Real-world HK study: Nirmatrelvir/ritonavir reduces hospitalizations in COVID-19 patients

The oral antiviral nirmatrelvir/ritonavir, but not molnupiravir, reduces the risk of hospitalization among community COVID-19 patients in Hong Kong, a real-world territory-wide retrospective cohort study has shown.

The study included 93,883 nonhospitalized COVID-19 patients (mean age, 49.2 +/- 21.8 years; male, 44.4 percent) who attended designated COVID-19 outpatient clinics (OPCs) in Hong Kong between 16 February and 31 March 2022. Among these patients, 83,154 (88.6 percent) were oral antiviral nonusers, 5,808 (6.2 percent) were molnupiravir users, and 4,921 (5.2 percent) were nirmatrelvir/ritonavir users. [Clin Infect Dis 2022;doi:10.1093/cid/ciac687]

At baseline, oral antiviral users were older, and had more comorbidities, lower complete COVID-19 vaccination rate and more hospitalizations in the previous year than nonusers. Compared with nirmatrelvir/ritonavir users, molnupiravir users were older, and had more comorbidities, lower complete COVID-19 vaccination rate and more hospitalizations in the previous year.

At a median follow-up of 30 days, the primary endpoint of hospitalization occurred in 1.6 percent of oral antiviral nonusers, 7.5 percent of molnupiravir users, and 3.5 percent of nirmatrelvir/ritonavir users.

After propensity score weighting, nirmatrelvir/ritonavir use was associated with a significantly reduced risk of hospitalization compared with nonuse of oral antivirals (weighted hazard ratio [wHR], 0.79; 95 percent confidence interval [CI], 0.65–0.95; p=0.011) and use of molnupiravir (wHR, 0.67; 95 percent CI, 0.55–0.81; p<0.001). In contrast, molnupiravir use was not associated with a reduced risk of hospitalization compared with nonuse of oral antivirals (wHR, 1.17; 95 percent CI, 0.99–1.39; p=0.062).

Similar results for hospitalization were shown in patients aged ≥60 years or <60 years with ≥1 comorbidity (wHR, 0.76 [95 percent CI, 0.63–0.92; p=0.004] for nirmatrelvir/ritonavir use, 1.07 [95 percent CI, 0.90–1.26; p=0.472] for molnupiravir use).

“In patients above and below 70 years of age, the complete vaccination rate was 30 percent and 60 percent, respectively. Similar associations between use of nirmatrelvir/ritonavir [wHR, 0.78 and 0.77, respectively] or molnupiravir [wHR, 1.15 and 1.07, respectively] and hospitalization were observed,” wrote the investigators from the Chinese University of Hong Kong.

The investigators also evaluated effectiveness of the oral antivirals on intensive care unit (ICU) admission, invasive mechanical ventilation (IMV) use, and/or death as a composite secondary endpoint. Results showed no significant risk reduction in either nirmatrelvir/ritonavir users (wHR, 0.81; 95 percent CI, 0.47–1.39; p=0.448) or molnupiravir users (wHR, 1.12; 95 percent CI, 0.68–1.82; p=0.663) compared with oral antiviral nonusers.

“Also, nirmatrelvir/ritonavir use was not associated with a lower risk of ICU admission, IMV use, and/or death than molnupiravir use [wHR, 0.73; 95 percent CI, 0.41–1.27; p=0.265],” the investigators pointed out.

Similar findings for the composite secondary endpoint were also observed in patients aged ≥60 years or <60 years with ≥1 comorbidity (wHR, 0.81 [95 percent CI, 0.47–1.39; p=0.447] for nirmatrelvir/ritonavir use, 1.04 [95 percent CI, 0.63–1.73; p=0.874] for molnupiravir use).

“In patients aged above and below 70 years, similar associations between use of nirmatrelvir/ritonavir [wHR, 0.89 and 0.55, respectively] and molnupiravir [wHR, 1.08 and 0.97, respectively] with the composite secondary endpoint were observed,” the researchers noted.

In Hong Kong, nirmatrelvir/ritonavir and molnupiravir are prescribed to elderly patients and patients with high risk of progression to severe COVID-19 and incomplete vaccination, within 5 days of symptom onset, at designated OPCs since 12 March 2022 and 16 March 2022, respectively.