Study finds added benefits of molnupiravir for non-hospitalized COVID-19 patients

In a recent investigation published in the Annals of Internal Medicine journal, scientists demonstrated the positive impacts of molnupiravir among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients and the healthcare sector apart from lowering disease-linked deaths and hospitalizations in at-risk cohorts.

Study: Effect of Molnupiravir on Biomarkers, Respiratory Interventions, and Medical Services in COVID-19. Image Credit: wan wei / ShutterstockStudy: Effect of Molnupiravir on Biomarkers, Respiratory Interventions, and Medical Services in COVID-19. ​​​​​​​Image Credit: wan wei / Shutterstock


SARS-CoV-2 resulted in an unprecedented pandemic that has led to more than 532 million infections and over 6.3 million global deaths so far. Coronavirus disease 2019 (COVID-19) has a variety of clinical manifestations. While some SARS-CoV-2-infected individuals are asymptomatic, others develop moderate to severe illness due to the hyperinflammatory response in the host toward the virus. 

Keeping life-saving therapies, like ventilatory or hemodynamic support, available for all critical or severe COVID-19 patients has been a significant issue throughout the pandemic. This was particularly noticeable in locations with low resources amid COVID-19 surges and at baseline.

In non-hospitalized SARS-CoV-2 patients with risk variables for severe COVID-19, such as diabetes and obesity, some antivirals and monoclonal antibodies (mAbs) reduced the likelihood of hospitalization or mortality compared to placebo. However, the impact of these therapeutic interventions on other clinically significant outcomes, including variations in oxygen saturation (Spo2), inflammatory markers, or ventilation demands in non-hospitalized SARS-CoV-2 patients or those who require hospitalization following the receipt of these therapies, has yet to be thoroughly elucidated. Moreover, there is an unmet requirement for antiviral medications that can be conveniently self-administered in the outpatient context to enhance patient outcomes while reducing COVID-19's burden on the healthcare sector.

Molnupiravir is a small-molecule orally available ribonucleoside β-D-N4-hydroxycytidine (NHC) prodrug with broad-spectrum, potent in vitro action against CoVs, such as SARS-CoV-2 variants of concern (VOCs), and a superior barrier towards resistance development. Molnupiravir showed a clinically substantial reduction in the likelihood of hospitalization or mortality in adults with mild or moderate COVID-19 and risk variables for progression to severe illness in the MOVe-OUT trial. MOVe-OUT was a phase II/III parallel-group, double-blind, placebo-controlled, randomized trial that assessed the safety and efficacy of molnupiravir against placebo.

About the study

In the present research, the scientists analyzed if there were any further therapeutic benefits of molnupiravir over placebo in COVID-19 treatment. Based on data of clinical biomarkers and the requirement for respiratory treatments and medical services from the phase III section of the MOVe-OUT trial, the team conducted additional studies to examine other possible advantages of molnupiravir for the treatment of mild and moderate COVID-19.

The investigators performed a secondary assessment of the randomized, double-blind, placebo-controlled phase III component of MOVe-OUT among 107 sites worldwide. The study participants included 1433 non-hospitalized 18 years or older adults experiencing mild or moderate SARS-CoV-2 infection.

The subjects were given 800 mg of molnupiravir or a placebo 12-hourly for five days. Until day 29, the team tracked variations in high-sensitivity C-reactive protein (CRP) level and oxygen saturation (Spo2), the requirement for respiratory treatments, such as invasive mechanical ventilation, and medical services across all randomly selected individuals. In addition, the demand for respiratory interventions and the duration of hospital discharge were evaluated in the subset of subjects hospitalized post-randomization.


The authors found that those taking molnupiravir had rapid normalization of Spo2 and CRP, with gains seen on day 3 of treatment, compared to placebo patients. These clinically meaningful substitute markers hiked early in the five-day treatment course, lasting until day 29.

Compared to placebo-treated patients, molnupiravir-treated subjects had a lower requirement for respiratory treatments like invasive mechanical ventilation with a relative risk reduction [RRR] of 34.3%. Indeed, subjects hospitalized following randomization had identical findings with a RRR of 21.3%. Moreover, molnupiravir-treated hospitalized volunteers were discharged three days earlier than placebo-treated patients.

Finally, molnupiravir-treated subjects had fewer acute care visits associated with and without COVID-19 than placebo-treated participants. Notably, 7.2% of molnupiravir-treated subjects needed acute care visits compared to 10.6% of placebo recipients, with a RRR of 32.1%. Furthermore, 6.6% of molnupiravir recipients relative to 10% of placebo-treated volunteers required SARS-CoV-2-linked acute care visits, with a RRR of 33.8%.      

The authors did point out that some analyses were done post hoc. Additionally, this analysis did not include the assessment of the long-term advantages of molnupiravir therapy. Furthermore, none of the subjects were immunized against COVID-19.


Collectively, the present findings show that molnupiravir has additional relevant clinical advantages in COVID-19 therapy beyond a drop in mortality or hospitalization in non-hospitalized adults with mild or moderate illnesses. On day 3, subjects administered molnupiravir exhibited earlier clinical improvement than placebo users, as seen by improvements in CRP level and Spo2, and a shortened duration of stay in hospitalized volunteers, offering a potential for more productive usage of hospital beds.

One of the advantages of the present study was that MOVe-OUT was a global, large, prospective, placebo-controlled, double-blind experiment that permitted a strictly controlled examination of Spo2 and CRP throughout time. The team stated that the benefits of molnupiravir to patients and healthcare systems might outweigh the previously established benefits of lowering hospitalizations and deaths resulting from disease progression and relieving symptoms in at-risk COVID-19 patients.

Journal reference:
  • Matthew G. Johnson, Amy Puenpatom, Pablo Andrés Moncada, et al; Effect of Molnupiravir on Biomarkers, Respiratory Interventions, and Medical Services in COVID-19: A Randomized, Placebo-Controlled Trial. Ann Intern Med. [Epub 7 June 2022]. DOI:10.7326/M22-0729,
Shanet Susan Alex

Written by

Shanet Susan Alex

Shanet Susan Alex, a medical writer, based in Kerala, India, is a Doctor of Pharmacy graduate from Kerala University of Health Sciences. Her academic background is in clinical pharmacy and research, and she is passionate about medical writing. Shanet has published papers in the International Journal of Medical Science and Current Research (IJMSCR), the International Journal of Pharmacy (IJP), and the International Journal of Medical Science and Applied Research (IJMSAR). Apart from work, she enjoys listening to music and watching movies.


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