Tag: COVID-19

Respiratory disease season is in full swing, with influenza, RSV, and COVID-19 case counts rising in various parts of the U.S. Hospitals in some states are also reporting upticks in pediatric pneumonia diagnoses, which experts say seems to be unrelated to the recent spike of pneumonias reported in China.

On the heels of last year’s severe flu and RSV reason, all this contagion has some people wondering if SARS-CoV-2, the virus that causes COVID-19, may be to blame. Some studies suggest the virus leaves its mark on the immune system even after an acute illness passes, raising an important question: does having COVID-19 increase your risk of getting sick from other viruses in the future?

“Any time that we get an infection, it changes us,” says Dr. David Smith, chief of infectious diseases and global public health at UC San Diego Health. “It changes our B cells, which make antibodies, and it changes our T cells, which do cellular functions to clear out infections.”

Sometimes, these changes can be long-lasting. After a case of chickenpox, for example, the body typically builds lifelong immunity that prevents future bouts of the illness. But other viruses have more insidious effects. Measles essentially forces the body to re-learn how to fend off other infections, research shows, while HIV leaves people severely immunocompromised.

SARS-CoV-2 seems to fall somewhere between those two poles, though Smith emphasizes that research is ongoing. Reinfections are not only possible but common, ruling out the idea of widespread lifelong immunity—but there also isn’t currently evidence to suggest COVID-19 is causing population-wide immune deficiency, says Sheena Cruickshank, a professor of immunology at the University of Manchester in the U.K.

Some studies do, however, suggest that SARS-CoV-2 infections—particularly severe ones—can trigger changes to the immune system, including reductions in the number and performance of T cells; disruptions to B cells; deficiencies in dendritic cells, which regulate the immune response; and altered gene expression linked to increased inflammation. Some of these changes seem to last months after a serious case of COVID-19.

Scary as those findings sound, however, “you may see a gazillion changes, but you don’t know which of those changes may be relevant to future function,” says John Tsang, a professor of immunobiology at the Yale School of Medicine. In other words: changes to specific immune cells don’t necessarily mean that the whole system, or even part of it, will stop working.

It’s normal for immune markers to “ebb and flow” after an infection, Cruickshank adds, and even changes that sound bad won’t necessarily have long-lasting implications. “Studies that have looked more long-term have shown that, for most people, the immune response bounces back to normal and restores,” Cruickshank says. In one study co-authored by Tsang, men who recovered from mild COVID-19 actually mounted stronger immune responses to flu vaccines than men who had never had COVID-19, which could be beneficial. (Tsang and his co-authors didn’t observe the same trend in women.)

There are exceptions, though. People who have severe cases of COVID-19 may experience lasting health problems, either from the virus itself or from certain drugs used to treat serious COVID-19, such as steroids and immune-system modulators, Smith says. Many scientists also think that chronic Long COVID symptoms could be a sign of immune dysfunction, and recent research suggests people with Long COVID are more likely to get reinfected by SARS-CoV-2 than people who fully recover.

For people who had mild cases and no long-lasting symptoms, though, Tsang says the scientific literature does not support the idea of widespread immunosuppression after COVID-19. So why does it seem that people are getting sick more often now than before the pandemic?

There’s always the chance that COVID-19 is causing immune changes that haven’t shown up in the research yet, says Katelyn Jetelina, an epidemiologist who devoted a recent edition of her newsletter to COVID-19’s impact on the immune system. But she feels it’s likelier that people are simply more attuned to any respiratory symptoms they experience than they were a few years ago.

It’s also possible, Tsang adds, that the same revved-up immune response that COVID-19 survivors in his study mounted in response to the flu vaccine leads some people to experience more severe symptoms of common illnesses. “We may feel a bit sicker because of the inflammatory response,” Tsang says, “but it’s not because our system now no longer responds to an infection.”

Several years of decreased exposure to pathogens due to masking and social distancing may also have changed disease-transmission patterns, Cruickshank says. Children who were born during the pandemic may not have been exposed to germs they typically would have encountered as babies, leaving them to catch those bugs for the first time as toddlers or young kids. And even adults who’d had multiple prior brushes with common cold or flu viruses may now be faced with new strains of those viruses, to which their bodies are less familiar, Cruickshank says.

