key: cord-0952893-cm88mpme
authors: Schulte-Pelkum, Johannes
title: Comment on Favresse et al. Persistence of Anti-SARS-CoV-2 Antibodies Depends on the Analytical Kit: A Report for Up to 10 Months after Infection. Microorganisms 2021, 9, 556
date: 2021-08-23
journal: Microorganisms
DOI: 10.3390/microorganisms9081786
sha: bddccc761d5b310b3d0f067ae248e9040785d699
doc_id: 952893
cord_uid: cm88mpme

We thank the authors of the article [...].

We thank the authors of the article [1] for their observations and recommendations, discussed in the context of the recommended cut-off for the EliA SARS-CoV-2-Sp1 IgG test (referred to by the authors as Phadia S1 IgG). The authors consider a redefinition of the manufacturer's cut-off in order to increase the sensitivity of the test.

The EliA SARS-CoV-2-Sp1 IgG assay is intended to identify individuals with an adaptive immune response to a recent or prior SARS-CoV-2 infection, with a focus on high specificity. High specificity for antibody tests against SARS-CoV-2 is particularly important when used in individuals who have not had a documented, PCR-confirmed SARS-CoV-2 infection. The decision on the optimal cut-off for the EliA SARS-CoV-2-Sp1 IgG test was taken in the early phase of the pandemic, with an overall infection rate of no more than 0.2%. Even today, with a global case number of 148 million [2] (resembling approx. 1.9% of the world population), the need for high specificity is evident: a diagnostic test with a high specificity of 98.1% would result in an equal amount of false and true positive test results.

In order to develop the EliA SARS-CoV-2-Sp1 IgG assay, we tested 163 samples (serum and lithium heparin) from PCR-confirmed COVID-19 patients with the EliA SARS-CoV-2-Sp1 IgG test and set the cut-off to 10 EliA U/mL (low limit of equivocal zone set to 7 EliA U/mL). Positive percent agreement (sensitivity) was observed at 97.6% (80/82) (95% CI: 91.5-99.3%) >15 days post symptom onset (Table 1) . Specificity was determined with a set of 340 serum samples collected before December 2019 from healthy blood donors. Negative percent agreement (specificity) was observed at 99.4% (338/340) (95% CI: 97.9-99.8%) using the low limit of the equivocal zone, as shown in Table 2 [3] . We recognize that in cases where an individual has a documented PCR-confirmed SARS-CoV-2 infection, high specificity may be less of a concern. To address questions depending on high sensitivity rather than on high specificity, including longitudinal studies of patients with a known infection history, the cut-off can be set to 97.9% specificity at 0.7 EliA U/mL, the detection limit of the test. This modification resulted in a sensitivity of >99% in an internal study with 694 longitudinal samples 2-27 weeks post symptom onset (Tables 3 and 4) . The control group consisted of 478 samples including 330 healthy blood donors, reflecting all ethnicities in the US, and 148 infectious disease samples. An interesting observation in the long-term monitoring of anti-SARS-CoV-2 immunity was that, despite a significant drop in anti-Spike 1 IgG titers over a period of up to 6 months, strong virus-neutralizing activity was still measurable with an ACE2 receptor binding inhibition assay. These findings may indicate the importance of including assays to measure the neutralizing potential of anti-SARS-CoV-2 antibodies in long-term followup studies. This approach could help to answer the perennial question of immunity to reinfection and its longevity.

Antibodies Depends on the Analytical Kit: A Report for Up to 10 Months after Infection. Microorganisms 2021

Johns Hopkins University as of 04/27/2021, 3:21 nachm

Phadia EliA SARS-CoV-2-Sp1 IgG IFU