Millions of people worldwide are suffering from often debilitating symptoms of long COVID that can persist weeks, months, or even years following an acute infection. But researchers are still in the dark on the mechanisms underlying and how to treat the mysterious post-viral syndrome. A new clinical trial using the oral antiviral Paxlovid will provide urgently needed insights for COVID long-haulers and their providers.
Since the pandemic's onset, Harlan Krumholz, MD, Harold H. Hines, Jr. Professor of Medicine (Cardiology) and professor in the Institute for Social and Policy Studies, of investigative medicine, and of public health (health policy) and Akiko Iwasaki, Ph.D., Sterling Professor of Immunobiology and professor of dermatology, of molecular, cellular & developmental biology, and of epidemiology (infectious diseases) have been leaders in unraveling the mysteries of long COVID and advocating for those who are suffering.
Through their clinical trial, they plan to combine their expertise in the clinic and lab to understand the biological mechanisms that occur throughout the course of receiving Paxlovid. The trial will be held through a unique decentralized format designed to boost accessibility for its participants.
Krumholz and Iwasaki hope their findings will generate clinical insights on potential markers for diagnostic testing and targets for future interventions. Because studies on long COVID are still scarce, finding answers for long-haulers is crucial. "We need to get out there and start testing things for this group that basically has nothing available to them" says Krumholz. "And by pairing expert biological investigation with expert clinical investigation, we're opening the door for an entirely different approach to how we're going to do this research and the kind of progress we can make."
Viral persistence is one of several long COVID hypotheses
Krumholz and Iwasaki believe that the manifestation of long COVID may have different pathologies in different patients. Iwasaki was one of the first to propose that long COVID may be the result of the acute SARS-CoV-2 infection reactivating a latent virus, disturbing the microbiome, causing damage that results in downstream inflammation, triggering hyperreactivity of the immune system that fails to shut off post-infection, or, relevant to their trial, that the virus may be stubbornly persisting in some individuals.
"We think that some people never really get rid of the virus, so it continues to cause mischief over time, creating lingering symptoms," says Krumholz. Because of the varying pathologies, some patients may respond more strongly to one treatment than to others.
"We are not expecting everyone to respond, but we should be able to find out who improves from Paxlovid and what their immune signatures are, so we can get better insights into the disease pathogenesis and identify people who are likely to benefit by taking this drug," Iwasaki says.
Although researchers don't know which hypothesis or combination of hypotheses is the true culprit, Krumholz says there is no time to waste as patients continue to suffer. "We've been feeling that we can't really wait until we have a full understanding of the mechanisms," he says. "But one way to gain a better understanding may be to test some strategies that are specific to one particular theory."
Furthermore, he continues, it will be important to pair these studies with sub-studies that characterize the immune responses of the subjects. That way, if some patients benefit but not others, researchers may be able to identify markers that indicate which individuals may respond best to a certain treatment.
The new clinical trial was inspired by the viral persistence theory, which says that in some individuals, long COVID symptoms may be caused by a lingering virus. Prior research has shown that Paxlovid has antiviral activity against SARS-CoV-2 when used acutely. Therefore, Krumholz and Iwasaki wondered if prescribing patients with the antiviral medication for a longer period may benefit those who are still suffering after the acute infection. By joining forces with Iwasaki, he hopes to identify which participants show the greatest benefit, as well as the underlying immunological changes that occur as they receive the antiviral drug.
Long COVID trial has a novel, accessible design
The randomized trial will involve prescribing symptomatic long haulers with Paxlovid for 15 days, as well as taking blood samples before, during, and after taking the drug for assessing immune responses to the drug. But participation in clinical trials can be burdensome. For many patients, especially those who earn hourly wages, traveling to a study site can interfere with their ability to make ends meet. The study's innovative, decentralized design addresses this obstacle and makes it easier than ever for patients to join. "Through our decentralized trial design, we're going straight to people. We're saying, if you've got this condition, you don't have to come to us. We can come to you," says Krumholz.