None of this is to say that COVID-19 is harmless. It is still a leading cause of death in the U.S.; Long COVID remains a serious risk; and there’s evidence that even seemingly mild infections can affect the heart, brain, and other organs. Avoiding the SARS-CoV-2 virus is still the safest move for your health—regardless of how it affects your risk of getting sick in the future.

Every COVID-19 vaccine is a step behind the virus. In the time it takes companies to make the shot, SARS-CoV-2 is already busy mutating into different versions that can evade the immune response produced by it.

But even though the latest vaccine targets XBB.1.5, a variant no longer dominant in the U.S., it seems to be doing a decent job at warding off some of the emerging variants. In a study published on the preprint server bioRxiv, scientists led by Dr. David Ho, director of the Aaron Diamond AIDS Research Center at Columbia University, report that the vaccine can generate strong antibodies that can neutralize not just XBB but variants such as HV.1, which now accounts for 31% of U.S. infections, and HK.3, which contributes to half of new infections in Asia (and about 7% in the U.S.).

The team analyzed blood samples from 60 people with different COVID-19 infection and vaccination histories, representing real-world scenarios. All had four to five doses of mRNA vaccines—most recently, the bivalent BA.4/5 vaccine that was recommended before the new XBB.1.5 shot. One group had never had COVID-19 and received the XBB.1.5 booster. Another group recently recovered from an XBB infection and did not receive the XBB booster. The final group had previously been infected with an Omicron variant and did not receive the XBB.1.5 booster. Blood samples from these volunteers were pitted against lab-based versions of SARS-CoV-2 virus variants: the original, BA.5, XBB.1.5, and EG.5.1 (a variant that spread widely this fall). The samples were also tested against four emerging subvariants: HV.1, HK.3, JD.1.1, and JN.1.

The results suggest that the new XBB.1.5 vaccine helps generate antibodies against variants that the vaccine wasn’t specifically designed to target—namely HV.1, HK.3, JD.1.1, and JN.1. These antibody levels were 13 to 27 times higher in the blood of people who had never had COVID-19 but had an XBB.1.5 vaccine. They increased 10-fold among people with this new shot who had a prior Omicron infection. These responses were slightly lower than antibody levels generated against XBB.1.5, but still suggest that the latest vaccine can provide broader protection against a variety of variants.

That’s encouraging news as the battle between vaccines and the virus continues this season, and new variants that first appeared in other parts of the world make their way to the U.S. These new data support the need for people stay up to date on their vaccines so they can continue to be protected against new versions of the virus.

As we head into winter, health experts expect that cases of flu and COVID-19 will start to creep up. One piece of good news: if you do get sick, there’s a way to get tests and treatments for both—without paying a cent.

The National Institutes of Health (NIH), the Administration for Strategic Preparedness and Response and the Centers for Disease Control and Prevention have teamed up with digital health company eMed to create an at-home test-to-treat program that offers free tests for both flu and COVID-19, and, if you are positive, free telehealth visits and antiviral treatments that are sent to your home.

For now, there are some restrictions about who can enroll and receive the free tests. After the program officially launched last month, following a flood of requests from people eager to stock up on the tests, NIH and eMed decided to prioritize people who could not afford them, including those without health insurance and those on government plans such as Medicare, Medicaid, and Veterans Affairs coverage.

But the treatment part of the program is open to anyone over 18 who tests positive for flu or COVID-19, regardless of whether they used one of the free tests from the program. People who enroll will be connected to a telemedicine provider via eMed, to discuss whether they could benefit from an antiviral treatment. For the flu, that includes four approved drugs:

For COVID-19, there are two approved oral medications to choose from:

While there is one other approved COVID-19 treatment, remdesivir (Veklury), it’s an intravenous infusion that requires medical professionals so likely won’t be widely prescribed through this program. Dr. Michael Mina, chief science officer at eMed, expects that doctors will most likely rely on Tamiflu or Xofluza for flu, and Paxlovid for COVID-19.

The idea behind the program is to see if moving testing and treatment out of the hands of doctors and into those of patients will increase and speed up access, ideally reducing spread of flu and COVID-19. “We imagine it will benefit people who live in rural areas who can’t easily travel to health care facilities,” says Andrew Weitz, the NIH lead for the Home Test-to-Treat program, “or people who get sick over the weekend and aren’t able to immediately see their primary care doctors.” The antiviral drugs for both influenza and COVID-19 are most effective when people use them within days after symptoms start—one or two days in the case of flu, and five for COVID-19. So shortening the window between when people notice their first symptoms and when they take their first antiviral pill could substantially reduce the time they are sick. And having a supply of tests on hand could be a way to move people from symptoms to treatments even sooner.

