he'd finished a phd then long covid hit

July 25, 2024

What We Know about Long COVID Right Now

Researchers are still working to understand the complicated and debilitating condition dubbed long COVID

By Ziyad Al-Aly & The Conversation US

Researchers are gaining key insights into the ways that the SARS-CoV-2 virus can lead to long COVID symptoms.

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Since 2020, the condition known as long COVID-19 has become a widespread disability affecting the health and quality of life of millions of people across the globe and costing economies billions of dollars in reduced productivity of employees and an overall drop in the work force .

The intense scientific effort that long COVID sparked has resulted in more than 24,000 scientific publications , making it the most researched health condition in any four years of recorded human history.

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Long COVID is a term that describes the constellation of long-term health effects caused by infection with the SARS-CoV-2 virus. These range from persistent respiratory symptoms, such as shortness of breath, to debilitating fatigue or brain fog that limits people’s ability to work, and conditions such as heart failure and diabetes, which are known to last a lifetime.

I am a physician scientist, and I have been deeply immersed in studying long COVID since the early days of the pandemic. I have testified before the U.S. Senate as an expert witness on long COVID , have published extensively on it and was named as one of Time’s 100 most influential people in health in 2024 for my research in this area.

Over the first half of 2024, a flurry of reports and scientific papers on long COVID added clarity to this complex condition. These include, in particular, insights into how COVID-19 can still wreak havoc in many organs years after the initial viral infection, as well as emerging evidence on viral persistence and immune dysfunction that last for months or years after initial infection.

How long COVID affects the body

A new study that my colleagues and I published in the New England Journal of Medicine on July 17, 2024, shows that the risk of long COVID declined over the course of the pandemic. In 2020, when the ancestral strain of SARS-CoV-2 was dominant and vaccines were not available, about 10.4% of adults who got COVID-19 developed long COVID. By early 2022, when the omicron family of variants predominated, that rate declined to 7.7% among unvaccinated adults and 3.5% of vaccinated adults. In other words, unvaccinated people were more than twice as likely to develop long COVID.

While researchers like me do not yet have concrete numbers for the current rate in mid-2024 due to the time it takes for long COVID cases to be reflected in the data, the flow of new patients into long COVID clinics has been on par with 2022.

We found that the decline was the result of two key drivers: availability of vaccines and changes in the characteristics of the virus – which made the virus less prone to cause severe acute infections and may have reduced its ability to persist in the human body long enough to cause chronic disease.

Despite the decline in risk of developing long COVID, even a 3.5% risk is substantial. New and repeat COVID-19 infections translate into millions of new long COVID cases that add to an already staggering number of people suffering from this condition.

Estimates for the first year of the pandemic suggests that at least 65 million people globally have had long COVID. Along with a group of other leading scientists, my team will soon publish updated estimates of the global burden of long COVID and its impact on the global economy through 2023.

In addition, a major new report by the National Academies of Sciences Engineering and Medicine details all the health effects that constitute long COVID . The report was commissioned by the Social Security Administration to understand the implications of long COVID on its disability benefits.

It concludes that long COVID is a complex chronic condition that can result in more than 200 health effects across multiple body systems. These include new onset or worsening:

heart disease

neurologic problems such as cognitive impairment , strokes and dysautonomia . This is a category of disorders that affect the body’s autonomic nervous system – nerves that regulate most of the body’s vital mechanisms such as blood pressure, heart rate and temperature.

post-exertional malaise , a state of severe exhaustion that may happen after even minor activity — often leaving the patient unable to function for hours, days or weeks

gastrointestinal disorders

kidney disease

metabolic disorders such as diabetes and hyperlipidemia , or a rise in bad cholesterol

immune dysfunction

Long COVID can affect people across the lifespan from children to older adults and across race and ethnicity and baseline health status. Importantly, more than 90% of people with long COVID had mild COVID-19 infections.

