key: cord-0684028-gl83kv6v authors: Zhang, Zu‐Li; Hou, Yu‐Lei; Li, De‐Tao; Li, Feng‐Zeng title: Diagnostic efficacy of anti‐SARS‐CoV‐2 IgG/IgM test for COVID‐19: A meta‐analysis date: 2020-07-11 journal: J Med Virol DOI: 10.1002/jmv.26211 sha: 66c218713035c4749b92a7f0f3a75e82cf446b39 doc_id: 684028 cord_uid: gl83kv6v The serological testing of anti‐SARS‐CoV‐2 immunoglobulin G (IgG) and/or IgM is widely used in the diagnosis of COVID‐19. However, its diagnostic efficacy remains unclear. In this study, we searched for diagnostic studies from the Web of Science, PubMed, Embase, CNKI, and Wanfang databases to calculate the pooled diagnostic accuracy measures using bivariate random‐effects model meta‐analysis. As a result, 22 from a total of 1613 articles, including 2282 patients with SARS‐CoV‐2 and 1485 healthy persons or patients without SARS‐CoV‐2, were selected for a meta‐analysis. Pooled sensitivity, specificity, and area under curve of the summary receiver operator curve (SROC) were: (a) 0.85 (95% confidence interval [CI]: 0.79‐0.90), 0.99 (95% CI: 0.98‐1.00), and 0.99 (95% CI: 0.97‐0.99) for anti‐SARS‐CoV‐2 IgG and (b) 0.74 (95% CI: 0.65‐0.81), 0.99 (95% CI: 0.97‐1.00), and 0.95 (95% CI: 0.93‐0.97) for IgM. A subgroup analysis among detection methods indicated the sensitivity of IgG and IgM using enzyme‐linked immunosorbent assay were slightly lower than those using gold immunochromatography assay (GICA) and chemiluminescence immunoassay (P > .05). These results showed that the detection of anti‐SARS‐CoV‐2 IgG and IgM had high diagnostic efficiency to assist the diagnosis of SARS‐CoV‐2 infection. And, GICA might be used as the preferred method for its accuracy and simplicity. The coronavirus, SARS-CoV-2, is now widely spreading over the world and has infected millions of people. It causes a low respiratory infection pandemic. In some patients, it may lead to acute respiratory distress syndrome that contributes to most of the COVID-19 deaths. As of 18 May 2020, nearly five million people around the world have been diagnosed with SARS-CoV-2, and more than 300 000 people have died from serve COVID-19. 1 Timely diagnosis of SARS-CoV-2 infections and isolation of infected persons and close contacts remain priorities and challenges of epidemic prevention. The diagnosis of SARS-CoV-2 infections mainly depends on the detection of SARS-CoV-2 nucleic acid (RNA) and SARS-CoV-2 immunoglobulin antibodies (IgM and/or IgG). 2 Detection of virus RNA by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) is considered as the golden criteria of diagnosis. However, RNA molecular detection suffers from many limitations 3 : (a) It requires expensive equipment and trained technicians in a certified laboratory, (b) it usually takes more than 2 hours to generate results, and (c) it carries the risk of falsenegatives due to low viral loads in clinical specimens. 4 Serological testing of anti-SARS-CoV-2 IgG/IgM (has been used to diagnose illness, but its diagnostic efficacy remains unclear. 5 This study aims to summarize the diagnostic efficacy of the anti-SARS-CoV-2 IgG/IgM test in each study, the results of which can assist in the diagnosis of SARS-CoV-2. This meta-analysis was registered on PROSPERO (ID: CRD42020184771 Two reviewers assess the quality of studies enrolled in this study using QUADAS-2, a tool for quality assessment of diagnostic accuracy studies, 6 to assess the risk of bias. We assessed statistical heterogeneity and publication bias using the I 2 statistic, Q test, and Deeks' test, respectively. Deeks' funnel plots were drawn to evaluate the risk of publication bias. We performed a meta-analysis by the "meta4diag" package (version We evaluated the quality of the 22 included studies according to QUADAS-2 guidelines. Bias in each study was assessed as "low risk of bias," "high risk of bias," and "unclear risk of bias." As shown in and RT-PCR), which limits the ability to conclude on study quality. The P values of the Q test were all less than .01, accompanied by I 2 > 50%. The I 2 ranging from 69.85% to 93.52% in the evaluation of anti-SARS-CoV-2 IgG and/or IgM showed the heterogeneity of the statistical significance. The result of this bivariate random-effects meta-analysis is shown in Table 2 . In the selected studies, the detection methods of anti-SARS-CoV-2 IgG and IgM included gold immunochromatography assay immunosorbent assay (ELISA). We performed subgroup analyses among these three groups. The results showed that the sensitivity of IgG and IgM using ELISA were lower than those using GICA or CLIA. However, the meta-regression analysis results showed that no significant differences in sensitivity and specificity were observed among these groups (P > .05) ( Table 3) . Additionally, the I 2 for the sensitivity of IgG, IgM, and IgG/IgM in the subgroup analyses were more than 50%. And the I 2 for the specificity of IgG using CLIA (0%) and IgG or IgM using GICA (23.78%) declined significantly. As shown in Figure S2 , we generated crosshair plots and performed influence analysis to identify outliers. Two study 3, 11 