If you qualify, the test you receive in the mail is a single kit that combines COVID-19 and flu, and it’s more sophisticated than the rapid-antigen COVID-19 tests. It’s a version of the gold-standard molecular, or PCR, test that labs use and looks for influenza and SARS-CoV-2 genes. “It’s actually an amazing deal for [those who qualify] to get two free molecular tests,” says Mina, since purchasing them would cost about $140. The U.S. Food and Drug Administration is expected to authorize a cheaper rapid-antigen test that detects both flu and COVID-19 in December; if that does happen, the test-to-treat program will offer those as well.

It’s all about moving the process for testing and treating the most common respiratory diseases out of the cumbersome health care system and into people’s homes. COVID-19 taught doctors—and patients—that almost anyone can reliably test themselves with a relatively easy-to-use kit. Couple that with a telehealth option for people who test positive, and more sick patients could get prescriptions for antiviral treatments that can not only help them feel better but potentially reduce their risk of passing on their infection to others.

As part of the program, the NIH will also collect data to try to answer some important questions about the role of self-testing and test-to-treat programs in U.S. health care. For example, researchers will investigate whether such programs increase access to antiviral treatments, and if they raise the proportion of people treated in the time frame when the drugs are most effective. “One of our primary goals is to understand how quickly people go from feeling sick to the time they have treatments in their hands, and if this program can do that faster than someone who waits for an appointment with their doctor or at an urgent care, then has to go to the pharmacy for their medication,” says Weitz.

Researchers will send program participants who receive telemedicine visits and a drug prescription a survey 10 days following their visit, and again six weeks afterward, to get a sense for how many actually received and took the antiviral medications, as well as to ask broader questions about the rates of Long COVID among participants and how many experience Paxlovid rebound, in which infections return after people test negative following a course of the drug.

There will be a separate, more rigorous research part of the program in which many people who enroll will be invited to participate in a study, conducted in collaboration with the University of Massachusetts, that will help scientists better understand whether treating people early can reduce the spread of influenza and COVID-19, by asking whether other people in the infected person’s household got infected. That could enrich doctors’ understanding of how contagious COVID-19 is, how long people are infectious, and how effective the treatments are in reducing infectiousness. That in turn could help to refine current recommendations for how long people should isolate.

The program is an effort to “leverage the latest technology to meet people where they are, and hopefully have them avoid going to a health care facility and potentially infecting others,” says Weitz. “We are interested in understanding how to push the limits to provide alternative opportunities in delivering health care.”

People vaccinated before their first case of COVID-19 are diagnosed with Long COVID almost four times less than unvaccinated people, suggests a large new study published Nov. 22 in the BMJ.

That’s not an entirely new finding. For years, studies have shown that, while vaccinated people can and do develop Long COVID, they are at lower risk than people who haven’t had their shots. But researchers have come to drastically different estimates about exactly how much protection vaccines offer against Long COVID, with their findings ranging from about 15% efficacy to around 50%.

The new study offers encouraging evidence that people who get vaccinated before their first COVID-19 case are at significantly lower risk of developing long-term symptoms like brain fog and fatigue, with each additional dose received prior to infection offering extra protection. A single pre-infection dose of one of the original COVID-19 vaccines reduced the risk of Long COVID by 21%, two doses by 59%, and three or more doses by 73%, the researchers estimated.

To reach those conclusions, they studied data from more than half a million adults in Sweden who caught COVID-19 for the first time from December 2020 to February 2022. National vaccine records showed that about half of those people had gotten at least one COVID-19 vaccine dose before they got sick, while the others were unvaccinated. Using the participants’ health records, the researchers then assessed who went on to be diagnosed with Long COVID during the study’s follow-up period, which ended in November 2022.

The study looked only at original COVID-19 vaccines, not newer boosters like the one released this fall. It also did not assess Long COVID after reinfections, which in some cases do lead to long-lasting health problems. As such, the findings may not translate perfectly to the present day, when many people have received updated shots and had COVID-19 multiple times.

Long COVID diagnoses were rare across the board during the study’s follow-up period, but even less common among people who’d been vaccinated before getting sick. About 1.4% of unvaccinated people received a Long COVID diagnosis during the study period, compared to 0.4% of previously vaccinated people.

