Diagnostic performance of seven rapid IgG/IgM antibody tests and the Euroimmun IgA/IgG ELISA in COVID-19 patients

Abstract

Objectives: To evaluate the diagnostic performance of seven rapid IgG/IgM tests and the Euroimmun IgA/ IgG ELISA for antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in COVID-19 patients. Methods: Specificity was evaluated in 103 samples collected before January 2020. Sensitivity and time to seropositivity was evaluated in 167 samples from 94 patients with COVID-19 confirmed with RT-PCR on nasopharyngeal swab. Results: Specificity (confidence interval) of lateral flow assays (LFAs) was 91.3% (84.0e95.5) for IgM, 90.3% (82.9e94.8) for IgG, and 85.4% (77.2e91.1) for the combination IgM OR IgG. Specificity of the ELISA was 96.1% (90.1e98.8) for IgG and only 73.8% (64.5e81.4) for IgA. Sensitivity 14e25 days after the onset of symptoms was between 92.1% (78.5e98.0) and 100% (95.7e100) for IgG LFA compared to 89.5% (75.3e96.4) for IgG ELISA. Positivity of IgM OR IgG for LFA resulted in a decrease in specificity compared to IgG alone without a gain in diagnostic performance, except for VivaDiag. The results for IgM varied significantly between the LFAs with an average overall agreement of only 70% compared to 89% for IgG. The average dynamic trend to seropositivity for IgM was not shorter than for IgG. At the time of hospital admission the sensitivity of LFA was <60%. Conclusions: Sensitivity for the detection of IgG antibodies 14e25 days after the onset of symptoms was 92.1% for all seven LFAs compared to 89.5% for the IgG ELISA. The results for IgM varied significantly, and including IgM antibodies in addition to IgG for the interpretation of LFAs did not improve the diagnostic performance.

Performance evaluation of five ELISA kits for detecting anti-SARS-COV-2 IgG antibodies

“…However, this was not possible here as we were testing sensitivity and specificity in specific time frames. Considering that these borderline samples were collected from RT-PCR-positive patients, borderline results were considered positive, consistent with similar studies ( Van Elslande et al, 2020 , Meyer et al, 2020 ). Interestingly, only one pre-pandemic sample with positive anti-MERS-CoV IgG antibodies was found positive by four ELISA kits ( Table 3 and S3), except Lionex, which demonstrated the highest specificity at 98.6% ( Figure 1 ).…”

“…A microplate reader, Epoch 2 microplate spectrophotometer (Bio-Tek, Italy) was used to read the optical density (OD) in all ELISA reactions. Borderline results were considered positive ( Van Elslande et al, 2020 , Meyer et al, 2020 ).…”

“…Since the start of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak in December 2019 in Wuhan, China, the virus has rapidly spread and become a major public health concern all over the world ( Van Elslande et al, 2020 , Ong et al, 2020 ). As of July 1, 2020, the virus has caused more than 10 million confirmed infections and over 500,000 reported deaths ( Organization, W.H., 2020 ).…”

“…Specific antibodies against SARS-CoV-2 can be detected as early as 4-7 days in approximately 40% of COVID-19 patients, with seroconversion rates reaching more than 90% by day 14 ( Zhao et al, 2020 ). Therefore, serology could be used as a complementary test to RT-PCR to improve the diagnostic sensitivity, particularly in suspected COVID-19 individuals with negative RT-PCR results or those with no respiratory sample collected during the acute phase of illness ( Van Elslande et al, 2020 , Ong et al, 2020 ).…”

Meta-analysis of diagnostic performance of serology tests for COVID-19: impact of assay design and post-symptom-onset intervals

“…LFIA tests could prove useful in the emergency room, ambulatory and outpatient settings rather than simply abandoned for its relatively poor performance. We didn’t pool our analysis based on assays from different companies, but other head-to-head studies had shown a variable accordance between different assays within only a small group of participants 28 , 38 , 46 , 55 . A recent study showed a high accordance between Abbott Architect, DiaSorin Liaison, Ortho VITROS, and Euroimmun among 1200 serum samples 56 .…”