加拿大麦克马斯特大学Reed A C Siemieniuk团队对Covid-19预防策略进行了一项系统回顾和网络荟萃分析。2021年4月26日，该研究发表在《英国医学杂志》上。
为了探讨药物预防对SARS-CoV-2和Covid-19感染的影响，研究组在世界卫生组织covid-19数据库等多个多语种数据库中检索，筛选出接受预防或不接受预防（标准护理或安慰剂）的covid-19风险人群的随机试验，并进行系统回顾和网络荟萃分析。
该网络荟萃分析的初次分析包括9个随机试验，其中6个为羟氯喹（6059名参与者），1个为伊维菌素联合iota型卡拉胶（234名），2个为单独伊维菌素（540名），均与标准护理或安慰剂进行比较。两个试验（一个是雷米普利，一个是盐酸溴己新）不符合网络荟萃分析的样本量要求而被排除。
羟氯喹对患者入院或死亡的改善很小或几乎没有影响。羟氯喹可能不会降低实验室确诊的SARS-CoV-2感染的风险（中度确定性），可能增加导致停药的不良反应（中度确定性），可能对疑似或实验室确诊的SARS-CoV-2感染有轻微影响或无影响（低确定性）。由于严重的偏倚风险和较大的不精确性，证据的确定性非常低，伊维菌素联合iota型卡拉胶对实验室确诊的covid-19的影响，以及单独伊维菌素对疑似或实验室确诊的感染的影响仍然非常不确定。
研究结果表明，羟氯喹预防对患者住院和死亡的影响很小，甚至没有效果，但可能会增加不良反应，且可能不会降低SARS-CoV-2感染的风险。由于严重的偏倚风险和非常严重的不精确性，伊维菌素联合iota型卡拉胶和伊维菌素单独使用是否能降低SARS-CoV-2感染风险非常不确定。
附：英文原文
Title: Prophylaxis against covid-19: living systematic review and network meta-analysis
Author: Jessica J Bartoszko, Reed A C Siemieniuk, Elena Kum, Anila Qasim, Dena Zeraatkar, Long Ge, Mi Ah Han, Behnam Sadeghirad, Arnav Agarwal, Thomas Agoritsas, Derek K Chu, Rachel Couban, Andrea J Darzi, Tahira Devji, Maryam Ghadimi, Kimia Honarmand, Ariel Izcovich, Assem Khamis, Francois Lamontagne, Mark Loeb, Maura Marcucci, Shelley L McLeod, Sharhzad Motaghi, Srinivas Murthy, Reem A Mustafa, John D Neary, Hector Pardo-Hernandez, Gabriel Rada, Bram Rochwerg, Charlotte Switzer, Britta Tendal, Lehana Thabane, Per O Vandvik, Robin W M Vernooij, Andrés Viteri-García, Ying Wang, Liang Yao, Zhikang Ye, Gordon H Guyatt, Romina Brignardello-Petersen
Issue&Volume: 2021/04/26
Abstract:
Objective To determine and compare the effects of drug prophylaxis on SARS-CoV-2 infection and covid-19.
Design Living systematic review and network meta-analysis.
Data sources World Health Organization covid-19 database, a comprehensive multilingual source of global covid-19 literature to 25 March 2021, and six additional Chinese databases to 20 February 2021.
Study selection Randomised trials of people at risk of covid-19 who were assigned to receive prophylaxis or no prophylaxis (standard care or placebo). Pairs of reviewers independently screened potentially eligible articles.
Methods Random effects bayesian network meta-analysis was performed after duplicate data abstraction. Included studies were assessed for risk of bias using a modification of the Cochrane risk of bias 2.0 tool, and certainty of evidence was assessed using the grading of recommendations assessment, development, and evaluation (GRADE) approach.
Results The first iteration of this living network meta-analysis includes nine randomised trials—six of hydroxychloroquine (n=6059 participants), one of ivermectin combined with iota-carrageenan (n=234), and two of ivermectin alone (n=540), all compared with standard care or placebo. Two trials (one of ramipril and one of bromhexine hydrochloride) did not meet the sample size requirements for network meta-analysis. Hydroxychloroquine has trivial to no effect on admission to hospital (risk difference 1 fewer per 1000 participants, 95% credible interval 3 fewer to 4 more; high certainty evidence) or mortality (1 fewer per 1000, 2 fewer to 3 more; high certainty). Hydroxychloroquine probably does not reduce the risk of laboratory confirmed SARS-CoV-2 infection (2 more per 1000, 18 fewer to 28 more; moderate certainty), probably increases adverse effects leading to drug discontinuation (19 more per 1000, 1 fewer to 70 more; moderate certainty), and may have trivial to no effect on suspected, probable, or laboratory confirmed SARS-CoV-2 infection (15 fewer per 1000, 64 fewer to 41 more; low certainty). Owing to serious risk of bias and very serious imprecision, and thus very low certainty of evidence, the effects of ivermectin combined with iota-carrageenan on laboratory confirmed covid-19 (52 fewer per 1000, 58 fewer to 37 fewer), ivermectin alone on laboratory confirmed infection (50 fewer per 1000, 59 fewer to 16 fewer) and suspected, probable, or laboratory confirmed infection (159 fewer per 1000, 165 fewer to 144 fewer) remain very uncertain.
Conclusions Hydroxychloroquine prophylaxis has trivial to no effect on hospital admission and mortality, probably increases adverse effects, and probably does not reduce the risk of SARS-CoV-2 infection. Because of serious risk of bias and very serious imprecision, it is 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.
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.
DOI: 10.1136/bmj.n949
Source: https://www.bmj.com/content/373/bmj.n949
BMJ-British Medical Journal:《英国医学杂志》，创刊于1840年。隶属于BMJ出版集团，最新IF：93.333
官方网址：http://www.bmj.com/
投稿链接：https://mc.manuscriptcentral.com/bmj
本期文章：《英国医学杂志》：Online/在线发表
