tetano
Editor, Senior Moderator
Nat Commun
. 2021 Apr 1;12(1):2037.
doi: 10.1038/s41467-021-22236-7.
Systems serology detects functionally distinct coronavirus antibody features in children and elderly
Kevin J Selva[SUP] #[/SUP][SUP] 1 [/SUP], Carolien E van de Sandt[SUP] #[/SUP][SUP] 1 2 [/SUP], Melissa M Lemke[SUP] #[/SUP][SUP] 3 [/SUP], Christina Y Lee[SUP] #[/SUP][SUP] 3 [/SUP], Suzanne K Shoffner[SUP] #[/SUP][SUP] 3 [/SUP], Brendon Y Chua[SUP] 1 [/SUP], Samantha K Davis[SUP] 1 [/SUP], Thi H O Nguyen[SUP] 1 [/SUP], Louise C Rowntree[SUP] 1 [/SUP], Luca Hensen[SUP] 1 [/SUP], Marios Koutsakos[SUP] 1 [/SUP], Chinn Yi Wong[SUP] 1 [/SUP], Francesca Mordant[SUP] 1 [/SUP], David C Jackson[SUP] 1 [/SUP], Katie L Flanagan[SUP] 4 5 6 7 [/SUP], Jane Crowe[SUP] 8 [/SUP], Shidan Tosif[SUP] 9 10 11 [/SUP], Melanie R Neeland[SUP] 9 11 [/SUP], Philip Sutton[SUP] 9 11 [/SUP], Paul V Licciardi[SUP] 9 11 [/SUP], Nigel W Crawford[SUP] 9 12 [/SUP], Allen C Cheng[SUP] 13 14 [/SUP], Denise L Doolan[SUP] 15 [/SUP], Fatima Amanat[SUP] 16 17 [/SUP], Florian Krammer[SUP] 16 [/SUP], Keith Chappell[SUP] 18 [/SUP], Naphak Modhiran[SUP] 18 [/SUP], Daniel Watterson[SUP] 18 [/SUP], Paul Young[SUP] 18 [/SUP], Wen Shi Lee[SUP] 1 [/SUP], Bruce D Wines[SUP] 19 20 21 [/SUP], P Mark Hogarth[SUP] 19 20 21 [/SUP], Robyn Esterbauer[SUP] 1 22 [/SUP], Hannah G Kelly[SUP] 1 22 [/SUP], Hyon-Xhi Tan[SUP] 1 22 [/SUP], Jennifer A Juno[SUP] 1 [/SUP], Adam K Wheatley[SUP] 1 22 [/SUP], Stephen J Kent[SUP] 1 22 23 [/SUP], Kelly B Arnold[SUP] 3 [/SUP], Katherine Kedzierska[SUP] 24 [/SUP], Amy W Chung[SUP] 25 [/SUP]
Affiliations
Abstract
The hallmarks of COVID-19 are higher pathogenicity and mortality in the elderly compared to children. Examining baseline SARS-CoV-2 cross-reactive immunological responses, induced by circulating human coronaviruses (hCoVs), is needed to understand such divergent clinical outcomes. Here we show analysis of coronavirus antibody responses of pre-pandemic healthy children (n = 89), adults (n = 98), elderly (n = 57), and COVID-19 patients (n = 50) by systems serology. Moderate levels of cross-reactive, but non-neutralizing, SARS-CoV-2 antibodies are detected in pre-pandemic healthy individuals. SARS-CoV-2 antigen-specific Fc? receptor binding accurately distinguishes COVID-19 patients from healthy individuals, suggesting that SARS-CoV-2 infection induces qualitative changes to antibody Fc, enhancing Fc? receptor engagement. Higher cross-reactive SARS-CoV-2 IgA and IgG are observed in healthy elderly, while healthy children display elevated SARS-CoV-2 IgM, suggesting that children have fewer hCoV exposures, resulting in less-experienced but more polyreactive humoral immunity. Age-dependent analysis of COVID-19 patients, confirms elevated class-switched antibodies in elderly, while children have stronger Fc responses which we demonstrate are functionally different. These insights will inform COVID-19 vaccination strategies, improved serological diagnostics and therapeutics.
