Nirmatrelvir–ritonavir combo averts hospitalization in high-risk COVID patients

Treatment with nirmatrelvir plus ritonavir appears to reduce the incidence of hospitalization in a highly vaccinated population of high-risk COVID-19 patients in Malaysia, as shown in a study.

Compared with nontreatment, nirmatrelvir–ritonavir was associated with 36 percent less likelihood of being hospitalized (adjusted hazard ratio [aHR], 0.64, 95 percent confidence interval [CI], 0.43–0.94). [Int J Infect Dis 2023;doi:10.1016/j.ijid.2023.08.003]

The analysis was based on a nationally representative, propensity-score matched cohort of 20,966 high-risk adult COVID-19 outpatients, of whom 10,483 received nirmatrelvir–ritonavir (treatment group; mean age 48.51 years, 50.3 percent men) and 10,483 did not (control group, mean age 47.16 years, 42.6 percent men).

“[A]pproximately 0.52 percent of the COVID-19 patients initially managed as outpatients at primary health clinics subsequently required hospital admission,” according to the investigators, adding that the risk estimates for intensive care unit (ICU) admission and mortality could not be obtained due to the small number of events.

“There was a single ICU admission for the control group, and one death each was reported in the treatment and control group, respectively,” they pointed out.

The benefit of nirmatrelvir plus ritonavir on hospitalization risk was seen across subgroups defined by age (18–40 years: aHR, 0.44, 95 percent CI, 0.23–0.85), sex (women: aHR, 0.49, 95 percent CI, 0.29–0.83), and day of illness when treatment was initiated (1–3 days: aHR, 0.57, 95 percent CI, 0.37–0.87). Age and sex-specific analysis showed a significant reduction in hospitalization risk among women not more than 40 years of age (aHR, 0.31, 95 percent CI, 0.14–0.69).

“Our findings [are] consistent with recent studies that showed countries with high COVID-19 vaccination rates have … low hospitalization and mortality rates,” the investigators said. [J Gen Intern Med 2023;38:1248-1255]

“Nevertheless, it is possible that the very low in-hospital case fatality rate could be attributed to the less lethal infection observed with Omicron subvariants compared to other SARS-CoV-2 variants,” they acknowledged. [JAMA Intern Med 2022;182:1071-1081; Public Health Pract 2023;5:100350; Cureus 2023;15:e35261; J Med Virol 2023;95:e28118]

Malaysia has a remarkably high vaccination rate, with over 98 percent of the population either fully vaccinated or having received a booster dose. The present data, according to the investigators, suggest that the use of nirmatrelvir plus ritonavir may provide additional benefits in reducing hospitalization and mortality rate locally than in countries where vaccination uptake is lower (40-85 percent). [Lancet Infect Dis 2023;23:696-705; N Engl J Med 2022;387:790-798; Lancet Infect Dis 2023;23:639-640; MMWR Morb Mortal Wkly Rep 2022;71:1531-1537]

“Our findings support the use of nirmatrelvir plus ritonavir for the treatment of COVID-19 in outpatient settings, [as well as contribute] to the existing body of evidence endorsing the use of [the combination] for COVID-19, particularly for individuals residing in remote areas where access to hospital care is limited,” they said.

The investigators also highlighted the importance of early initiation of nirmatrelvir-ritonavir in the course of the disease. “Nevertheless, nirmatrelvir-ritonavir should be prioritized [in] high-risk patients due to the high cost of the drug and considering the milder Omicron infection in highly vaccinated population.”