Early sotrovimab use cuts risk of severe outcomes in high-risk COVID-19 patients

Use of the monoclonal antibody sotrovimab within 10 days of COVID-19 diagnosis appears to reduce the risk of hospitalization, mortality, and need for respiratory support in patients at high risk of progression to severe illness, according to large real-world data.

During the 29-day follow-up, the primary endpoint of all-cause hospitalization occurred in significantly fewer sotrovimab-treated patients than in those who were untreated (4.0 percent vs 4.7 percent; p<0.0001). [Clin Ther 2025;47:284-292]

Results for the secondary endpoints were also more favourable in the sotrovimab arm vs the untreated arm. The monoclonal antibody was associated with markedly reduced hospitalization and/or mortality (4.0 percent vs 5.2 percent; p<0.0001), all-cause mortality (0.2 percent vs 0.8 percent; p<0.0001), ICU admission (0.4 percent vs 0.6 percent; p<0.0001), ventilatory support and/or extracorporeal membrane oxygenation (3.6 percent vs 6.5 percent; p<0.0001), and length of inpatient stay (4.8 vs 6.2 days; p<0.0001).

In stratified analyses, the benefit of sotrovimab treatment on all-cause hospitalization was limited to patients aged >55 years, with greatest benefit seen for those aged 65 years and older (odds ratio [OR] 0.56, 95 percent confidence interval [CI], 0.49–0.63). With regard to COVID-19 variant dominance period, the odds of all-cause hospitalization were lower among sotrovimab-treated versus untreated patients during the Delta (OR, 0.66, 95 percent CI 0.57–0.76), Omicron BA.1 (OR, 0.88, 95 percent CI, 0.81–0.95), and BA.2 (OR, 0.58, 95 percent CI, 0.43–0.79) eras.

For the study, the investigators used data from Komodo Health in the US and identified patients (aged ≥12 years) diagnosed with COVID-19 in an ambulatory setting. They included 38,195 sotrovimab-treated patients (mean age 54.3 years, 38.7 percent male) and 2,278,583 untreated patients (mean age 45.8 years, 38.3 percent male) in the comparative effectiveness analyses.

Sotrovimab is a dual-action recombinant human IgG1κ mAb derived from the parental mAb S309, a potent neutralizing mAb directed against the spike protein of SARS-CoV-2. Its benefit to patients who tested positive for SARS-CoV-2 and were at a high risk of progression to severe illness was demonstrated in the pivotal COMET-ICE trial. [JAMA 2022;327:1236-1246; N Engl J Med 2021;385:1941-1950]

Since then, multiple studies, both within the US and internationally, have corroborated the real-world effectiveness of sotrovimab treatment during Omicron subvariant surges and in high-risk populations. [Infection 2023;552:1-17; Infect Dis Ther 2023;12:607-621; J Infect Dis 2022;226:2129-2136; BMJ 2022;379:e071932]

“The [present] study provides important insights on clinical outcomes in >38,000 patients considered at high risk of COVID-19 progression receiving early treatment with sotrovimab,” the investigators said.

Especially noteworthy are the findings during the period of Omicron BA.2 predominance, given previous reports of reduced sotrovimab neutralization against BA.2 in vitro, they added. [Science 2022;378:619-627]

The investigators believe the results of their study are of global relevance and may help inform treatment decisions in countries where sotrovimab is approved for the early treatment of mild-to-moderate COVID-19.