In a recent study published in BMJ, researchers examine whether molnupiravir administration during the initial five days of acute coronavirus disease 2019 (COVID-19) could lower post-acute sequelae of COVID-19 (PASC) or long COVID risks.

Study: Molnupiravir and risk of post-acute sequelae of COVID-19: cohort study. Image Credit: Sonis Photography / Study: Molnupiravir and risk of post-acute sequelae of COVID-19: cohort study. Image Credit: Sonis Photography /


PASC, which represents the spectrum of chronic and post-acute sequelae of COVID-19, has affected millions of individuals worldwide. However, drug interventions for its prevention or treatment are not yet available.

The authors of the present study previously documented that the combined use of nirmatrelvir and ritonavir within five days of COVID-19 diagnosis could lower the risk of long COVID.

Molnupiravir, which is an antiviral medication that inhibits severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication, was provided emergency usage authorization by the United States Food and Drug Administration (FDA) for acute COVID-19 patients at an increased risk of severe COVID-19 outcomes for whom alternative therapies were inaccessible or not clinically appropriate.

About the study

The study cohort consisted of 229,286 individuals who tested positive for COVID-19 between January 5, 2022, and January 15, 2023, had one or more risk factors for severe SARS-CoV-2 infection, and lived beyond 30 days of COVID-19 diagnosis. The risk factors assessed were age above 60 years, body mass index (BMI) value exceeding 30, and comorbidities, including cardiovascular diseases, diabetes, chronic renal diseases, chronic pulmonary diseases, immunological dysfunction, and cancer.

The team excluded individuals with contraindications to molnupiravir treatment, including end-stage renal disease or estimated glomerular filtration rate (eGFR) below 30 mL/minute/1.7 m2. In addition, individuals receiving other outpatient COVID-19 antivirals or antibody treatments within 30 days of testing positive, as well as individuals who died within 30 days of a SARS-CoV-2-positive result, were excluded from the analysis.

Among the study participants, 11,472 individuals received molnupiravir treatment within five days of testing positive for COVID-19, whereas 217,814 individuals received no antibiotic or antiviral treatment. The electronic medical records of individuals uploaded in the U.S. Department of Veterans Affairs (VA) database were analyzed to identify eligible individuals.  

Data were obtained from 1,293 VA health facilities, including 171 and 1,112 medical centers and outpatient departments, respectively. Data included routine healthcare visits, inpatient and outpatient diagnoses, pharmacy records, and laboratory test reports. COVID-19 vaccination data were also obtained from the VA COVID-19 Shared Data Resource.

The main study outcomes and measures were the risks of PASC, which were based on 13 predefined sequelae of COVID-19. Additional outcomes included hospitalizations and deaths in the post-acute period of infection.

Each sequela was assessed by inverse probability-type weighting to balance the health and personal characteristics of each individual. These outcomes were analyzed from 30 days following COVID-19 diagnosis until February 15, 2023.

Multivariate logistic regression modeling was performed. The relative risks (RR), hazard ratios (HR), and absolute risk reductions after 180 days of treatment initiation were determined.  

Data were adjusted for age, BMI, race, sex, area of deprivation index, residency, smoking habits, prior COVID-19 history, and long-term use of care services, steroids, eGFR, blood pressure, and comorbidities including chronic pulmonary disease, diabetes, dementia, hyperlipidemia, immunological dysfunction, and cancer.

PASC scores were determined using the Global Burden of Disease (GBD) Long COVID Collaborators method, assigning weights to the sequelae. The eligibility criteria were concordant with those of the Efficacy and Safety of Molnupiravir in Non-Hospitalized Adult Participants With COVID-19 (MOVe-OUT) trial and FDA guidelines for emergency use of molnupiravir.

Study findings

As compared to patients who did not receive any pharmaceutical intervention, molnupiravir treatment within five days of testing positive for COVID-19 was related to lowered PASC risks, deaths, and hospitalization in the post-acute period.

Molnupiravir treatment also reduced the risk of developing eight long COVID manifestations, including pulmonary embolism, dysrhythmia, deep vein thrombosis (DVT), hepatic disease, neurocognitive impairments, pain in the muscles, acute renal injury, malaise, and fatigue.

PASC risks were also reduced following molnupiravir treatment among individuals unvaccinated against COVID-19, single- or two-dose COVID-19 vaccines, booster dose vaccine recipients, and individuals with or without prior history of COVID-19. All sensitivity analyses yielded similar findings, thus indicating that the study findings were robust.


Among COVID-19 patients with one or more risk factors for severe disease outcomes, molnupiravir treatment within five days of COVID-19 diagnosis could lower PASC risks, irrespective of COVID-19 vaccination status and history of COVID-19.

More specifically, molnupiravir lowered the risks of long COVID hospitalizations and deaths in the post-acute period by 14%, 14%, and 38%, respectively. These values corresponded to absolute risk reductions of 3%, 0.9%, and 1.3%, respectively, per 100 individuals treated between 30 and 180 days following COVID-19 diagnosis.

Thus, among high-risk individuals, molnupiravir treatment in the acute phase of infection could prevent long COVID.

Journal reference:

  • Cie, Y., Choi, T., & Al-Aly, Z. (2023). Molnupiravir and risk of post-acute sequelae of COVID-19: cohort study. BMJ 381. doi:10.1136/bmj-2022-074572

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