Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses

Anna McNaughton; Robert S Paton; Matthew Edmans; Jonathan Cw Youngs; Judith Wellens; Prabhjeet Phalora; Alex Fyfe; Sandra Belij-Rammerstorfer; Jai S Bolton; Jonathan Ball; George W Carnell; Wanwisa Dejnirattisai; Christina Dold; Philip Hopkins; Alison Howarth; Kreepa Kooblall; Hannah Klim; Susannah Leaver; Lian N Lee; César López-Camacho; Sheila F Lumley; Derek C Macallan; Alexander J Mentzer; Nicholas M Provine; Jeremy Ratcliff; Jose L Slon-Campos; Donal T Skelly; Lucas B Stolle; Piyada Supasa; Nigel Temperton; Chris Walker; Beibei Wang; Duncan Wyncoll; Teresa Lambe; John K Ballie; Malcolm G Semple; Peter Jm Openshaw; Uri Obolski; Marc Turner; Miles Carroll; Juthathip Mongkolsapaya; Gavin Screaton; Stephen H Kennedy; Lisa M Jarvis; Eleanor Barnes; Susanna Dunachie; José Lourenço; Philippa C Matthews; Tihana Bicanic; Paul Klenerman; Sunetra Gupta; Craig P Thompson

doi:10.1172/jci.insight.156372

Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses

Anna McNaughton, Robert S Paton, Matthew Edmans, Jonathan Cw Youngs, Judith Wellens, Prabhjeet Phalora, Alex Fyfe, Sandra Belij-Rammerstorfer, Jai S Bolton, Jonathan Ball, George W Carnell, Wanwisa Dejnirattisai, Christina Dold, Philip Hopkins, Alison Howarth, Kreepa Kooblall, Hannah Klim, Susannah Leaver, Lian N Lee, César López-CamachoSheila F Lumley, Derek C Macallan, Alexander J Mentzer, Nicholas M Provine, Jeremy Ratcliff, Jose L Slon-Campos, Donal T Skelly, Lucas B Stolle, Piyada Supasa, Nigel Temperton, Chris Walker, Beibei Wang, Duncan Wyncoll, Teresa Lambe, John K Ballie, Malcolm G Semple, Peter Jm Openshaw, Uri Obolski, Marc Turner, Miles Carroll, Juthathip Mongkolsapaya, Gavin Screaton, Stephen H Kennedy, Lisa M Jarvis, Eleanor Barnes, Susanna Dunachie, José Lourenço, Philippa C Matthews, Tihana Bicanic, Paul Klenerman, Sunetra Gupta, Craig P Thompson^*

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

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Abstract

The role of immune responses to previously seen endemic coronavirus epitopes in severe acute respiratory coronavirus 2 (SARS-CoV-2) infection and disease progression has not yet been determined. Here, we show that a key characteristic of fatal coronavirus disease (COVID-19) outcomes is that the immune response to the SARS-CoV-2 spike protein is enriched for antibodies directed against epitopes shared with endemic beta-coronaviruses, and has a lower proportion of antibodies targeting the more protective variable regions of the spike. The magnitude of antibody responses to the SARS-CoV-2 full-length spike protein, its domains and subunits, and the SARS-CoV-2 nucleocapsid also correlated strongly with responses to the endemic beta-coronavirus spike proteins in individuals admitted to intensive care units (ICU) with fatal COVID-19 outcomes, but not in individuals with non-fatal outcomes. This correlation was found to be due to the antibody response directed at the S2 subunit of the SARS-CoV-2 spike protein, which has the highest degree of conservation between the beta-coronavirus spike proteins. Intriguingly, antibody responses to the less cross-reactive SARS-CoV-2 nucleocapsid were not significantly different in individuals who were admitted to ICU with fatal and non-fatal outcomes, suggesting an antibody profile in individuals with fatal outcomes consistent with an original antigenic sin type-response.

Original language	English
Article number	e156372
Number of pages	18
Journal	JCI Insight
Volume	7
Issue number	13
Early online date	24 May 2022
DOIs	https://doi.org/10.1172/jci.insight.156372
Publication status	Published - 8 Jul 2022

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Copyright: © 2022, McNaughton et al.