Of course, there’s a difference between having Long COVID and being diagnosed with Long COVID. Many people with symptoms of the condition struggle to get formally diagnosed, and the study’s authors acknowledge that some clinicians may not have known how to assess the emerging condition during the period the paper considers. Indeed, prevalence estimates tend to be higher than those reported in the study. In the U.S., for example, an estimated 14% of adults have ever had Long COVID, and an estimated 5% currently do.

Further, observational studies like this one cannot definitively prove cause and effect, only uncover patterns. Even still, the trends reported in the study are promising, given that more than 5.5 billion people around the world have now received at least one dose of a COVID-19 vaccine.

In the study, vaccines were linked with particularly high efficacy against Long COVID in men, tracking with prior findings that women are disproportionately likely to develop the condition. Vaccines also seemed to work especially well for adults ages 55 to 64, contrary to some previous studies that concluded Long COVID risk increases with age.

Recent immunization also seemed to be especially protective against Long COVID, compared to vaccination more than four months prior to acute illness—which may be an extra argument for continuing to get boosters as they come out.

As you make your shopping list, plan travel, and schedule parties this holiday season, there’s something else you should add to your to-do list: making sure you’re up-to-date on the latest guidance around COVID-19, the flu, and RSV, as respiratory disease season hits full swing.

“It’s always important to factor in the possibility of either transmitting an infection to other people or becoming infected, especially when getting together in large groups,” says Matthew Binnicker, director of clinical virology at the Mayo Clinic. “There are ways to safely gather and enjoy the holiday season,” but it requires taking the right precautions.

Here’s what to know about—and how to say safe from—COVID, the flu, and RSV this holiday season.

Will there be a COVID-19 surge this winter? What about flu and RSV?

Late fall and winter are typically peak times for COVID-19, the flu, and RSV to spread—and mid-November surveillance data suggests all three are already on the rise in the U.S. Based on historical trends, Binnicker says he expects to see continued upticks in infections in late November into December. “We typically see a surge in respiratory viruses as the temperatures drop and we proceed into the winter months,” he says.

Which shots should I get and when?

If you haven’t had COVID-19 or been vaccinated against it in at least six months, Binnicker recommends getting the updated booster shot, which was authorized in September. “If you were vaccinated a year ago or two years ago…your immunity likely isn’t going to protect you from infection with the currently circulating strains,” he says.

As of the two-week period ending Nov. 11, the U.S. Centers for Disease Control and Prevention (CDC) estimated about 50% of new sequenced cases were caused by the Omicron subvariants HV.1 and EG.5. Both are descendants of the XBB family, the lineage vaccine manufacturers designed the latest booster shot to target.

Sooner is better when it comes to getting boosted. “You can’t get it an hour before and then jump into a party,” says Emily Smith, an assistant professor at Duke University with a specialty in global health. It takes about two weeks for the body to mount a full immune response after getting vaccinated.

The same goes for flu shots, Smith says. Recent research suggests you can get your COVID-19 booster and flu shot at the same time without reducing either’s efficacy, so you can schedule both appointments at once.

Finally, those eligible—people who are pregnant or elderly—should consider getting the newly approved RSV vaccine. Young babies can also get an antibody treatment meant to protect against RSV.

How long do I have to isolate if I get COVID-19?

The CDC still says anyone who tests positive for COVID-19 should isolate themselves for at least five full days. And through the 10th day after testing positive—even once the five-day isolation period is over—they should wear a high-quality mask, such as an N95 or KN95, any time they have to be around other people indoors.

If your holiday plans fall within that initial five-day isolation period, “the responsible thing to do is the hardest thing to do, which is wait until you’re better to see family,” Smith says.

The decision is a little trickier if you’re done with your five-day isolation, but still within the 10 days of recommended masking. It is possible to be contagious even after your five days of isolation are up, Binnicker notes, so it’s best to continue taking precautions. If your holiday plans involve being around people who are high-risk for severe disease, including elderly adults or people who are immunocompromised, CDC guidance suggests you should stay home. If you do keep your plans, agency guidance supports staying masked or outdoors the entire time.

The exception: if you test negative on two separate at-home tests taken 48 hours apart, the CDC says you can remove your mask, even if it hasn’t been a full 10 days.

Can I travel if I have or recently had COVID-19?

