Disease Severity, Fever, Age, and Sex Correlate With SARS-CoV-2 Neutralizing Antibody Responses

Abstract

Clinical trials on the use of COVID-19 convalescent plasma remain inconclusive. While data on safety is increasingly available, evidence for efficacy is still sparse. Subgroup analyses hint to a dose-response relationship between convalescent plasma neutralizing antibody levels and mortality. In particular, patients with primary and secondary antibody deficiency might benefit from this approach. However, testing of neutralizing antibodies is limited to specialized biosafety level 3 laboratories and is a time- and labor-intense procedure. In this single center study of 206 COVID-19 convalescent patients, clinical data, results of commercially available ELISA testing of SARS-CoV-2 spike-IgG and –IgA, and levels of neutralizing antibodies, determined by plaque reduction neutralization testing (PRNT), were analyzed. At a medium time point of 58 days after symptom onset, only 12.6% of potential plasma donors showed high levels of neutralizing antibodies (PRNT50 ≥ 1:320). Multivariable proportional odds logistic regression analysis revealed need for hospitalization due to COVID-19 (odds ratio 6.87; p-value 0.0004) and fever (odds ratio 3.00; p-value 0.0001) as leading factors affecting levels of SARS-CoV-2 neutralizing antibody titers in convalescent plasma donors. Using penalized estimation, a predictive proportional odds logistic regression model including the most important variables hospitalization, fever, age, sex, and anosmia or dysgeusia was developed. The predictive discrimination for PRNT50 ≥ 1:320 was reasonably good with AUC: 0.86 (with 95% CI: 0.79–0.92). Combining clinical and ELISA-based pre-screening, assessment of neutralizing antibodies could be spared in 75% of potential donors with a maximal loss of 10% of true positives (PRNT50 ≥ 1:320).

Utility of Different Surrogate Enzyme-Linked Immunosorbent Assays (sELISAs) for Detection of SARS-CoV-2 Neutralizing Antibodies

“…Our observation of high SARS-CoV-2 specific antibody titers in individuals reporting side effects after receiving the COVID-19 vaccine is in concordance with a positive correlation between disease severity after SARS-CoV-2 infection and level of detected antibodies [ 30 , 31 , 32 ]. However, overall negative economic, individual, and health system consequences after SARS-CoV-2 infection outweigh reported side effects after vaccination by far.…”

Complement activation induces excessive T cell cytotoxicity in severe COVID-19

“…Detection of IgG and IgA to the S1 domain of the SARS-CoV-2 spike (S) protein were assessed by anti-SARS-CoV-2 S1 IgG ELISAs (Euroimmun AG, Germany), as described elsewhere (Schlickeiser et al, 2020). Serum samples were tested at a 1:101 dilution and optical density (OD) ratios were calculated by dividing the OD at 450 nm by the OD of a calibrator sample tested within each run.…”

Reactive T Cells in Convalescent COVID-19 Patients With Negative SARS-CoV-2 Antibody Serology

“…Persistence of specific IgG antibodies to SARS-CoV-2 in serum correlates with clinical severity during acute infection and antibodies were found to decline more rapidly in asymptomatic patients ( 9 ). While high neutralizing antibody titer are only found in the minority of convalescent patients ( 7 , 10 ), they were shown to correlate with numbers of virus-specific T cells ( 8 , 11 ). Moreover, in convalescent patients, polyfunctional SARS-CoV-2-specific T cells have been described, indicating the generation of a memory-like phenotype ( 6 , 12 , 13 ).…”