. 2021 Apr 1;12(1):2037.
doi: 10.1038/s41467-021-22236-7.
Systems serology detects functionally distinct coronavirus antibody features in children and elderly
Kevin J Selva[SUP] #[/SUP][SUP] 1 [/SUP], Carolien E van de Sandt[SUP] #[/SUP][SUP] 1 2 [/SUP], Melissa M Lemke[SUP] #[/SUP][SUP] 3 [/SUP], Christina Y Lee[SUP] #[/SUP][SUP] 3 [/SUP], Suzanne K Shoffner[SUP] #[/SUP][SUP] 3 [/SUP], Brendon Y Chua[SUP] 1 [/SUP], Samantha K Davis[SUP] 1 [/SUP], Thi H O Nguyen[SUP] 1 [/SUP], Louise C Rowntree[SUP] 1 [/SUP], Luca Hensen[SUP] 1 [/SUP], Marios Koutsakos[SUP] 1 [/SUP], Chinn Yi Wong[SUP] 1 [/SUP], Francesca Mordant[SUP] 1 [/SUP], David C Jackson[SUP] 1 [/SUP], Katie L Flanagan[SUP] 4 5 6 7 [/SUP], Jane Crowe[SUP] 8 [/SUP], Shidan Tosif[SUP] 9 10 11 [/SUP], Melanie R Neeland[SUP] 9 11 [/SUP], Philip Sutton[SUP] 9 11 [/SUP], Paul V Licciardi[SUP] 9 11 [/SUP], Nigel W Crawford[SUP] 9 12 [/SUP], Allen C Cheng[SUP] 13 14 [/SUP], Denise L Doolan[SUP] 15 [/SUP], Fatima Amanat[SUP] 16 17 [/SUP], Florian Krammer[SUP] 16 [/SUP], Keith Chappell[SUP] 18 [/SUP], Naphak Modhiran[SUP] 18 [/SUP], Daniel Watterson[SUP] 18 [/SUP], Paul Young[SUP] 18 [/SUP], Wen Shi Lee[SUP] 1 [/SUP], Bruce D Wines[SUP] 19 20 21 [/SUP], P Mark Hogarth[SUP] 19 20 21 [/SUP], Robyn Esterbauer[SUP] 1 22 [/SUP], Hannah G Kelly[SUP] 1 22 [/SUP], Hyon-Xhi Tan[SUP] 1 22 [/SUP], Jennifer A Juno[SUP] 1 [/SUP], Adam K Wheatley[SUP] 1 22 [/SUP], Stephen J Kent[SUP] 1 22 23 [/SUP], Kelly B Arnold[SUP] 3 [/SUP], Katherine Kedzierska[SUP] 24 [/SUP], Amy W Chung[SUP] 25 [/SUP]
Affiliations
- PMID: 33795692
- DOI: 10.1038/s41467-021-22236-7
Abstract
The hallmarks of COVID-19 are higher pathogenicity and mortality in the elderly compared to children. Examining baseline SARS-CoV-2 cross-reactive immunological responses, induced by circulating human coronaviruses (hCoVs), is needed to understand such divergent clinical outcomes. Here we show analysis of coronavirus antibody responses of pre-pandemic healthy children (n = 89), adults (n = 98), elderly (n = 57), and COVID-19 patients (n = 50) by systems serology. Moderate levels of cross-reactive, but non-neutralizing, SARS-CoV-2 antibodies are detected in pre-pandemic healthy individuals. SARS-CoV-2 antigen-specific Fc? receptor binding accurately distinguishes COVID-19 patients from healthy individuals, suggesting that SARS-CoV-2 infection induces qualitative changes to antibody Fc, enhancing Fc? receptor engagement. Higher cross-reactive SARS-CoV-2 IgA and IgG are observed in healthy elderly, while healthy children display elevated SARS-CoV-2 IgM, suggesting that children have fewer hCoV exposures, resulting in less-experienced but more polyreactive humoral immunity. Age-dependent analysis of COVID-19 patients, confirms elevated class-switched antibodies in elderly, while children have stronger Fc responses which we demonstrate are functionally different. These insights will inform COVID-19 vaccination strategies, improved serological diagnostics and therapeutics.