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

By Pooja Toshniwal PahariaReviewed by Danielle Ellis, B.Sc.May 25 2022

In a recent study posted to Preprints with The Lancet*, researchers assessed the effectiveness of two orally administered antiviral medications, nirmatrelvir/ritonavir, and molnupiravir, in decreasing hospitalization and deaths among real-world non-hospitalized coronavirus disease 2019 (COVID-19) patients in Hong Kong.

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources

Background

Preventive and therapeutic strategies for COVID-19 have evolved rapidly ever since the COVID-19 pandemic commenced in 2020. Initial studies have emphasized treating severe COVID-19 among hospitalized patients; however, the most recent COVID-19 therapeutics are aimed at decreasing COVID-19 incidence and preventing the development of severe outcomes (hospitalizations and deaths) among non-hospitalized patients.

Two orally administered antiviral medications, nirmatrelvir/ritonavir and molnupiravir, have been authorized for treatment of mild to moderate COVID-19 among adult patients with a high risk of disease progression based on the MOVe-OUT clinical trial findings. However, knowledge on whether the antiviral medications would demonstrate comparable effectiveness in the real world is lacking.

About the study

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

The study participants comprised 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 both the orally administered antiviral medications were excluded from the analysis.

Data were obtained from the clinical data analysis and reporting system (CDARS) database managed by the hospital authority (HA) of Hong Kong. The primary endpoint was COVID-19-associated hospitalization and the secondary endpoint was a composite endpoint comprising invasive mechanical ventilation (IMV) usage, intensive care unit (ICU) admissions, and deaths. The clinical characteristics of the participants were balanced by propensity score (PS) weighting.

Comorbidities such as diabetes mellitus (DM) and hypertension were identified on the basis of laboratory tests, medications, and ICD-9-CM (International classification of diseases, ninth revision, clinical modification) codes. Complete SARS-CoV-2 vaccination was described as double BNT162b2 messenger ribonucleic acid (mRNA) vaccination or triple CoronaVac inactivated SARS-CoV-2 whole-virion vaccination.

Additionally, high-risk non-hospitalized COVID-19 patients ≥60 years of age without comorbidities or <60 years of age with comorbidities were considered for subgroup analysis. Cox models along with weighted hazard ratio (HR) were used for the analysis.

Results

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

In comparison to oral antiviral non-users, those who used antiviral drugs were elder with more comorbid conditions, lesser full vaccinations, and a greater number of previous year hospitalizations. Compared to nirmatrelvir/ritonavir users, molnupiravir drug users were older with more comorbid conditions, lesser full vaccinations, and more previous year hospitalizations.

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

Nirmatrelvir/ritonavir usage (weighted HR 0.8) or molnupiravir usage (weighted HR 1.1) were not associated with a lower risk of IMV usage/ICU admissions/deaths in comparison to oral antiviral non-users. Nirmatrelvir/ritonavir usage was also not associated with a reduced risk of developing the secondary endpoints compared to molnupiravir drug users (weighted HR 0·7). The cumulative incidence of the secondary endpoint (IMV usage/ICU admissions/deaths) for the 30-day follow-up period was 0.5%, 0.4%, and 0.6% among oral antiviral non-users, nirmatrelvir/ritonavir drug users and molnupiravir drug users, respectively.

After PS weighting, nirmatrelvir/ritonavir usage (weighted HR 0·8) but not molnupiravir usage (weighted HR 1.2) was associated with lower hospitalization risks than oral antiviral non-users. However, neither molnupiravir nor nirmatrelvir/ritonavir usage reduced the risk of the secondary endpoint in comparison to non-users. In the subgroup analysis, nirmatrelvir/ritonavir usage but not molnupiravir usage was associated with lower hospitalization risks than non-users.

Conclusion

Overall, the study findings showed that nirmatrelvir/ritonavir usage was associated with a lower risk of hospitalization but not molnupiravir usage among non-hospitalized SARS-CoV-2-positive patients in the real world. However, both the antiviral medications did not reduce the risk of COVID-19-associated IMV usage, ICU admissions, and deaths.

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources