A Key to Long Covid Is Virus Lingering in the Body, Scientists Say

Virus remaining in some people’s bodies for a long time may be causing longer-term complications, recent research suggests

Authors:  Sumathi Reddy Sept. 8, 2022 The Wall Street Journal

The virus that causes Covid-19 can remain in some people’s bodies for a long time.  A growing number of scientists think that lingering virus is a root cause of long Covid.

New research has found the spike protein of the SARS-CoV-2 virus in the blood of long Covid patients up to a year after infection but not in people who have fully recovered from Covid. Virus has also been found in tissues including the brain, lungs, and lining of the gut, according to scientists and studies 

The findings suggest that leftover reservoirs of virus could be provoking the immune system in some people, causing complications such as blood clots and inflammation, which may fuel certain long Covid symptoms, scientists say. 

A group of scientists and doctors are joining forces to focus research on viral persistence and aim to raise $100 million to further the search for treatments. Called the Long Covid Research Initiative, the group is run by the PolyBio Research Foundation, a Mercer Island, Wash., based nonprofit focused on complex chronic inflammatory diseases. 

“We really want to understand what’s at the root of [long Covid] and we want to focus on that,” says Amy Proal, a microbiologist at PolyBio and the initiative’s chief scientific officer. Dr. Proal has devoted her career to researching chronic infections after developing myalgic encephalomyelitis/chronic fatigue syndrome, an illness that shares similar symptoms with long Covid, in her 20s.  She has mostly recovered now but has symptoms she manages.

Three long Covid patients, frustrated at the lack of answers and treatments, have helped connect researchers. 

“Long Covid is this really incredible emergency,” says Henry Scott-Green, one of the patients, a 28-year-old in London who says brain fog, extreme fatigue and other debilitating long Covid symptoms prevented him from resuming full-time work as a product manager, though he plans to return soon. “We’re really trying to run really efficiently and cut out as many layers of bureaucracy as possible.”

So far, the group says it has received a pledge of $15 million from Balvi, an investment and direct giving fund established by Vitalik Buterin, the co-creator of the cryptocurrency platform Ethereum. een says debilitating long Covid symptoms have prevented him from resuming full-time work.

Among the strongest evidence of viral persistence in long Covid patients is a new study by Harvard researchers published Friday in the journal of Clinical Infectious Diseases. Researchers detected the spike protein of the SARS-CoV-2 virus in a large majority of 37 long Covid patients in the study and found it in none of 26 patients in a control group.

Patients’ blood was analyzed up to a year after initial infection, says David R. Walt, a professor of pathology at Brigham and Women’s Hospital in Boston and Harvard Medical School and lead researcher of the study. Dr. Walt isn’t currently involved with the long Covid initiative. 

A year after infection, some patients had levels of viral spike protein that were as high as they did earlier in their illness, Dr. Walt says. Such levels long after initial infection suggest that a reservoir of active virus is continuing to produce the spike protein because the spike protein typically doesn’t have a long lifetimehe adds.

Dr. Walt plans to test antivirals such as Paxlovid or remdesivir to see if the drugs help clear the virus and eliminate spike protein from the blood.  He says it’s possible that for some people, the normal course of medication isn’t enough to clear the virus. Such cases may require “a much longer exposure to these antivirals to fully clear,” says Dr. Walt.

One of the research group’s goals is to find a way for people to identify whether they continue to have the virus in their bodies. There is no easy way to determine this now. 

Long Covid patients experience such a wide range of long-term symptoms that scientists think there is likely more than one cause, however. Some cases may be fueled by organ damage, for instance. 

Yet consensus is growing around the idea that lingering virus plays a significant role in long Covid. Preliminary research from immunologist Akiko Iwasaki’s laboratory at Yale University documented T or B cell activity in long Covid patients’ blood, suggesting that patients’ immune systems are continuing to react to virus in their bodies. Dr. Iwasaki is a member of the new initiative. 

In a 58-person study published in the Annals of Neurology in March, University of California, San Francisco researchers also found SARS-CoV-2 proteins circulating in particles in long Covid patients’ blood, especially in those with symptoms such as fatigue and trouble concentrating.

Now, the group is completing a study using imaging techniques and tissue biopsies to detect persistent virus or reactivation of other viruses in tissue. It also is looking at T-cell immune responses in tissues and whether they correlate with symptoms. 

Some people may harbor the virus and don’t have long-term symptoms, says Timothy Henrich, an associate professor of medicine at UCSF involved with the study and a member of the long Covid initiative. For others, lingering virus may produce problems.

“I think there’s a real amount of mounting evidence that really suggests that there is persistent virus in some people,” says Dr. Henrich.

Medical experts question Paxlovid study on symptoms in people under 65

Authors: Bart Jones August 27, 2022 Newsday

Some medical experts on Long Island are disputing a new study that said Paxlovid did not help relieve COVID-19 symptoms in people under 65.

Pfizer’s COVID-19 pill appears to provide little or no benefit for younger adults, while still reducing the risk of hospitalization and death for high-risk seniors, according to a large study published Wednesday.

The results from the 109,000-patient Israeli study are likely to renew questions about the U.S. government’s use of Paxlovid, which has become the go-to treatment for COVID-19 due to its at-home convenience.

