noteworthy that substantial heterogeneity among the included trials could potentially account for the observed asymmetry, introducing some uncertainty into our findings.

In this updated living vaccine project valid until the end of 2023, we focused on gathering evidence from 29 trials comparing heterologous-based booster versus homologous-based booster regimens, of which two compared multivalent versus bivalent boosters. We found no evidence of different effects on mortality, laboratory-confirmed symptomatic COVID-19, laboratory-confirmed severe COVID-19, or SAE. Our TSAs revealed that the accrued sample size was suboptimal to make any robust conclusions of any difference of effects on these outcomes. We found no data on QoL. Nevertheless, we found that heterologous booster regimens may increase the occurrence of AE considered non-serious, but more data will be required to confirm this finding.

Heterogeneity was only encountered assessing AE considered non-serious. Notably, for this outcome, subgroup analyses across vaccine platforms, doses, risk of bias, and health status of participants did not reduce the high level of heterogeneity, which remained above 50%. Due to limited sample sizes, we cannot confidently determine significant differences or lack thereof for all outcomes.

Thus, at this juncture, the very low certainty of evidence yielded from this systematic review does not allow an assessment of beneficial and harmful effects of combining the two different types of vaccine platform, thereby providing limited evidence supporting any firm conclusions. Thus, it would be premature to infer whether lack of statistical significance is due to insufficient sample size or due to no differences between heterologous and homologous booster regimens.

To our knowledge, no other systematic review comprising only randomised clinical trials exists, thus hindering direct comparisons to be made. Three meta-analyses were published between April and August 2022, with the bulk of evidence emanating from observational studies [ 5 , 6 , 7 ]. Deng et al. [ 6 ] reported higher vaccine effectiveness for symptomatic COVID-19 and severe symptoms associated with COVID-19 with heterologous boosters (56.8% compared to 17.3% and 97.4% compared to 93.4%, respectively) [ 6 ]. Conversely, Au et al. (2022) found comparable effectiveness between heterologous and homologous three-dose regimens in preventing COVID-19 symptomatic and severe infections [ 7 ]. Regarding safety outcomes, our findings align with Deng et al. [ 6 ], who reported higher odds for adverse events considered non-serious in the heterologous booster group, in disagreement with Cheng et al. [ 5 ] who reported a higher incidence of total adverse events in the homologous group booster group [ 5 ]. However, these discrepancies may be attributed to confounding factors, including location-based differences in vaccination strategies.

Strengths and limitations

Strengths related to our methodology include the use of five biomedical databases drawing from a combination of approaches to increase the likelihood of capturing all eligible trials. Second, we only included randomised clinical trials. Third, we employed our general search strategy as defined by the protocol followed by a specific search strategy tailored to our specific research question, which was later complemented with the use of the snowballing method. Fourth, we conducted TSAs to control type I and type II errors and strengthen our assessment of the imprecision domain in GRADE.

Our eligible trials have several strengths. Firstly, the inclusion of participants from diverse geographical regions supports the generalisation of results, increasing the applicability of our findings to broader populations. Furthermore, by utilising various vaccine regimen combinations in the heterologous arm, compared with different homologous vaccine regimens, we further enhance the generalisation of our results in addressing our broad research question, whether heterologous regimens are more likely to improve vaccine efficacy and safety.

However, interpretation of our findings warrants caution and cognisance of certain methodological limitations, as reflected in the very low certainty we have in the evidence, largely attributable to the non-negligible percentage of RCT not being free of potential biases, imprecision, and heterogeneity. Secondly, we were unable to adequately assess the quality of RCT reporting on vaccine efficiency as none of the eligible trials reporting on these outcomes described the methodology for assessing this efficiency. In addition, whilst including trials from different geographical regions with varying patterns of sublineage predominance, vaccination combinations, and intervals between prime and boost doses using different vaccine regimens may help generalise findings, this diversity may also lead to residual heterogeneity, as seen in the case of adverse events considered non-serious.

Whilst our study provides valuable insights into the efficacy and safety outcomes of homologous compared with heterologous vaccine regimens across various vaccine platforms, we acknowledge that the absence of trials involving recombinant protein boosters may have limited our exploration of the effect of protein-based heterologous boosters. Additionally, the majority of the trials had a follow-up time of less than 3 months, along with large inoculation time intervals between doses, potentially resulting in failure to adequately gauge benefits and harms. The absence of disaggregated data for older adults, who along with the immunocompromised population, are poised to benefit the most from a booster dose, further limits our analyses.