While testing requirements for travel are mostly a thing of the past, the CDC still says not to get on planes, trains, or buses during your five-day isolation period. Through day 10, if you absolutely must use public transit, you should remain masked the entire time, unless you’ve gotten your pair of negative test results.

How can I make my holiday gatherings safer?

If you’re hosting a party, Smith says it’s a good idea to ask everyone to test first, particularly if you’ll have high-risk guests in attendance. “Make a game out of it, where people have to test before they come in the house and hand them hot cocoa” while they wait, she suggests.

Hosts may also want to keep a supply of masks on hand in case any guests show up ill (or simply want to wear one while around others)—or have a plan for moving the party to an outdoor area.

In fact, if the weather in your area allows, consider hosting an entirely outdoor gathering. If it’s too cold to be outside, Smith says opening a few windows to improve air flow is better than nothing.

What if I spent time with someone who tests positive for COVID-19?

At this point, “it’s probably inevitable that there will be many people in the country who will show up to a gathering and someone will be coughing, sneezing, acting visibly unwell,” Binnicker says.

If that person turns out to have COVID-19, you don’t have to completely isolate yourself unless you also develop symptoms or test positive, the CDC says. However, the agency recommends taking certain precautions in the following days, including wearing a mask when you’re around other people indoors, monitoring yourself for symptoms, and testing yourself. Recent research suggests that, after an Omicron exposure, it can take only about three days for an illness to start.

The health outlook for Long COVID sufferers is no better today than it was when the condition was first recognized in early 2020. This has been attributed in large measure to the disappointing results of clinical research, particularly when compared to the magnitude of the problem. 

Now with hundreds of published results emerging from federally conducted or sponsored research, outraged experts and patient advocates say that there is little to show for it. The critique is that the pace of the work is slow and opaque, and that little has emerged that directly impacts prevention or patient care. The biomedical community has been under steady attack for lack of progress in prevention and treatment underlying a failure to help patients.

There is a lot at stake in getting the U.S.’s Long COVID research strategy right. With a national prevalence of the disease in the range of 5% to 15%, an estimated 10 to 35 million working-age adults have Long COVID, and it may be keeping as many as 4 million people out of work. There is a desperate need for effective treatments to mitigate their devastating frustration, suffering, functional impairment, and disability.

But what if the medical research community spends years and hundreds more millions of dollars digging a dry hole? The answer is not to dig deeper but to dig elsewhere with a more promising outlook and sharper tools.

A national health catastrophe

This national health catastrophe was foreseen early in the Long COVID pandemic. With a firm belief in the value of scientific innovation in mitigating harm, the federal government in late 2020 responded with a $1.15 billion investment in Long COVID research. Several agencies including the National Institutes of Health, the Centers for Disease Control and Prevention, and the Veterans Administration embarked on an ambitious program to delve into its mysteries.

The promise of harnessing the power of research was further raised in August 2022, when the White House unveiled the National Research Plan on Long COVID. In the public mind, this heavily promoted commitment had similarities to previous high-profile government disease research campaigns such as the “war on cancer” and Operation Warp Speed.

With these raised expectations now mostly dashed, there has been much finger-pointing among researchers, patients and advocates, experts and the media. Blame has been laid in several areas of the research domain: an unproductive focus on how the disease develops rather than on directly helping patients, duplicative descriptive studies on symptoms and trajectory which contribute little new knowledge, too many observational studies and not enough clinical trials to discover new therapies, the undertaking of large-scale multi-institutional research that buckles under the weight of bureaucracy, and straying into studies of alternative cures or even potentially harmful remedies. Government inattention and underfunding have also been deemed to play a significant role.

Unsurprisingly, the recommended fix for this predicament from many in the Long COVID ecosystem is to call for increased government investment and for channeling it into more productive biomedical research. 

Although intuitively unimpeachable, what if this logic is simply wrong?

Before reaching the conclusion that more and better biomedical research is needed, we must address why over three years of research has failed to move the needle. Lessons from the past should influence this calculus, as well as serve as a guide for future return-on-investment and likelihood of success.

A new theory to explain Long COVID

We suggest a unifying hypothesis that explains the striking lack of progress in understanding Long COVID through a traditional biomedical and public health lens. Our recent editorial in STAT posits that Long COVID is a new name for an old syndrome. It is virtually indistinguishable from the condition long known in the medical lexicon as post-infectious syndrome or myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)—in colloquial terms known simply as “chronic fatigue syndrome.” Logic and reason dictate that acute SARS-CoV-2 infection causes Long COVID. Or, more accurately, acute COVID-19 triggers ME/CFS in the same way many other infectious agents trigger ME/CFS. 

