Test performance evaluation of SARS-CoV-2 serological assays

Abstract

Background Serological tests are crucial tools for assessments of SARS-CoV-2 exposure, infection and potential immunity. Their appropriate use and interpretation require accurate assay performance data. Method We conducted an evaluation of 10 lateral flow assays (LFAs) and two ELISAs to detect anti-SARS-CoV-2 antibodies. The specimen set comprised 128 plasma or serum samples from 79 symptomatic SARS-CoV-2 RT-PCR-positive individuals; 108 pre-COVID-19 negative controls; and 52 recent samples from individuals who underwent respiratory viral testing but were not diagnosed with Coronavirus Disease 2019 (COVID-19). Samples were blinded and LFA results were interpreted by two independent readers, using a standardized intensity scoring system. Results Among specimens from SARS-CoV-2 RT-PCR-positive individuals, the percent seropositive increased with time interval, peaking at 81.8-100.0% in samples taken >20 days after symptom onset. Test specificity ranged from 84.3-100.0% in pre-COVID-19 specimens. Specificity was higher when weak LFA bands were considered negative, but this decreased sensitivity. IgM detection was more variable than IgG, and detection was highest when IgM and IgG results were combined. Agreement between ELISAs and LFAs ranged from 75.7-94.8%. No consistent cross-reactivity was observed. Conclusion Our evaluation showed heterogeneous assay performance. Reader training is key to reliable LFA performance, and can be tailored for survey goals. Informed use of serology will require evaluations covering the full spectrum of SARS-CoV-2 infections, from asymptomatic and mild infection to severe disease, and later convalescence. Well-designed studies to elucidate the mechanisms and serological correlates of protective immunity will be crucial to guide rational clinical and public health policies.

Sensitivity and specificity of a rapid test for assessment of exposure to SARS-CoV-2 in a community-based setting in Brazil

“…Although the diagnostic accuracy of the current study was lower than the original study, this was not unexpected given the geographic and genetic differences between the study populations. Our results are in accordance with a validation study performed in the United States, in which the sensitivity ranged from 40% to 82% (5 and >20 days after the symptoms onset, respectively) while the specificity was 99.06% [19].…”

Lessons from a rapid systematic review of early SARS-CoV-2 serosurveys

“…7 Meanwhile, a variety of groups have conducted independent evaluations of SARS-CoV-2 antibody tests utilizing different volumes and types of sera in their reference panels. [13][14][15] Investigators from UCSF included SARS-CoV-2 positive sera at multiple time points from infection and negative sera as part of the test evaluation for their study, 13 while Danish study investigators included robust assessment of cross-reactivity with other coronaviruses and respiratory viruses. 14 FINDDx is leading an ongoing independent evaluation program of 27 rapid diagnostic tests and seven ELISAs.…”

Asthma and COVID-19 in children – a systematic review and call for data

“…None of the BioRxiv posts were relevant to our topic. Of the 86 pre-prints in MedRxiv, 14 non-duplicate studies included information on asthma [27][28][29][30][31][32][33][34][35][36][37][38][39][40], but none of them included specific information in children.…”