Study: Impact of the Use of Oral Antiviral Agents on the Risk of Hospitalisation in Community COVID-19 Patients. Image Credit: Cryptographer/Shutterstock

The effectiveness of molnupiravir and nirmatrelvir/ritonavir in reducing hospitalizations and deaths in non-hospitalized COVID-19 patients

In a recent study published on Preprints with The Lancet*, researchers evaluated the effectiveness of two orally administered antiviral drugs, nirmatrelvir/ritonavir and molnupiravir, in reducing hospitalizations and deaths in non-hospitalized patients with coronavirus disease 2019 (COVID-19) in Hong Kong.

Study: Impact of the use of oral antiviral agents on the risk of hospitalization in community-based COVID-19 patients. Image Credit: Cryptographer/Shutterstock


Preventive and therapeutic strategies for COVID-19 have evolved rapidly since the onset of the COVID-19 pandemic in 2020. Early studies focused on treating severe COVID-19 in hospitalized patients; however, the most recent COVID-19 treatments aim to reduce the incidence of COVID-19 and prevent the development of serious consequences (hospitalizations and deaths) in non-hospitalized patients.

Two orally administered antiviral medicines, nirmatrelvir/ritonavir and molnupiravir, have been approved for the treatment of mild to moderate COVID-19 in adult patients at high risk of disease progression based on results of the MOVe-OUT clinical trial. However, it is unclear whether antiviral drugs would demonstrate comparable real-world efficacy are lacking.

About the study

In this retrospective cohort study, researchers compared the effectiveness of nirmatrelvir/ritonavir and molnupiravir in preventing COVID-19 progression (hospitalizations and deaths) in non-hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients.

Study participants included non-hospitalized SARS-CoV-2 positive individuals who attended designated outpatient clinics between February 16 and March 31, 2021. Patients hospitalized at the first appointment or those who received the two orally administered antiviral drugs were excluded from the analysis. .

The data was obtained from the Clinical Data Analysis and Reporting System (CDARS) database operated by the Hospital Authority (HA) of Hong Kong. The primary endpoint was COVID-19-associated hospitalization and the secondary endpoint was a composite endpoint including use of invasive mechanical ventilation (IMV), intensive care unit (ICU) admissions, and death. The clinical characteristics of the participants were balanced by propensity score (PS) weighting.

Comorbidities such as diabetes mellitus (DM) and hypertension were identified based on laboratory tests, medications, and ICD-9-CM (International Classification of Diseases, Ninth Revision, Clinical Modification) codes. Complete vaccination against SARS-CoV-2 has been described as double vaccination with messenger ribonucleic acid (mRNA) BNT162b2 or triple vaccination with the whole virion of SARS-CoV-2 inactivated by CoronaVac.

Additionally, high-risk non-hospitalized COVID-19 patients aged ≥60 years without comorbidities or younger than 60 years with comorbidities were considered for subgroup analysis. Cox models as well as the weighted risk ratio (HR) were used for the analysis.


At baseline, 94,167 SARS-CoV-2 positive participants were identified who were appointed to designated outpatient clinics during the study period, from which researchers excluded participants who were hospitalized during the first outpatient appointment (n=271) and who received the two drugs nirmatrelvir/ritonavir and molnupiravir (n=13). Accordingly, 93,883 participants were considered for analysis, including 83,154 (89%), 4,921 (5%), and 5,808 (6%), and the participants were non-users of oral antivirals , nirmatrelvir/ritonavir and molnupiravir users. drug addicts, respectively.

Compared to nonusers of oral antivirals, those using antivirals were older with more comorbidities, fewer full vaccinations, and more hospitalizations in the previous year. Compared to nirmatrelvir/ritonavir users, molnupiravir users were older with more comorbidities, fewer full vaccinations, and more hospitalizations in the previous year.

After PS weighting, molnupiravir use was not associated with a lower risk of hospitalization than non-users of oral antivirals (weighted HR 1.2). On the other hand, nirmatrelvir/ritonavir use was associated with a lower risk of hospitalization than oral antiviral non-users (HR weighted 0.8) and molnupiravir users (HR weighted 0.7) . The cumulative incidence of the primary endpoint (hospitalization) for the 30-day follow-up period was 5%, 5%, and 4% among antiviral nonusers, molnupiravir users, and nirmatrelvir/ritonavir users, respectively .

Use of nirmatrelvir/ritonavir (weighted HR 0.8) or molnupiravir (weighted HR 1.1) was not associated with a lower risk of IMV use/ICU admissions/ deaths compared to non-users of oral antivirals. Nirmatrelvir/ritonavir use was also not associated with a reduced risk of developing the secondary endpoints compared to molnupiravir users (weighted HR 0.7). The cumulative incidence of the secondary endpoint (IMV use/ICU admissions/death) for the 30-day follow-up period was 0.5%, 0.4%, and 0.6% in non- oral antiviral users, nirmatrelvir/ritonavir and molnupiravir users. users, respectively.

After PS weighting, use of nirmatrelvir/ritonavir (weighted HR 0.8) but not use of molnupiravir (weighted HR 1.2) was associated with lower risks of hospitalization than non-users of antivirals oral. However, neither molnupiravir nor the use of nirmatrelvir/ritonavir reduced the risk of the secondary endpoint compared to nonusers. In the subgroup analysis, nirmatrelvir/ritonavir use, but not molnupiravir use, was associated with lower risks of hospitalization than nonusers.


Overall, the study results showed that the use of nirmatrelvir/ritonavir was associated with a lower risk of hospitalization, but not the use of molnupiravir in SARS-CoV-2 positive patients. not hospitalized in the real world. However, the two antiviral drugs did not reduce the risk of IMV use, ICU admissions, and death associated with COVID-19.

*Important Notice

Preprints with The Lancet publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be considered conclusive, guide clinical practice/health-related behaviors, or treated as established information.

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