Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses
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 outcomes with coronavirus disease 2019 (COVID-19) is tha...
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| Format: | Article |
| Language: | English |
| Published: |
American Society for Clinical investigation
2022-07-01
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| Series: | JCI Insight |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/jci.insight.156372 |
| _version_ | 1811237547819401216 |
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| author | Anna L. McNaughton Robert S. Paton Matthew Edmans Jonathan Youngs Judith Wellens Prabhjeet Phalora Alex Fyfe Sandra Belij-Rammerstorfer Jai S. Bolton Jonathan Ball George W. Carnell Wanwisa Dejnirattisai Christina Dold David W. Eyre Philip Hopkins Alison Howarth Kreepa Kooblall Hannah Klim Susannah Leaver Lian Ni Lee César López-Camacho Sheila F. Lumley Derek C. Macallan Alexander J. Mentzer Nicholas M. Provine Jeremy Ratcliff Jose Slon-Compos Donal Skelly Lucas Stolle Piyada Supasa Nigel Temperton Chris Walker Beibei Wang Duncan Wyncoll Oxford Protective T Cell Immunology for COVID-19 (OPTIC) consortium Scottish National Blood Transfusion Service (SNBTS) consortium Peter Simmonds Teresa Lambe John Kenneth Baillie Malcolm G. Semple Peter J.M. Openshaw International Severe Acute Respiratory and emerging Infection Consortium Coronavirus Clinical Characterisation Consortium (ISARIC4C) investigators Uri Obolski Marc Turner Miles Carroll Juthathip Mongkolsapaya Gavin Screaton Stephen H. Kennedy Lisa Jarvis Eleanor Barnes Susanna Dunachie José Lourenço Philippa C. Matthews Tihana Bicanic Paul Klenerman Sunetra Gupta Craig P. Thompson |
| author_facet | Anna L. McNaughton Robert S. Paton Matthew Edmans Jonathan Youngs Judith Wellens Prabhjeet Phalora Alex Fyfe Sandra Belij-Rammerstorfer Jai S. Bolton Jonathan Ball George W. Carnell Wanwisa Dejnirattisai Christina Dold David W. Eyre Philip Hopkins Alison Howarth Kreepa Kooblall Hannah Klim Susannah Leaver Lian Ni Lee César López-Camacho Sheila F. Lumley Derek C. Macallan Alexander J. Mentzer Nicholas M. Provine Jeremy Ratcliff Jose Slon-Compos Donal Skelly Lucas Stolle Piyada Supasa Nigel Temperton Chris Walker Beibei Wang Duncan Wyncoll Oxford Protective T Cell Immunology for COVID-19 (OPTIC) consortium Scottish National Blood Transfusion Service (SNBTS) consortium Peter Simmonds Teresa Lambe John Kenneth Baillie Malcolm G. Semple Peter J.M. Openshaw International Severe Acute Respiratory and emerging Infection Consortium Coronavirus Clinical Characterisation Consortium (ISARIC4C) investigators Uri Obolski Marc Turner Miles Carroll Juthathip Mongkolsapaya Gavin Screaton Stephen H. Kennedy Lisa Jarvis Eleanor Barnes Susanna Dunachie José Lourenço Philippa C. Matthews Tihana Bicanic Paul Klenerman Sunetra Gupta Craig P. Thompson |
| author_sort | Anna L. McNaughton |
| collection | DOAJ |
| description | 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 outcomes with coronavirus disease 2019 (COVID-19) 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 an intensive care unit (ICU) with fatal COVID-19 outcomes, but not in individuals with nonfatal 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 an ICU with fatal and nonfatal outcomes, suggesting an antibody profile in individuals with fatal outcomes consistent with an “original antigenic sin” type response. |
| first_indexed | 2024-04-12T12:25:33Z |
| format | Article |
| id | doaj.art-842340fbdef543a0831407713fb7ad30 |
| institution | Directory Open Access Journal |
| issn | 2379-3708 |
| language | English |
| last_indexed | 2024-04-12T12:25:33Z |
| publishDate | 2022-07-01 |
| publisher | American Society for Clinical investigation |