Hence, this systematic review underscores the imperative for more robust randomised clinical trials to corroborate either all non-significant differences observed or explore the possibility of a differential effect between heterologous versus homologous booster regimen, also among older adults.

Our living systematic review provides current insights into the comparative efficacy and safety of heterologous versus homologous COVID-19 booster regimens. Upon evaluating three vaccine efficacy outcomes, i.e., all-cause mortality, symptomatic COVID-19, and severe COVID-19, no adequate accrued sample size was reached to be able to conclude a lack of difference in prevention between the heterologous versus homologous booster vaccine regimens. In terms of safety outcomes, whilst heterologous vaccine regimens may lead to higher occurrences of AE considered non-serious in contrast to SAE which showed a pooled relative risk range that encompassed the line of no effect, our TSAs pointed to inadequate sample size for both outcomes. As multivalent vaccine heterologous boosters become more prominent, future randomised clinical trials should prioritise diverse populations, including older adults and immunocompromised people and ensure standardised assessment to optimise vaccination strategies and global pandemic control efforts.

Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Abbreviations

Adverse events

Confidence intervals

Coronavirus disease 2019

Grading of Recommendations, Assessment, Development, and Evaluation

Messenger RNA

Randomised clinical trials

Relative risk or risk ratio

Reverse transcription polymerase chain reaction

Severe respiratory syndrome coronavirus 2

Trial sequential analysis

Variants of interest

Variants under monitoring

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Acknowledgements

We would like to thank Sarah Klingenberg for her invaluable assistance as an information specialist at the Copenhagen Trial Unit, The Cochrane Hepato-Biliary Group, in developing and conducting the searches.

The Copenhagen Trial Unit provided support in the form of salaries for those affiliated with the centre.

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Mark Aninakwah Asante and Martin Ekholm Michelsen shared first authors.

Authors and Affiliations

Copenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region, Copenhagen University Hospital – Rigshospitalet, Copenhagen, Denmark

Mark Aninakwah Asante, Martin Ekholm Michelsen, Mithuna Mille Balakumar, Buddheera Kumburegama, Steven Kwasi Korang, Christian Gluud & Sonia Menon

Department of Pharmaceutical Care, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran

Amin Sharifan

Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

Allan Randrup Thomsen

Department of Pediatrics, Children’s Hospital Los Angeles, Los Angeles, CA, USA

Steven Kwasi Korang

Department of Regional Health Research, The Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark

Christian Gluud

Epitech Research, Brussels, Belgium

Sonia Menon

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SM and MA conceived the specific research question and coordinated the systematic review. SKK designed the search strategy. MAA, MEM, MMB, BK, AS, and SM screened the abstracts and full texts. MAA, MEM, MMB, BK, and AS extracted the data. MAA, MEM, MMB, BK, and SM assessed the risk of bias. MAA, MEM, MMB, BK, AS, and SM were involved in the quality control of the extracted data. MAA and SM performed the data analysis. MAA, MEM, AS, and SM contributed to the first draft of the manuscript. All authors were involved in the interpretation of results and critical revision of manuscript. SM is the guarantor and attests that all authors mentioned meet authorship criteria. All authors read and approved the final manuscript.

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Correspondence to Sonia Menon .

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Competing interests.

SM received consulting fees as a consultant for the P-95 consulting firm. ART reports leadership or fiduciary role in other board, society, committee or advocacy group, unpaid with the Danish Society of Immunology as chairman. AS reports leadership or fiduciary role in other board, society, committee or advocacy group, unpaid with Cochrane as a steering member of the Cochrane Early Career Professionals Network. All other authors declared no competing interests.

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Asante, M.A., Michelsen, M.E., Balakumar, M.M. et al. Heterologous versus homologous COVID-19 booster vaccinations for adults: systematic review with meta-analysis and trial sequential analysis of randomised clinical trials. BMC Med 22 , 263 (2024). https://doi.org/10.1186/s12916-024-03471-3

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Received : 08 October 2023

Accepted : 06 June 2024

Published : 24 June 2024

DOI : https://doi.org/10.1186/s12916-024-03471-3

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