Covid-19血清學檢測診斷準確性的系統回顧和薈萃分析
作者：
小柯機器人發布時間：2020/7/3 10:20:12
加拿大麥吉爾大學健康中心研究所Faiz Ahmad Khan團隊對Covid-19血清學檢測的診斷準確性進行了系統回顧和薈萃分析。相關論文於2020年7月1日發表在《英國醫學雜誌》上。
為了確定Covid-19血清學檢測的診斷準確性，研究組在Medline、bioRxiv和medRxiv資料庫中檢索2020年1月1日至4月30日，關於Covid-19血清學檢測的文獻，並進行系統審查和薈萃分析。
主要結果是總體敏感性和特異性，按血清學檢測方法：酶聯免疫吸附試驗（ELISA）、側流免疫分析（LFIAs）、化學發光免疫分析（CLIA）和免疫球蛋白類（IgG、IgM或兩者兼而有之）進行分層。
研究組共篩查了5016篇參考文獻，最終確定40篇研究，共進行了49次偏倚風險評估。在98%（48/49）的評估中發現患者選擇偏倚高風險，73%（36/49）的評估中存在較高或不明確的偏倚風險。10%（4/40）的研究包括門診病人，只有兩項研究評估了護理點的檢測。對於每種檢測方法，合併的敏感性和特異性與所測量的免疫球蛋白類別無關。
測量IgG或IgM的ELISA的合併敏感性為84.3％，LFIAs為66.0％，CLIA為97.8％。在所有分析中，LFIAs的合併敏感性較低，這是一種潛在的護理方法。合併特異性在96.6%到99.7%之間。在用於估計特異性的樣本中，83％來自流行之前或未懷疑有covid-19的人群。在LFIA中，商業試劑盒的合併敏感性為65.0％，低於非商業檢測的敏感性（88.2％）。在所有分析中都可以看到異質性。症狀發作後至少三周的敏感性為69.9-98.9％，顯著高於第一周（13.4-50.3％）。
研究組表明迫切需要更高質量的臨床研究來評估Covid-19血清學檢測的診斷準確性，且不支持繼續使用現有的臨時護理血清學檢測。
附：英文原文
Title: Diagnostic accuracy of serological tests for covid-19: systematic review and meta-analysis
Author: Mayara Lisboa Bastos, Gamuchirai Tavaziva, Syed Kunal Abidi, Jonathon R Campbell, Louis-Patrick Haraoui, James C Johnston, Zhiyi Lan, Stephanie Law, Emily MacLean, Anete Trajman, Dick Menzies, Andrea Benedetti, Faiz Ahmad Khan
Issue&Volume: 2020/07/01
Abstract: Objective To determine the diagnostic accuracy of serological tests for coronavirus disease-2019 (covid-19).
Design Systematic review and meta-analysis.
Data sources Medline, bioRxiv, and medRxiv from 1 January to 30 April 2020, using subject headings or subheadings combined with text words for the concepts of covid-19 and serological tests for covid-19.
Eligibility criteria and data analysis Eligible studies measured sensitivity or specificity, or both of a covid-19 serological test compared with a reference standard of viral culture or reverse transcriptase polymerase chain reaction. Studies were excluded with fewer than five participants or samples. Risk of bias was assessed using quality assessment of diagnostic accuracy studies 2 (QUADAS-2). Pooled sensitivity and specificity were estimated using random effects bivariate meta-analyses.
Main outcome measures The primary outcome was overall sensitivity and specificity, stratified by method of serological testing (enzyme linked immunosorbent assays (ELISAs), lateral flow immunoassays (LFIAs), or chemiluminescent immunoassays (CLIAs)) and immunoglobulin class (IgG, IgM, or both). Secondary outcomes were stratum specific sensitivity and specificity within subgroups defined by study or participant characteristics, including time since symptom onset.
Results 5016 references were identified and 40 studies included. 49 risk of bias assessments were carried out (one for each population and method evaluated). High risk of patient selection bias was found in 98% (48/49) of assessments and high or unclear risk of bias from performance or interpretation of the serological test in 73% (36/49). Only 10% (4/40) of studies included outpatients. Only two studies evaluated tests at the point of care. For each method of testing, pooled sensitivity and specificity were not associated with the immunoglobulin class measured. The pooled sensitivity of ELISAs measuring IgG or IgM was 84.3% (95% confidence interval 75.6% to 90.9%), of LFIAs was 66.0% (49.3% to 79.3%), and of CLIAs was 97.8% (46.2% to 100%). In all analyses, pooled sensitivity was lower for LFIAs, the potential point-of-care method. Pooled specificities ranged from 96.6% to 99.7%. Of the samples used for estimating specificity, 83% (10465/12547) were from populations tested before the epidemic or not suspected of having covid-19. Among LFIAs, pooled sensitivity of commercial kits (65.0%, 49.0% to 78.2%) was lower than that of non-commercial tests (88.2%, 83.6% to 91.3%). Heterogeneity was seen in all analyses. Sensitivity was higher at least three weeks after symptom onset (ranging from 69.9% to 98.9%) compared with within the first week (from 13.4% to 50.3%).
Conclusion Higher quality clinical studies assessing the diagnostic accuracy of serological tests for covid-19 are urgently needed. Currently, available evidence does not support the continued use of existing point-of-care serological tests.
DOI: 10.1136/bmj.m2516
Source: https://www.bmj.com/content/370/bmj.m2516