But two leading infectious disease specialists on Long Island said they had seen the opposite — Paxlovid did help people in various age groups.

“I don’t think that’s really correct,” Dr. Sharon Nachman, chief of the division of pediatric diseases at Stony Brook Children’s Hospital, said of the study. “I do think that those that were under 65 and have taken Paxlovid have actually done quite well with it.”

“We haven’t seen that much relapse of COVID in that population and we’ve certainly not seen those who took Paxlovid coming to the hospital with COVID and being sick,” she said. “The vast majority infected it did help.”

“Sometimes when you do a study you have to be careful how you ask the question and who you ask it of, because that may skew what you are able to interpret from the results,” she added.

Dr. Bruce Hirsch, an infectious disease specialist at Northwell Health, said he agreed that Paxlovid had helped many patients of different age groups.

“Paxlovid really improves clinical well-being within two or three days of taking the medicine,” he said.

“The younger people are doing OK anyway” for the most part when they get infected with the Omicron variant, he added, “but I have seen people who are younger feel better faster with Paxlovid.”

The Biden administration has spent more than $10 billion purchasing the drug and making it available at thousands of pharmacies through its test-and-treat initiative.

The researchers found that Paxlovid reduced hospitalizations among people 65 and older by roughly 75% when given shortly after infection. That’s consistent with earlier results used to authorize the drug in the United States and other nations.

But people between the ages of 40 and 65 saw no measurable benefit, according to the analysis of medical records.

The findings reflect the changing nature of the pandemic, in which the vast majority of people already have some protection against the virus due to vaccination or prior infection. For younger adults, in particular, that greatly reduces their risks of severe COVID-19 complications. The Centers for Disease Control and Prevention recently estimated that 95% of Americans 16 and older have acquired some level of immunity against the virus.

“Paxlovid will remain important for people at the highest risk of severe COVID-19, such as seniors and those with compromised immune systems,” said Dr. David Boulware, a University of Minnesota researcher and physician, who was not involved in the study. “But for the vast majority of Americans who are now eligible, this really doesn’t have a lot of benefit.”

A spokesman for Pfizer declined to comment on the results, which were published in the New England Journal of Medicine.

The U.S. Food and Drug Administration authorized Paxlovid late last year for adults and children 12 and older who are considered high risk due to conditions like obesity, diabetes and heart disease.

“Game-changer” Paxlovid turns into pandemic enigma

Authors: Arielle Dreher Axios September 2, 2022

Paxlovid, once hailed as a “game-changer” for its ability to treat COVID-19 infections at home, is becoming one of the pandemic’s biggest enigmas.

The intrigue: There’s growing concern about the link between Pfizer’s antiviral pill and COVID rebound, in which patients test positive or have symptoms days after a course of the drug is completed. President Biden, First Lady Jill Biden and NIAID Director Anthony Fauci have each relapsed.

  • The FDA has asked Pfizer to investigate whether a second five-day course of the drug will prevent the virus from returning.
  • Pfizer executives in May suggested patients who can’t clear the virus with the first course should take more, Bloomberg reported.

The big picture: Paxlovid use surged over the summer, with as many as one-third of reported coronavirus cases treated with the drug.

  • But uncertainty over what’s causing the relapses, and whether the drug helps younger patients, is making some people wary of taking the treatment, physicians say.
  • At least part of the problem is that people are not routinely tested after taking Paxlovid, which makes it hard to establish how often rebound happens or why the virus lingers in some people, Leana Wen, an emergency physician and a professor at George Washington University, told CNN.
  • A large study of more than 109,000 people in the New England Journal of Medicine concluded the drug significantly reduced hospitalizations and deaths among patients aged 65 and older but that there was no evidence of benefit in younger adults.
  • The prospect of reinfection shouldn’t discourage older or high-risk patients from taking the pills, said Yale infectious diseases specialist Scott Roberts.
  • “Rebound is almost always more mild than initial course,” Roberts told Axios.
  • Paxlovid could have the added benefit of warding off long COVID, or symptoms that linger beyond the first 30 days after testing positive, and studies to determine this are underway.

But availability of the drug could change before clear answers emerge.

  • The Biden administration has only bought enough pills to supply Paxlovid through the middle of next year, after which it will transition to the commercial market, HHS Assistant Secretary for Preparedness and Response Dawn O’Connell wrote in a blog post on Tuesday.

Between the lines: COVID rebound has also been observed in people who have not taken Paxlovid, and some experts believe it might be a natural course of the infection to see symptoms ebb, then return.

  • COVID’s course “is not a purely linear process; it waxes and wanes a little bit,” said Jonathan Li, a Harvard Medical School researcher and co-author of a pre-print that found high levels of rebound in people who hadn’t been treated with the drug.

State of play: The CDC recommends Paxlovid for those over the age of 50, and for those with medical conditions like lung or heart disease that makes them high-risk, although the drug’s emergency authorization covers anyone 12 years old and up.

  • Research in Clinical Infectious Diseases found the drug remains effective for vaccinated people who contract COVID-19, reducing emergency room visits by lowering the risk of complications like lower respiratory tract infection and cardiac arrhythmia.
  • Beyond the Pfizer study requested by the FDA, a clinical trial of immunocompromised people is evaluating if Paxlovid should be used for five, 10 or 15 days.

