Sotrovimab benefits select hospitalized COVID-19 patients

In the RECOVERY* trial, the neutralizing monoclonal antibody (mAb) sotrovimab reduces mortality in hospitalized patients with COVID-19 pneumonia with a high baseline serum SARS-CoV-2 antigen concentration. However, this was not the case in the overall population.

“Efficacy appears to be restricted to patients who have not yet mounted an effective immune response to their infection, in whom mortality remains high despite current treatment,” the investigators said.

There was a reduction in 28-day mortality with sotrovimab plus usual care (UC) vs UC alone in patients with a high baseline antigen level (23 percent vs 29 percent; rate ratio [RR], 0.75; p=0.046) but not in all randomized patients (21 percent vs 22 percent; RR, 0.95; p=0.60). [Lancet Infect Dis 2026;26:34-45]

The addition of sotrovimab to UC did not appear to be beneficial in terms of time to discharge from hospital within 28 days in patients with a high antigen level (median 13 vs 16 days; 66 percent vs 62 percent; RR, 1.12) and in the overall population (median 11 vs 11 days; 68 percent vs 68 percent; RR, 0.96).

Add-on sotrovimab also did not reduce the risk of progressing to invasive ventilation (IV) or death in participants who were not on IV at baseline (24 percent vs 29 percent; RR, 0.82 [high antigen level subgroup] and 23 percent vs 23 percent; RR, 0.98 [overall population]).

Twelve sotrovimab recipients experienced infusion reactions. Of these, two required antihistamines or steroids only, one required adrenaline, while the rest did not require any intervention. Two of the reactions (one anaphylactic episode) were deemed serious adverse reactions, but both resolved. There were no other serious adverse reactions to sotrovimab reported.

A more relevant Tx alternative

“When the first Omicron variant, BA.1, became globally dominant in December 2021, it contained spike mutations conferring high-level resistance to most mAbs in clinical use, including the casirivimab-imdevimab combination, leading to its withdrawal from guidelines,” the investigators noted. [Nat Rev Microbiol 2023;21:112-124]

The neutralizing potency of sotrovimab was modestly reduced against BA.1 compared with the wild-type virus, but it retained more activity than other neutralizing mAbs, making it a promising candidate for continued use in hospitalized patients and prompting its evaluation in RECOVERY. [Nature 2022;602:657-663; Science 2022;378:619-627]

However, a further decline in activity against the Omicron subvariant BA.2 led to sotrovimab’s withdrawal from the US FDA Emergency Use Authorization in April 2022, they said. “[Nonetheless], sotrovimab retained enough in vitro activity against viral variants prevalent in 2022-2023 to suggest it could retain clinical benefit via direct neutralization … or Fc-dependent effector mechanisms.”

A total of 1,723 participants (mean age 70.7 years, 60 percent men) were enrolled in the RECOVERY sotrovimab comparison. They were randomized 1:1 to UC alone or with a single infusion of sotrovimab 1 g. Forty-two percent of participants had a high antigen level, 42 percent had a low antigen level, and 17 percent had unknown antigen status.

As the current study was conducted during a period of Omicron infection and widespread vaccination and natural immunity, it appears to be a more relevant treatment option for current and future hospitalized COVID-19 patients, the researchers noted.

“The emergence of high-level resistance to sotrovimab among subsequent SARS-CoV-2 variants limits its current usefulness, but these results indicate that targeted neutralizing mAb therapy could still benefit some hospitalized patients at high risk of death in an era of widespread vaccination and Omicron infection [and that antigen testing could help identify these patients],” the investigators said.

While no currently available mAbs have satisfactory activity against current SARS-CoV-2 variants, these findings should inform future mAb evaluation and treatment strategies, they added.