ABSTRACT
In the context of an unprecedented shortage of nasopharyngeal swabs (NPS) or sample transport media during the coronavirus disease 2019 (COVID-19) crisis, alternative methods for sample collection are needed. To address this need, we validated a cell culture medium as a viral transport medium, and compared the analytical sensitivity of SARS-CoV-2 real-time RT-PCR in nasal wash (NW), oropharyngeal swab (OPS) and NPS specimens. Both the clinical and analytical sensitivity were comparable in these three sample types. OPS and NW specimens may therefore represent suitable alternatives to NPS for SARS-CoV-2 detection.
ABSTRACT
ObjectivesTo validate the diagnostic accuracy of a Euroimmun SARS-CoV-2 IgG and IgA immunoassay for COVID-19. MethodsIn this unmatched (1:1) case-control validation study, we used sera of 181 laboratory-confirmed SARS-CoV-2 cases and 176 controls collected before SARS-CoV-2 emergence. Diagnostic accuracy of the immunoassay was assessed against a whole spike protein-based recombinant immunofluorescence assay (rIFA) by receiver operating characteristic (ROC) analyses. Discrepant cases between ELISA and rIFA were further tested by pseudo-neutralization assay. ResultsCOVID-19 patients were more likely to be male and older than controls, and 50.3% were hospitalized. ROC curve analyses indicated that IgG and IgA had high diagnostic accuracies with AUCs of 0.992 (95% Confidence Interval [95%CI]: 0.986-0.996) and 0.977 (95%CI: 0.963-0.990), respectively. IgG assays outperformed IgA assays (p=0.008). Taking an assessed 15% inter-assay imprecision into account, an optimized IgG ratio cut-off > 1.5 displayed a 100% specificity (95%CI: 98-100) and a 100% positive predictive value (95%CI: 97-100). A 0.5 cut-off displayed a 97% sensitivity (95%CI: 93-99) and a 97% negative predictive value (95%CI: 93-99). Substituting these thresholds for the manufacturers, improved assay performance, leaving 12% of IgG ratios indeterminate between 0.5-1.5. ConclusionsThe Euroimmun assay displays a nearly optimal diagnostic accuracy using IgG against SARS-CoV-2 in patient samples, with no obvious gains from IgA serology. The optimized cut-offs are fit for rule-in and rule-out purposes, allowing determination of whether individuals in our study population have been exposed to SARS-CoV-2 or not. IgG serology should however not be considered as a surrogate of protection at this stage.