The National Academies report also concluded that long COVID can result in the inability to return to work or school; poor quality of life; diminished ability to perform activities of daily living; and decreased physical and cognitive function for months or years after the initial infection.

The report points out that many health effects of long COVID, such as post-exertional malaise and chronic fatigue, cognitive impairment and autonomic dysfunction, are not currently captured in the Social Security Administration’s Listing of Impairments , yet may significantly affect an individual’s ability to participate in work or school.

A long road ahead

What’s more, health problems resulting from COVID-19 can last years after the initial infection.

A large study published in early 2024 showed that even people who had a mild SARS-CoV-2 infection still experienced new health problems related to COVID-19 in the third year after the initial infection.

Such findings parallel other research showing that the virus persists in various organ systems for months or years after COVID-19 infection. And research is showing that immune responses to the infection are still evident two to three years after a mild infection. Together, these studies may explain why a SARS-CoV-2 infection years ago could still cause new health problems long after the initial infection.

Important progress is also being made in understanding the pathways by which long COVID wreaks havoc on the body. Two preliminary studies from the U.S. and the Netherlands show that when researchers transfer auto-antibodies – antibodies generated by a person’s immune system that are directed at their own tissues and organs – from people with long COVID into healthy mice, the animals start to experience long COVID-like symptoms such as muscle weakness and poor balance.

These studies suggest that an abnormal immune response thought to be responsible for the generation of these auto-antibodies may underlie long COVID and that removing these auto-antibodies may hold promise as potential treatments.

An ongoing threat

Despite overwhelming evidence of the wide-ranging risks of COVID-19, a great deal of messaging suggests that it is no longer a threat to the public. Although there is no empirical evidence to back this up, this misinformation has permeated the public narrative.

The data, however, tells a different story.

COVID-19 infections continue to outnumber flu cases and lead to more hospitalization and death than the flu. COVID-19 also leads to more serious long-term health problems . Trivializing COVID-19 as an inconsequential cold or equating it with the flu does not align with reality.

This article was originally published on The Conversation . Read the original article .

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The Long History of Long COVID and Other Chronic Illnesses

Long COVID is by no means unique in causing a wide array of symptoms that persist for weeks, months, or even years after a person has recovered from the acute infection. “Post-acute infection syndromes have been going on for decades—or maybe hundreds of years—but we haven’t been paying attention,” says Akiko Iwasaki, PhD , Yale School of Medicine’s Sterling Professor of Immunobiology. “They’ve historically been ignored.”

Many chronic illnesses have been largely ignored, dismissed, and ridiculed. Long COVID has taught the world that these diseases are real, there is a biological basis for them, and we need to study them. Akiko Iwasaki, PhD

The term post-acute infection syndrome refers to chronic diseases that occur after an acute viral, bacterial, or parasitic infection, including chronic Lyme and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). And evidence from a study published this month suggests that acute respiratory infections may also lead to long-term symptoms, named “long cold.”

“The pandemic opened the world’s eyes to the fact that many chronic illnesses have been largely ignored, dismissed, and ridiculed,” says Iwasaki. “Long COVID has taught the world that these diseases are real, there is a biological basis for them, and we need to study them.”

What causes Long COVID and other post-acute infection syndromes?

Causes of Long COVID and other post-acute infection syndromes are still unknown, but Iwasaki lists four hypotheses. First, lingering viral remnants could be inducing chronic inflammation, which is known to cause a wide range of symptoms. Second, the acute infection may also have triggered an autoimmune response within the body. Third, it could be the result of a latent virus like the Epstein-Barr virus—the pathogen behind mononucleosis—becoming reactivated after the infection. Finally, tissue damage caused by infection that the body fails to repair properly is another possible cause. These hypotheses, says Iwasaki, are not mutually exclusive, and many people with Long COVID could be suffering from a combination of these outcomes.

