The use of neutralizing monoclonal antibody in patients with COVID-19: a systematic review and meta-analysis

Abstract

Neutralizing monoclonal antibody (mAb) therapies targeting with high specificity to SARS-CoV-2 has been considered as one of the potential therapies for COVID-19 since the beginning of the pandemic. Preclinical studies demonstrated a marked reduction in viral loads in the upper and lower respiratory tract with the use of neutralizing mAbs 1 .The mAbs have the ability to coordinate the immune defense to link to the virus and control the virus load. The mAbs are defined as an antibody derived from a single B-cell clone and recognize a single and unique epitope that can link to their specific epitope on target antigens and can mediate multiple effects such as disruption of the function and eliminate cells or pathogens 2 . These mAbs for COVID-19 are fully human and were discovered from COVID-19 patient' donors, and one of their targets is to block the S protein of the SARS-CoV-2, preventing viral entry into host cells 3 .The U.S. Food and Drug Administration (FDA) issued an emergency use authorization for mAbs to be used as pre-exposure prophylaxis and mild-moderate COVID-19. However, given to the Omicron variant, the FDA did not recommend using casirivimab+imdevimab. In Brazil, mAbs were approved by the Brazilian regulatory agency, i.e., The National Health Surveillance Agency (ANVISA), for use in patients with mild-to-moderate nonhospitalized COVID-19 patients and for the prevention of COVID-19 infection.This systematic review aimed to identify, describe, evaluate, and synthesize evidence of effectiveness of mAbs in clinical outcomes in COVID-19 patients. METHODSThis systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations 4 . Eligibility criteriaThe study protocol followed the patients of interest, intervention to be studied, comparison of interventions, and outcome of interest (PICO) methodology. With the use of a mAb as the main study point, the PICO framework was as follows: patients, adult COVID-19 patients; intervention, use of an mAb (casiriv-imab+imdevimab, bamlanivimab, bamlanivimab+etesevimab, sotrovimab, regdanvimab, and tixagevimab+cilgavimab); comparison between the standard of care (SOC) and placebo; and outcome, symptomatic COVID-19 infection, symptom resolution, adverse event, severe adverse event, hospitalization, and the mortality rate due to any cause in 29 days. The protocol was registered in the PROSPERO International Prospective Register of Systematic Reviews: CRD42022320972.All phase 3 randomized controlled trials (RCTs) on the topic were included. No restrictions were imposed with regard to the date of publication, language, or availability of the full text of the article. Information sources and search strategyTwo authors developed a search strategy that was revised and approved by the team, selected information sources, and systematically searched MEDLINE, EMBASE, Central Cochrane, and ClinicalTrials.gov. Specific search strategies were used for each database: ("COVID-19" OR "COVID" OR "coronavirus" OR