Antibody Course and Memory B-Cell Response in the First Year After Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

BACKGROUND: The possibility of repeat infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) raises questions regarding quality and longevity of the virus-induced immune response. METHODS: The antibody course and memory B-cell (MBC) response against SARS-CoV-2 proteins, influenza virus nucleoprotein (NP), and tetanus toxin were examined in adults with mild to moderate SARS-CoV-2 infection in the first year after infection. RESULTS: The concentration of SARS-CoV-2 receptor binding domain (RBD)-specific antibodies was low compared with the concentration of influenza virus NP-specific antibodies. The SARS-CoV-2 RBD antibody half-life increased from 95 days in the first 6 months to 781 days after 9-12 months. The SARS-CoV-2 NP antibody half-life increased from 88 to 248 days. Two thirds of the subjects had SARS-CoV-2-specific MBC responses 12 months after infection. The SARS-CoV-2 antibody levels correlated with the MBC frequency at 12 months. CONCLUSIONS: The low concentration of SARS-CoV-2 spike protein antibodies indicates that re-exposure to the virus or vaccination are required to use the B-cell immunity to full capacity. The existence of a robust SARS-CoV-2 MBC response at 12 months in most subjects and the substantially increasing antibody half-life provide evidence that the immune response is developing into long-term immunity. The early antibody reaction and the ensuing MBC response are interdependent.

Performance of a SARS CoV-2 antibody ELISA based on simultaneous measurement of antibodies against the viral nucleoprotein and receptor-binding domain.

SARS CoV-2 antibody assays measure antibodies against the viral nucleoprotein (NP) or spike protein. The study examined if testing of antibodies against both antigens increases the diagnostic sensitivity. Sera (N=98) from infected individuals were tested with ELISAs based on the NP, receptor-binding domain (RBD), or both proteins. The AUROCs were 0.958 (NP), 0.991 (RBD), and 0.992 (NP/RBD). The RBD- and NP/RBD-based ELISAs showed better performance than the NP-based assay. Simultaneous testing for antibodies against NP and RBD increased the number of true and false positives. If maximum diagnostic sensitivity is required, the NP/RBD-based ELISA is preferable. Otherwise, the RBD-based ELISA is sufficient.

Comparison of the measured values of quantitative SARS-CoV-2 spike antibody assays.

BACKGROUND: The concentration of antibodies against the SARS-CoV-2 spike protein is frequently being measured for clinical and epidemiological purposes. The aim of this study was to examine whether the results of different quantitative SARS-CoV-2 spike antibody assays are comparable. MATERIAL AND METHODS: The Siemens SARS-CoV-2 IgG, Abbott SARS-CoV-2 IgG II Quant, Roche ElecsysT Anti-SARS-CoV-2 S, and Euroimmun Anti-SARS-CoV-2-QuantiVac assay were compared with 110 sera from patients 6-9 months after SARS-CoV-2 infection and the WHO First International SARS-CoV-2 antibody standard 20/136. The antibody values were converted into WHO binding antibody units (BAU)/ml. The diagnostic sensitivity of the assays was determined and the antibody values were compared. RESULTS: The diagnostic sensitivity ranged from 57.3% (Euroimmun) to 100% (Roche). The antibody concentration values of different assays correlated with Pearson coefficients of correlation between 0.729 and 0.953. The geometric mean antibody values of the Abbott, Siemens and Euroimmun assay varied by a factor of 1.1-1.2. The geometric mean antibody values of the Roche assay were 2.4-2.8 times higher than those from the other assays. The assays yielded varying results with the WHO International antibody standard. CONCLUSIONS: The quantitative SARS-CoV-2 antibody assays from Abbott, Siemens, Roche and Euroimmun correlate strongly but differ in the antibody concentrations. Therefore, the same assay should be used when testing patients repeatedly. In addition, the name of the assay used and the manufacturer should be indicated along with the test results.

Sensitivity of SARS-CoV-2 antibody tests with late convalescent sera.

SARS-CoV-2-specific IgM antibodies wane during the first three months after infection and IgG antibody levels decline. This may limit the ability of antibody tests to identify previous SARS-CoV-2 infection at later time points. To examine if the diagnostic sensitivity of antibody tests falls off, we compared the sensitivity of two nucleoprotein-based antibody tests, the Roche Elecsis II Anti-SARS-CoV-2 and the Abbott SARS-CoV-2 IgG assay and three glycoprotein-based tests, the Abbott SARS-CoV-2 IgG II Quant, Siemens Atellica IM COV2T and Euroimmun SARS-CoV-2 assay with 53 sera obtained 6 months after SARS-CoV-2 infection. The sensitivity of the Roche, Abbott SARS-CoV-2 IgG II Quant and Siemens antibody assays was 94.3% (95% confidence interval (CI) 84.3-98.8%), 98.1 % (95% CI: 89.9-100%) and 100 % (95% CI: 93.3-100%). The sensitivity of the N-based Abbott SARS-CoV-2 IgG and the glycoprotein-based Euroimmun ELISA was 45.3 % (95% CI: 31.6-59.6%) and 83.3% (95% CI: 70.2-91.9%). The nucleoprotein-based Roche and the glycoprotein-based Abbott receptor binding domain (RBD) and Siemens tests were more sensitive than the N-based Abbott and the Euroimmun antibody tests (p = 0.0001 to p = 0.039). The N-based Abbott antibody test was less sensitive 6 months than 4-10 weeks after SARS-CoV-2 infection (p = 0.0001). The findings show that most SARS-CoV-2 antibody assays correctly identified previous infection 6 months after infection. The sensitivity of pan-Ig antibody tests was not reduced at 6 months when IgM antibodies have usually disappeared. However, one of the nucleoprotein-based antibody tests significantly lost diagnostic sensitivity over time.