Research Finds Paxlovid and Legevrio Reduced COVID-19 Hospitalization and Death

Observational study analyzed nearly 70,000 patients diagnosed with the disease at Cleveland Clinic

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New Cleveland Clinic-led research shows commonly used COVID-19 anti-viral drugs Paxlovid (nirmatrelvir) and Lagevrio (molnupiravir) reduce risk of hospitalization and death in high-risk patients with mild disease, even with Omicron subvariants. 

The observational study, published in JAMA Network Open, analyzed nearly 70,000 patients diagnosed with COVID-19 at Cleveland Clinic between April 2022 to February 2023. It found that nirmatrelvir lowered risk of death by 84% and molnupiravir by 77% compared to no treatment.

Both drugs also reduced the combined risk of hospitalization and death — nirmatrelvir by 37% and lagevrio by 41%. Importantly, the treatments were effective across all patient subgroups and against newer strains like BQ.1.1 and XBB.1.5. 

Both medications work by stopping the virus from replicating in the body. This reduces the chances of a patient getting more serious symptoms and being hospitalized. There are some restrictions for taking these oral antivirals, including potential interactions with other medications. 

“Our research highlights the importance of utilizing observational studies to assess the efficacy of COVID-19 treatments based on real-world evidence,” said Xiaofeng Wang, Ph.D., staff member and professor of medicine in Cleveland Clinic’s Lerner Research Institute and senior author of the paper. “The findings regarding the effectiveness of Lagevrio are especially crucial due to notable Paxlovid drug-drug interactions.”

The real-world data confirms nirmatrelvir and molnupiravir remain go-to treatments for vulnerable COVID-19 patients, despite the virus continuing to mutate. The findings, conducted in collaboration with University of North Carolina, support continued use of these oral antivirals to prevent severe outcomes in non-hospitalized patients at high risk of progressing to severe COVID-19. The 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. 

“The results of this study also underscore the importance of continuing to test for COVID-19, especially for those who are high risk because we have effective treatments available,” said Abhijit Duggal, M.D., Director of Critical Care Clinical Research at Cleveland Clinic and an author on the paper. “If you test positive for COVID-19, talk to your doctor about your treatment options.” 

To be effective, the medications must be taken within 5 days of the onset of symptoms. 

The study results come as the country is gearing up for respiratory virus season. Preventive measures such as vaccination, practicing good hand hygiene, staying home when sick and wearing masks in certain situations can help reduce the spread of not only COVID-19, but other viral illnesses such as influenza and RSV.  

About Cleveland Clinic

Cleveland Clinic is a nonprofit multispecialty academic medical center that integrates clinical and hospital care with research and education. Located in Cleveland, Ohio, it was founded in 1921 by four renowned physicians with a vision of providing outstanding patient care based upon the principles of cooperation, compassion and innovation. Cleveland Clinic has pioneered many medical breakthroughs, including coronary artery bypass surgery and the first face transplant in the United States. Cleveland Clinic is consistently recognized in the U.S. and throughout the world for its expertise and care. Among Cleveland Clinic’s 77,000 employees worldwide are more than 5,658 salaried physicians and researchers, and 19,000 registered nurses and advanced practice providers, representing 140 medical specialties and subspecialties. Cleveland Clinic is a 6,699-bed health system that includes a 173-acre main campus near downtown Cleveland, 23 hospitals, more than 275 outpatient facilities, including locations in northeast Ohio; southeast Florida; Las Vegas, Nevada; Toronto, Canada; Abu Dhabi, UAE; and London, England. In 2022, there were 12.8 million outpatient encounters, 303,000 hospital admissions and observations, and 270,000 surgeries and procedures throughout Cleveland Clinic’s health system. Patients came for treatment from every state and 185 countries. Visit us at Follow us at News and resources available at

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