Monoclonal antibodies: How they prevent the virus from entering cells

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Monoclonal antibodies: How they prevent the virus from entering cells

Anti-SARS-CoV-2 therapies that can be used to prevent the development of asymptomatic infection into a symptomatic disease but also to reduce the transmission of the virus from infected individuals can be an important aid in the treatment of COVID-19. especially among certain special groups of the population who cannot be vaccinated or in whom vaccination is not effective. SARS-CoV-2 protein monoclonal antibodies are a treatment that can reduce the chance of serious disease in people who are infected and who have a high risk of complications from severe COVID-19. The Professors of the Therapeutic Clinic of the Medical School of the National and Kapodistrian University of Athens, Efstathios Kastritis and Thanos Dimopoulos (Rector of EKPA) summarize these data

Casirivimab and imdevimab are two neutralizing monoclonal antibodies that bind non-overlapping epitopes in the receptor binding site to the SARS-CoV-2 spike protein and prevent the virus from entering cells. The combination of two antibodies reduces the risk of developing COVID-19 and treatment with Casirivimab and imdevimab has been shown to be effective in treating untreated patients with COVID-19 and preventing infection in people who have been in close contact with cases.

A clinical trial, the results of which were published in the prestigious medical journal JAMA on January 14, 2022, evaluated the effect of a combination (casually administered) of casirivimab and imdevimab on the progression from early asymptomatic SARS-CoV-2 infection to symptomatic COVID-19. This is a randomized, phase 3, double-blind, placebo-controlled clinical trial performed on people who were in close contact with a case of SARS-CoV-2 infection and had not yet shown symptoms of the disease. In addition, these individuals should have no antibodies to SARS-CoV-2 (ie, have not been previously ill). These asymptomatic individuals (≥12 years of age) were eligible as less than 96 hours after the first positive molecular test in the initial first case (which was the initial high-risk contact). The study was conducted in 112 centers in the USA, Romania and Moldova from July 2020 to January 2021. Participants were randomized in a 1: 1 ratio to receive a subcutaneous dose of casirivimab and imdevimab (at a dose of 1200 mg, 600 mg per each, n = 158) or take placebo (n = 156).

The main endpoint of the study was the percentage of seronegative participants (ie individuals who had no previous immunity to the virus) who developed symptomatic COVID-19 disease during the 28-day efficacy evaluation period. The main secondary efficacy endpoints were the number of weeks of symptomatic SARS-CoV-2 infection and the number of weeks with high viral load (> 4 log10 copies / mL).

Among the 314 randomized participants (median age 41 years, of whom 51.6% were women), 310 (99.7%) completed the follow-up for the effectiveness evaluation period. The 204 subjects were asymptomatic and seronegative (i.e., had no antibodies to SARS-CoV-2) at baseline and were included in the primary efficacy assay. Subcutaneous administration of casirivimab and imdevimab significantly prevented the development of symptomatic disease (29/100 [29%] with the drug versus 44/104 [42.3%] with placebo. The relative probability ratio was 0.54 and absolute risk difference −13.3%. This difference was statistically significant (p = 0.04). Casirivimab / imdevimab reduced the number of “symptomatic weeks per 1000 participants” (895.7 weeks versus 1637.4 weeks with placebo, P = 0.03), which corresponds to a reduction of approximately 5.6 days in symptoms per participant who showed symptoms. Treatment with casirivimab and imdevimab also reduced the number of weeks with high viral load per 1000 participants (489.8 weeks versus 811.9 weeks with placebo, P = 0.001). The proportion of participants receiving casirivimab and imdevimab who had one or more side effects was 33.5% vs. 48.1% for placebo, including events related (25.8% vs. 39.7%) or unrelated (11% vs. 16%) to COVID- 19.

Therefore, the study authors conclude that among asymptomatic individuals who tested positive for SARS-CoV-2 after close home contact with an infected person, treatment with the subcutaneous combination of monoclonal antibodies casirivimab and imdevimab significantly reduced the incidence of occurrence of symptomatic COVID-19 versus placebo.

But the study has some limitations. Most importantly, this study was performed prior to extensive vaccination and the emergence of Delta virus variants (B.1.617.2) and Omicron (B.1.1.529) while the sample size was relatively small.

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