COVID-19 oral antivirals reduce in-hospital mortality and healthcare utilization in real-world setting

Use of molnupiravir or nirmatrelvir/ritonavir in high-risk patients with mild-to-moderate COVID-19 is associated with reduced in-hospital mortality, reduced hospital admissions or readmissions, and potential healthcare cost savings, according to a real-world retrospective cohort study led by researchers from the Chinese University of Hong Kong and the University of Hong Kong.

The study included 54,355 patients in Hong Kong with mild-to-moderate COVID-19 and an increased risk of deterioration (ie, age ≥60 years, or age <60 years with ≥1 chronic disease). Of these patients, 33,217 attended designated outpatient clinics (outpatient cohort) and 21,138 were hospitalized (inpatient cohort) between 22 February and 31 March 2022. [Lancet Reg Health West Pac 2022;doi:10.1016/j.lanwpc.2022.100602]

At baseline, the most common comorbidities were diabetes without complications (8.0 percent in the outpatient cohort, 12.4 percent in the inpatient cohort), cerebrovascular diseases (3.4 percent and 10.0 percent, respectively), cancer (2.6 percent and 3.8 percent, respectively), and renal diseases (6.6 percent in the inpatient cohort, 1.8 percent in the in\]outpatient cohort).

In the outpatient cohort (age ≥70 years, 51.6 percent; female, 53.1 percent; mean follow-up, 38.85 days), 16.1 percent of patients were prescribed molnupiravir, while 13.4 percent were prescribed nirmatrelvir/ritonavir. In the inpatient cohort (age ≥70 years, 82.5 percent; female, 44.6 percent; from care homes, 37.9 percent; mean follow-up, 27.82 days), 3.8 percent and 1.3 percent of patients used molnupiravir and nirmatrelvir/ritonavir, respectively.

After inverse probability of treatment weighting (IPTW) to adjust for differences in baseline characteristics, the primary endpoint of 28-day all-cause mortality was significantly reduced with prescription of either molnupiravir (hazard ratio [HR], 0.31; 95 percent confidence interval [CI], 0.24–0.40; p<0.0001) or nirmatrelvir/ritonavir (HR, 0.10; 95 percent CI, 0.05–0.21; p<0.0001), compared with control, in the inpatient cohort. IPTW-adjusted survival analysis was not performed in the outpatient cohort due to the small number of deaths observed.

In the outpatient cohort, significant reductions in 28-day unplanned hospital admissions were observed with both molnupiravir (odds ratio [OR], 0.72; 95 percent CI, 0.52–0.98; p=0.039) and nirmatrelvir/ritonavir (OR, 0.37; 95 percent CI, 0.23–0.60; p<0.0001).

Interestingly, however, outpatients who used either oral antiviral were more likely to reattend designated outpatient clinics at 28 days (molnupiravir: OR, 1.80; 95 percent CI, 1.60–2.01; p<0.0001) (nirmatrelvir/ritonavir: OR, 1.45; 95 percent CI, 1.11–1.91; p=0.0069). According to the investigators, reattendance is a possible marker of persistent symptoms, including long COVID syndrome, which warrants further analysis. “However, it must be noted that each of the antivirals reduced emergency department visits … the length of [hospital] stay was shorter if patients were admitted after antiviral treatment,” they reported.

Among hospitalized patients, the likelihood of 28-day readmission was significantly reduced with both molnupiravir (OR, 0.71; 95 percent CI, 0.52–0.97; p=0.031) and nirmatrelvir/ritonavir: OR, 0.47; 95 percent CI, 0.24–0.93; p=0.030). 

The incremental cost-effectiveness ratio (ICER) per death averted for molnupiravir was USD 493,345.09 in outpatient settings and USD 2,629.08 in inpatient settings. For nirmatrelvir/ritonavir, ICERs per death averted were USD 331,105.27 in outpatient settings and -USD 5,502.53 in inpatient settings.

“In the inpatient cohort, nirmatrelvir/ritonavir … is more cost-effective than standard care,” the investigators pointed out.