Nirmatrelvir/ritonavir reduces the risk of COVID-19-associated hospitalization

In a recent study published in the Clinical Infectious Diseases Journal, researchers performed a retrospective cohort study between March 15 and October 15, 2022, among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected high-risk outpatients in Québec, Canada.

The study aimed to assess whether nirmatrelvir/ritonavir treatment reduced the risk of coronavirus disease 2019 (COVID-19)-related hospitalization.

Study: Real-World Effectiveness of Nirmatrelvir/Ritonavir on Covid-19-Associated Hospitalization Prevention: A Population-Based Cohort Study in the Province of Québec, Canada. Image Credit: Cryptographer/Shutterstock.comStudy: Real-World Effectiveness of Nirmatrelvir/Ritonavir on Covid-19-Associated Hospitalization Prevention: A Population-Based Cohort Study in the Province of Québec, Canada. Image Credit: Cryptographer/


Previous studies, like the renowned EPIC-HR trial, have established that the combination of nirmatrelvir/ritonavir benefitted nonhospitalized outpatients even during the predominance era of the most lethal variant of concern (VOC) of SARS-CoV-2, Delta.

All trial participants were unvaccinated and received the drug within five days of symptom onset or COVID-19 diagnosis, which reduced the risk of hospitalization and death by 89%.

After the emergence of Omicron in late 2021, COVID-19 cases surged worldwide, even among populations with high vaccine uptake and pre-existing immunity.

About the study

In the present study, researchers set out to assess the effectiveness of nirmatrelvir/ritonavir therapy during Omicron BA.2 and BA.4/5 surge in real-world settings, i.e., in the Québec province of Canada.

Specifically, they used a Poisson regression model to assess the relative risk of COVID-19-related hospitalization within 30 days of the study index date, which varied for two groups.

It was the date of the first prescription of nirmatrelvir/ritonavir for the treatment group and the first COVID-19 positive test for the control group.

They used the Québec clinical-administrative databases to recruit the two study cohorts, outpatients with COVID-19 (treatment group) and propensity-score matched individuals (control group), to compare the effectiveness of nirmatrelvir/ritonavir in the two groups.

The treatment group individuals received at least one dose of the study drug during the study, while the control group did not.

The study variables comprised socio-demographic characteristics, e.g., age, gender, COVID-19 vaccination status, number of vaccine doses, and time since the last vaccine dose, to name a few.

The team also recorded 226 health conditions for each study participant using a case-mix classification based on the Population Grouping Methodology (POP Grouper).

Finally, they computed the number needed to treat (NNT) with a 95%  confidence interval (CI) using raw hospitalization data. In their sensitivity analysis using a multivariable regression model, the team considered both hospitalizations for which the primary cause was COVID-19 and hospitalization and death related to COVID-19 as outcomes.


The study analysis covered 16,601 and 242,341 outpatients in treatment and control groups. The follow-up of each outpatient continued till November 14, 2022, i.e., for 30 days minimum.

Of 16,601 outpatients who received nirmatrelvir/ritonavir therapy,  57% were females, 67% were ≥60 years, and 73% had a minimum of one health condition, e.g., immunosuppression, cancer, that increased the risk of complications.

Eventually, 2.1% of drug recipients sought hospital admission, and the hospitalization rate was highest in older outpatients.

During the study, Omicron BA.2 and the BA.4/5 sublineages were predominant in the province of Québec. Yet, nirmatrelvir/ritonavir therapy reduced the risk of COVID-19-related hospitalization among outpatients at high risk of progressing to severe disease, irrespective of their vaccination status.

Intriguingly, this therapy was more beneficial for those with incomplete primary vaccination series vs. those who received a complete primary vaccination series {risk ratio (RR) 0.04 [95%CI], NNT=8 vs. RR: 0.93 [95%CI]}.

Encouragingly, it worked for severely immunocompromised individuals (RR: 0.66 [95%CI], NNT=16) regardless of their vaccination timing and elderly aged 70 years and older (RR: 0.50 [95%CI], NNT=10).

However, time since vaccination was an important consideration for other outpatients at high risk, highlighting the need for timely taking COVID-19 vaccine boosters.

Compared to this study, the observed efficacy results for nirmatrelvir/ritonavir therapy in outpatients who did not complete a primary vaccination series were slightly higher in the EPIC-HR trial (RR 69% vs. 89%).

According to the authors, the reason for this discrepancy was due to different study populations, study designs, and SARS-CoV-2 variants examined in the two studies. Notably, this study had a higher representation of older adults and severely immunocompromised individuals.


To summarize, the study results showed that nirmatrelvir/ritonavir therapy substantially reduced COVID-19-related hospitalization during Omicron predominant era in real-world settings, especially in infected high-risk outpatients. More importantly, the study results suggested that an up-to-date vaccination status, i.e., receiving a booster shot at six months, remains an effective method for preventing severe illness.

Journal reference:
Neha Mathur

Written by

Neha Mathur

Neha is a digital marketing professional based in Gurugram, India. She has a Master’s degree from the University of Rajasthan with a specialization in Biotechnology in 2008. She has experience in pre-clinical research as part of her research project in The Department of Toxicology at the prestigious Central Drug Research Institute (CDRI), Lucknow, India. She also holds a certification in C++ programming.


Please use one of the following formats to cite this article in your essay, paper or report:

  • APA

    Mathur, Neha. (2023, May 10). Nirmatrelvir/ritonavir reduces the risk of COVID-19-associated hospitalization. News-Medical. Retrieved on June 21, 2024 from

  • MLA

    Mathur, Neha. "Nirmatrelvir/ritonavir reduces the risk of COVID-19-associated hospitalization". News-Medical. 21 June 2024. <>.

  • Chicago

    Mathur, Neha. "Nirmatrelvir/ritonavir reduces the risk of COVID-19-associated hospitalization". News-Medical. (accessed June 21, 2024).

  • Harvard

    Mathur, Neha. 2023. Nirmatrelvir/ritonavir reduces the risk of COVID-19-associated hospitalization. News-Medical, viewed 21 June 2024,


The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
Post a new comment

While we only use edited and approved content for Azthena answers, it may on occasions provide incorrect responses. Please confirm any data provided with the related suppliers or authors. We do not provide medical advice, if you search for medical information you must always consult a medical professional before acting on any information provided.

Your questions, but not your email details will be shared with OpenAI and retained for 30 days in accordance with their privacy principles.

Please do not ask questions that use sensitive or confidential information.

Read the full Terms & Conditions.

You might also like...
Study finds short-term side effects of COVID-19 mRNA vaccines boost long-term antibody response