key: cord-0870201-tih33rys
authors: Castro, Rodolfo; Luz, Paula M; Wakimoto, Mayumi D; Veloso, Valdilea G; Grinsztejn, Beatriz; Perazzo, Hugo
title: COVID-19: a meta-analysis of diagnostic test accuracy of commercial assays registered in Brazil
date: 2020-04-18
journal: The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases
DOI: 10.1016/j.bjid.2020.04.003
sha: a9b8cedbc75e76fb5d9d8220abc6eb63c3b22a39
doc_id: 870201
cord_uid: tih33rys

Abstract The accuracy of commercially available tests for COVID-19 in Brazil remains unclear. We aimed to perform a meta-analysis to describe the accuracy of available tests to detect COVID-19 in Brazil. We searched at the Brazilian Health Regulatory Agency (ANVISA) online platform to describe the pooled sensitivity (Se), specificity (Sp), diagnostic odds ratio (DOR) and summary receiver operating characteristic curves (SROC) for detection of IgM/IgG antibodies and for tests using naso/oropharyngeal swabs in the random-effects models. We identified 16 tests registered, mostly rapid-tests. Pooled diagnostic accuracy measures [95%CI] were: (i) for IgM antibodies Se=82% [76-87]; Sp=97% [96-98]; DOR=168 [92-305] and SROC=0.98 [0.96-0.99]; (ii) for IgG antibodies Se=97% [90-99]; Sp=98% [97-99]; DOR=1994 [385-10334] and SROC=0.99 [0.98-1.00]; and (iii) for detection of SARS-CoV-2 by antigen or molecular assays in naso/oropharyngeal swabs Se=97% [85-99]; Sp=99% [77-100]; DOR=2649 [30-233056] and SROC=0.99 [0.98-1.00]. These tests can be helpful for emergency testing during the COVID-19 pandemic in Brazil. However, it is important to highlight the high rate of false negative results from tests which detect SARS-CoV-2 IgM antibodies in the initial course of the disease and the scarce evidence-based validation results published in Brazil. Future studies addressing the diagnostic performance of tests for COVID-19 in the Brazilian population are urgently needed.

J o u r n a l P r e -p r o o f 3 The World Health Organization (WHO) declared Coronavirus disease 2019 (COVID-19) as pandemic on March 11, 2020. Due to the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viruses, we are currently facing a scenario of sustained community transmission of COVID-19 worldwide. 1 Early implementation of mitigation associated with suppression strategies can drastically reduce the number of hospitalizations and deaths. 2 Large-scale testing, rapid diagnosis and immediate isolation of cases coupled with rigorous tracking and preventive self-isolation of close contacts are essential measures to reduce the burden of the COVID-19 pandemic. 3 Therefore, tests for COVID-19 should be point-ofcare, widely available, and implemented outside of hospital settings to prevent overwhelming the health care system as well as the risk of nosocomial transmission to other patients and healthcare workers. Results from the mathematical modelling study performed by the Imperial College of London for Brazil, the implementation of suppression strategies could save up to a million lives and prevent the collapse of the Brazilian Unified Health System (Sistema Único de Saúde, SUS) compared to an unmitigated strategy. 4 Though massive testing is a cornerstone to reduce the burden of COVID-19, the accuracy of commercially available tests for COVID-19 in Brazil remains unclear. The aim of this study was to perform a meta-analysis to describe the accuracy of available tests to detect COVID-19 in Brazil.

To identify the registered tests for COVID-19 diagnosis in Brazil, we performed searches on March 30, 2020 using the following terms "COVID-19" OR "SARS-CoV-2" OR "2019-nCoV" OR "coronavirus" at the Brazilian Health Regulatory Agency (Agência Nacional de Vigilância Sanitária, ANVISA, website: https://consultas.anvisa.gov.br/#/saude/). Data were extracted by two independent researchers to an electronic database. The identified tests were stratified according to those which detect SARS-CoV-2 immunoglobulin antibodies (IgM and/or IgG) and nucleic acid (RNA) or antigen (Ag) from SARS-CoV-2. The following data were extracted from documents uploaded by manufacturers for each registered test: test name, Table 1 higher rates of false-negative results when collected in the early-phase of symptoms onset. Our study reports that antigen testing and/or molecular assays using nasopharyngeal and oropharyngeal specimens had high accuracy for SARS-CoV-2 detection. In China, the rate of SARS-CoV-2 detection was higher in oropharyngeal compared to nasopharyngeal swabs during the COVID-19 outbreak. 9 Naso/oropharyngeal tests might miss early infection leading to a strategy of repeated testing since the likelihood of the SARS-CoV-2 being present in the nasopharynx increases with time. 8 In the present study, the pooled sensitivity of tests using the detection of COVID-19 IgM antibodies in blood was lower compared to antigen/molecular 

COVID-19) pandemic: increased transmission in the EU/EEAand the UK-sixth update: European Centre for Disease Prevention and Control

The Global Impact of COVID-19 and 4. Imperial College London. The Global Impact of COVID-19 and Strategies for

Stata module for meta-analytical integration of diagnostic test accuracy studies,: Boston College; Department of Economics

Developing antibody tests for SARS-CoV-2

Development and Clinical Application of A Rapid IgM-IgG Combined Antibody Test for SARS-CoV-2 Infection Diagnosis

Detection of SARS-CoV-2 in Different Types of Clinical Specimens

FIGURE LEGENDS Figure 1. Pooled diagnostic accuracy analysis (A) and summary receiver operating characteristic curve (B) of tests (n=8) for detection of