Yale School of Medicine (YSM) is investigating the many questions surrounding post-acute infection syndromes in its new Center for Infection & Immunity (CII) , established within the Department of Immunobiology. It is the first center of its kind, says Iwasaki, its creator and director. Ongoing research conducted by multidisciplinary teams within the new center will focus on the underlying pathology of Long COVID, ME/CFS, and chronic Lyme. These post-acute infection syndromes stem from different pathogens but, because they often have overlapping symptoms—such as fatigue, unrefreshing sleep, dysautonomia, and pain—Iwasaki believes they may have similar disease mechanisms. “If we can identify the underlying cause of even one of these diseases then we can apply that knowledge to prevent and treat other kinds of post-acute infection syndromes.”

What treatments can help patients with Long COVID and other such conditions?

The Yale Paxlovid for Long COVID (PAX LC) Trial , for instance, was inspired by the viral persistence hypothesis. The trial, led by Iwasaki and Harlan Krumholz, MD , Harold H. Hines, Jr. Professor of Medicine (Cardiology), is studying whether a 15-day course of Paxlovid, a prescription antiviral treatment for COVID-19, might be beneficial for patients with Long COVID. Iwasaki and Krumholz combine their expertise in the clinic and lab to understand the biological mechanisms that occur throughout the course of receiving Paxlovid. The researchers hope their findings will generate clinical insights on potential markers for diagnostic testing and targets for future interventions.

Patients suffering from Long COVID have been through a lot already ( often including skepticism as to whether their illnesses are real) and participation in a clinical trial can further add to the burden. For many patients, especially those who earn hourly wages, traveling to a study site can interfere with their ability to make ends meet. Thus, the trial is being conducted via a unique decentralized format designed to boost accessibility for its participants by allowing people with Long COVID to participate from their homes. “Through our decentralized trial design, we’re going straight to people. We’re saying, 'If you’ve got this condition, you don’t have to come to us. We can come to you,'” says Krumholz. Participation in the trial is already available in all contiguous states of the United States and Washington DC.

Disease prevention is another focus of the CII. This includes research on different vaccination strategies along with studies examining whether universal vaccines for different agents might someday play a role. “Vaccines are really important in preventing these diseases,” says Iwasaki. “So I’m also hopeful that we can develop better preventative mechanisms to go along with our more disease treatment-focused research.”

More than 1,000 patients seen at Yale for Long COVID

Treating a disease as complex as Long COVID requires a personalized and multi-disciplinary approach. In the spring of 2023, Lisa Sanders, MD , associate professor of medicine (general medicine), launched the Yale New Haven Long COVID Multidisciplinary Care Center . The new centralized program utilizes the expertise of cardiologists, neurologists, pulmonologists, rheumatologists, and other specialists, and also offers on-site physical therapy and social work services.

The new program requires a referral from a physician, a physician assistant, or an advanced practice nurse. Interested patients can learn more at Yale New Haven Health System’s Long COVID program website.

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Featured in this article

• Akiko Iwasaki, PhD Sterling Professor of Immunobiology and Professor of Dermatology and of Molecular, Cellular, and Developmental Biology and of Epidemiology (Microbial Diseases); Investigator, Howard Hughes Medical Institute, (HHMI)
• Harlan Krumholz, MD, SM Harold H. Hines, Jr. Professor of Medicine (Cardiology) and Professor in the Institute for Social and Policy Studies, of Investigative Medicine and of Public Health (Health Policy); Founder, Center for Outcomes Research and Evaluation (CORE)
• Lisa Sanders, MD, FACP Professor of Medicine (General Medicine); Director, Writers Workshop; Medical Director of the Yale New Haven Health Systems Long COVID Consultation Clinic, General Internal Medicine

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What Causes Long COVID Is A Mystery. Here's How Scientists Are Trying To Crack It

A year and a half into the pandemic, doctors are getting better at recognizing long COVID — the collection of persistent health problems that some people develop after a coronavirus infection — but research has yet to pinpoint what could be driving the illness.

