The effectiveness of sotrovimab vs. molnupiravir in preventing severe COVID-19 outcomes in inpatients at high risk of COVID-19

In a recently published study medRxiv* Preprint server, researchers compared the effectiveness of sotrovimab [an intravenously administered neutralizing monoclonal antibody (nMAb)] and molnupiravir (an oral antiviral drug) to prevent the fallout from severe coronavirus disease 2019 (COVID-19) in non-hospitalized high-risk COVID-19 patients across England.

Study: Comparative efficacy of sotrovimab and molnupiravir in preventing severe COVID-19 outcomes in outpatients: an observational cohort study using the OpenSAFELY platform.  Photo Credit: Billions Photos/Shutterstock
Study: Comparative efficacy of sotrovimab and molnupiravir in preventing severe COVID-19 outcomes in outpatients: an observational cohort study using the OpenSAFELY platform. Photo Credit: Billions Photos/Shutterstock


Two phase 3 randomized controlled trials (RCTs) conducted in unvaccinated, out-of-hospital COVID-19 patients who were at high risk of progression to severe COVID-19 or death showed that treatment with sotrovimab was highly effective in preventing hospitalization or death, while molnupiravir was moderately effective (relative risk reduction 79% versus 30%).

However, studies comparing the efficacy of the two drugs in routine care are limited. It is not yet clear whether their effectiveness will continue in vaccinated individuals, patients infected with the Omicron variant of coronavirus 2 (SARS-CoV-2) with severe acute respiratory syndrome, and patients with renal or hepatic impairment. In addition, it is uncertain whether treatment with molnupiravir is effective in non-white patients with previous SARS-CoV-2 infections and diabetes.

About the study

In the present national observational cohort study, researchers compared the effectiveness of sotrovimab and molnupiravir in preventing the progression of COVID-19 in non-hospitalised, high-risk SARS-CoV-2 positive patients across England. They also examined the potential modifying effects of various clinical and demographic clinical factors on the efficacy of the two drugs.

The study cohort included SARS-CoV-2 positive, non-hospitalized adults confirmed by lateral flow testing or polymerase chain reaction (PCR) and highly susceptible to severe COVID-19 and between December 16, 2021 and February 10, 2022 treated with molnupiravir or sotrovimab COVID-19 drug delivery units (CMDUs) administered the drugs in community settings. Patients were excluded if they were previously treated with other anti-COVID-19 antivirals or nMAbs (n=21).

The high-risk participants were identified as those who belonged to one of the following categories: Down syndrome patients, solid organ cancer patients, patients with hematological diseases, kidney diseases, liver diseases, inflammatory diseases associated with the immune system, primary immunodeficiencies, HIV/AIDS (human immunodeficiency virus/acquired immunodeficiency syndrome), recipients of solid organs or stem cell transplants, or rare neurological disorders.

Data was obtained in near real-time from electronic medical records (EHR) of patients in a general practice (GP) using the Test Productivity Pack (TPP) software. The EHR data has been securely linked to the OpenSAFELY TPP platform data on SARS-CoV-2 infections and their therapeutics, hospitalizations and deaths.

The primary endpoint was COVID-19-associated hospitalizations or death within 28 days of treatment initiation. Secondary endpoints were 28-day hospitalization or death from all causes and 60-day COVID-19-associated hospitalization/death. Cox proportional hazards models and hazard ratio (HR) were used for the analysis.


Of 5,951 participants, 2,633 and 3,288 participants were treated with molnupiravir and sotrovimab, respectively. The mean age of the participants was 52 years and most of them (59%) were female, 89% were white and 87.4% had received ≥ 3 doses of SARS-CoV-2 vaccine.

Within 28 days of starting treatment, 84 COVID-19-related hospitalizations/deaths were identified in participants treated with either sotrovimab (n=31) or molnupiravir (n=53). Of the 84 patients, 25 (0.4%) COVID-19-related deaths were observed during the 28-day follow-up period (7 and 18 patients treated with sotrovimab and molnupiravir, respectively). Of the patients who died, 16 and 9 patients were hospitalized and not hospitalized, respectively.

Cox regression modeling showed that the high-risk categories, calendar week, immunization status, body mass index (BMI), presence of comorbidities, and sotrovimab treatment were associated with significantly fewer 28-day COVID-19-related hospitalizations/deaths than treatment with Molnupiravir (HF=0.5). Results were consistent after propensity score-weighted Cox modeling (HR = 0.5) and when the analysis was restricted to participants who received all doses of COVID-19 vaccine. (HF = 0.5).

Among the secondary endpoints, 92 cases (1.5%) of COVID-19-associated hospitalizations/deaths were observed during the 60-day follow-up from the start of treatment (32 and 60 cases in participants treated with sotrovimab and molnupiravir, respectively ). Cox regression modeling showed a significantly lower risk in sotrovimab-treated participants than in molnupiravir-treated participants (HRs ranged from 0.4 to 0.5).


Overall, the study results showed that the risk of severe COVID-19 outcomes (hospitalizations and deaths) was significantly lower with sotrovimab treatment than with molnupiravir treatment in high-risk COVID-19 inpatients treated in routine care settings across England . The results support current United Kingdom (UK) clinical guidelines, which prioritize sotrovimab over molnupiravir to prevent progression of COVID-19 in SARS-CoV-2 positive patients outside the hospital setting.

*Important NOTE

medRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be relied upon as conclusive, guide clinical practice/health behavior, or be treated as established information.

Leave a Comment