Nirmatrelvir-ritonavir reduces risk of post-COVID syndrome in non-hospitalized vaccinated patients

In a recent study posted to the medRxiv* preprint server, researchers assess the effect of nirmatrelvir plus ritonavir (NMV-r) on the occurrence of post-acute sequelae of severe acute respiratory syndrome coronavirus 2-infection (PASC), which is otherwise known as long coronavirus disease 2019 (COVID-19).

Study: Incidence of Symptoms Associated with Post-Acute Sequelae of SARS-CoV-2 infection in Non-Hospitalized Vaccinated Patients Receiving Nirmatrelvir-Ritonavir. Image Credit: fizkes / Shutterstock.com

*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Background

As of April 2023, nearly 680 million individuals have recovered from COVID-19 throughout the world. Studies have documented PASC prevalence between 6% and 54% due to variable PASC definitions and varied populations studied. Despite its lower prevalence, the global burden of PASC is rapidly surging, which will have adverse public healthcare and economic impact.

NMV-r has become the favored antiviral therapy for outpatient mild-to-moderate COVID-19 cases, even for unvaccinated patients. However, no published literature, including peer-reviewed articles, suggests that NMV-r could be effective against PASC or reduce its incidence. Given its increasing incidence and adverse consequences, evaluating the efficacy of NMV-r for PASC management is crucial.

About the study

In the present retrospective cohort study, researchers compile the electronic health records (EHR)-based data from the TriNetX research network to determine the incidence of PASC-related symptoms in people treated with NMV-r vs. Moreover, long-term outcomes after COVID-19 diagnosis, specifically between 30 and 180 days and 90 and 180 days after the index SARS-CoV-2 infection, were assessed.

The study population included 279,380 vaccinated adults over 18 years of age patients who contracted COVID-19 between December 2021 and April 2022 and received NMV-r within five days of diagnosis. Importantly, all these individuals did not seek hospitalization throughout the study duration.

The researchers identified patients experiencing PASC-related symptoms through two definitions based on the International Classification of Diseases (ICD) code. Likewise, they defined the vaccination status and COVID-19 diagnosis based on prespecified diagnostic and laboratory codes.

Study findings

Of the 279,380 study participants, only 1,004 individuals received NMV-r within five days of diagnosis and had sufficient follow-up data for inclusion after propensity score matching.

Although initial COVID-19 severity is one of the factors contributing to the subsequent development of PASC, even people with mild COVID-19 sometimes experience disabling PASC symptoms. The pathophysiology of this complex condition remains unclear, thus contributing to the lack of available and effective drugs to treat PASC.

Between 30 to 180 days post-infection (pi), PASC-related symptoms were reported in 42%and 48%of NMV-r and control patients, respectively, with an odds ratio (OR) of 0.8. During the same duration, NMV-r therapy was less likely to be associated with a narrow definition of a three-symptom cluster of PASC as compared to the control cohort at 34% as compared to 40%, respectively.

NMV-r therapy also reduced the likelihood of cardiovascular, respiratory, and gastrointestinal symptoms. Further, its use lowered anxiety or mood disorders, with an OR value of 0.77 between 30 to 180 days pi; however, with no marked effects on musculoskeletal and nervous system symptoms.

The authors noted narrowly defined PASC-related symptoms in 22% and 28% of the NMV-r and control cohort, respectively, with an OR of 0.7. During this time, NMV-r treatment initiated between five days of infection also reduced the likelihood of cardiovascular and respiratory system involvement with an OR value of 0.72.

Conclusions

The current study data showed an association between NMV-r therapy and a reduced incidence of most commonly reported PASC-related symptoms. As compared to the beginning of the COVID-19 pandemic, the case severity of COVID-19 has considerably declined.

Nevertheless, there remains an urgent need for a rigorous analysis of COVID-19-related hospitalization and mortality outcomes. Prospective studies should also analyze the potential impact of antiviral therapies like NMV-r on the incidence of PASC.

*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.