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McNaughton, A., Paton, R. S., Edmans, M., Youngs, J. C., Wellens, J., Phalora, P., Fyfe, A., Belij-Rammerstorfer, S., Bolton, J. S., Ball, J., Carnell, G. W., Dejnirattisai, W., Dold, C., Hopkins, P., Howarth, A., Kooblall, K., Klim, H., Leaver, S., Lee, L. N., ... Thompson, C. P. (2022). Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses. JCI Insight, 7(13), Article e156372. https://doi.org/10.1172/jci.insight.156372

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title = "Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses",

abstract = "The role of immune responses to previously seen endemic coronavirus epitopes in severe acute respiratory coronavirus 2 (SARS-CoV-2) infection and disease progression has not yet been determined. Here, we show that a key characteristic of fatal coronavirus disease (COVID-19) outcomes is that the immune response to the SARS-CoV-2 spike protein is enriched for antibodies directed against epitopes shared with endemic beta-coronaviruses, and has a lower proportion of antibodies targeting the more protective variable regions of the spike. The magnitude of antibody responses to the SARS-CoV-2 full-length spike protein, its domains and subunits, and the SARS-CoV-2 nucleocapsid also correlated strongly with responses to the endemic beta-coronavirus spike proteins in individuals admitted to intensive care units (ICU) with fatal COVID-19 outcomes, but not in individuals with non-fatal outcomes. This correlation was found to be due to the antibody response directed at the S2 subunit of the SARS-CoV-2 spike protein, which has the highest degree of conservation between the beta-coronavirus spike proteins. Intriguingly, antibody responses to the less cross-reactive SARS-CoV-2 nucleocapsid were not significantly different in individuals who were admitted to ICU with fatal and non-fatal outcomes, suggesting an antibody profile in individuals with fatal outcomes consistent with an original antigenic sin type-response.",

author = "Anna McNaughton and Paton, {Robert S} and Matthew Edmans and Youngs, {Jonathan Cw} and Judith Wellens and Prabhjeet Phalora and Alex Fyfe and Sandra Belij-Rammerstorfer and Bolton, {Jai S} and Jonathan Ball and Carnell, {George W} and Wanwisa Dejnirattisai and Christina Dold and Philip Hopkins and Alison Howarth and Kreepa Kooblall and Hannah Klim and Susannah Leaver and Lee, {Lian N} and C{\'e}sar L{\'o}pez-Camacho and Lumley, {Sheila F} and Macallan, {Derek C} and Mentzer, {Alexander J} and Provine, {Nicholas M} and Jeremy Ratcliff and Slon-Campos, {Jose L} and Skelly, {Donal T} and Stolle, {Lucas B} and Piyada Supasa and Nigel Temperton and Chris Walker and Beibei Wang and Duncan Wyncoll and Teresa Lambe and Ballie, {John K} and Semple, {Malcolm G} and Openshaw, {Peter Jm} and Uri Obolski and Marc Turner and Miles Carroll and Juthathip Mongkolsapaya and Gavin Screaton and Kennedy, {Stephen H} and Jarvis, {Lisa M} and Eleanor Barnes and Susanna Dunachie and Jos{\'e} Louren{\c c}o and Matthews, {Philippa C} and Tihana Bicanic and Paul Klenerman and Sunetra Gupta and Thompson, {Craig P}",

note = "Publisher Copyright: Copyright: {\textcopyright} 2022, McNaughton et al.",

year = "2022",

month = jul,

day = "8",

doi = "10.1172/jci.insight.156372",

language = "English",

volume = "7",

journal = "JCI Insight",

issn = "2379-3708",

publisher = "American Society for Clinical Investigation",

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McNaughton, A, Paton, RS, Edmans, M, Youngs, JC, Wellens, J, Phalora, P, Fyfe, A, Belij-Rammerstorfer, S, Bolton, JS, Ball, J, Carnell, GW, Dejnirattisai, W, Dold, C, Hopkins, P, Howarth, A, Kooblall, K, Klim, H, Leaver, S, Lee, LN, López-Camacho, C, Lumley, SF, Macallan, DC, Mentzer, AJ, Provine, NM, Ratcliff, J, Slon-Campos, JL, Skelly, DT, Stolle, LB, Supasa, P, Temperton, N, Walker, C, Wang, B, Wyncoll, D, Lambe, T, Ballie, JK, Semple, MG, Openshaw, PJ, Obolski, U, Turner, M, Carroll, M, Mongkolsapaya, J, Screaton, G, Kennedy, SH, Jarvis, LM, Barnes, E, Dunachie, S, Lourenço, J, Matthews, PC, Bicanic, T, Klenerman, P, Gupta, S & Thompson, CP 2022, 'Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses', JCI Insight, vol. 7, no. 13, e156372. https://doi.org/10.1172/jci.insight.156372