Krumholz is a co-founder of Hugo Health, a company that gives patients agency over their health data. Since its launch, it has fostered a community of long COVID patients looking to take part in studies. "It's creating a means through which we can enroll people really rapidly and offer a participant-centric approach," he says. Through the platform, participants can give permission for their data to be used and fill out questionnaires from their mobile devices or computers. Furthermore, individuals will be able to receive blood draws in their own homes and have the drug delivered to their doorstep.
"We're making it so that they can fully participate from home," he says. "We're not only trying to push our long COVID knowledge forward, but also we hope to demonstrate how we can change the way this research is done so that we can test hypotheses much more rapidly, less expensively, and much faster than we would otherwise."
"I am so excited that we are able to offer this patient-centric decentralized trial design to study the impact of Paxlovid on long COVID," Iwasaki adds. "This was only made possible because of Professor Krumholz's deep experience and his perseverance in getting all our ducks in a row."
Another novel aspect of the study is Krumholz's and Iwasaki's unique partnership. Three years ago, no one was a specialist in long COVID. The pandemic forced researchers from different fields who weren't naturally working together to team up. "It required people, no matter what they were doing, to stand up and say that they were willing to try," says Krumholz. "We're creating a study that's truly leveraging my expertise on the best clinical research practices with Professor Iwasaki's expertise on the best laboratory research practices to produce the best insights at a fast pace."
New avenues of understanding for long COVID and beyond
The team hopes that its study will not only help those struggling with long COVID, but also provide a greater understanding of other post-infectious syndromes. "Infectious triggers are responsible for a whole lot of downstream suffering among people," says Krumholz. "This study will help us begin to understand this phenomenon diagnostically and start identifying targets to help relieve the widespread suffering."
"There are a number of other similar post-acute infection syndromes that happen after many different virus infections and some bacteria and parasitic infections," says Iwasaki. "The fact that the downstream consequences, including myalgic encephalomyelitis, are so similar to each other makes us believe that once we figure out one of these syndromes, we can apply a similar insight into other post-acute phase diseases."
Patients with long COVID and other post-acute infection syndromes frequently report feeling unbelieved and dismissed by the health care system. "The more we can begin to demonstrate biological correlates, the better we can anchor these as legitimate conditions," says Krumholz. "There's no question in our minds that these are real, but patients often have a hard time with a health care system that doesn't know what to do with them."
Krumholz and Iwasaki are looking forward to working alongside patients as they seek answers to alleviating their suffering.
"For people who join us, they'll be truly a part of something that's important," says Krumholz. "We will treat the people who join as part of the team. We want to make sure they know what is going on and learn the results as soon as we know them. And we want this to become the norm for how research is conducted."
"Throughout this pandemic, we have already learned a great deal about long COVID from patients and advocates," says Iwasaki. "We are about to learn something incredible from patients through our trial. I feel very fortunate to be working as partners in my journey with patients to find a viable therapy against this devastating disease."
Citation: New clinical trial to test Paxlovid's effectiveness against long COVID (2023, April 7) retrieved 10 April 2023 from https://medicalxpress.com/news/2023-04-clinical-trial-paxlovid-effectiveness-covid.html
This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.
FAQs
Does Paxlovid reduce long term COVID? ›
The analysis showed that Paxlovid reduced the risk of long COVID-19 by 26% over a six-month period. Similarly, during the same time span, Paxlovid decreased the risk of death by 47% and the risk of hospitalization by 24%. “All hypotheses of long COVID point to SARS-CoV-2 as the initiating agent,” Al-Aly said.
How effective is Paxlovid clinical trial? ›PAXLOVID nirmatrelvir and ritonavir: US fact sheet for healthcare providers. The EPIC-HR trial found in 2246 unvaccinated high-risk, ambulatory COVID-19 patients, that, as compared to placebo, Paxlovid reduced hospitalization and 28-day mortality rates by 89.1% and 88.9%, respectively. Hammond J. Leister-Tebbe H.
Does Paxlovid really help? ›Paxlovid is the first-choice treatment for mild to moderate COVID in people with a higher risk of severe illness. In initial clinical studies, it was about 90% effective at preventing COVID-related hospitalization and death.
Is there a definitive test for long COVID? ›Dr Nyarie Sithole, also from the Department of Medicine at the University of Cambridge, who co-leads the team and helps to manage long COVID patients, said: “Because we currently have no reliable way of diagnosing long COVID, the uncertainty can cause added stress to people who are experiencing potential symptoms.
