Prophylaxis for covid-19: living systematic review and network meta-analysis
Authors: Bartoszko Jessica J , Siemieniuk Reed AC , Kum Elena , Qasim Anila , Zeraatkar Dena , Ge Long , Han Mi Ah , Sadeghirad Behnam , Agarwal Arnav , Agoritsas Thomas , Chu Derek K , Couban Rachel , Darzi Andrea J , Devji Tahira , Ghadimi Maryam , Honarmand Kimia , Izcovich Ariel , Khamis Assem , Lamontagne Francois , Loeb Mark , Marcucci Maura , McLeod Shelley L , Motaghi Shahrzad , Murthy Srinivas , Mustafa Reem A , Neary John D , Pardo-Hernandez Hector , Rada Gabriel , Rochwerg Bram , Switzer Charlotte , Tendal Britta , Thabane Lehana , Vandvik Per O , Vernooij Robin WM , Viteri-García Andrés , Wang Ying , Yao Liang , Ye Zhikang , Guyatt Gordon H , Brignardello-Petersen Romina 
Published: February 2021

Objective

To determine and compare the effects of drug prophylaxis on severe acute respiratory syndrome coronavirus virus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (covid-19).

Design

Living systematic review and network meta-analysis.

Data sources

WHO covid-19 database, a comprehensive multilingual source of global covid-19 literature to 19 January 2021, and six additional Chinese databases to 20 January 2021.

Study selection

Randomized trials in which people at risk of covid-19 were randomized to drug prophylaxis or no prophylaxis (standard care or placebo). Pairs of reviewers independently screened potentially eligible articles.

Methods

After duplicate data abstraction, we conducted random-effects bayesian network meta-analysis. We assessed risk of bias of the included studies using a modification of the Cochrane risk of bias 2.0 tool and assessed the certainty of the evidence using the grading of recommendations assessment, development and evaluation (GRADE) approach.

Results

The first iteration of this living network meta-analysis includes nine randomized trials – six addressing hydroxychloroquine (6,059 participants), one addressing ivermectin combined with iota-carrageenan (234 participants) and two addressing ivermectin alone (540 participants), all compared to standard care or placebo. Hydroxychloroquine has no important effect on admission to hospital (risk difference (RD) 1 fewer per 1,000, 95% credible interval (CrI) 3 fewer to 4 more, high certainty) or mortality (RD 1 fewer per 1,000, 95% CrI 2 fewer to 3 more, high certainty). Hydroxychloroquine probably has no important effect on laboratory-confirmed infection (RD 2 more per 1,000, 95% CrI 18 fewer to 28 more, moderate certainty), probably increases adverse effects leading to drug discontinuation (RD 19 more per 1,000, 95% CrI 1 fewer to 70 more, moderate certainty) and may have no important effect on suspected, probable or laboratory-confirmed infection (RD 15 fewer per 1,000, 95% CrI 64 fewer to 41 more, low certainty). Due to serious risk of bias and very serious imprecision – and thus very low certainty evidence, the effects of ivermectin combined with iota-carrageenan on laboratory-confirmed infection (RD 52 fewer per 1,000, 95% CrI 58 fewer to 37 fewer), and ivermectin alone on laboratory-confirmed infection (RD 50 fewer per 1,000, 95% CrI 59 fewer to 16 fewer) and suspected, probable or laboratory-confirmed infection (RD 159 fewer per 1,000, 95% CrI 165 fewer to 144 fewer) remain uncertain.

Conclusion

Hydroxychloroquine prophylaxis does not have an important effect on hospital admission and mortality, probably increases adverse effects, and probably does not have an important effect on laboratory-confirmed SARS-CoV-2 infection. Because of serious risk of bias and very serious imprecision, we are highly uncertain whether ivermectin combined with iota-carrageenan and ivermectin alone reduce the risk of SARS-CoV-2 infection.

Systematic review registration

This review was not registered. The protocol established a priori is included as a supplement.

Funding

This study was supported by the Canadian Institutes of Health Research (grant CIHR-IRSC:0579001321).

Readers’ note

This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication.