Is nirmatrelvir treatment of SARS-CoV-2 associated with reduced risk of post-COVID-19 condition?

In a recent article published in JAMA Internal Medicine journalMissouri, United States (US) researchers conducted an observational cohort study using the United States Department of Veterans Affairs (VA) medical database.

Study: Association between Nirmatrelvir treatment and risk of post-COVID-19 condition. Image Credit: ergeiShimanovich/

The aim of this study was to investigate whether nirmatrevir treatment during acute coronavirus disease 2019 (COVID-19) reduces the risk of post-COVID-19 condition (PCC), also called long-term COVID.


The long COVID, including acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC), has affected millions of people worldwide. Prevention of PCC is an urgent public health priority, but there are no drugs approved for its prevention or treatment.

Studies have shown that the oral antiviral drug nilmatrelvir, when combined with ritonavir, marketed as paxlobid, reduces the risk of progression to severe COVID-19 and subsequently PCC. I’m here. However, Paxlovid’s effects are greatest if he starts within 5 days of the onset of COVID-19.

Millions of people have been on nirmatrelvir therapy since oral nirmatrelvir received Emergency Use Authorization (EUA) in the United States in December 2021. However, few studies have investigated the effectiveness of this treatment in reducing the risk of PCC.

More data are urgently needed on the use of paxlobid in non-hospitalized COVID-19 cases who are at high risk of progressing to severe disease. This will guide new therapeutic approaches for SARS-CoV-2 infection and help optimize her current PCC prevention and treatment strategies.

About research

In this study, researchers first identified patients with acute SARS-CoV-2 infection who had at least one risk factor for developing severe COVID-19. The study screened 281,793 individuals who met the following prespecified criteria:

i) have been diagnosed as COVID-19 positive between 3 January 2022 and 31 December 2022;

ii) have not been hospitalized since the day they tested positive for COVID-19;

iii) have at least one risk factor for developing severe COVID-19; and

iv) Survived the first 30 days after diagnosis of COVID-19.

The team divided study participants into two cohorts. The first cohort, consisting of 35,717 patients, tested positive for COVID-19 and he received oral nirmatrelvir therapy within 5 days. Her second cohort of 246,076 patients did not receive antiviral therapy during the acute phase of their illness.

The primary study outcome was an estimate of hospitalization, death, or PCC associated with nilmatrelvir therapy after the acute phase of disease. The team used an inverse probability-weighted survival model to obtain these estimates.

They recorded whether participants had any of the 13 prespecified PCC components (or acute sequelae) on a relative scale, recorded as risk (RR) or hazard ratio (HR), and scored as 180 The day-to-day risk reduction rate (ARR) was recorded as follows: absolute scale.


Initial nirmatrelvir therapy initiated within 5 days of a positive SARS-CoV-2 test reduced the risk of 10 out of 13 acute sequelae. Its use was also associated with a 26%, 47%, and 24% reduction in the risk of PCC, after acute death, and after acute hospitalization, respectively.

The degree of absolute risk reduction with nirmatrelvir therapy was also significant. In 100 people who received oral nirmatrelvir pharmacotherapy between 30 and 180 days after symptom onset, acute post-mortem, post-acute hospitalization, and PCC he corresponded to 0.65, 1.72, and 4.51 fewer cases.

In addition, nilmatrelvir therapy was effective in different subgroups, regardless of vaccination status or history of COVID-19.

This study will initiate a randomized clinical trial to evaluate people without risk factors for progression to serious disease (who currently meet the requirements to receive nirmatrelvir treatment under current EUA guidelines in the United States). provide sufficient evidence to assess the benefits of nirmatrellvir in non-medical populations.

Studies should also evaluate the effects of longer durations of nirmatrelvir therapy, higher doses, or both in reducing the risk of PCC. Different molecular mechanisms mediate different acute sequelae, which may lead to the discovery of new information. Therefore, some people may not be affected by administration of antiviral medications such as nilmatrelvir.

Finally, other antiviral drugs with similar efficacy to nilmatrelvir, such as molnupiravir, should be investigated. This will help researchers understand whether the implications reported in this study apply to other antiviral drugs, and reduce dependence on single drugs, especially given the increasing emergence of antiviral resistance. It may help reduce


In the current cohort study, nilmatrelvir therapy initiated within 5 days of SARS-CoV-2 infection in persons with at least one risk factor for progression to severe disease was investigated in this cohort. was associated with reduced risk of PCC across the entire risk spectrum.

Indeed, these findings point to numerous benefits of nirmatrelvir extending into the post-acute phase of COVID-19.

written by

Neha Mathur

Neha is a digital marketing professional based in Gurugram, India. She completed her master’s degree in Biotechnology in 2008 from the University of Rajasthan. She has her preclinical research experience as part of her research project at the prestigious Central Pharmaceutical Research Institute (CDRI) Department of Toxicology. India. She also holds a C++ programming certification.


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