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Paxlovid as a treatment for long COVID

Reports of two patients who found relief from long COVID after taking Pfizer’s antiviral Paxlovid, including a researcher who tested it on herself, provide intriguing evidence for clinical trials to help those suffering from the debilitating condition, according to a Research Square preprint.

The researcher said her chronic fatigue symptoms, which “felt like a truck hit me” disappeared after taking the two-drug oral therapy.

Long COVID is a looming health crisis, estimated to affect up to 30% of people infected with the coronavirus, reports Reuters. It can last for months, leaving many unable to work. More than 200 symptoms have been associated with the condition, including pain, fatigue, brain fog, breathing difficulty and exhaustion after minimal amounts of physical activity.

Dr Steven Deeks, a professor of medicine at the University of California, San Francisco (USSF), and an expert in HIV cure research, said drug companies tend to discount single-patient case studies. But such instances have helped drive HIV cure research, and Deeks thinks these Paxlovid cases could do the same for long COVID.

“This provides really strong evidence that we need to be studying antiviral therapy in this context as soon as possible,” he said, adding that he has heard of yet another anecdotal case at UCSF in which a long COVID patient’s symptoms cleared after taking Paxlovid.

Scientists caution that these cases are “hypothesis-generating only”, and not proof that the drug caused relief of lingering symptoms. But they lend support to a leading theory that long COVID may be caused by the virus persisting in parts of the body for months, affecting patients’ daily lives long after acute symptoms disappear.

The best evidence so far comes from a National Institutes of Health (NIH) study, currently under peer review, in which researchers conducted autopsies in 44 people who died of COVID-19 or another cause but were infected with COVID. They found widespread infection throughout the body, including in the brain, that can last more than seven months beyond the onset of symptoms.

Paxlovid, which combines a new Pfizer pill with the old antiviral ritonavir, is currently authorised for use in the first days of a COVID infection to prevent severe disease in high-risk patients.

Pfizer spokesman Kit Longley said the company does not have any long COVID studies under way and did not comment on whether it would consider them.

The drugmaker has two large clinical trials testing whether Paxlovid can prevent initial COVID infection. That “may provide us with relevant data to help inform future studies”, said Longley.

Patients who have been suffering for months are growing frustrated with the lack of pharmaceutical research for their condition.

There are currently fewer than 20 clinical trials led by individual researchers or small drugmakers testing treatments for long COVID, only a handful of which have moved beyond early stages.

Diana Berrent, founder of grassroots COVID advocacy group Survivor Corps, has been lobbying the Biden Administration to fund large long COVID clinical trials. “We shouldn’t be doing our research based on anecdotal reports,” she said. “That’s not good enough.”

Back to normal

In one of the case reports, published as a preprint ahead of peer review, a previously healthy and vaccinated 47-year-old woman became infected with COVID last year. Most of her acute symptoms dissipated within 48 hours, but she continued to have severe fatigue, brain fog, exhaustion after exercise, insomnia, racing heartbeat and body aches severe enough that she could no longer work.

Reuters adds that about six months after her initial infection, she was reinfected, possibly with COVID, and many of her acute symptoms also returned. Her doctor prescribed a five-day course of Paxlovid.

On day 3, she noticed a rapid improvement of symptoms. “She’s back to normal,” said Dr Linda Geng, co-director of Stanford Health Care’s long COVID clinic and author of the case report posted on Research Square.

In the second case, Lavanya Visvabharathy, 37, an immunologist working at Northwestern Medicine’s long COVID clinic, was infected in December 2021.Her initial symptoms were mild, but she later experienced chronic fatigue, headaches and sleep disturbances for four months after infection. She also kept testing positive on rapid antigen tests, a sign of viral persistence

Visvabharathy was aware of the NIH study and the Stanford case, and decided to try Paxlovid to see if it could clear any lingering virus. Toward the end of the five-day course, her fatigue and insomnia had improved, and her headaches were less frequent. Two weeks after treatment ended, her fatigue was gone. “That’s 100% fixed,” she said.

But to prove Paxlovid provides that kind of relief would require carefully controlled clinical trials, Visvabharathy said.

Dr Igor Koralnik, who heads Northwestern Medicine’s clinic focused on the neurological effects of long COVID, noted the long list of widely-used medications that are affected by ritonavir and said Paxlovid “can’t be used willy nilly”. “Paxlovid is not a benign medication,” he said. “There should be studies.”

South African situation

In South Africa, writes MedicalBrief, Paxlovid has not been approved or recommended for treatment.

According to the Department of Health, an assessment committee “suggests that nirmatrelvir+RTV not be used for the treatment of COVID-19”.

Rationale: Although there is evidence from a single RCT that nirmatrelvir+RTV reduces the risk of hospitalisation and death in adults with mild to moderate COVID-19 who are at high-risk for progression to severe COVID-19, and is well tolerated, its use requires rapid access to definitive diagnosis and initiation within 5 days of the onset of symptoms. Use of nirmatrelvir+RTV is contraindicated in pregnancy, so women of childbearing potential need to take effective contraception.

“Ritonavir increases the concentration of nirmatrelvir by slowing its breakdown through the cytochrome P450 pathway. This results in many potential drug-drug interactions. The efficacy and safety of nirmatrelvir+RTV has not been studied in patients previously vaccinated against COVID-19. Products containing nirmatrelvir and ritonavir (as co-packaged, separate oral solid dosage form) have yet to be registered in South Africa.”

Study details

Case Report of Breakthrough Long COVID and the Use of Nirmatrelvir-Ritonavir

Linda Geng, Hector Bonilla, Robert Shafer, Mitchell Miglis, Phillip Yang.

Pre-print published on Research Square on 15 March 2022


Post-Acute Sequelae of SARS-CoV-2 (PASC), or long COVID, is a major public health problem. Encouraging data suggest that vaccination can reduce the risk of PASC. We report a cautionary case of breakthrough PASC and its resolution following a course of the novel combination antiviral nirmatrelvir-ritonavir.

Post-Acute Sequelae of SARS-CoV-2 (PASC), or long COVID, is a major public health problem with paucity of clinical guidelines. The denition of PASC is evolving and it currently encompasses a heterogeneous spectrum of individuals who develop persistent symptoms that last for many weeks or longer after the initial COVID-19 infection.

The pathobiology of PASC is not understood and there is no effective therapy at this time. There is limited but encouraging data to suggest that vaccination can reduce the risk of PASC, but it is not clear in whom and how PASC presents after breakthrough infections.

Here, we present one of the first reports of breakthrough PASC and its resolution following a course of the novel combination antiviral nirmatrelvir-ritonavir (Paxlovid).


Reuters article – The case for testing Pfizer’s Paxlovid for treating long COVID (Open access)


Research Square pre-print – Case Report of Breakthrough Long COVID and the Use of Nirmatrelvir-Ritonavir (Open access)


National Institute of Health study – SARS-CoV-2 infection and persistence throughout the human body and brain (Open access)


SA Health Dept article – Should nirmatrelvir+RTV be used to treat confirmed COVID-19? (Open access)


See more from MedicalBrief archives:


SARS-CoV-2: No brain infection but can inflict significant damage — 40 autopsies


Long COVID can trigger type 2 diabetes in some – VA cohort study


Long COVID breathlessness: Novel scans uncover hidden lung damage


Long-term damaged sense of smell in 50% of 1st wave COVID cases – Karolinska study


Confronting America's next national health disaster: long-haul COVID-19



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