What they’re saying: “The consensus by the vast majority of people caring for COVID patients is that the rebound is not really a side effect of Paxlovid, it is more that are we really treating people for long enough or not?” Sarju Ganatra, a cardiologist at Lahey Hospital and co-author of the Clinical Infectious Diseases study, told Axios.

Yes, but: “This is where having a well-designed, well-controlled study helps us understand disease better, and this is the challenge of anecdotal reports. Without a control, it’s really hard to know what’s actually happening,” said Kara Chew, an infectious disease physician at University of California Los Angeles.

The bottom line: Paxlovid remains an important tool to keep some people out of the hospitals, especially with the highly contagious Omicron variant still circulating and many people not staying current on boosters, experts said.

  • Isolation will also be critical as long as enough people are experiencing COVID rebound and stay infectious beyond the five-day isolation period recommended by the CDC.

Omicron’s Mutations Impaired Vaccine Effectiveness, CDC Says

Authors: Madison Muller  August 25, 2022 Bloomberg

Almost 40% of people hospitalized in the US with the Covid subvariant that circulated this spring were vaccinated and boosted, highlighting how new strains have mutated to more readily escape the immunity offered by current shots.

The findings from scientists at the US Centers for Disease Control and Prevention underscore the importance of having Covid shots that are better at targeting omicron subvariants. 

From the end of March through May, when the omicron BA.2 and BA.2.12.1 subvariants were dominant in the US, weekly hospitalization rates increased for all adults — with those over 65 hit the hardest. Even so, the total number of hospitalizations remained much lower than when the delta variant was rampant last fall. 

The overall number of hospitalizations is an important point, said Abraar Karan, an infectious disease doctor at Stanford University.

“When you look at who’s hospitalized, it’s much more likely that they will have been vaccinated because so many people are vaccinated now,” Karan said. “The real comparison is how many hospitalizations do we have now versus in the past when people were not vaccinated or not up-to-date with boosters.”

CDC scientists found that vaccines and boosters did a better job of keeping people with delta infections out of the hospital than those with later variants. Effectiveness decreased slightly with the BA.1 variant, then changed significantly with BA.2 — with a much greater share of hospitalized adults who had been vaccinated with at least one booster. 

Read more: Retiring Fauci expected Covid to be ‘behind us’

Immunity from vaccines starts to wane within six months, so staying up-to-date with shots is key to being fully protected. Fewer than half of Americans have gotten a booster shot.

Adults with at least two booster shots fared better than other people when BA.2 was dominant. The majority of those admitted to the hospital also had at least one underlying condition. Unvaccinated adults were more than three times as likely to be hospitalized, but breakthrough infections still represented a significant number of the severe Covid cases, the data show.

US regulators have pushed Moderna Inc., Pfizer Inc. and BioNTech SE to expedite development of omicron-specific boosters for a September rollout. The drugmakers this week submitted early data to the US Food and Drug Administration seeking emergency clearance for updated shots that target the BA.4 and BA.5 virus strains. Scientists and vaccinemakers are already beginning to look toward next-generation shots that may provide longer-lasting protection against more variants. 

The new report’s findings also indicate that along with vaccination, other pharmaceutical and non-pharmaceutical measures should be used by those at highest risk of getting Covid. That includes easy access to therapeutics such as Pfizer’s antiviral drug Paxlovid and Gilead Sciences’ remdesivir, as well as AstraZeneca’s Evusheld for immunocompromised people. Scientists also note that wearing a mask can help guard the wearer from getting sick.  

Though the number of Covid deaths is the lowest it has been since last July, the US continues to see hundreds of deaths each day from Covid, CDC data show.

What, Exactly, Is ‘Paxlovid Mouth’ and How Do You Get Rid of It?

The Covid-19 antiviral drug can leave a foul taste. The afflicted are scouring for remedies online.

Authors: Alex Janin Aug. 16, 2022 Wall Street Journal

Jeanette Witten recently rummaged through her pantry for Red Hots, the cinnamon-flavored candy.

The 56-year-old in Montclair, N.J., was looking for a reprieve from a persistent residual taste—“like your mouth is just clenched around a grapefruit rind”—that came after she took Paxlovid, Pfizer’s antiviral drug to treat Covid-19. 

Ms. Witten is one of many people who have scouted remedies for what is informally known as Paxlovid mouth, a taste that can linger for as long as you take the drug. Patients who have taken Paxlovid have described it as sun-baked trash-bag liquid, a mouthful of dirty pennies and rotten soymilk. They have tried to erase the taste with salves from cinnamon to milk to pineapple. They are also trading strategies online. 

Pfizer spokesperson acknowledged the side effect, called dysgeusia, and pointed to a study that found the symptom occurred 5.6% of the time people took the drug. The study was funded by Pfizer and published in the New England Journal of Medicine. The company said most patients’ dysgeusia symptoms were mild.

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The culprit is likely ritonavir, a part of the drug that is used to boost levels of antiviral medicines, doctors say. Ritonavir has a known association with dysgeusia. It is a small price to pay given the nearly 90% reduction in hospitalization and death among those at risk for severe disease from Covid-19, say doctors and people who have taken the medication. 

But it’s still hard for many patients to stomach.

