The Use of Nirmatrelvir or Molnupiravir Could Prevent Mortality in Severe COVID-19


The use of nirmatrelvir or molnupiravir can aid treatment for individuals that are at high risk of developing severe COVID-19, regardless of varying demographics.

During the COVID-19 pandemic, the FDA approved the emergency use of ritonavir-boosted nirmatrelvir (Paxlovid; Pfizer) and molnupiravir to treat mild-to-moderate COVID-19 cases for individuals at risk of developing severe disease. Now, new study results confirmed that this treatment reduced mortality and hospitalization rates in infected individuals.

Coronavirus Covid-19 background - 3d rendering - Image credit: Production Perig |

Image credit: Production Perig |

Published in JAMA Network, researchers conducted a large cohort study that focused on electronic medical records of individuals diagnosed with COVID-19 from the Cleveland Clinic Health System in Cleveland, Ohio. The researchers aimed to assess the risk of hospitalization and death connected to the use of nirmatrelvir or molnupiravir throughout the period during which the Omicron subvariant was dominant.

The study used data collected from April 1, 2022, to February 20, 2023, during the transitional phase of the Omicron variant. The variant evolved from BA.2 to BA.4/ BA.5, then to BQ.1/BQ.1.1, and eventually to XBB/XBB.1.5.

The researchers noted that nirmatrelvir and molnupiravir were prescribed virtually to individuals diagnosed with COVID-19 within 5 days of symptoms, through the Cleveland Clinic outpatient pharmacies.

“For patients with normal kidney function, the dosage was 300 mg of nirmatrelvir with 100 mg of ritonavir taken together orally twice daily for 5 days. For patients with moderately reduced kidney function, the dosage of nirmatrelvir was reduced to 150 mg. For patients with [estimated glomerular filtration rate] less than 30 mL per minute or with severe hepatic impairment, nirmatrelvir was not prescribed. The dosage of molnupiravir was 800 mg taken every 12 hours for 5 days,” said the study authors.

The study noted that the primary outcome was to measure the time of death prior to the diagnosis of COVID-19, and the secondary outcome was to measure time spent in the hospital or if death occurred. The individuals were monitored for 90 days or when the study concluded, if earlier than the 90-day period.

The researchers included 68,867 individuals in the study—29,386 were 65 years or older, 26,755 were male, and 51,452 were non-Hispanic White individuals. A subgroup analysis was conducted that connected to the individuals’ age, race and ethnicity, vaccination status, previous infection status, and coexisting conditions. The study noted that the researchers used the Kaplan-Meier estimator, which can analyze survival over time, to measure the incidence in death between treated and untreaded individuals.

Out of the 68,867 individuals included in the study, 22,594 individuals were treated with nirmatrelvir, 5311 individuals were treated with molnupiravir, and 40,962 individuals did not receive treatment.

The study noted that elevated risk of death was reported and observed among participants. Individuals with a higher risk of mortality included older aged, male, low socioeconomic status, immunocompromised patients, and individuals with cardiovascular diseases.

The results concluded that there was a lower mortality rate for individuals that received treatment with nirmatrelvir or molnupiravir, compared to individuals who did not receive treatment. The study noted that 30 individuals that used nirmatrelvir died, 27 individuals that used molnupiravir died, and 588 individuals that did not use any treatment died within the 90 days of infection with the Omicron COVID-19 variant.

“The associations of both antiviral drugs with both outcomes were observed consistently across subgroups defined by age, race and ethnicity, date of COVID-19 diagnosis, vaccination status, previous infection status, and coexisting conditions,” said the study authors.

The findings suggest that the use of nirmatrelvir or molnupiravir can aid treatment for individuals that are at high risk of developing severe COVID-19, regardless of varying demographics.


Nirmatrelvir or Molnupiravir Use and Severe Outcomes From Omicron Infections. JAMA Network. News release. September 21, 2023. Accessed October 3, 2023.

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