Nirmatrelvir and ritonavir combo cuts COVID-19 risks for high-vulnerability groups

The ongoing coronavirus disease 2019 (COVID-19) pandemic, caused by the rapid outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has immensely affected the global healthcare system and economy.

A recent JAMA Network Open study investigates the association between nirmatrelvir and ritonavir treatment and the risk of death and hospitalization due to COVID-19 in patients vulnerable to infection.

Study: Nirmatrelvir-Ritonavir and COVID-19 Mortality and Hospitalization Among Patients With Vulnerability to COVID-19 Complications. Image Credit: Kateryna Kon /


Nirmatrelvir and ritonavir, collectively known as Paxlovid, is an oral anti-viral combination used to treat SARS-CoV-2 infection. The United States Food and Drug Administration (FDA) approved the use of nirmatrelvir and ritonavir based on efficacy and safety data obtained during the Evaluation of Inhibition for COVID-19 in High-Risk Patients (EPIC-HR) trial, which was conducted prior to the emergence of the SARS-CoV-2 Omicron variant.

The EPIC-HR trial included 2,246 unvaccinated participants randomized to receive nirmatrelvir and ritonavir (test group) or placebo (control) within five days of COVID-19 symptom onset. Compared to the control group, the test group exhibited a non-statistically significant reduction in mortality and hospitalization rates due to SARS-CoV-2 infection.

Another observational study also indicated that nirmatrelvir and ritonavir treatment reduced hospitalization or death due to COVID-19. However, this reduction was almost half the magnitude of that reported during the EPIC-HR trial.

Multiple studies across variable populations have indicated a protective function of nirmatrelvir and ritonavir therapy against SARS-CoV-2 infection. Nevertheless, it is essential to assess the benefit-harm profile of this treatment.

About the study

The current study analyzed how nirmatrelvir and ritonavir therapy influenced the rate of hospitalizations and deaths due to COVID-19 in individuals at an increased risk of complications. This retrospective cohort study was conducted between February 1, 2022, and February 3, 2023.

The study compared the rates of hospitalization and all-cause deaths linked to COVID-19 between individuals either prescribed or not prescribed nirmatrelvir and ritonavir. Data related to nirmatrelvir and ritonavir prescriptions were obtained from the PharmaNet database. COVID-19 vaccination status was collected from the Ministry of Health.

Four mutually exclusive population groups were formed that included highly vulnerable participants at high risk of severe SARS-CoV-2 infection and were eligible for nirmatrelvir and ritonavir drugs within the study period. These included clinically extremely vulnerable (CEV) people, including severely (CEV1) or moderately immunocompromised (CEV2).

CEV3 included individuals who were not immunocompromised but had medical conditions that increased the risk of severe SARS-CoV-2 infection. The fourth group was referred to as the expanded eligibility (EXEL) group, which included higher-risk individuals who did not belong to the CEV group. For example, unvaccinated individuals above 70 years of age were included in the EXEL group.

The study assessed emergency hospital visits, admission, or death from any cause linked to SARS-CoV-2 infection in all study groups.

Study findings

A total of 6,866 participants were included in this study, 56.6% female with a median age of 79. Nirmatrelvir and ritonavir-treated patients were matched by age and sex in all four groups. The vaccination rate was over 90% in all three CEV groups and less than 80% in the EXEL group.

Medical conditions, such as non-severe kidney conditions, stroke, severe respiratory disorders, neurological conditions, cancer, and diabetes, were also compared for each matched group.

Individuals who were highly vulnerable to complications from COVID-19 were at a lower risk of death and hospitalization due to SARS-CoV-2 infection when treated with nirmatrelvir and ritonavir.

However, a similar association was not observed in individuals at a lower risk of complications in the EXEL group. This observation was true irrespective of sex and age.

The study findings were consistent with the EPIC-HR trial results, which found that nirmatrelvir and ritonavir treated reduced hospitalizations and deaths due to COVID-19.

Strengths and limitations

A primary strength of this study is an assessment of the efficacy of nirmatrelvir and ritonavir based on different degrees of vulnerability to COVID-19. It was important to subdivide individuals based on their degree of vulnerability, as this approach revealed that nirmatrelvir and ritonavir treatment was not effective in individuals above 70 years of age in the EXEL group. In the future, this patient population can be protected from unnecessary overtreatment.

The current study has several limitations, as the Omicron variant was the dominant circulating variant during the study period. Therefore, the study findings may not be relevant when other SARS-CoV-2 variants are in circulation. Furthermore, the Omicron variant is less virulent as compared to the Delta variant, which was more prevalent during the EPIC-HR trial period.

Despite these limitations, the use of nirmatrelvir and ritonavir could reduce the risk of death and hospitalization due to COVID-19 in highly vulnerable groups.

Journal reference:
  • Dormuth, C. R., Kim, J. D., Fisher, A., et al. (2023) Nirmatrelvir-Ritonavir and COVID-19 Mortality and Hospitalization Among Patients With Vulnerability to COVID-19 Complications. JAMA Network Open 6(10). doi:10.1001/jamanetworkopen.2023.36678

Posted in: Medical Research News | Disease/Infection News | Pharmaceutical News

Tags: Cancer, Coronavirus, Coronavirus Disease COVID-19, Diabetes, Drugs, Efficacy, Food, Healthcare, Hospital, Kidney, Mortality, Omicron, Pandemic, Placebo, Respiratory, Ritonavir, SARS, SARS-CoV-2, Severe Acute Respiratory, Severe Acute Respiratory Syndrome, Stroke, Syndrome

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Written by

Dr. Priyom Bose

Priyom holds a Ph.D. in Plant Biology and Biotechnology from the University of Madras, India. She is an active researcher and an experienced science writer. Priyom has also co-authored several original research articles that have been published in reputed peer-reviewed journals. She is also an avid reader and an amateur photographer.