Pfizer Stops Enrollment in COVID-19 Pill Trial After Latest Results

Authors: Mimi Nguyen Ly June 16, 2022 The Epoch Times

Paxlovid, a Pfizer COVID-19 pill, is seen manufactured in Ascoli, Italy, in this undated photo obtained by Reuters on Nov. 16, 2021. (Pfizer/Handout via Reuters)

Pfizer has announced it will stop enrollment in a clinical trial for Paxlovid—its COVID-19 antiviral pill—for standard-risk COVID-19 patients after the latest results suggested the drug did not reduce symptoms or hospitalizations and deaths to a statistically significant degree.

Paxlovid, which consists of two different antiviral drugs—nirmatrelvir and ritonavir—is currently approved or authorized for conditional or emergency use in more than 65 countries, including the United States, to treat COVID-19 patients at high risk of severe illness, including hospitalization or death.

Pfizer said on June 14 that it will “cease enrollment into the EPIC-SR trial due to low rate of hospitalization or death in the standard-risk population.”

However, the company said it will still include the new data in its upcoming application to the U.S. Food and Drug Administration (FDA) to seek full approval for Paxlovid to be prescribed for high-risk COVID-19 patients.

“The company will focus efforts on generating further data on PAXLOVID in vulnerable populations, including longer treatment durations in immunocompromised individuals, as well as exploring other clinical development opportunities, such as its potential use in hospitalized patients with severe disease,” Pfizer added.

Standard-risk patients refers to COVID-19 patients who don’t have risk factors for severe disease. They can be vaccinated or unvaccinated.

Results From Trial

The EPIC-SR trial, which started in August 2021, sought to compare Paxlovid to a placebo in adult patients with symptomatic COVID-19, who are not in hospital and “are at low risk of progressing to severe illness.”

In December 2021, Pfizer announced that results for Paxlovid did not meet the study’s goal of continuous symptom relief, or “self-reported, sustained alleviation of all symptoms for four consecutive days, as compared to placebo.”

At the time, Pfizer noted that there was a 70 percent reduction in hospitalizations in the Paxlovid group (three out of 428 hospitalized, with no deaths) compared to placebo (10 out of 426 hospitalized, with no deaths). The results were not statistically significant, however, which means it could possibly be down to chance.

On June 14, Pfizer announced that an updated analysis from 1,153 patients enrolled through December 2021 showed a 51 percent difference in hospitalization or death between the two groups—with five out of 576 in the Paxlovid group, compared to 10 out of 569 in the placebo group having required hospitalization or dying. The results were again not statistically significant.

There were no deaths in patients who received Paxlovid, but there was one death in the placebo group, the company stated.

The EPIC-SR study originally included fully-vaccinated people with at least one risk factor for progression to severe COVID-19, but after Paxlovid was authorized for the group in December 2021, this cohort was no longer enrolled in the study. Pfizer then adjusted its study eligibility criteria to allow people whose last vaccination was 12 months or more prior to enrollment.

A sub-group analysis of 721 vaccinated people with at least one risk factor for progression to severe COVID-19 showed there was a 57 percent risk reduction for hospitalization or death—with three out of 361 in the Paxlovid group, and seven out of 360 in the placebo group needing to be hospitalized or dying. The results did not reach statistical significance, Pfizer said.

Paxlovid also showed a non-significant 62 percent decrease in medical visits related to COVID-19 per day across all patients, relative to placebo.

Albert Bourla, the CEO and chairman of Pfizer, said in a statement that results from the company’s studies so far “support the efficacy and safety profile for PAXLOVID in the treatment of mild-to-moderate COVID-19 patients with at least one risk factor for progressing to severe COVID-19, regardless of vaccination status.”

“With up to 40–50 [percent] of people around the world estimated to be high risk, we believe there remains a significant unmet need for treatment options to help combat this disease, and we will continue to prioritize efforts to advance the development of PAXLOVID,” he added.

Data from a retrospective cohort study in Israel in early June, in a largely-vaccinated population, reported that Paxlovid reduces COVID-19 hospitalization and deaths by 46 percent. The study said the drug was “more effective in older patients, immunosuppressed patients, and patients with underlying neurological or cardiovascular disease.”

Paxlovid, a Pfizer COVID-19 pill, is seen manufactured in Ascoli, Italy, in this undated photo obtained by Reuters on Nov. 16, 2021. (Pfizer/Handout via Reuters)

WORLD

Pfizer Stops Enrollment in COVID-19 Pill Trial After Latest Results

By Mimi Nguyen Ly June 16, 2022 Updated: June 16, 2022

Pfizer has announced it will stop enrollment in a clinical trial for Paxlovid—its COVID-19 antiviral pill—for standard-risk COVID-19 patients after the latest results suggested the drug did not reduce symptoms or hospitalizations and deaths to a statistically significant degree.

Paxlovid, which consists of two different antiviral drugs—nirmatrelvir and ritonavir—is currently approved or authorized for conditional or emergency use in more than 65 countries, including the United States, to treat COVID-19 patients at high risk of severe illness, including hospitalization or death.

Pfizer said on June 14 that it will “cease enrollment into the EPIC-SR trial due to low rate of hospitalization or death in the standard-risk population.”