What are the disadvantages of Paxlovid? ›Paxlovid (nirmatrelvir / ritonavir) can cause liver injury or damage. Your risk is higher if you already have liver problems or you're taking medications that can damage your liver.
What is the rate of relapse after Paxlovid? ›The 7-day and 30-day COVID-19 rebound rates after Paxlovid treatment were 3.53% and 5.40% for COVID-19 infection, 2.31% and 5.87% for COVID-19 symptoms, and 0.44% and 0.77% for hospitalizations.
How much difference does Paxlovid make? ›The press release said that Paxlovid led to a 57% reduction in hospitalization or death in that vaccinated group, although the difference didn't meet the statistical standards for showing a real difference.
What are the rebound trials for Paxlovid? ›About COVID-19 symptom rebound
A previous study of high-risk participants who were treated with PAXLOVIDTM found a small number of participants (0.8%) experienced a return (rebound) of COVID-19 signs/symptoms after completing treatment.
Of the COVID-19 patients who took Paxlovid, 14.2 percent tested positive again days after testing negative, and 18.9 percent had a symptom rebound.
What is the latest research on Paxlovid? ›The study found: Effectiveness in preventing hospital admission or death within 30 days after a positive test was 80% for people who were dispensed Paxlovid within 5 days after symptom onset. Within the subgroup of patients who were dispensed Paxlovid on the day of their positive COVID-19 test, effectiveness was 90%.
When is Paxlovid most effective? ›
Patients take a combination of pills twice a day for 5 days. Paxlovid should be administered as early as possible following the appearance of any symptoms and needs to be initiated within 5 days of symptom onset.
Who should not use Paxlovid? ›have ever had an allergic reaction to Paxlovid, or any other medicine. have problems with your kidneys. have problems with your liver. are intolerant to lactose or galactose – nirmatrelvir contains a lot of lactose.
How do I get rid of long COVID? ›- Relaxation techniques and gentle activities to help with fatigue and sleep problems.
- Medications to relieve common symptoms such as cough, pain, or headache.
- Counseling for emotional and mental health problems, such as depression or anxiety.
Naturally-occurring food supplements, such as acetyl L-carnitine, hydroxytyrosol and vitamins B, C and D hold significant promise in the management of post-COVID syndrome.
How do you treat long COVID fatigue? ›- Exercise to help cope with COVID-19. ...
- Talk about your frustrations. ...
- Engage in constructive thinking. ...
- Practice mindfulness and gratitude. ...
- Take it day by day or even moment by moment. ...
- Be compassionate with yourself. ...
- Find things to look forward to.
Paxlovid is not recommended for patients with severe renal or hepatic impairment.
Is it worth taking antivirals for COVID? ›In most cases, the virus clears up without these drugs, but when your infection is chronic or life-threatening, your doctor may want to treat you with the COVID antiviral medications.
What is the most effective antiviral for COVID? ›Remdesivir is the only antiviral drug that is approved by the Food and Drug Administration (FDA) for the treatment of COVID-19.
Does taking Paxlovid make you more likely to get COVID again? ›Feb. 15, 2023 – People who took the antiviral Paxlovid to treat COVID-19 infections were not more likely to get back-to-back bouts of the virus, a new study shows.
Is rebound COVID more likely after Paxlovid? ›Currently, studies are exploring if additional days of Paxlovid can reduce the rebound rate. In the meantime, the current FDA EUA only allows for five consecutive days of treatment. If you experience rebound symptoms, you are likely contagious again. You should isolate yourself to prevent passing the disease to others.
Does Paxlovid reduce symptoms? ›
The drug has been shown to reduce the risk of hospitalization and death from COVID-19 by 88% if taken within five days of getting symptoms.
How effective is Paxlovid in vaccinated people? ›Both Paxlovid and adequate COVID-19 vaccination status were associated with significant decrease in the rate of severe COVID-19 or mortality with adjusted HRs of 0.54 (95% confidence interval [CI], . 39-.
