SARS-CoV-2-neutralising monoclonal antibodies to prevent COVID-19

• Published in: Cochrane database of systematic reviews 2022-06, Vol.6 (6), p.CD014945
• Main Authors: Hirsch, Caroline, Park, Yun Soo, Piechotta, Vanessa, Chai, Khai Li, Estcourt, Lise J, Monsef, Ina, Salomon, Susanne, Wood, Erica M, So-Osman, Cynthia, McQuilten, Zoe, Spinner, Christoph D, Malin, Jakob J, Stegemann, Miriam, Skoetz, Nicole, Kreuzberger, Nina
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal, Humanized; Antibodies, Neutralizing; Antineoplastic Agents, Immunological; COVID-19 - prevention & control; Humans; Infectious disease; Middle Aged; SARS-CoV-2
• ISSN: 1469-493X
• DOI: 10.1002/14651858.CD014945.pub2

Monoclonal antibodies (mAbs) are laboratory-produced molecules derived from the B cells of an infected host. They are being investigated as potential prophylaxis to prevent coronavirus disease 2019 (COVID-19). To assess the effects of SARS-CoV-2-neutralising mAbs, including mAb fragments, to prevent infection with SARS-CoV-2 causing COVID-19; and to maintain the currency of the evidence, using a living systematic review approach. We searched the Cochrane COVID-19 Study Register, MEDLINE, Embase, and three other databases on 27 April 2022. We checked references, searched citations, and contacted study authors to identify additional studies. We included randomised controlled trials (RCTs) that evaluated SARS-CoV-2-neutralising mAbs, including mAb fragments, alone or combined, versus an active comparator, placebo, or no intervention, for pre-exposure prophylaxis (PrEP) and postexposure prophylaxis (PEP) of COVID-19. We excluded studies of SARS-CoV-2-neutralising mAbs to treat COVID-19, as these are part of another review. Two review authors independently assessed search results, extracted data, and assessed risk of bias using Cochrane RoB 2. Prioritised outcomes were infection with SARS-CoV-2, development of clinical COVID-19 symptoms, all-cause mortality, admission to hospital, quality of life, adverse events (AEs), and serious adverse events (SAEs). We rated the certainty of evidence using GRADE. We included four RCTs of 9749 participants who were previously uninfected and unvaccinated at baseline. Median age was 42 to 76 years. Around 20% to 77.5% of participants in the PrEP studies and 35% to 100% in the PEP studies had at least one risk factor for severe COVID-19. At baseline, 72.8% to 82.2% were SARS-CoV-2 antibody seronegative. We identified four ongoing studies, and two studies awaiting classification. Pre-exposure prophylaxis Tixagevimab/cilgavimab versus placebo One study evaluated tixagevimab/cilgavimab versus placebo in participants exposed to SARS-CoV-2 wild-type, Alpha, Beta, and Delta variant. About 39.3% of participants were censored for efficacy due to unblinding and 13.8% due to vaccination. Within six months, tixagevimab/cilgavimab probably decreases infection with SARS-CoV-2 (risk ratio (RR) 0.45, 95% confidence interval (CI) 0.29 to 0.70; 4685 participants; moderate-certainty evidence), decreases development of clinical COVID-19 symptoms (RR 0.18, 95% CI 0.09 to 0.35; 5172 participants; high-certainty evidence), and may decrease admission