Sotrovimab, a monoclonal antibody drug against the spike protein coronavirus, reduces the risk of covid progression in mild to moderate patients by 85 percent. As reported in The New England Journal of Medicine, scientists found no severe side effects with the drug.
Sotrovimab, isolated in 2003 from a patient who was cured of severe acute respiratory syndrome (SARS), binds to the spike glycoprotein of the coronavirus and prevents the viral particle from entering the cell.
These monoclonal antibodies are known to bind to a region of the virus containing glycan N343, which is highly conserved in the sarbekovirus subtype. This region does not compete with angiotensin-converting enzyme binding and does not overlap with the mutations now observed in SARS-Cov-2.
In a preliminary study, it was shown that sotrovimab binds in vitro to various SARS-CoV-2 variants, including the "South African" beta variant. Also in vitro, sotrovimab demonstrated two antiviral mechanisms: antibody-dependent cellular cytotoxicity and phagocytosis. Modification of the Fc-particle of the monoclonal antibody increased the half-life of the drug and its distribution in the lungs.
Adrienne E. Shapiro of the University of Washington and colleagues from Canada, Brazil and Spain investigated the safety and efficacy of sotrovimab in reducing the risk of severe disease in patients with mild to moderate covid. To do this, the researchers gave 500 milligrams of sotrovimab once intravenously to patients being treated at home. The high-risk group for developing severe disease included people over 55 years of age, as well as patients with diabetes, obesity, chronic kidney disease, congestive heart failure, chronic obstructive pulmonary disease, or moderate to severe asthma.
A total of 583 patients were randomized: 291 patients received sotrovimab and 292 received placebo. Twenty-two percent of the participants were over age 65, and 42 percent had two or more conditions that were considered risk factors for covid progression. The most common risk factors were obesity, age 55 or older and diabetes. The most common symptoms (more than 62 percent of all patients) were cough, muscle pain, headache and fatigue.
A total of three of 291 patients in the sotrovimab group (1 percent), compared with 21 of 292 patients in the placebo group (7 percent), had disease progression resulting in hospitalization for all causes for more than 24 hours or death (relative risk reduction, 85 percent, p = 0.002).
The primary cause of 24 hospitalizations was symptoms of severe covid with the exception of one: a patient with a history of significant small bowel obstruction in the sotrovimab group was found to have intestinal obstruction on day 22 from administration of the drug.
All five patients who were admitted to the ICU did not receive the drug; two of these five patients received invasive ventilatory support, and the third patient refused intubation and subsequently died on day 29. There were also fewer emergency department visits without hospitalization in the sotrovimab group.
During the drug's safety study (868 people divided equally into the study and control groups), researchers were able to identify one side effect associated with the drug - diarrhea in one percent of patients who received sotrovimab.
The results of this interim study suggest that sotrovimab may be therapeutic for outpatients with COVID-19.
Given its in vitro activity against variants of the coronavirus, scientists suggest that sotrovimab may remain therapeutically active even if SARS-CoV-2 continues to mutate.
Physicians, however, are trying to find working monoclonal antibodies not only to the coronavirus itself, but also to the mediators of the inflammation it causes. Recently, Russian scientists found that monoclonal antibodies to interleukin-6 alleviated the course of severe covid.
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