What is the success rate of Paxlovid in vaccinated patients? ›By leveraging a large, well-validated, COVID-19 data repository housed within their system, Mass General Brigham researchers confirmed that the drug is associated with a 44% reduction in hospitalization or death in a highly vaccinated population of adults over the age of 50.
Is Paxlovid effective against BA 5? ›“Real-world” assessment finds nirmatrelvir-ritonavir reduces risk of severe COVID-19 from BA4 and BA5 omicron subvariants.
How long does Long COVID last? ›People with Long COVID can have a wide range of symptoms that can last weeks, months, or even years after infection. Sometimes the symptoms can even go away and come back again. For some people, Long COVID can last weeks, months, or years after COVID-19 illness and can sometimes result in disability.
What is the risk benefit of Paxlovid? ›The data showed an 86% reduction in risk of COVID-19-related hospitalization or death from any cause through Day 28 in patients treated with PAXLOVID within 5 days of symptoms onset, compared to placebo.
How effective is Paxlovid in older adults? ›(The original study establishing Paxlovid's effectiveness had been conducted while the delta strain was prevalent and included only unvaccinated patients.) In patients 65 and older, most of whom had been vaccinated or previously had Covid, hospitalizations were reduced by 73% and deaths by 79%.
How effective is Paxlovid CDC? ›Oral nirmatrelvir with ritonavir (Paxlovid)
In a clinical trial, Paxlovid reduced the risk of hospitalization and death by 89% in unvaccinated outpatients with COVID-19 at higher risk of severe disease.
Like COVID-19 symptoms, the signs of Paxlovid rebound may vary between people. But typically, your initial COVID-19 symptoms will get better (or even go away) while taking Paxlovid. Then between 2 and 8 days after finishing the medication, your symptoms will get worse again.
Which medication is not recommended for patients older than 65 years? ›- Antidepressants amitriptyline (Elavil) and imipramine (Tofranil)
- Anti-Parkinson drug trihexyphenidyl (Artane)
- Irritable bowel syndrome drug dicyclomine (Bentyl)
Will Paxlovid work after 5 days? ›
Paxlovid is 80% effective when taken within 5 days of severe COVID.
Why are doctors hesitant to prescribe Paxlovid? ›However, some patients have reported doctors not prescribing Paxlovid due to potential side effects or contraindications (circumstances that suggest the drug shouldn't be used).
Is Paxlovid bad for your kidneys? ›PAXLOVID is not recommended in patients with severe renal impairment (eGFR <30 mL/min) until more data are available; the appropriate dosage for patients with severe renal impairment has not been determined [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].
Should you take mucinex with Paxlovid? ›Yes. In general, it's OK to take over-the-counter (OTC) cold and flu medicines with Paxlovid.
Are you contagious if you have long COVID? ›Am I Contagious if I Have Long COVID? No. Conditions associated long COVID cannot be passed on to others.
Am I still contagious after 7 days of COVID? ›You are most infectious (or contagious) in the first 5 days after your symptoms start. You can also spread COVID-19 in the 48 hours before your symptoms start. If you never have symptoms, consider yourself most infectious in the 5 days after you test positive.
Am I still contagious after 10 days if I still have symptoms? ›Those with severe COVID-19 may remain infectious beyond 10 days and may need to extend isolation for up to 20 days. People who are moderately or severely immunocompromised should isolate through at least day 20.
How do I get my energy levels back after Covid? ›Get up and move around slowly and gently a few times each day. This will keep your body mobile and help with circulation. Both physical and cognitive (thinking) activities use energy. Try to do only a small number of these activities each day, including basic activities of daily living, such as washing and dressing.
What is the best recovery supplement after COVID? ›Omega 3 fatty acids (Omega 3's) may help with reducing excess inflammation. As you recover, your body may be experiencing a significant amount of inflammation as a result of fighting this infection, so consuming food based sources of omega 3's could be helpful.
How do I get my energy back after recovering from Covid? ›...
It's important to:
- eat well.
- have a healthy sleep routine.
- drink plenty of water to keep hydrated.