"Most likely it's more than just one condition," said Dr. Francis Collins, director of the National Institutes of Health, which is pouring $470 million into a national study on long COVID. "The really troubling aspects of this terrible pandemic might be the lingering of this long-tail effect on people."

Long COVID is a kind of shape-shifting illness that can span dozens of symptoms — a large international study identified more than 200 of them. Some of the most common include headaches, fatigue, brain fog, and shortness of breath. It can happen after severe and mild infections, in both old and young people.

Anywhere from 10% to 30% of people who get infected with the coronavirus will have persistent symptoms lasting at least one month, according to the Centers for Disease Control and Prevention. Many with long COVID continue to deal with symptoms for many months, even more than a year after the initial infection.

Scientists are pursuing many different lines of research about the possible biological mechanisms underlying the condition, hoping this research will ultimately yield meaningful treatments for the millions of people who are afflicted, sometimes with debilitating symptoms.

Here are four major theories researchers are investigating.

1. Maybe the virus never left

One theory some scientists are looking into is viral persistence. The idea is that someone catches the SARS-CoV-2 virus and eventually gets over the initial infection, but it's possible the virus sticks around in some parts of the body, causing the kinds of persistent symptoms seen in long COVID patients.

"That's one of the first questions we need to answer," says Dr. Walter Koroshetz , director of the National Institute of Neurological Disorders and Stroke. "Is COVID hiding in the body somewhere?"

This wouldn't be unprecedented. Other viruses are known to linger in parts of the body for months or even years, creating a "viral reservoir" in places where the immune system is not as likely to root it out, says Amy Proal , a microbiologist at the PolyBio Research Foundation, who has proposed a variety of theories for what could be causing long COVID.

"Pathogens, in simple terms, tend to hide in tissue and, in fact, they have a lot of mechanisms to do that," she says. "The proteins they create allow them to better burrow into tissue."

For example, scientists have found evidence of the virus that causes Ebola in tissue and body fluids long after the initial infection. Some Ebola survivors suffer from chronic symptoms, and they appear to have waxing and waning immune responses against the virus, as if they were still infected, Proal says. Recent research even suggests an outbreak of Ebola in West Africa originated with someone who was infected years earlier and had harbored the virus.

Some studies suggest the coronavirus remains in parts of the body, including the gut, well after someone has recovered, although this doesn't necessarily mean the person can spread the virus easily.

This theory of viral persistence would also explain why some people with long COVID start to feel better after receiving the COVID vaccines , because the shot would essentially boost their immune response against the lingering virus. A team at Yale School of Medicine is currently studying this possibility. .

2. Once on, the immune system fails to turn off

The long COVID patients that come to see Dr. Nancy Klimas remind her a lot of another group of patients she's used to treating — people with chronic fatigue syndrome , also called ME/CFS.

"That's an illness that more often than not is post viral," says Klimas, an immunologist at NOVA Southeastern University. "There's a virus that just pushes the on button on the immune system and doesn't seem to release it."

ME/CFS isn't fully understood, either, but Klimas says the viruses that trigger it tend to be the most inflammatory — similar to the SARS-CoV-2 virus, which can be so deadly because it creates such an extraordinarily inflammatory reaction. "So it's not too surprising that the coronavirus would be another trigger of a similar illness," she says.

Many patients and researchers hope that all the attention on long COVID will offer new insights about the mechanisms underlying ME/CFS and other post-viral illnesses, because with the coronavirus there are now so many people who can recall the details of the origin of the illness, says Dr. Peter Rowe of Johns Hopkins University School of Medicine.

"Part of our hope is that the increased interest is going to bring in more scientific firepower to help tackle these unanswered questions," he says.

3. The immune system starts attacking itself

It's possible the virus has triggered autoimmunity in some long COVID patients. This is when a person's own immune system gets confused and attacks tissues and organs in the body.

