SARS-CoV-2 Antibody responses do not predict COVID-19 disease severity

Abstract

Background: Initial reports indicate adequate performance of some serological-based SARS-CoV-2 assays. However, additional studies are required to facilitate interpretation of results, including how antibody levels impact immunity and disease course. Methods: In this study, a total of 968 subjects were tested for IgG antibodies reactive to SARS-CoV-2. We confirmed analytic specificity using 656 plasma samples from healthy donors, 49 sera from patients with rheumatic disease, and 90 specimens from individuals positive for PCR-based respiratory viral panel. One-hundred seventy-three cases of confirmed or suspected SARS-CoV-2 were tested for IgG. A subgroup of 37 SARS-CoV-2 PCR-positive cases was tested for nucleocapsid-specific IgM antibody using an in-house developed microarray method. Antibody levels were compared between disease severity groups. Results: All specificity specimens were negative for SARS-CoV-2 IgG antibodies (0/656, 0%). Cross reactivity was not detected in specimens with antinuclear antibodies and rheumatoid factor, or cases with previous diagnosis of viral infection including human coronavirus. Positive agreement of IgG with PCR was 83% of samples confirmed to be more than 14 days from symptom onset, with less than 100% sensitivity attributable to a case with severe immunosuppression. Virus-specific IgM was positive in a higher proportion of cases less than 3 days from symptom onset. No association was observed between mild and severe disease course with respect to IgG and IgM levels. Conclusions: The studied SARS-CoV-2 IgG assay had 100% specificity and no adverse cross-reactivity. Index values of IgG and IgM antibodies did not predict disease severity in our patient population.

Age-severity matched cytokine profiling reveals specific signatures in Covid-19 patients

“…The generation of IgG antibodies against SARS-CoV-2 proteins might represent an applicable parameter for COVID-19 patient stratification. Nevertheless, the parallel between SARS-CoV2 seropositivity and the clinical outcome is still a matter of investigation 14,15 . In our cohort, 34% of the patients (15/44 patients) showed positive IgG titer against the SARS-CoV-2 spike protein at the admission time (AT).…”

High titers of multiple antibody isotypes against the SARS-CoV-2 spike receptor-binding domain and nucleoprotein associate with better neutralization

“…Moreover, we found that individuals who had IgG in combination with IgM and IgA against the RBD had the greatest neutralization capacity, suggesting that the generation of combinations of antibody isotypes against the RBD may provide the best neutralization. It has been shown that severity of disease can play an important role in the antibody response and it may be that in these individuals, disease is a driver for multiple isotypes and increased neutralization 15,34 . Thus, understanding how enhanced disease burden leads to the generation of multiple neutralizing isotypes will be crucial for vaccine development.…”

Multicenter evaluation of two chemiluminescence and three lateral flow immunoassays for the diagnosis of COVID-19 and assessment of antibody dynamic responses to SARS-CoV-2 in Taiwan

“…We further included 194 control serum samples to evaluate the cross-reactivity and diagnostic specificity of the five antibody tests in this study: 70 from hospitalized patients with an acute respiratory infection (ARI) who tested negative ≥2 times using SARS-CoV-2 qRT-PCR and without any other confirmed aetiology for ARI collected in 2020, 50 from patients with ARI who tested negative ≥2 times using SARS-CoV-2 qRT-PCR and presence of specific microbiological aetiologies collected in 2020, 36 from patients who tested positive for any specific auto-antibody collected in 2020, and 38 from patients with pre-COVID-19 sera with presence of specific microbiological antigens or antibodies collected in 2019. Finally, control serum sample of positive result from any of the five serological tests was further examined if the presence of rheumatoid factor (RF) with Siemens N Latex RF Kit (Siemens BN™ II System) to examine the possibility of cross reaction between RF and anti-SARS-CoV-2 antibody [ 24 , 25 ].…”