Does Paxlovid prevent long COVID? ›
The analysis showed that Paxlovid reduced the risk of long COVID-19 by 26% over a six-month period. Similarly, during the same time span, Paxlovid decreased the risk of death by 47% and the risk of hospitalization by 24%. “All hypotheses of long COVID point to SARS-CoV-2 as the initiating agent,” Al-Aly said.
How I cured my chronic fatigue? ›While there is currently no cure for ME/CFS, there are treatments that may help you manage the condition. Treatments include: cognitive behavioural therapy (CBT) energy management – where you're given advice about how to make best use of the energy you have without making your symptoms worse.
What drug is used for long COVID? ›Other recent studies have also suggested that Paxlovid, an antiviral drug used to prevent severe COVID-19 among high-risk patients, may help prevent Long COVID in a similar way.
What drug reduces long COVID? ›The study, published as a pre-print with The Lancet, indicated that treatment with metformin reduced their chances of developing Long COVID by 42%, compared to placebo. The incidence of Long COVID in this group was 6.3%, compared to 10.6% among those who received a placebo drug.
When should you stop taking Paxlovid? ›Stopping Paxlovid
Do not stop taking Paxlovid before you have finished all 5 days of the course without talking to your doctor first. If you stop taking Paxlovid, it may no longer protect you from the severe symptoms of COVID-19.
Paxlovid, the COVID antiviral developed by Pfizer, was hailed as a miracle drug against COVID-19 when it was approved for use by the FDA in December.
What can you take to shorten the duration of COVID? ›Take Over-The-Counter Medications
Antivirals are most effective if started within the first 48 hours of symptoms. If used accurately, they can shorten the duration of illness by about 24 hours and decrease the risk of complications, especially in high-risk populations.
The risk of a Paxlovid rebound may be higher than previously reported, according to a study published Feb. 22 in Clinical Infectious Diseases, an Oxford University Press journal.
Do steroids help COVID long haulers? ›Potent anti-inflammatory medications, corticosteroids like dexamethasone, methylprednisolone, and prednisone are inexpensive and readily available. Based on the National Institute of Health guidelines, dexamethasone is recommended for patients hospitalized with severe COVID-19.
Is Paxlovid safe for kidneys? ›PAXLOVID is not recommended in patients with severe renal impairment (eGFR <30 mL/min) until more data are available; the appropriate dosage for patients with severe renal impairment has not been determined [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].
Does Paxlovid make COVID come back worse? ›
But typically, your initial COVID-19 symptoms will get better (or even go away) while taking Paxlovid. Then between 2 and 8 days after finishing the medication, your symptoms will get worse again.
What is considered high risk for Paxlovid? ›Who Qualifies as High Risk? Examples of high-risk patient characteristics include older adults (age 50 yr+), asthma, smoking (current or former), overweight, diabetes, pregnant, immune compromised, mental health disorders, substance use disorders, and cardiovascular disease.
How do I get rid of long Covid? ›- Relaxation techniques and gentle activities to help with fatigue and sleep problems.
- Medications to relieve common symptoms such as cough, pain, or headache.
- Counseling for emotional and mental health problems, such as depression or anxiety.
Paxlovid is not suitable for some people. Tell your doctor before starting to take this medicine if you: are pregnant, trying to get pregnant or breastfeeding.
How do you treat long Covid fatigue? ›- Exercise to help cope with COVID-19. ...
- Talk about your frustrations. ...
- Engage in constructive thinking. ...
- Practice mindfulness and gratitude. ...
- Take it day by day or even moment by moment. ...
- Be compassionate with yourself. ...
- Find things to look forward to.
Hospitalization and death rates for patients prescribed Paxlovid were 1.86% and 0.12% respectively, meaning patients prescribed Paxlovid were nearly 5 times less likely to be admitted and 10 times less likely to die after their COVID-19 infection.
Does Paxlovid improve symptoms? ›The drug has been shown to reduce the risk of hospitalization and death from COVID-19 by 88% if taken within five days of getting symptoms.
Which works better Paxlovid or molnupiravir? ›Pfizer's clinical trial found Paxlovid reduced a person's risk of hospitalization by 89% when given within three days of symptom onset. Merck's clinical trial showed molnupiravir cut the rate of hospitalization or death by 30% when the drug was given within five days of symptoms onset.