in the metaanalysis of IgG were identified as outliers. After excluding the outliers, the overall pooled sensitivity of IgG slightly increased from 0.85 to 0.87, specificity and AUC did not change. Moreover, the I 2 for sensitivity and specificity slightly declined from 93.52% and 69.85% to 90.53% and 66.63%, respectively. These results suggested that the outliers contributed a little heterogeneity in this meta-analysis. This review has several limitations. First, none of the persons with cover, cough, and runny nose of unknown origin was enrolled in the studies. Controls in all the included studies were proven without SARS-CoV-2, leading to an exaggerated specificity. Second, this meta-analysis had high heterogeneity. The bivariate random-effects model was applied to weaken influences by heterogeneity. And also, we performed subgroup and sensitivity analysis to explore the source of heterogeneity. Finally, all the patients included in this analysis were first infected with SARS-CoV-2, and the diagnostic efficiency of the specific immunoglobulin for reinfection of SARS-CoV-2 is unclear. This meta-analysis showed that the detection of anti-SARS-CoV-2 IgG and IgM had high diagnostic efficiency to assist the diagnosis of SARS-CoV-2. It was suitable for patients with symptoms for at least 5 days. T A B L E 3 The pooled sensitivity and specificity of subgroup meta-analyses and meta-regression Real-time updates on the global epidemic of COVID-19 The laboratory diagnosis of COVID-19 infection: current issues and challenges Development and clinical application of a rapid IgM-IgG combined antibody test for SARS-CoV-2 infection diagnosis Potential rapid diagnostics, vaccine and therapeutics for 2019 novel coronavirus (2019-nCoV): a systematic review SARS-CoV-2 serology: much hype, little data QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies Rapid point-of-care testing for SARS-CoV-2 in a community screening setting shows low sensitivity Evaluation of a COVID-19 IgM and IgG rapid test; an efficient tool for assessment of past exposure to SARS-CoV-2 Diagnostic accuracy of an automated chemiluminescent immunoassay for anti-SARS-CoV-2 IgM and IgG antibodies: an Italian experience Diagnostic value and dynamic variance of serum antibody in coronavirus disease 2019 Evaluation of nucleocapsid and spike protein-based ELISAs for detecting antibodies against SARS-CoV-2 Serological immunochromatographic approach in diagnosis with SARS-CoV-2 infected COVID-19 patients Profile of IgG and IgM antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Clinical evaluation of a rapid colloidal gold immunochromatography assay for SARS-Cov-2 IgM/IgG Reliability and usefulness of a rapid IgM-IgG antibody test for the diagnosis of SARS-CoV-2 infection: A preliminary report Antibody detection and dynamic characteristics in patients with COVID-19 Clinical application value of immunochromatography in detecting SARS-CoV-2 IgM and IgG antibodies The clinical value of GICA in the detection of serum antibodies to SARS-CoV-2 Preliminary study of serum 2019-nCoV IgM and IgG antibodies in the diagnosis of Novel Coronavirus pneumonia Value of SARS-CoV-2 IgM/IgG antibody detection in diagnosis of new coronavirus pneumonia Clinical application value of novel coronavirus antibody detection in the diagnosis of COVID-19 Detection of specific SARS-CoV-2 IgM and IgG antibodies in COVID-19 and its clinical application Comparison between chemiluminescence and colloidal gold method in the detection of 2019 novel coronavirus specific antibodies and the value in the COVID-19 diagnosis and treatment Comparision of chemiluminescence and ELISA kits for SARS-CoV-2 IgM/IgG detection The diagnostic value of joint detection of serum IgMand IgG antibodies to 2019-nCoV in 2019-nCoV infection Clinical evaluation and application of detection for SARS-CoV-2 IgM and IgG antibodies with colloidal gold immunochromatography assay Clinical evaluation of different detection methods of SARS-CoV-2 IgM/IgG antibody in the COVID-19 diagnosis Still much to learn about the diagnostic role of SARS-CoV-2 antibody detection COVID-19: a meta-analysis of diagnostic test accuracy of commercial assays registered in Brazil Profiling early humoral response to diagnose novel coronavirus disease (COVID-19) Longitudinal change of SARS-Cov2 antibodies in patients with COVID-19 Antibody responses to SARS-CoV-2 in patients of novel coronavirus disease Different longitudinal patterns of nucleic acid and serology testing results based on disease severity of COVID-19 patients New IgM seroconversion and positive RT-PCR test after exposure to the virus in recovered COVID-19 patient COVID-19 reinfection: myth or truth? Laboratory findings of COVID-19: a systematic review and meta-analysis Diagnostic efficacy of anti-SARS-CoV-2 IgG/IgM test for COVID-19: A meta-analysis The authors thank Prof Hui Chen for his support and guidance. This study was supported by the First Affiliated Hospital of Chongqing Medical University (grant number HLJJ2014-21). The authors declare that there are no conflict of interests.