Two new studies, one from the United States and one from Canada, suggest that the oral antiviral drug Paxlovid (nirmatrelvir-ritonavir) is effective in lowering the odds of hospitalization or death from the SARS-CoV-2 Omicron subvariant.
Less clinically significant relapse
Late last week in The Lancet Infectious Diseases, University of Colorado researchers used electronic health records to conduct an observational study of the effectiveness of Paxlovid in nonhospitalized COVID-19 patients against the Omicron subvariants, including BA.4 and BA.5, from Mar 26 to Aug 25, 2022. Participants had either tested positive for COVID-19 or had an order for Paxlovid.
Of 21,493 patients, 9,881 received Paxlovid, and 11,612 were untreated. Paxlovid was tied to a lower rate of all-cause hospitalization than no antiviral treatment (61 of 7,138 [0.9%] vs 135 of 9,361 [1.4%] patients; adjusted odds ratio [aOR], 0.45).
Paxlovid treatment was also linked to a reduced 28-day all-cause death rate (2 of 7,168 [<0.1%] vs 15 of 9,361 [0.2%] patients; aOR, 0.15). Using subsequent emergency department (ED) visits as a surrogate for clinically significant COVID-19 relapse, researchers observed a decline in such visits after Paxlovid treatment (283 of 7,168 [3.9%] vs 437 of 9,361 [4·7%]; aOR, 0.74).
In a University of Colorado news release, senior author Adit Ginde, MD, said that healthcare professionals are struggling to provide effective therapeutic options for high-risk COVID-19 patients. "Particularly because the monoclonal antibody treatments we had been using and relying on for the past year-and-a-half are no longer effective against recent Omicron subvariants because the virus has changed," he said.
First author Neil Aggarwal, MD, said the results were reassuring. "As a physician who can treat patients in the outpatient setting, I would be very comfortable using Paxlovid as a first-line treatment for adults acutely infected with COVID during the current Omicron phase, vaccinated or not, provided there are no contraindications to its use," he said.
In a related commentary, Carlos Wong, PhD; Kristy Lau, MSc; and Gabriel Leung, MD, MPH, all of the University of Hong Kong, noted that emerging and recombinant Omicron variants, particularly XBB.1.5 and BQ.1.1, continue to pose a risk to public health.
"While in-vitro evidence has shown susceptibility of BQ.1.1 and XBB to [the antivirals] remdesivir, molnupiravir, and nirmatrelvir similar to omicron BA.2 and BA.5, real-world studies are needed to evaluate relative effectiveness in different populations and health-care settings," they wrote.
"This need is particularly relevant in the assessment of cost-effectiveness for different therapeutic strategies and their prioritisation for various patient populations, as the number needed to treat to prevent one case of severe COVID-19 might also increase in view of the growing population immunity."
Need to start Paxlovid within 5 days
A Public Health Ontario-led study today in the Canadian Medical Association Journal (CMAJ) included all provincial residents older than 17 years who tested positive for COVID-19 from Apr 4 to Aug 31, 2022. Rates of Omicron-related hospitalization and all-cause death within 30 days among participants who received Paxlovid were compared with those of their untreated peers.
Of 177,545 patients, 5.0% were given Paxlovid, and 95% were untreated. Most were older than 70 years, were vaccinated against COVID-19, and had the potential for drug-drug interactions.
Rates of hospitalization or death were lower in the Paxlovid group than in the untreated group (2.1% vs 3.7%; weighted OR 0.56). The weighted OR for death alone was 0.49, and the findings were comparable across age, drug-drug interactions, vaccination status, and underlying illnesses. The number of patients needed to treat to prevent one case of severe COVID-19 was 62, depending on the subgroup.
"Nirmatrelvir–ritonavir was associated with significantly reduced odds of hospital admission and death from COVID-19, which supports [its] use to treat patients with mild COVID-19 who are at risk for severe disease," the authors wrote.
A previous randomized, controlled trial by the same group before Omicron emerged showed that Paxlovid was effective against COVID-19 but hadn't included vaccinated participants or those with the potential for drug-drug interactions.
Nirmatrelvir–ritonavir was associated with significantly reduced odds of hospital admission and death from COVID-19, which supports [its] use to treat patients with mild COVID-19 who are at risk for severe disease.
In a CMAJ news release, lead author Kevin Schwartz, MD, said the results underscore the importance of testing symptomatic people for COVID-19 and having access to Paxlovid for high-risk patients. "If you test positive for COVID-19, are over 60 years of age, or if you have other risk factors for severe infection, such as chronic medical conditions or are undervaccinated, contact your health care provider or pharmacy within 5 days of symptoms starting and ask about Paxlovid," he said.