However, the company said it will still include the new data in its upcoming application to the U.S. Food and Drug Administration (FDA) to seek full approval for Paxlovid to be prescribed for high-risk COVID-19 patients.

“The company will focus efforts on generating further data on PAXLOVID in vulnerable populations, including longer treatment durations in immunocompromised individuals, as well as exploring other clinical development opportunities, such as its potential use in hospitalized patients with severe disease,” Pfizer added.

Standard-risk patients refers to COVID-19 patients who don’t have risk factors for severe disease. They can be vaccinated or unvaccinated.

Results From Trial

The EPIC-SR trial, which started in August 2021, sought to compare Paxlovid to a placebo in adult patients with symptomatic COVID-19, who are not in hospital and “are at low risk of progressing to severe illness.”

In December 2021, Pfizer announced that results for Paxlovid did not meet the study’s goal of continuous symptom relief, or “self-reported, sustained alleviation of all symptoms for four consecutive days, as compared to placebo.”

At the time, Pfizer noted that there was a 70 percent reduction in hospitalizations in the Paxlovid group (three out of 428 hospitalized, with no deaths) compared to placebo (10 out of 426 hospitalized, with no deaths). The results were not statistically significant, however, which means it could possibly be down to chance.

On June 14, Pfizer announced that an updated analysis from 1,153 patients enrolled through December 2021 showed a 51 percent difference in hospitalization or death between the two groups—with five out of 576 in the Paxlovid group, compared to 10 out of 569 in the placebo group having required hospitalization or dying. The results were again not statistically significant.

There were no deaths in patients who received Paxlovid, but there was one death in the placebo group, the company stated.

The EPIC-SR study originally included fully-vaccinated people with at least one risk factor for progression to severe COVID-19, but after Paxlovid was authorized for the group in December 2021, this cohort was no longer enrolled in the study. Pfizer then adjusted its study eligibility criteria to allow people whose last vaccination was 12 months or more prior to enrollment.

A sub-group analysis of 721 vaccinated people with at least one risk factor for progression to severe COVID-19 showed there was a 57 percent risk reduction for hospitalization or death—with three out of 361 in the Paxlovid group, and seven out of 360 in the placebo group needing to be hospitalized or dying. The results did not reach statistical significance, Pfizer said.

Paxlovid also showed a non-significant 62 percent decrease in medical visits related to COVID-19 per day across all patients, relative to placebo.

Albert Bourla, the CEO and chairman of Pfizer, said in a statement that results from the company’s studies so far “support the efficacy and safety profile for PAXLOVID in the treatment of mild-to-moderate COVID-19 patients with at least one risk factor for progressing to severe COVID-19, regardless of vaccination status.”

“With up to 40–50 [percent] of people around the world estimated to be high risk, we believe there remains a significant unmet need for treatment options to help combat this disease, and we will continue to prioritize efforts to advance the development of PAXLOVID,” he added.

Data from a retrospective cohort study in Israel in early June, in a largely-vaccinated population, reported that Paxlovid reduces COVID-19 hospitalization and deaths by 46 percent. The study said the drug was “more effective in older patients, immunosuppressed patients, and patients with underlying neurological or cardiovascular disease.”

In a separate instance where Paxlovid failed to produce a statistically significant result, Pfizer announced in April that the antiviral pill was not effective at preventing symptomatic COVID-19 infection in household contacts of the COVID-19 patient who took the pill.

The United States has spent more than $10 billion to order from Pfizer 20 million courses of Paxlovid, and the White House has been seeking for more funds from Congress to support purchasing more of the antiviral pill as well as other treatments and vaccine booster doses.

The Centers for Disease Control and Prevention (CDC), warned in late May that some people may experience a rebound in COVID-19 symptoms after taking Paxlovid—meaning they may experience symptoms again after having had their symptoms resolved, or test positive for COVID-19 after having tested negative. The CDC said at the time that the rebound may be unrelated to the pill and “may be part of the natural history of SARS-CoV-2” in some people, “independent of treatment with Paxlovid and regardless of vaccination status.”

CDC Director Issues Alert On Pfizer’s COVID-19 Pill

Authors: Jack Phillips via The Epoch Times, JUN 01, 2022 

Centers for Disease Control and Prevention Director Rochelle Walensky warned that Pfizer’s COVID-19 pill Paxlovid can lead to a rebound in symptoms.

“If you take Paxlovid, you might get symptoms again,” Walensky told CBS News on Tuesday.

“We haven’t yet seen anybody who has returned with symptoms needing to go to the hospital. So, generally, a milder course.”

Another researcher who is not affiliated with the CDC said that he has observed such a scenario.

“People who experience rebound are at risk of transmitting to other people, even though they’re outside what people accept as the usual window for being able to transmit,” Dr. Michael Charness of the Veterans Administration Medical Center in Boston told CNN on Tuesday.

After a patient recovers from COVID-19, the aforementioned rebound has occurred between two and eight days later, according to the CDC. The agency, however, told CBS that the benefits of taking Paxlovid outweigh the risks of COVID-19, namely among those who are at a high risk of developing severe symptoms from the virus.

A Pfizer technician handles the company’s COVID-19 pill, known as Paxlovid, in a file photograph. (Pfizer via AP)

About a week ago, the agency issued an alert to health care providers about the rebound, saying that patients who took Paxlovid either test positive for the virus after having tested negative or will experience COVID-19 symptoms.

