SARS-CoV-2 crossreactive B-cells outnumber seasonal coronavirus spike-specific clones at the end of the COVID-19 pandemic

Cristina Gonzalez-Lopez; Muriel Aguilar-Bretones; Julian Reinders; Jingshu Zhang; Petra van den Doel; Batuhan Bekki; Eric C. van Gorp; P. Hugo M. van der Kuy; Bart L. Haagmans; Corine H. GeurtsVanKessel; Marion P.G. Koopmans; Rory D. de Vries; Marit J. van Gils; Gijsbert P. van Nierop

doi:10.1038/s44298-026-00185-6

SARS-CoV-2 crossreactive B-cells outnumber seasonal coronavirus spike-specific clones at the end of the COVID-19 pandemic

Cristina Gonzalez-Lopez
, Muriel Aguilar-Bretones
, Julian Reinders
, Jingshu Zhang
, Petra van den Doel
, Batuhan Bekki
, Eric C. van Gorp
, P. Hugo M. van der Kuy
, Bart L. Haagmans
, Corine H. GeurtsVanKessel
, Marion P.G. Koopmans
, Rory D. de Vries
, Marit J. van Gils
, Gijsbert P. van Nierop^*

^*Corresponding author for this work

University of Groningen
Erasmus University Rotterdam
Amsterdam UMC

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

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Abstract

How B-cell responses towards seasonal human coronaviruses (sHCoVs) impacted those towards SARS-CoV-2 has been widely studied, yet potential reverse effects are ill-defined. We compared sHCoV immune responses between cross-sectional pre-pandemic and end-pandemic cohorts of immunocompetent adults. We assessed Spike (S) reactive IgG and IgA serum and B-cell responses towards sHCoVs and dominant SARS-CoV-2 variants, and evaluated their contribution to OC43 neutralization. Pre-pandemic individuals were uniformly sHCoV IgG and IgA seropositive, yet SARS-CoV-2 S-reactivity was negligible. End-pandemic donors, had predominant SARS-CoV-2 responses that in part cross-reacted with sHCoV which accounted for higher serum NL63, HKU1 and OC43 antibody levels. This effect was strongest for OC43 S2 and this cross-reactive response contributed to OC43 serum neutralization. We conclude that SARS-CoV-2-specific immune responses impacted sHCoVs responses, particularly for OC43. This could have implications for immune protection and offers insights for the development of pan-coronavirus treatments and vaccines.

Original language	English
Article number	19
Journal	NPJ Viruses
Volume	4
Issue number	1
DOIs	https://doi.org/10.1038/s44298-026-00185-6
Publication status	Published - 19 Mar 2026

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Publisher Copyright: © The Author(s) 2026.

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This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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Gonzalez-Lopez, C., Aguilar-Bretones, M., Reinders, J., Zhang, J., van den Doel, P., Bekki, B., van Gorp, E. C., van der Kuy, P. H. M., Haagmans, B. L., GeurtsVanKessel, C. H., Koopmans, M. P. G., de Vries, R. D., van Gils, M. J., & van Nierop, G. P. (2026). SARS-CoV-2 crossreactive B-cells outnumber seasonal coronavirus spike-specific clones at the end of the COVID-19 pandemic. NPJ Viruses, 4(1), Article 19. https://doi.org/10.1038/s44298-026-00185-6

@article{3751f949e8974167923e0f59c4ee1b8f,

title = "SARS-CoV-2 crossreactive B-cells outnumber seasonal coronavirus spike-specific clones at the end of the COVID-19 pandemic",

abstract = "How B-cell responses towards seasonal human coronaviruses (sHCoVs) impacted those towards SARS-CoV-2 has been widely studied, yet potential reverse effects are ill-defined. We compared sHCoV immune responses between cross-sectional pre-pandemic and end-pandemic cohorts of immunocompetent adults. We assessed Spike (S) reactive IgG and IgA serum and B-cell responses towards sHCoVs and dominant SARS-CoV-2 variants, and evaluated their contribution to OC43 neutralization. Pre-pandemic individuals were uniformly sHCoV IgG and IgA seropositive, yet SARS-CoV-2 S-reactivity was negligible. End-pandemic donors, had predominant SARS-CoV-2 responses that in part cross-reacted with sHCoV which accounted for higher serum NL63, HKU1 and OC43 antibody levels. This effect was strongest for OC43 S2 and this cross-reactive response contributed to OC43 serum neutralization. We conclude that SARS-CoV-2-specific immune responses impacted sHCoVs responses, particularly for OC43. This could have implications for immune protection and offers insights for the development of pan-coronavirus treatments and vaccines.",

