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Association of Treatment With Nirmatrelvir and the Risk of Post–COVID-19 Condition, 2023, Yan Xie, PhD et al

Discussion in 'Long Covid research' started by Mij, Mar 23, 2023.

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  1. Mij

    Mij Senior Member (Voting Rights)

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    Question Is treatment with nirmatrelvir in the acute phase of SARS-CoV-2 infection associated with a lower risk of post–COVID-19 condition (PCC)?

    Findings In this cohort study of 281 793 people with SARS-CoV-2 infection who had at least 1 risk factor for progression to severe COVID-19 illness, compared with 246 076 who had no treatment, nirmatrelvir use in the acute phase (n = 35 717) was associated with reduced risk of PCC, including reduced risk of 10 of 13 post–acute sequelae in various organ systems, as well as reduced risk of post–acute death and post–acute hospitalization. Nirmatrelvir was associated with reduced risk of PCC in people who were unvaccinated, vaccinated, and boosted, and in people with primary SARS-CoV-2 infection and reinfection.

    Meaning In people with SARS-CoV-2 infection and at least 1 risk factor for progression to severe COVID-19 illness, treatment with nirmatrelvir during the acute phase of COVID-19 was associated with reduced risk of PCC.

    Abstract
    Importance Post–COVID-19 condition (PCC), also known as long COVID, affects many individuals. Prevention of PCC is an urgent public health priority.

    Objective To examine whether treatment with nirmatrelvir in the acute phase of COVID-19 is associated with reduced risk of PCC.

    Design, Setting, and Participants This cohort study used the health care databases of the US Department of Veterans Affairs (VA) to identify patients who had a SARS-CoV-2 positive test result between January 3, 2022, and December 31, 2022, who were not hospitalized on the day of the positive test result, who had at least 1 risk factor for progression to severe COVID-19 illness, and who had survived the first 30 days after SARS-CoV-2 diagnosis. Those who were treated with oral nirmatrelvir within 5 days after the positive test (n = 35 717) and those who received no COVID-19 antiviral or antibody treatment during the acute phase of SARS-CoV-2 infection (control group, n = 246 076) were identified.

    Exposures Treatment with nirmatrelvir or receipt of no COVID-19 antiviral or antibody treatment based on prescription records.

    Main Outcomes and Measures Inverse probability weighted survival models were used to estimate the association of nirmatrelvir (vs control) with post–acute death, post–acute hospitalization, and a prespecified panel of 13 post–acute COVID-19 sequelae (components of PCC) and reported in relative scale as relative risk (RR) or hazard ratio (HR) and in absolute scale as absolute risk reduction in percentage at 180 days (ARR).

    Results A total of 281 793 patients (mean [SD] age, 61.99 [14.96]; 242 383 [86.01%] male) who had a positive SARS-CoV-2 test result and had at least 1 risk factor for progression to severe COVID-19 illness were studied. Among them, 246 076 received no COVID-19 antiviral or antibody treatment during the acute phase of SARS-CoV-2 infection, and 35 717 received oral nirmatrelvir within 5 days after the positive SARS-CoV-2 test result. Compared with the control group, nirmatrelvir was associated with reduced risk of PCC (RR, 0.74; 95% CI, 0.72-0.77; ARR, 4.51%; 95% CI, 4.01-4.99), including reduced risk of 10 of 13 post–acute sequelae (components of PCC) in the cardiovascular system (dysrhythmia and ischemic heart disease), coagulation and hematologic disorders (pulmonary embolism and deep vein thrombosis), fatigue and malaise, acute kidney disease, muscle pain, neurologic system (neurocognitive impairment and dysautonomia), and shortness of breath. Nirmatrelvir was also associated with reduced risk of post–acute death (HR, 0.53; 95% CI, 0.46-0.61); ARR, 0.65%; 95% CI, 0.54-0.77), and post–acute hospitalization (HR, 0.76; 95% CI, 0.73-0.80; ARR, 1.72%; 95% CI, 1.42-2.01). Nirmatrelvir was associated with reduced risk of PCC in people who were unvaccinated, vaccinated, and boosted, and in people with primary SARS-CoV-2 infection and reinfection.

    Conclusions and Relevance This cohort study found that in people with SARS-CoV-2 infection who had at least 1 risk factor for progression to severe disease, treatment with nirmatrelvir within 5 days of a positive SARS-CoV-2 test result was associated with reduced risk of PCC across the risk spectrum in this cohort and regardless of vaccination status and history of prior infection; the totality of findings suggests that treatment with nirmatrelvir during the acute phase of COVID-19 may reduce the risk of post–acute adverse health outcomes.

    https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2802878
     
    Mij, Mar 23, 2023
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  2. Hutan

    Hutan Moderator Staff Member

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    From the abstract, it looks like a very interesting study. Of course not all post-covid illness is ME/CFS-like, but there is reporting on specific symptoms including fatigue and malaise, and dysautonomia. I look forward to seeing if the drug reduced ME/CFS symptoms.

    The sample is heavily skewed towards male, as might be expected in a Dept of Veterans Affairs sample, and the mean age is high. People included had to have at least one risk factor for post-covid disease, hence the high mean age, and also high mean BMI, high rate of smoking, kidney disease, diabetes and more.

    Nirmatrelvir - it's part of the anti-viral Paxlovid
     
    Last edited: Mar 23, 2023
    Hutan, Mar 23, 2023
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  3. Hutan

    Hutan Moderator Staff Member

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    Treatment reduced the risk of severe acute disease enormously in this health-compromised sample (halved the rate of death; hospitalisation rates were 75% of untreated people).

    The post-acute disease symptoms that were reduced included symptoms that are part of ME/CFS. It's a shame that exercise intolerance and specifically PEM aren't recorded. The fact that it did not reduce cough and new-onset diabetes and liver disease increases the chances that the observed effect is relevant to ME/CFS. (For instance, if it was just reducing tissue damage during the acute stage, perhaps there would be more cough and organ disease.)
    It should be noted that they followed people testing positive with Covid during the whole of 2022, recording the incidence of any symptoms recorded in the person's medical records from 30 days after the test until the end of the study. So the study concentrates on symptoms in the early months after the acute illness.

    The risk of a Post-Covid-19 Condition overall was decreased to 74% of the untreated risk. Fatigue and malaise was reduced to 79%. Interestingly, there were substantial reductions in the rates of pulmonary embolism (to 61%), deep vein thrombosis (to 72%) and acute kidney injury (to 67%). Muscle pain was also a stand out reduction (to 65%). Neurocognitive impairment was reduced (to 74%) and dysautonomia (to 86%).

    The reduction of risk was robust, being seen across different risk profiles (that is, the number of risk factors contributing to a high risk of severe Covid-19), vaccination profiles, and even specific risk sub-groups e.g. smokers.
     
    Last edited: Mar 23, 2023
    Hutan, Mar 23, 2023
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  4. Hutan

    Hutan Moderator Staff Member

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    This of course is a big question. Paxlovid seems to be a simple enough treatment. With the lobbying might of Pfizer and the enormous socio-economic impact pushing decision-makers to act, there will surely be trials giving it to people without risk factors for progression to severe disease, primarily to reduce the chances of post-acute disease symptoms.

    The authors note that the course of treatment was just five days initiated in the first days after a positive test, and so there is the possibility that longer treatment and/or higher doses could lower the risks further. It also isn't known what effect treatments that are started later might have.

    They mention other anti-virals, specifically molnupiravir.

    I think this is a really solid study and I feel a bit excited. I think this study will prompt trials of anti-virals, and there seems to be a decent chance that the risk of people developing ME/CFS-like disease can be reduced substantially. If that is true, then it should be a major clue as to what is causing these symptoms. And it seems likely that there will be good trials of anti-virals as treatments for persisting post-Covid symptoms.
     
    Last edited: Mar 23, 2023
    Hutan, Mar 23, 2023
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  5. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

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    The trial to evaluate its effectiveness against LC is open (Akiko Iwasaki et al). What proportion of LC have viral persistence that responds? Judging from post-mortem and tissue biopsy studies, it's probably not going to be 0%.
     
    SNT Gatchaman, Mar 23, 2023
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  6. ME/CFS Skeptic

    ME/CFS Skeptic Senior Member (Voting Rights)

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    I was wondering if a trial of Paxlovid for EBV-patients would make sense to see if it would reduce the risk of ME/CFS. But I had not realised it was specifically designed to tackle SARS-CoV-2, so chances are probably low that it would work for EBV.

    Perhaps a trial with the diabetes drug Metformin would be interesting, given that it also seem to reduce the risk of Long Covid.
     
    Last edited: Aug 16, 2023
    ME/CFS Skeptic, Aug 16, 2023
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