The implications of this hypothesis should be addressed head-on. Blind faith in the critical role and payout of future biomedical research may be misplaced and set-up society and the research community itself for further disappointment.

Read More: Long COVID Recovery Remains Rare

It is true that ME/CFS is still not well-understood and its research has been chronically underfunded. However there are decades of relevant clinical and research experience that should be productively and rapidly applied to Long COVID. The established track-record of ME/CFS research exploring cause and pathogenesis has been singularly unproductive. By analogy, the current research directed at finding diagnostic and mechanistic clues to Long COVID is a resource-intensive, lengthy uncharted process. In the ME/CFS paradigm it will produce further leads for more biomedical research, but with a low ultimate likelihood of helping patients.

Why is this research unlikely to be productive? Because either there is nothing to find, or currently available tools are insufficient to detect and validate mechanisms behind the myriad of symptoms. This should not be viewed as a failure of science. Negative observations—the absence of a link between cause-and-effect—cannot be proven, no matter how intensively probed. Yes, we can always pursue those mechanistic studies more rigorously and smartly. But at what point does the public sector decide that doing so has reached a point of diminishing returns? This is where we appear to be heading with ME/CFS/Long COVID.

Does this mean that Long COVID is not “real?” This is a false binary divide when viewed through a biomedical lens. Through a post-infectious disease historical lens it’s absolutely real and needs to be addressed as such. This includes platforms for comprehensive care, multi-disciplinary expertise and professional empathy through well-described (but frequently inaccessible) symptom management and functional rehabilitation pathways.

Challenging an existing paradigm

Scientifically and humanistically this may not be a welcome construct. It challenges the foundation and belief in the power of scientific knowledge and techniques. It grates against the standards of the biomedical paradigm. However, this hypothesis is not only consistent with the current lack of research progress, but ominously predicts more of the same lack of meaningful impact, controversy, finger-pointing and patient disillusionment going forward.

Research still has a vital role in the new ME/CFS/Long COVID paradigm. But it should be a different kind of research. The kind that no longer focuses on biomarkers and mechanisms. These are sure to provide “promising” but false leads and divert resources. Focus should be on health services research and on measures that directly impact the welfare of Long COVID sufferers: prevention, improved prognosis, access to empathetic care and quality of life issues. This includes investigation into symptom management, the effectiveness of comprehensive care delivery models, and social science research on actionable solutions applicable to at-risk subgroups (e.g., women, obstetrics and pediatric patients, people of color, underserved populations). Patients and advocacy groups should be closely involved in every stage of study design and execution, as they will have the major stake in living with the findings and are the ultimate determinants of success.

Now with the benefit of hindsight and a new paradigm that fits most observed clinical characteristics of Long COVID, we can envision a more productive and less friction-filled forward path for research. Meeting the shared objectives of the research and patient communities will require a further willingness to build bridges of cooperation, pragmatism and foresight. Given the magnitude of the challenges and the complexity of the Long COVID ecosystem, the central organizing forum for research policy and strategy should be an agency of the U.S. government, with the mandate and resources commensurate to the task. The recently formed Health and Human Services Office of Long Covid Research and Practice should be tasked with this important planning and coordination responsibility.

With Long COVID research now reaching a mature stage, there is a realistic hope that patient and biomedical communities can collaboratively reset the national research agenda to mutual benefit under the umbrella of a new paradigm and sponsor.

COVID-19 has become less of an urgent threat than it was in 2019 largely because of vaccines and growing immunity from natural infections, but antiviral treatments have also changed the course of the disease. The most popular of these is nirmatrelvir-ritonavir, sold under the brand name Paxlovid, which the U.S. Centers for Disease Control and Prevention (CDC) recommends for older people and anyone over age 12 who is at higher risk of COVID-19 complications. But people taking the drug have reported incomplete recovery, or testing positive again after testing negative once they finished the five-day course of the oral medication.

In a study published in the Annals of Internal Medicine, researchers led by Dr. Mark Siedner, at Harvard Medical School and Massachusetts General Hospital, investigated the phenomenon, and report that around 20% of people taking Paxlovid could experience rebound infections. The researchers also cultured the virus from these rebound patients, and confirmed live virus, which suggests that patients are still infectious and therefore can spread the virus to others.

