Sotrovimab reduces hospitalization, death in patients with COVID-19 regardless of serostatus

Treatment with sotrovimab reduces the risk of all-cause hospitalization or death in patients with COVID-19 who are at high risk of progression to severe disease, regardless of anti-SARS-CoV-2 serostatus, according to a study presented at CROI 2022.

“[The] use of serostatus marker is complicated by lack of standardization in assays and the threshold defining seropositivity as well as lack of definitive threshold for protective immunity, especially in the context of evolving variants of concern[, including Delta and Omicron],” said presenting author Dr Adrienne Shapiro from the University of Washington and Fred Hutchinson Cancer Research Center in Seattle, Washington, US.

“To better understand serology as a potential surrogate marker for disease severity, we evaluated the effect of serostatus on the overall rate of disease progression as well as the efficacy of sotrovimab in preventing COVID-19 progression,” she noted.

Using data from the COMET-ICE* cohort, the researchers evaluated 1,057 patients with mild-to-moderate COVID-19 who were at high risk for disease progression. Of the 89.0 percent of the patients (median age 53 years) with available data on serostatus, 19.0 percent and 70.0 percent were seropositive and seronegative for anti-nucleocapsid protein at baseline, respectively. Participants were randomized to receive either intravenous infusion of sotrovimab 500 mg (n=105 [seropositive] and n=365 [seronegative]) or placebo (n=97 [seropositive] and n=375 [seronegative]). [CROI 2022, abstract 103]

At day 29, a lower risk of hospitalization ≥24 hours and/or death was observed among patients treated with sotrovimab vs placebo in either the seropositive (2.0 percent vs 4.0 percent) or seronegative subgroups (1.0 percent vs 7.0 percent).

Overall, those on sotrovimab showed a reduced risk of progression to severe COVID-19, irrespective of serostatus, than those on placebo (relative risk ratios, 0.49 [seropositive] and 0.16 [seronegative]), although the interpretation was limited due to the small number of patients in this subgroup, said Shapiro.

Grade 3–4 adverse events (AEs) occurred at a lower rate in the sotrovimab arm vs placebo arm for both seropositive (3.0 percent vs 5.0 percent) and seronegative subgroups (3.0 percent vs 8.0 percent). This result was consistent with that observed in the overall population.

The rates of serious AEs were also lower in the sotrovimab arm than the placebo arm in both the seropositive (2.0 percent vs 4.0 percent) or seronegative subgroups (2.0 percent vs 8.0 percent).

“This data suggests that treatment with sotrovimab reduced progression to severe COVID-19 regardless of serostatus, [with] no difference in the rate of progression,” said Shapiro.

“[T]he result of this analysis really don’t suggest that baseline serologic testing, even if were available immediately and at the point of care, will help identify people who were more likely to benefit from sotrovimab,” Shapiro concluded.

“In the pandemic setting where drug supply may be limited, selection of patients who will benefit the most from monoclonal antibody therapy based on serostatus remains challenging,” she noted.

*COMET-ICE: VIR-7831 for the early treatment of COVID-19 in outpatients