Researchers have found that a coronavirus infection can lead the body to create certain proteins, called "autoantibodies," that can end up being harmful. Autoantibodies are seen in many autoimmune diseases.

"We found that COVID-19 patients had astonishing numbers of autoantibodies that were actually more than what we see in autoimmune conditions like lupus," says Dr. Aaron Ring , an immunologist at Yale School of Medicine.

Ring is part of a research team that's identified some of these autoantibodies in sick COVID-19 patients. "A lot of the autoantibodies were actually directed against the immune system itself," he says, calling it "immune fratricide."

Those autoantibodies were also directed at many other parts of the body, from the brain and central nervous system to blood vessels and platelets. So far, it appears these autoantibodies can hang around in some patients who had COVID-19 for many months, if not longer.

"That could explain the diverse outcomes that we see in terms of long COVID and how it manifests, but this isn't proven yet," Ring says.

4. Other problem viruses wake up

One more idea: It could be that other viruses people had before getting the coronavirus reemerge during the infection and start to cause problems.

These viruses may have been kept in check when the person was healthy, but it's possible that fighting the SARS-CoV-2 virus dysregulates and throws off their immune system. "This provides a very good atmosphere for these other viruses to reactivate and potentially infect new nerves, new tissue or the central nervous system, even in the brain," says Proal.

Under this scenario, viruses other than the coronavirus could be contributing to the chronic symptoms seen in long COVID. In fact, a recent study found that long COVID patients were more likely to have reactivation of the Epstein-Barr virus — what causes mononucleosis — suggesting COVID-19 caused that virus to reactivate.

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Many people recover fully within a few days or weeks after being infected with SARS-CoV-2, the virus that causes COVID-19. However, others have symptoms that linger for weeks, months, or even years after their initial diagnosis. Some people seem to recover from COVID-19 but then see their symptoms return, or they develop different symptoms within a few months. Even people who had no symptoms when they were infected can develop them later. Either mild or severe COVID-19 can lead to long-lasting symptoms.

Long COVID, long-haul COVID, post-COVID-19 condition, chronic COVID, and post-acute sequelae of SARS-CoV-2 are all names for the health problems that some people experience a few months after a COVID-19 diagnosis. Symptoms of long COVID may be the same as or different than  symptoms of COVID-19 . Long COVID can also trigger other health conditions such as diabetes or kidney disease.

For more information on long COVID, check out these U.S. government resources:

National Institutes of Health (NIH)

• Explore  long COVID  information,  news , and more on the COVID-19 research website.
• Learn about NIH’s  RECOVER initiative and  find clinical trials on long COVID.
• Read how this NIH-funded RECOVER study developed  a new symptom scoring system that will improve future long COVID treatments .
• Read this NHLBI news story about the long COVID risk for pregnant women .
• Read how the RECOVER Initiative made it easier to access long COVID research data .
• Read this NHLBI news story about how  obstructive sleep apnea increases risks for long COVID .
• Read this NHLBI news story about how  lingering symptoms are common after COVID hospitalization .
• Read how an NIH-funded  RECOVER study identified potential long COVID disparities .
• Read this  NHLBI news story  about how long COVID may be less common in children.
• Read how an NHLBI-funded study found that  exercise lags are common after long COVID .
• Read this  NIH Director’s Blog post  about using artificial intelligence to advance the understanding of long COVID.
• Read this  NHLBI news story  about how long COVID impacts children. 
• Find tips for talking with your healthcare provider about long COVID.
• Check out this fact sheet about caring for people living with post-COVID conditions

Centers for Disease Control and Prevention (CDC)

Find information on living with long COVID, including tips for talking with your healthcare provider .

This White House fact sheet provides information about comprehensive government efforts to prevent, diagnose, and treat long COVID.

RECOVER Research Review (R3) Seminar Series

The NIH RECOVER initiative’s R3 Seminar Series promotes a shared understanding of the scientific research on Long COVID. This forum speeds up discovery by allowing experts to