Paxlovid rebound has been a highly debated topic in the COVID-19 medical community, since the drug’s maker, Pfizer, reported in its studies submitted to the U.S. Food and Drug Administration (FDA) that it occurred in about 2.3% of people. Since Paxlovid has been on the market, other studies have documented even higher rebound rates, around 14%. Unlike those studies, which mostly looked retrospectively at whether people developed symptoms again or tested positive again after testing negative, Siedner’s study set out to specifically investigate the rebound effect. The researchers took samples from 142 people who tested positive for COVID-19 and received prescriptions for Paxlovid and took the pills three times a week for two weeks and then weekly until their virus was detectable. The scientists not only tested for the virus, but if they found any, they also cultured it to determine if it could potentially cause infections.

They found that 20% of people rebounded after completing the five-day treatment course of Paxlovid, and that those who experienced rebound continued to harbor live virus in their noses for up to 14 days.

“Our study was small and needs to be verified, but based on our data, we need to balance the fact that Paxlovid is a very important drug and should be used in higher risk people, with the risk of rebound in 20% of people,” says Siedner.

Siedner also explored the discrepancy between Pfizer’s initial estimates of rebound, and the higher estimates from other studies. He found that the key to quantifying the rate of rebound is testing people more frequently, to capture changing levels of the virus. Pfizer’s study was not designed to study rebound and its scientists only tested participants three times: at days five, 10 and 15 after the first positive COVID-19 test. When Siedner and this team looked only at samples they collected on the same days that Pfizer’s researchers did, they found a similar 2.4% rebound rate as Pfizer had. Looking at samples from only those three days missed 80% of the rebound cases, he says. “When you don’t sample enough, you miss the rebound, and our study was able to fill in the gaps,” he says. “If you’re not studying it closely enough, you may not find it.”

Read more: Why Not Everyone Should Take Paxlovid

Understanding the rate, along with the mechanics of rebound, is important since rebounding virus remains contagious, as Siedner’s group found. They did not study whether people experiencing rebound actually spread the virus to others, but given that they found live virus in those nasal samples, it’s reasonable to assume that rebounding people are still contagious. Currently the CDC recommends that people isolate for five days after they first test positive—Siedner says that many of those who rebound after taking Paxlovid “are still shedding live virus for about three times that length of time. People who rebound in my opinion should have prolonged isolation periods”

Dr. David Ho, a professor of microbiology and immunology at Columbia University was among the first to report higher rates of rebound. Based on on-going studies from his lab, he says an eight-day Paxlovid treatment, instead of a five-day course, could significantly reduce the amount of rebound. Without any immune response, the virus’s half life in the body—the time it takes for the amount of virus to drop by half—is about 24 hours. Adding Paxlovid can drop the amount of virus by 32-fold, but the timing of the drug treatment needs to align with peak levels of the virus. Since that can be hard to achieve, taking the drug for a longer period of time could help. “We think that if you treat for eight days you can pretty much wipe out the rebound phenomenon,” says Ho.

Siedner’s study supports the longer course of treatment. People in the trial who began taking Paxlovid early, within a day or two of testing positive, were more likely to rebound than those starting the treatment a few days later. But he is reluctant to advise delaying treatment, since it’s challenging to find the right window when there is enough virus present. And extending the treatment course would require a change in the drug’s label, and the FDA would likely require an additional study documenting the benefits of the longer treatment. While Pfizer is currently studying such a longer course in people with weakened immune systems, it’s not clear if the company would undertake similar research in other groups.

“We are continuing to monitor the data, but believe the return of elevated, detected nasal viral RNA—also known as viral rebound or COVID-19 rebound—is not uniquely associated with any specific treatment,” a Pfizer spokesperson tells TIME. “We remain very confident in Paxlovid’s clinical effectiveness at preventing severe outcomes from COVID-19 in patients at increased risk.”

Given the current recommendations for Paxlovid, there isn’t an effective way to avoid rebound, but Siedner says it’s possible to manage it and reduce the risk of spreading COVID-19 because of it. People on the drug could test themselves again with an at-home antigen test five days after they test negative. If they remain negative, they likely have not rebounded, but if they are positive, they need to isolate again until they test negative. 

“We really want to reinforce the fact that clinical trials established the fact that people at very high risk of COVID-19 complications can benefit from taking Paxlovid,” says Siedner. “Our data in no way counters that evidence. But people need to be aware that Paxlovid rebound is common, and understand that they need to isolate properly if they do rebound.”

