Serological markers of SARS-CoV-2 infection; anti-nucleocapsid antibody positivity may not be the ideal marker of natural infection in vaccinated individuals

Dear Editor, We write in response to correspondence from Whitaker et al. in this Journal (1). The authors demonstrate increases in seropositivity for SARS-CoV-2 antibodies against the spike protein as the roll out of COVID-19 vaccines continues, whilst parallel assessment of nucleocapsid antibodies remained stable. This study is an example of the use of parallel assessment of spike (S) and nucleocapsid (N) antibodies to discriminate between natural infection and vaccine related seropositivity (2) (3). This approach remains attractive, but as the pandemic rolls on it is worth considering the paucity of evidence about the impact of vaccination on antibody production in response to a subsequent natural infectio

Table_1_Point of care detection of SARS-CoV-2 antibodies and neutralisation capacity—lateral flow immunoassay evaluation compared to commercial assay to inform potential role in therapeutic and surveillance practices.DOCX

IntroductionAs the COVID-19 pandemic moves towards endemic status, testing strategies are being de-escalated. A rapid and effective point of care test (POCT) assessment of SARS-CoV-2 immune responses can inform clinical decision-making and epidemiological monitoring of the disease. This cross-sectional seroprevalence study of anti-SARS-CoV-2 antibodies in Irish healthcare workers assessed how rapid anti-SARS-CoV-2 antibody testing can be compared to a standard laboratory assay, discusses its effectiveness in neutralisation assessment and its uses into the future of the pandemic.MethodsA point of care lateral flow immunoassay (LFA) detecting anti-SARS-CoV-2 spike (S)-receptor binding domain (RBD) neutralising antibodies (Healgen SARS-CoV-2 neutralising Antibody Rapid Test Cassette) was compared to the Roche Elecsys/-S anti-SARS-CoV-2 antibody assays and an in vitro surrogate neutralisation assay. A correlation between anti-spike (S), anti-nucleocapsid (N) titres, and in vitro neutralisation was also assessed.Results1,777 serology samples were tested using Roche Elecsys/-S anti-SARS-CoV-2 assays to detect total anti-N/S antibodies. 1,562 samples were tested using the POC LFA (including 50 negative controls), and 90 samples were tested using an in vitro ACE2-RBD binding inhibition surrogate neutralisation assay. The POCT demonstrated 97.7% sensitivity, 100% specificity, a positive predictive value (PPV) of 100%, and a negative predictive value (NPV) of 61% in comparison to the commercial assay. Anti-S antibody titres determined by the Roche assay stratified by the POC LFA result groups demonstrated statistically significant differences between the “Positive” and “Negative” LFA groups (p ConclusionHigh sensitivity, specificity, and PPV were demonstrated for the POC LFA for the detection of anti-S-RBD antibodies in comparison to the commercial assay. The LFA was not a reliable determinant of the neutralisation capacity of identified antibodies. POC LFA are useful tools in sero-epidemiology settings, pandemic preparedness and may act as supportive tools in treatment decisions through the rapid identification of anti-Spike antibodies.</p

Prevalence of antibodies to SARS-CoV-2 in Irish Hospital Healthcare Workers

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