| record_format | Article |
| series | JCI Insight |
| spelling | doaj.art-842340fbdef543a0831407713fb7ad302022-12-22T03:33:10ZengAmerican Society for Clinical investigationJCI Insight2379-37082022-07-01713Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronavirusesAnna L. McNaughtonRobert S. PatonMatthew EdmansJonathan YoungsJudith WellensPrabhjeet PhaloraAlex FyfeSandra Belij-RammerstorferJai S. BoltonJonathan BallGeorge W. CarnellWanwisa DejnirattisaiChristina DoldDavid W. EyrePhilip HopkinsAlison HowarthKreepa KooblallHannah KlimSusannah LeaverLian Ni LeeCésar López-CamachoSheila F. LumleyDerek C. MacallanAlexander J. MentzerNicholas M. ProvineJeremy RatcliffJose Slon-ComposDonal SkellyLucas StollePiyada SupasaNigel TempertonChris WalkerBeibei WangDuncan WyncollOxford Protective T Cell Immunology for COVID-19 (OPTIC) consortiumScottish National Blood Transfusion Service (SNBTS) consortiumPeter SimmondsTeresa LambeJohn Kenneth BaillieMalcolm G. SemplePeter J.M. OpenshawInternational Severe Acute Respiratory and emerging Infection Consortium Coronavirus Clinical Characterisation Consortium (ISARIC4C) investigatorsUri ObolskiMarc TurnerMiles CarrollJuthathip MongkolsapayaGavin ScreatonStephen H. KennedyLisa JarvisEleanor BarnesSusanna DunachieJosé LourençoPhilippa C. MatthewsTihana BicanicPaul KlenermanSunetra GuptaCraig P. ThompsonThe 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 outcomes with coronavirus disease 2019 (COVID-19) 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 an intensive care unit (ICU) with fatal COVID-19 outcomes, but not in individuals with nonfatal 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 an ICU with fatal and nonfatal outcomes, suggesting an antibody profile in individuals with fatal outcomes consistent with an “original antigenic sin” type response.https://doi.org/10.1172/jci.insight.156372ImmunologyInfectious disease |
| spellingShingle | Anna L. McNaughton Robert S. Paton Matthew Edmans Jonathan Youngs Judith Wellens Prabhjeet Phalora Alex Fyfe Sandra Belij-Rammerstorfer Jai S. Bolton Jonathan Ball George W. Carnell Wanwisa Dejnirattisai Christina Dold David W. Eyre Philip Hopkins Alison Howarth Kreepa Kooblall Hannah Klim Susannah Leaver Lian Ni Lee César López-Camacho Sheila F. Lumley Derek C. Macallan Alexander J. Mentzer Nicholas M. Provine Jeremy Ratcliff Jose Slon-Compos Donal Skelly Lucas Stolle Piyada Supasa Nigel Temperton Chris Walker Beibei Wang Duncan Wyncoll Oxford Protective T Cell Immunology for COVID-19 (OPTIC) consortium Scottish National Blood Transfusion Service (SNBTS) consortium Peter Simmonds Teresa Lambe John Kenneth Baillie Malcolm G. Semple Peter J.M. Openshaw International Severe Acute Respiratory and emerging Infection Consortium Coronavirus Clinical Characterisation Consortium (ISARIC4C) investigators Uri Obolski Marc Turner Miles Carroll Juthathip Mongkolsapaya Gavin Screaton Stephen H. Kennedy Lisa Jarvis Eleanor Barnes Susanna Dunachie José Lourenço Philippa C. Matthews Tihana Bicanic Paul Klenerman Sunetra Gupta Craig P. Thompson Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses JCI Insight Immunology Infectious disease |
| title | Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses |
| title_full | Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses |
| title_fullStr | Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses |
| title_full_unstemmed | Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses |
| title_short | Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses |
| title_sort | fatal covid 19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses |
| topic | Immunology Infectious disease |
| url | https://doi.org/10.1172/jci.insight.156372 |
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