“A brief return of symptoms may be part of the natural history of SARS-CoV-2 infection in some persons, independent of treatment with Paxlovid and regardless of vaccination status,” the federal health agency said at the time. SARS-CoV-2 is another name for the CCP (Chinese Communist Party) virus, which causes COVID-19.

“Limited information currently available from case reports suggests that persons treated with Paxlovid who experience COVID-19 rebound have had mild illness; there are no reports of severe disease. There is currently no evidence that additional treatment is needed with Paxlovid or other anti-SARS-CoV-2 therapies in cases where COVID-19 rebound is suspected,” the CDC added.

The Epoch Times has contacted Pfizer for comment. Pfizer told CBS that it is observing a rebound rate of approximately 2 percent and is continuing to monitor patients.

“We have not seen any [COVID-19] resistance emerge to date in patients treated with Paxlovid,” a spokesperson for the company told Reuters this week.

In recent weeks, doctors have increasingly prescribed Paxlovid, which has been authorized to treat at-risk people. But some health care workers told Reuters they are putting off prescribing the medication.

“I am shying away from giving it to people who are very low- risk, and are not terribly ill, particularly people who are vaccinated and boosted,” said Dr. Bruce Farber, chief of public health and epidemiology for Northwell Health, in an interview with the news agency. He will still prescribe the bill to people who have significant health conditions or are aged 75 and older.

Patients Treated with Pfizer’s Paxlovid Experience Second Round of Covid-19 Shortly After Recovering – Doctors are Baffled

Authors:  Benjamin Ryan Published April 29, 2022 NBC Health

Pfizer’s antiviral pills are highly effective at keeping people with Covid out of the hospital, but there are growing reports that, in rare cases, patients treated for the coronavirus with Paxlovid can experience a second round of the disease shortly after recovering.

Infectious disease experts stress that cases of apparent viral rebound, when someone gets better and then soon gets sick again, following Covid treatment are not cause for alarm. However, there are increasing calls for federal agencies to provide greater clarity and guidance about how patients and health care providers should respond.

With mostly just anecdotal reports coming out, questions remain as to whether people whose Covid symptoms return shortly after they take Paxlovid are contagious and should keep isolating to avoid passing the virus to others.

For those who do experience a second round of symptoms, the sudden shift can also leave them anxious about whether they should seek further treatment.

Michael Henry, 31, a vaccinated and boosted software engineer in Philadelphia, first got sick with Covid on April 4, suffering from chills and a fever.

Henry, who has medical conditions that raise his risk of severe disease, got a Paxlovid prescription from an urgent care center the next day. Within 48 hours, he was feeling “totally fine.” But then, one week after his last dose, he got sick once again, with milder cold-like symptoms, and remained sick for about five days.

“I was kind of shocked,” Henry said of testing positive once more.

“There’s no guidance on what to do. Should I be isolating?” he recalled. “How do I keep my family safe?”

He called his doctor, Philadelphia’s Covid information line and a health insurance nurse looking for clarity. “Everyone I talked to gave me different answers.”

Paxlovid has been prescribed since December, when the Food and Drug Administration granted emergency authorization for people at high risk of severe Covid. The five-day course of prescription pills reduced the risk of hospitalization or death by 88 percent in a clinical trial. The federal government, which fully covers the treatment, has shipped to the states over 1.7 million courses since Paxlovid was green-lit. On Monday, the White House said it will double the number of locations where Paxlovid is available, since many of the doses have gone unused.

“There’s still so much we don’t know about Covid-19 and the best way to treat it,” said Dr. H. Clifford Lane, deputy director for clinical research and special projects at the National Institute for Allergy and Infectious Diseases. “These anecdotes give us reason to re-examine duration of therapy, approaches to therapy, other laboratory tests we might use to predict who could benefit from longer courses of treatment.”

No sign of drug resistance

On Tuesday, Dr. Michael Charness, chief of staff at the VA Boston Healthcare System, posted a pre-print detailing the case of a fully vaccinated and boosted 71-year-old man who recently saw his virus rebound after he took Paxlovid. The case study is under review by a medical journal.

Charness’ patient, who has intermittent asthma, started Paxlovid the day his Covid symptoms began. Two days later, he began a symptom-free week — only to get sick once again for about four days.

Genetic sequences of his virus indicated it did not develop resistance to the two medications in Paxlovid, nor was he re-infected. Tests for other respiratory viruses revealed that the coronavirus was the sole pathogen ailing him.

No evidence has yet emerged that anyone experiencing post-Paxlovid viral rebound had virus that had developed resistance to the treatment, Pfizer and other experts report. Nevertheless, the possibility is a concern.

“If someone has a case of post-Paxlovid SARS-CoV-2 relapse versus reinfection, it’s important that this be flagged to public health authorities,” said infectious disease specialist Dr. Céline Gounder, an editor at large for public health at Kaiser Health News. “The virus should be sequenced so we can learn if it’s mutated and developed resistance to Paxlovid.”

Pfizer spokesperson Kit Longley said the company is continuing “to monitor data from our ongoing clinical studies of Paxlovid, as well as real-world evidence” related to cases of post-Paxlovid relapse.

