Longitudinal Analysis and Comparison of Six Serological Assays up to Eight Months Post-COVID-19 Diagnosis

Abstract

Background: There is much data available concerning the initiation of the immune response after SARS-CoV-2 infection, but long-term data are scarce. Methods: We thus longitudinally evaluated and compared the total and neutralizing immune response of 61 patients to SARS-CoV-2 infection up to eight months after diagnosis by RT–PCR using several commercial assays. Results: Among the 208 samples tested, the percentage of seropositivity was comparable between assays up to four months after diagnosis and then tended to be more heterogeneous between assays (p < 0.05). The percentage of patients with a neutralizing titer decreased from 82% before two months postdiagnosis to 57% after six months. This decrease appeared to be more marked for patients under 65 years old and those not requiring hospitalization. The percentage of serology reversion at 6 months was from 11% with the WANTAI total assay to over 39% with the ABBOTT IgG assay. The neutralizing antibody titers decreased in parallel with the decrease of total antibody titers, with important heterogeneity between assays. Conclusions: In conclusion, serological tests show equivalent sensitivity in the first months after the diagnosis of SARS-CoV-2 infection, but their performance later, postinfection, must be considered when interpreting the results.

Development and Evaluation of a Set of Spike and Receptor Binding Domain-Based Enzyme-Linked Immunosorbent Assays for SARS-CoV-2 Serological Testing

“…A first performance test was conducted with a large number of serum samples from COVID-19 patients collected at different times after the onset of COVID-19 symptoms. The results indicated good correspondence between IgG titers and progression of the immune response, in agreement with reports on other serological tests based on ELISA or automated assays [30,31]. A second performance test conducted at InDRE confirmed that UDITEST-V2G ® has high sensitivity (99.33%) and specificity (97.82%) with no interference from other viral infections.…”

A multiplex serological assay for the characterization of IgG immune response to SARS-CoV-2

“…Gillot et al evaluated the CoviDiag ® assay and concluded that the combination of several antigens in the same test improves the overall specificity and sensitivity of the test [ 17 ]. Similarly, in our previous work based on the same set of sample, we have found equivalent to improved diagnostic performances, especially for ancient infections, for the CoViDiag ® multiplex IgG assay compared to other simplex IgG commercial assays [ 13 ]. Is is now generally admitted that antibody levels are weaker for asymptomatic and mild form of the disease and can decrease over time.…”

“…The CoViDiag assay algorithm adapts the cut-offs depending on the number of different IgGs detected to deliver SARS-CoV-2 positivity status, and maintain diagnostic sensitivity and specificity performances over time. Those results may explain our previous observations on the same cohort [13], where we have observed that the CoViDiag 1 diagnostic sensitivity performance remained more stable over time than for two other commercial references of simplex IgG immunoassay (Abbot 1 and Euroimmun 1 IgG assays, based on the NP and the S1 antigen, respectively).…”

“…Briefly, we used n = 209 samples collected between March and April 2020 from n = 61 patients (27 hospitalized patients and 34 non-hospitalized patients) with PCR-confirmed SARS-CoV-2 infections to perform immunoassay and virus seroneutralization test as already described in Aubry et al [ 13 ]. All samples have been tested according to manufacturer’s instruction on the CoViDiag ® serological assay and the raw results are available in supplementary data.…”

“…for ancient infections, for the CoViDiag 1 multiplex IgG assay compared to other simplex IgG commercial assays [13]. Is is now generally admitted that antibody levels are weaker for asymptomatic and mild form of the disease and can decrease over time.…”