author = "Cristina Gonzalez-Lopez and Muriel Aguilar-Bretones and Julian Reinders and Jingshu Zhang and \{van den Doel\}, Petra and Batuhan Bekki and \{van Gorp\}, \{Eric C.\} and \{van der Kuy\}, \{P. Hugo M.\} and Haagmans, \{Bart L.\} and GeurtsVanKessel, \{Corine H.\} and Koopmans, \{Marion P.G.\} and \{de Vries\}, \{Rory D.\} and \{van Gils\}, \{Marit J.\} and \{van Nierop\}, \{Gijsbert P.\}",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2026.",

year = "2026",

month = mar,

day = "19",

doi = "10.1038/s44298-026-00185-6",

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Gonzalez-Lopez, C , Aguilar-Bretones, M, Reinders, J, Zhang, J, van den Doel, P, Bekki, B, van Gorp, EC , van der Kuy, PHM , Haagmans, BL , GeurtsVanKessel, CH , Koopmans, MPG , de Vries, RD, van Gils, MJ & van Nierop, GP 2026, 'SARS-CoV-2 crossreactive B-cells outnumber seasonal coronavirus spike-specific clones at the end of the COVID-19 pandemic', NPJ Viruses, vol. 4, no. 1, 19. https://doi.org/10.1038/s44298-026-00185-6

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T1 - SARS-CoV-2 crossreactive B-cells outnumber seasonal coronavirus spike-specific clones at the end of the COVID-19 pandemic

AU - Gonzalez-Lopez, Cristina

AU - Aguilar-Bretones, Muriel

AU - Reinders, Julian

AU - Zhang, Jingshu

AU - van den Doel, Petra

AU - Bekki, Batuhan

AU - van Gorp, Eric C.

AU - van der Kuy, P. Hugo M.

AU - Haagmans, Bart L.

AU - GeurtsVanKessel, Corine H.

AU - Koopmans, Marion P.G.

AU - de Vries, Rory D.

AU - van Gils, Marit J.

AU - van Nierop, Gijsbert P.

PY - 2026/3/19

Y1 - 2026/3/19

N2 - How B-cell responses towards seasonal human coronaviruses (sHCoVs) impacted those towards SARS-CoV-2 has been widely studied, yet potential reverse effects are ill-defined. We compared sHCoV immune responses between cross-sectional pre-pandemic and end-pandemic cohorts of immunocompetent adults. We assessed Spike (S) reactive IgG and IgA serum and B-cell responses towards sHCoVs and dominant SARS-CoV-2 variants, and evaluated their contribution to OC43 neutralization. Pre-pandemic individuals were uniformly sHCoV IgG and IgA seropositive, yet SARS-CoV-2 S-reactivity was negligible. End-pandemic donors, had predominant SARS-CoV-2 responses that in part cross-reacted with sHCoV which accounted for higher serum NL63, HKU1 and OC43 antibody levels. This effect was strongest for OC43 S2 and this cross-reactive response contributed to OC43 serum neutralization. We conclude that SARS-CoV-2-specific immune responses impacted sHCoVs responses, particularly for OC43. This could have implications for immune protection and offers insights for the development of pan-coronavirus treatments and vaccines.

AB - How B-cell responses towards seasonal human coronaviruses (sHCoVs) impacted those towards SARS-CoV-2 has been widely studied, yet potential reverse effects are ill-defined. We compared sHCoV immune responses between cross-sectional pre-pandemic and end-pandemic cohorts of immunocompetent adults. We assessed Spike (S) reactive IgG and IgA serum and B-cell responses towards sHCoVs and dominant SARS-CoV-2 variants, and evaluated their contribution to OC43 neutralization. Pre-pandemic individuals were uniformly sHCoV IgG and IgA seropositive, yet SARS-CoV-2 S-reactivity was negligible. End-pandemic donors, had predominant SARS-CoV-2 responses that in part cross-reacted with sHCoV which accounted for higher serum NL63, HKU1 and OC43 antibody levels. This effect was strongest for OC43 S2 and this cross-reactive response contributed to OC43 serum neutralization. We conclude that SARS-CoV-2-specific immune responses impacted sHCoVs responses, particularly for OC43. This could have implications for immune protection and offers insights for the development of pan-coronavirus treatments and vaccines.

UR - https://www.scopus.com/pages/publications/105033552575

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DO - 10.1038/s44298-026-00185-6

M3 - Article

C2 - 41857372

AN - SCOPUS:105033552575

SN - 2948-1767

VL - 4

JO - NPJ Viruses

JF - NPJ Viruses

IS - 1

M1 - 19

ER -

SARS-CoV-2 crossreactive B-cells outnumber seasonal coronavirus spike-specific clones at the end of the COVID-19 pandemic

Abstract

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