People who experience such a rebound, Longley said, can relay their experience to Pfizer’s portal for reporting Paxlovid-related adverse events.

Putting pressure on Pfizer

Scientific documentation about post-Paxlovid relapse has actually been available since last fall. Pfizer’s application to the FDA for emergency use authorization of Paxlovid stated that in the placebo-controlled clinical trial — which included 2,246 participants — “several subjects appeared to have a rebound in SARS-CoV-2 RNA levels around Day 10 or Day 14” after beginning treatment.

In a statement, Pfizer spokesperson Longley said that in Paxlovid’s clinical trial, the rare cases of the coronavirus rebounding soon after participants completed treatment occurred at a similar rate among those who received a placebo.

“We did not see an association between the observed viral load increase and subsequent severe disease,” Longley said. “Although it is too early to determine the cause, this suggests the observed increase in viral load is unlikely to be related to Paxlovid.”

However, in an April 25 blog post in NEJM Journal Watch, Dr. Paul Sax, an infectious disease specialist at Harvard Medical School, called upon Pfizer to release more data on these rebound cases, including information on how the participants’ health fared.

Charness speculated that when people start Paxlovid during the first day or two following Covid-19 symptoms, the early suppression of the coronavirus might compromise the immune system’s response to the infection.

Dr. Timothy Brewer, a professor of medicine and epidemiology at the University of California, Los Angeles further theorized that the body may sometimes harbor coronavirus in locations that Paxlovid has a hard time accessing, such as beyond the blood-brain barrier. After stopping the drug, the small stores of virus could eventually cause a rebound.

Some people, Brewer also suggested, might not absorb Paxlovid as effectively as others, leaving them with an insufficient amount of drug to wipe out the virus. A longer course of treatment might be needed, he suggested.

Because Paxlovid is not yet fully approved by FDA, doctors are not permitted to use their discretion to prescribe it for longer periods.

Pfizer’s Longley said the drugmaker is considering launching studies of longer Paxlovid treatments.

Some health care providers do, however, believe the emergency use authorization permits them to prescribe a second Paxlovid course to people experiencing relapse.

Dr. Ghady Haidar, a transplant infectious disease specialist at the University of Pittsburgh Medical Center, expressed concern about possible rebound cases in his particularly vulnerable patients.

“I really don’t think that five days of Paxlovid is going to be enough for certain subgroups of immunocompromised people,” he said.

Should returning symptoms require isolation?

Dr. Jeffrey Klausner, an infectious disease specialist at the University of Southern California, believes clear guidance is needed from federal regulators about symptoms recurring after Paxlovid treatment.

“Should recurrent cases isolate again? Does the EUA allow for repeat treatment and how does the NIH treatment guidelines committee consider use in those at high risk for recurrence like those immune compromised?,” Klausner asked.

FDA spokesperson Chanapa Tantibanchachai said that the agency “is evaluating the reports of viral load rebound after completing Paxlovid treatment and will share recommendations if appropriate.”

The CDC recommends that people who test positive for Covid isolate for at least five days and ultimately end their isolation five days after a 24-hour period of remaining fever free. People who get very sick or who have a compromised immune system are advised to isolate for at least 10 days.

CDC spokesperson Scott Pauley declined to comment on calls for the agency to clarify isolation guidelines for rebound cases.

Health care providers stress that Paxlovid hasn’t necessarily failed people whose Covid-19 symptoms return following treatment; it still may have saved them from hospitalization and death.

Dr. Leonard Joffe, 79, a retired ophthalmologist and pancreatic cancer survivor living with his wife in Tucson, Arizona, said that his recent experience with a second Covid-19 spell directly on the heels of Paxlovid treatment wasn’t so terrible.

“It was more of a nuisance than anything, because I had to wear a mask in my own home,” Joffe said. “My wife and I sat on opposite ends of the table, like Putin and other people.”

“We have a 10-foot table,” he clarified. 

Rare cases of COVID returning pose questions for Pfizer pill

Authors: MATTHEW PERRONE May 9, 2022 AP NEWS

As more doctors prescribe Pfizer’s powerful COVID-19 pill, new questions are emerging about its performance, including why a small number of patients appear to relapse after taking the drug.

Paxlovid has become the go-to option against COVID-19 because of its at-home convenience and impressive results in heading off severe disease. The U.S. government has spent more than $10 billion to purchase enough pills to treat 20 million people.

But experts say there is still much to be learned about the drug, which was authorized in December for adults at high risk of severe COVID-19 based on a study in which 1,000 adults received the medication.

WHY DO SOME PATIENTS SEEM TO RELAPSE?

Doctors have started reporting rare cases of patients whose symptoms return several days after completing Paxlovid’s five-day regimen of pills. That’s prompted questions about whether those patients are still contagious and should receive a second course of Paxlovid.

Last week, the Food and Drug Administration weighed in. It advised against a second round because there’s little risk of severe disease or hospitalization among patients who relapse.

Dr. Michael Charness reported last month on a 71-year-old vaccinated patient who saw his symptoms subside but then return, along with a spike in virus levels nine days into his illness.

Charness says Paxlovid remains a highly effective drug, but he wonders if it might be less potent against the current omicron variant. The $500 drug treatment was tested and OK’d based on its performance against the delta version of the coronavirus.

