The following is a summary of “Real-world use of nirmatrelvir–ritonavir in outpatients with COVID-19 during the era of omicron variants including BA.4 and BA.5 in Colorado, USA: a retrospective cohort study,” published in the June 2023 issue of the Infectious Diseases by Aggarwal et al.

Nirmatrelvir is a protease inhibitor with in-vitro activity against SARS-CoV-2, and ritonavir-boosted nirmatrelvir can decrease the risk of progression to severe COVID-19 in high-risk individuals infected with delta and early omicron variants. However, less is understood about the efficacy of nirmatrelvir–ritonavir during more recent BA.2, BA2.12.1, BA.4, and BA.5 omicron variant epidemics. Using their real-world data platform, the researchers assessed the impact of nirmatrelvir–ritonavir treatment on 28-day hospitalization, mortality, and emergency department visits among outpatients with early symptomatic COVID-19 during a SARS-CoV-2 omicron (BA.2, BA2.12.1, BA.4, and BA.2) predominant period in Colorado, USA. Using Colorado statewide health system records, they conducted a propensity-matched, retrospective, observational cohort study of non-hospitalized adult patients infected with SARS-CoV-2 between March 26 and August 25, 2022. 

Researchers obtained information from the electronic health records of the University of Colorado Health, the most extensive health system in Colorado, with 13 hospitals, 141,000 annual hospital admissions, and numerous ambulatory sites and affiliated pharmacies. Patients were included if they had a positive SARS-CoV-2 test or a prescription for nirmatrelvir–ritonavir. Exclusion criteria included an order for or administration of other SARS-CoV-2 treatments within 10 days of a positive SARS-CoV-2 test, hospitalization at the time of a positive SARS-CoV-2 test, and a positive SARS-CoV-2 test that occurred more than 10 days before a nirmatrelvir–ritonavir order. Using a propensity score, they matched patients treated with nirmatrelvir–ritonavir with untreated patients. The primary outcome was 28-day hospitalization for any cause. About 21,493 of the 28,167 patients infected with SARS-CoV-2 between March 26 and August 25, 2022, met the inclusion criteria. 

About 9,881 patients were administered nirmatrelvir–ritonavir, while 11,612 were left untreated. Nirmatrelvir–ritonavir treatment was associated with decreased 28-day all-cause hospitalization compared to no antiviral treatment (61 [0·9%] of 7,168 patients vs. 135 [1%] of 9,361 patients, adjusted odds ratio (OR) 045 [95% CI 033–062]; p<0.0001). Nirmatrelvir–ritonavir treatment was also associated with a reduction in 28-day all-cause mortality (two [<0·1%] of 7,168 patients versus 15 [0·2%] of 9,361 patients; adjusted OR 0·15 [95% CI 0·03–0·50]; p=0·0010). Using subsequent emergency department visits as a proxy for clinically significant relapse, they observed a reduction after nirmatrelvir–ritonavir treatment (283 [3·9%] of 7,168 patients vs. 437 [4·7%] of 9,361 patients; adjusted OR 0·74 [95% CI 063–087]; p=0·0002). Real-world data collected during a BA.2, BA2.12.1, BA.4, and BA.5 omicron surge revealed a correlation between nirmatrelvir–ritonavir treatment and diminished 28-day all-cause hospitalization, all-cause mortality, and emergency room visits. 

These data support nirmatrelvir–ritonavir as an ongoing first-line treatment for adults acutely infected with SARS-CoV-2. The results are among the first to suggest the effectiveness of nirmatrelvir–ritonavir for non-hospitalized patients during an omicron period, including the BA.4 and BA.5 subvariants.

Source: sciencedirect.com/science/article/pii/S1473309923000117