TY - JOUR
T1 - SARS-CoV-2 antibody responses associate with sex, age and disease severity in previously uninfected people admitted to hospital with COVID-19
T2 - An ISARIC4C prospective study
AU - ISARIC4C Investigators
AU - Parker, Eleanor
AU - Thomas, Jordan
AU - Roper, Kelly J.
AU - Ijaz, Samreen
AU - Edwards, Tansy
AU - Marchesin, Federica
AU - Katsanovskaja, Ksenia
AU - Lett, Lauren
AU - Jones, Christopher
AU - Hardwick, Hayley E.
AU - Davis, Chris
AU - Vink, Elen
AU - McDonald, Sarah E.
AU - Moore, Shona C.
AU - Dicks, Steve
AU - Jegatheesan, Keerthana
AU - Cook, Nicola J.
AU - Hope, Joshua
AU - Cherepanov, Peter
AU - McClure, Myra O.
AU - Baillie, J. Kenneth
AU - Openshaw, Peter J.M.
AU - Turtle, Lance
AU - Ho, Antonia
AU - Semple, Malcolm G.
AU - Paxton, William A.
AU - Tedder, Richard S.
AU - Pollakis, Georgios
N1 - Publisher Copyright:
Copyright © 2023 Parker, Thomas, Roper, Ijaz, Edwards, Marchesin, Katsanovskaja, Lett, Jones, Hardwick, Davis, Vink, McDonald, Moore, Dicks, Jegatheesan, Cook, Hope, Cherepanov, McClure, Baillie, Openshaw, Turtle, Ho, Semple, Paxton, Tedder, Pollakis and ISARIC4C Investigators.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - COVID-19
KW - SARS-CoV-2
KW - disease
KW - immunology
KW - neutralisation
KW - serology
KW - virus
UR - http://www.scopus.com/inward/record.url?scp=85152401588&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2023.1146702
DO - 10.3389/fimmu.2023.1146702
M3 - Article
C2 - 37056776
AN - SCOPUS:85152401588
SN - 1664-3224
VL - 14
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 1146702
ER -