“The ability to clear the virus after it’s suppressed may be different from omicron to delta, especially for vaccinated people,” said Charness, who works for Boston’s VA health system.

Could some people just be susceptible to a relapse? Both the FDA and Pfizer point out that 1% to 2% of people in Pfizer’s original study saw their virus levels rebound after 10 days. The rate was about the same among people taking the drug or dummy pills, “so it is unclear at this point that this is related to drug treatment,” the FDA stated.

Some experts point to another possibility: The Paxlovid dose isn’t strong enough to fully suppress the virus. Andy Pekosz of Johns Hopkins University worries that could spur mutations that are resistant to the drug.

“We should really make sure we’re dosing Paxlovid appropriately because I would hate to lose it right now,” said Pekosz, a virologist. “This is one of the essential tools we have to help us turn the corner on the pandemic.”

HOW WELL DOES PAXLOVID WORK IN VACCINATED PEOPLE?

Pfizer tested Paxlovid in the highest-risk patients: unvaccinated adults with no prior COVID-19 infection and other health problems, such as heart disease and diabetes. The drug reduced their risk of hospitalization and death from 7% to 1%.

But that doesn’t reflect the vast majority of Americans today, where 89% of adults have had at least one shot. And roughly 60% of Americans have been infected with the virus at some point.

“That’s the population I care about in 2022 because that’s who we’re seeing — vaccinated people with COVID — so do they benefit?” asked Dr. David Boulware, a University of Minnesota researcher and physician.

There’s no clear answer yet for vaccinated Americans, who already have a hospitalization rate far below 1%.

That may come from a large, ongoing Pfizer study that includes high-risk vaccinated people. No results have been published; the study is expected to wrap up in the fall.

Pfizer said last year that initial results showed Paxlovid failed to meet the study’s goals of significantly resolving symptoms and reducing hospitalizations. It recently stopped enrolling anyone who’s received a vaccination or booster in the past year, a change Boulware says suggests those patients aren’t benefitting.

At a minimum, the preliminary data should be released to federal officials, Boulware said. “If the U.S. government is spending billions of dollars on this medicine, what’s the obligation to release that data so that they can formulate a good policy?”

CAN PAXLOVID BE USED TO HELP PREVENT COVID-19 INFECTION?

Pfizer recently reported that proactively giving Paxlovid to family members of people infected with COVID-19 didn’t significantly reduce their chances of catching it. But that’s not the end of the story. Pfizer is studying several other potential benefits of early use, including whether Paxlovid reduces the length and severity of COVID-19 among households.

“It’s a high bar to protect against infection but I’d love to see data on how Paxlovid did against severe disease because it may be more effective there,” said Pekosz.

FDA Investigating Reports Of COVID Relapses Following Use Of Pfizer’s Pill

Authors: Zachary Stieber  May 8, 2022

The U.S. Food and Drug Administration (FDA) is investigating reports of relapses among people who took Pfizer’s COVID-19 pill.

The FDA “is evaluating the reports of viral load rebound after completing paxlovid treatment and will share recommendations if appropriate,” an agency spokesperson told The Epoch Times in an email.

In a recent preprint case report, Veterans Affairs researchers reported that a 71-year-old male who took the pill, also known as nirmatrelvir, experienced a “rapid and progressive reduction” in the viral load of SARS-CoV-2, the virus that causes COVID-19.

But four days after completing the treatment course, there was a “surprising rebound of viral load and symptoms,” they reported.

The report “highlights the potential for recurrent, symptomatic SARS-CoV-2 replication after successful early treatment” with the pill, the researchers said.

A number of others have said they saw renewed symptoms after taking paxlovid.

In the FDA’s evaluation (pdf) of data on paxlovid, which the agency cleared on an emergency basis in 2021, the agency reported that in an ongoing phase 2/3 trial run by Pfizer, several participants “appeared to have a rebound” in viral load five to nine days after completing their treatment courses.

In light of the new reports, additional analyses of the paxlovid trial data were performed and showed that 1 to 2 percent of the patients had one or more positive COVID-19 tests after testing negative, or an increase in the amount of viral load, after completing the treatment, Dr. John Farley of the FDA said in an interview the agency published on May 4.

“This finding was observed in patients treated with the drug as well as patients who received placebo, so it is unclear at this point that this is related to drug treatment,” he said, adding that, at this time, the reports “do not change the conclusions from the paxlovid clinical trial which demonstrated a marked reduction in hospitalization and death.”

As part of the authorization agreement, the FDA said Pfizer must later submit information regarding “prolonged virologic shedding or rebound in clinical trials.”

Pfizer did not respond to a request for comment.

The company told Bloomberg that the rate of rebound in its trial was not higher among people who took paxlovid than in people who took a placebo.

“This suggests the observed increase in viral load is unlikely to be related to paxlovid,” the company said.

Dr. Clifford Lane, deputy director for clinical research at the National Institute of Allergy and Infectious Diseases, told the outlet that the agency will study the issue, calling it “a priority.”

Lane and the agency did not return queries.

The FDA authorized paxlovid for the treatment of mild to moderate COVID-19 in Americans 12 years or older. To get the pill, a person must test positive for COVID-19 and be deemed at high risk of progressing to severe disease.