TY - JOUR

T1 - Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses

AU - McNaughton, Anna

AU - Paton, Robert S

AU - Edmans, Matthew

AU - Youngs, Jonathan Cw

AU - Wellens, Judith

AU - Phalora, Prabhjeet

AU - Fyfe, Alex

AU - Belij-Rammerstorfer, Sandra

AU - Bolton, Jai S

AU - Ball, Jonathan

AU - Carnell, George W

AU - Dejnirattisai, Wanwisa

AU - Dold, Christina

AU - Hopkins, Philip

AU - Howarth, Alison

AU - Kooblall, Kreepa

AU - Klim, Hannah

AU - Leaver, Susannah

AU - Lee, Lian N

AU - López-Camacho, César

AU - Lumley, Sheila F

AU - Macallan, Derek C

AU - Mentzer, Alexander J

AU - Provine, Nicholas M

AU - Ratcliff, Jeremy

AU - Slon-Campos, Jose L

AU - Skelly, Donal T

AU - Stolle, Lucas B

AU - Supasa, Piyada

AU - Temperton, Nigel

AU - Walker, Chris

AU - Wang, Beibei

AU - Wyncoll, Duncan

AU - Lambe, Teresa

AU - Ballie, John K

AU - Semple, Malcolm G

AU - Openshaw, Peter Jm

AU - Obolski, Uri

AU - Turner, Marc

AU - Carroll, Miles

AU - Mongkolsapaya, Juthathip

AU - Screaton, Gavin

AU - Kennedy, Stephen H

AU - Jarvis, Lisa M

AU - Barnes, Eleanor

AU - Dunachie, Susanna

AU - Lourenço, José

AU - Matthews, Philippa C

AU - Bicanic, Tihana

AU - Klenerman, Paul

AU - Gupta, Sunetra

AU - Thompson, Craig P

PY - 2022/7/8

Y1 - 2022/7/8

N2 - The role of immune responses to previously seen endemic coronavirus epitopes in severe acute respiratory coronavirus 2 (SARS-CoV-2) infection and disease progression has not yet been determined. Here, we show that a key characteristic of fatal coronavirus disease (COVID-19) outcomes is that the immune response to the SARS-CoV-2 spike protein is enriched for antibodies directed against epitopes shared with endemic beta-coronaviruses, and has a lower proportion of antibodies targeting the more protective variable regions of the spike. The magnitude of antibody responses to the SARS-CoV-2 full-length spike protein, its domains and subunits, and the SARS-CoV-2 nucleocapsid also correlated strongly with responses to the endemic beta-coronavirus spike proteins in individuals admitted to intensive care units (ICU) with fatal COVID-19 outcomes, but not in individuals with non-fatal outcomes. This correlation was found to be due to the antibody response directed at the S2 subunit of the SARS-CoV-2 spike protein, which has the highest degree of conservation between the beta-coronavirus spike proteins. Intriguingly, antibody responses to the less cross-reactive SARS-CoV-2 nucleocapsid were not significantly different in individuals who were admitted to ICU with fatal and non-fatal outcomes, suggesting an antibody profile in individuals with fatal outcomes consistent with an original antigenic sin type-response.

AB - The role of immune responses to previously seen endemic coronavirus epitopes in severe acute respiratory coronavirus 2 (SARS-CoV-2) infection and disease progression has not yet been determined. Here, we show that a key characteristic of fatal coronavirus disease (COVID-19) outcomes is that the immune response to the SARS-CoV-2 spike protein is enriched for antibodies directed against epitopes shared with endemic beta-coronaviruses, and has a lower proportion of antibodies targeting the more protective variable regions of the spike. The magnitude of antibody responses to the SARS-CoV-2 full-length spike protein, its domains and subunits, and the SARS-CoV-2 nucleocapsid also correlated strongly with responses to the endemic beta-coronavirus spike proteins in individuals admitted to intensive care units (ICU) with fatal COVID-19 outcomes, but not in individuals with non-fatal outcomes. This correlation was found to be due to the antibody response directed at the S2 subunit of the SARS-CoV-2 spike protein, which has the highest degree of conservation between the beta-coronavirus spike proteins. Intriguingly, antibody responses to the less cross-reactive SARS-CoV-2 nucleocapsid were not significantly different in individuals who were admitted to ICU with fatal and non-fatal outcomes, suggesting an antibody profile in individuals with fatal outcomes consistent with an original antigenic sin type-response.

U2 - 10.1172/jci.insight.156372

DO - 10.1172/jci.insight.156372

M3 - Article (Academic Journal)

C2 - 35608920

SN - 2379-3708

VL - 7

JO - JCI Insight

JF - JCI Insight

IS - 13

M1 - e156372

ER -

Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses

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