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Meta-Analysis
. 2022 Nov;135(11):1349-1361.e18.
doi: 10.1016/j.amjmed.2022.06.019. Epub 2022 Jul 23.

Beneficial and Harmful Effects of Monoclonal Antibodies for the Treatment and Prophylaxis of COVID-19: Systematic Review and Meta-Analysis

Adrian V Hernandez  1 , Alejandro Piscoya  2 , Vinay Pasupuleti  3 , Mi T Phan  4 , Sreya Julakanti  4 , Phirin Khen  4 , Yuani M Roman  4 , César O Carranza-Tamayo  5 , Angel A Escobedo  6 , C Michael White  4
Affiliations
Meta-Analysis

Beneficial and Harmful Effects of Monoclonal Antibodies for the Treatment and Prophylaxis of COVID-19: Systematic Review and Meta-Analysis

Adrian V Hernandez et al. Am J Med. 2022 Nov.

Abstract

Background: We systematically assessed beneficial and harmful effects of monoclonal antibodies for coronavirus disease 2019 (COVID-19) treatment, and prophylaxis in individuals exposed to severe acute respiratory syndrome coronavirus 2.

Methods: We searched 5 engines and 3 registries until November 3, 2021 for randomized controlled trials evaluating monoclonal antibodies vs control in hospitalized or non-hospitalized adults with COVID-19, or as prophylaxis. Primary outcomes were all-cause mortality, COVID-19-related death, and serious adverse events; hospitalization for non-hospitalized; and development of symptomatic COVID-19 for prophylaxis. Inverse variance random effects models were used for meta-analyses. Grading of Recommendations, Assessment, Development, and Evaluations methodology was used to assess certainty of evidence.

Results: Twenty-seven randomized controlled trials were included: 20 in hospitalized patients (n = 8253), 5 in non-hospitalized patients (n = 2922), and 2 in prophylaxis (n = 2680). In hospitalized patients, monoclonal antibodies slightly reduced mechanical ventilation (relative risk [RR] 0.74; 95% confidence interval [CI], 0.60-0.9; I2 = 20%, low certainty of evidence) and bacteremia (RR 0.77; 95% CI, 0.64-0.92; I2 = 7%, low certainty of evidence); evidence was very uncertain about the effect on adverse events (RR 1.31; 95% CI, 1.02-1.67; I2 = 77%, very low certainty of evidence). In non-hospitalized patients, monoclonal antibodies reduced hospitalizations (RR 0.30; 95% CI, 0.17-0.53; I2 = 0%, high certainty of evidence) and may slightly reduce serious adverse events (RR 0.47; 95% CI, 0.22-1.01; I2 = 33%, low certainty of evidence). In prophylaxis studies, monoclonal antibodies probably reduced viral load slightly (mean difference -0.8 log10; 95% CI, -1.21 to -0.39, moderate certainty of evidence). There were no effects on other outcomes.

Conclusions: Monoclonal antibodies had limited effects on most of the outcomes in COVID-19 patients, and when used as prophylaxis. Additional data are needed to determine their efficacy and safety.

Keywords: COVID-19; Meta-analysis; Monoclonal antibodies; Prophylaxis; Treatment.

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Figures

Figure 1
Figure 1
PRISMA 2020 flowchart.
Figure 2
Figure 2
Effects of monoclonal antibodies on all-cause mortality stratified by type of COVID-19 patients.
Figure 3
Figure 3
Effects of monoclonal antibodies on COVID-19-related death stratified by type of COVID-19 patients.
Figure 4
Figure 4
Effects of monoclonal antibodies on serious adverse events stratified by type of COVID-19 patients.
Supplementary Figure 1
Supplementary Figure 1
Risk of bias of included randomized controlled trials (RCTs).
Supplementary Figure 2
Supplementary Figure 2
Effects of monoclonal antibodies on length of hospital stay stratified by type of COVID-19 patients.
Supplementary Figure 3
Supplementary Figure 3
Effects of monoclonal antibodies on invasive mechanical ventilation stratified by type of COVID-19 patients.
Supplementary Figure 4
Supplementary Figure 4
Effects of monoclonal antibodies on viral load stratified by type of COVID-19 patients.
Supplementary Figure 5
Supplementary Figure 5
Effects of monoclonal antibodies on adverse events stratified by type of COVID-19 patients.
Supplementary Figure 6
Supplementary Figure 6
Effects of monoclonal antibodies on bacteremia stratified by type of COVID-19 patients.
Supplementary Figure 7
Supplementary Figure 7
Effects of monoclonal antibodies on COVID-19-related hospitalization in non-hospitalized RCTs
Supplementary Figure 8
Supplementary Figure 8
Effects of monoclonal antibodies on symptomatic COVID-19 incidence in prophylaxis RCTs
Supplementary Figure 9
Supplementary Figure 9
Effects of monoclonal antibodies on symptomatic or asymptomatic COVID-19 incidence in prophylaxis RCTs
Supplementary Figure 10
Supplementary Figure 10A
Subgroup analyses by type of drug: tocilizumab vs. other MAbs in hospitalized patients Supplementary Figure 10A1 All-cause mortality.
Supplementary Figure 10
Supplementary Figure 10A2
COVID-19-related death .
Supplementary Figure 10
Supplementary Figure 10A3
Serious adverse events.
Supplementary Figure 10
Supplementary Figure 10A4
Length of hospital stay.
Supplementary Figure 10
Supplementary Figure 10A5
Invasive mechanical ventilation.
Supplementary Figure 10
Supplementary Figure 10A6
Adverse events.
Supplementary Figure 10
Supplementary Figure 10A7
Bacteremia
Supplementary Figure 10
Supplementary Figure 10B
Subgroup analyses by type of control in hospitalized patients. Supplementary Figure 10B1 All-cause mortality.
Supplementary Figure 10
Supplementary Figure 10B2
COVID-19-related death
Supplementary Figure 10
Supplementary Figure 10B3
Serious adverse events.
Supplementary Figure 10
Supplementary Figure 10B4
Length of hospital stay.
Supplementary Figure 10
Supplementary Figure 10B5
Invasive mechanical ventilation.
Supplementary Figure 10
Supplementary Figure 10B6
Adverse events.
Supplementary Figure 10
Supplementary Figure 10B7
Bacteremia.
Supplementary Figure 10
Supplementary Figure 10C
Subgroup analyses by type of control in hospitalized patients receiving tocilizumab. Supplementary Figure S10C1 All-cause mortality.
Supplementary Figure 10
Supplementary Figure 10C2
Serious adverse events.
Supplementary Figure 10
Supplementary Figure 10C3
Length hospital stay.
Supplementary Figure 10
Supplementary Figure 10C4
Invasive mechanical ventilation.
Supplementary Figure 10
Supplementary Figure 10C5
Adverse events.
Supplementary Figure 10
Supplementary Figure 10C6
Bacteremia.
See this image and copyright information in PMC

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