SARS-CoV-2 antibody responses associate with sex, age and disease severity in previously uninfected people admitted to hospital with COVID-19: An ISARIC4C prospective study

Abstract

The SARS-CoV-2 pandemic enables the analysis of immune responses induced against a novel coronavirus infecting immunologically naïve individuals. This provides an opportunity for analysis of immune responses and associations with age, sex and disease severity. Here we measured an array of solid-phase binding antibody and viral neutralising Ab (nAb) responses in participants (n=337) of the ISARIC4C cohort and characterised their correlation with peak disease severity during acute infection and early convalescence. Overall, the responses in a Double Antigen Binding Assay (DABA) for antibody to the receptor binding domain (anti-RBD) correlated well with IgM as well as IgG responses against viral spike, S1 and nucleocapsid protein (NP) antigens. DABA reactivity also correlated with nAb. As we and others reported previously, there is greater risk of severe disease and death in older men, whilst the sex ratio was found to be equal within each severity grouping in younger people. In older males with severe disease (mean age 68 years), peak antibody levels were found to be delayed by one to two weeks compared with women, and nAb responses were delayed further. Additionally, we demonstrated that solid-phase binding antibody responses reached higher levels in males as measured via DABA and IgM binding against Spike, NP and S1 antigens. In contrast, this was not observed for nAb responses. When measuring SARS-CoV-2 RNA transcripts (as a surrogate for viral shedding) in nasal swabs at recruitment, we saw no significant differences by sex or disease severity status. However, we have shown higher antibody levels associated with low nasal viral RNA indicating a role of antibody responses in controlling viral replication and shedding in the upper airway. In this study, we have shown discernible differences in the humoral immune responses between males and females and these differences associate with age as well as with resultant disease severity.

Analysis of related factors of plasma antibody levels in patients with severe and critical COVID-19

“…Clemens A. Schmitt et al 6 reported COVID-19 brought bigger influence in the elderly based on cellular senescence. Furthermore, Parker et al's investigation revealed that individuals aged 41–60 years exhibited higher plasma antibody levels than other age groups 12 . Our finding was consistent with these reported studies.…”

Correlation between Clinical Characteristics and Antibody Levels in COVID-19 Convalescent Plasma Donor Candidates

“…It is important to note that antibody response is delayed in patients with severe COVID-19 [ 33 ]. However, Parker et al found that although antibody levels in patients with severe disease began to rise one to two weeks later than in patients with moderate disease, they later reached similar levels [ 34 ]. Recently, Körper et al reported a trend toward a better outcome in patients receiving CCP from donors with more than three symptoms compared to controls, but the difference was not significant ( p = 0.061) [ 12 ].…”

Quantifying neutralising antibody responses against SARS-CoV-2 in dried blood spots (DBS) and paired sera

“…The ancestral SARS-CoV-2 S glycoprotein (Accession MN908947) was cloned into the pCDNA3.1 expression plasmid (produced by GeneArt Gene Synthesis) and was used in generating PVP stocks via a lentiviral system to generate single-cycle infectious viral particles as previously described 52 – 54 . HEK293T cells (5.0 × 10 5 in each well of a 6-well tissue culture flask) (Corning) were grown in 2.0 mL of complete DMEM overnight.…”

“…SARS-CoV-2 S enveloped PVP was used in neutralisation assays as previously described 54 . Serum samples from participants were serially diluted twofold with complete DMEM, and 28 µL serum dilution was incubated with 420 µL diluted SARS-CoV-2 PVP for 30 min at RT.…”