If you’ve traveled overseas recently, you might have been greeted upon your return by people in a handful of airport terminals in the U.S. recruiting passengers to get tested for the COVID-19 virus. It’s been a surprisingly productive way to keep track of how much COVID-19 might be entering the country, via travelers, as well as which variants they are bringing in.

Just in time for the busy holiday travel season, the program’s operators, the Centers for Disease Control and Prevention (CDC), Concentric by Ginkgo Bioworks (a Boston-based biotech firm), and XpresCheck, which recruits and tests the passengers, are expanding the screening to include viruses other than SARS-CoV-2. Since October, the program has been screening a subset of samples from travelers for influenza and RSV. Eventually, the program will phase in 30 more pathogens.

Since the program launched in 2021, the Traveler-based Genomic Surveillance (TGS) program has provided a crucial window into how the COVID-19 virus is circulating, especially since more people are relying on at-home tests that don’t require them to report results. About 6,000 passengers arriving in seven major international U.S. airports are tested each week on a voluntary basis. They also provide basic, non-identifying information about where their flight originated, and other countries included in their itinerary; and answer questions about their vaccination status, age, and whether they have been in close contact with anyone who tested positive for COVID-19 recently. People will be asked similar questions about flu and RSV.

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So far, the program has enrolled more than 360,000 passengers and sequenced more than 14,000 samples and added these data to public genetic databases to help public health officials better understand how and where the virus is circulating. TGS detected the first case of the variant BA.2.86 coming into the U.S. in August, from a traveler arriving at Washington, D.C.’s Dulles airport from Japan, even before that country had detected any cases. It was also the first time that variant had been found outside of Denmark and Israel, where it was first reported.

“We’ve had quite a bit of success with the platform,” says. Dr. Cindy Friedman, chief of the Travelers’ Health Branch at CDC. “Travelers can help us to fill in gaps in our global surveillance because they get and spread germs as they travel. They give us an early look at what is coming into the country, and what is going on globally.” Because not all countries have strong infectious disease testing and surveillance programs, TGS is providing valuable information not just about what’s happening in the U.S. but around the world as well. “We’re not waiting for someone to get sick and then go see a health care provider or go to the emergency room,” says Friedman. “We are trying to get the data one step earlier.”

Friedman says she and her team are also not depending entirely on the altruism of passengers to submit to nasal swabs as they get off long transcontinental flights. Since launching in 2021, the program also collects and studies samples of wastewater from planes, and wastewater from the common drain into which planes discard their waste. Such collection can provide a more efficient way to track pathogens coming into the country, says Friedman, since “that one sample is representative of 200 to 300 people on that plane.” Friedman says her team is also investigating taking air samples from airports, which could push our knowledge about the global spread of pathogens even further.

In the latest iteration of the program, passengers at four airports—John F. Kennedy in New York, San Francisco International, Logan in Boston, and Dulles—volunteer to swab their noses and Ginkgo genetically analyzes any positive tests at its labs for the presence of SARS-CoV-2, influenza, and RSV. Scientists have just begun screening wastewater for these additional viruses as well. If those sequences show signs of mutations or other changes, they are sent to CDC labs in Atlanta for deeper analysis. As with the original COVID-19 testing, all of the genetic data are uploaded onto public genetic databases so researchers can study them.

Read more: There’s a Shortage of RSV Treatments. Here’s What Doctors Recommend

In coming years, the program will add testing for dozens of other viruses and bacteria, as well as for mutations that signal that viruses or bacteria have become resistant to existing treatments. Eventually, Friedman says her team is hoping take air samples from airports to provide additional data on pathogens, and to bolster the program’s ability to know where in the world pathogens are coming from, and whether the strains entering the country pose any threat to public health because existing treatments won’t be able to control them.

One group of such pathogens that will eventually be screened include the parainfluenzas, which can contribute to croup or pneumonia, and can be dangerous for young babies. “There are no public genomes for some of these respiratory pathogens—none for parainfluenza 3, for example, and none for human metapneumovirus—so we will be getting the first sequences that we are able to look at more closely,” says Casandra Philipson, a computational biologist at Concentric. “We’re excited about establishing a global baseline dataset for these viruses. The more we make public, the more we can contribute to better general knowledge about these pathogens.”