SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination

Felicity Liew; Shubha Talwar; Andy Cross; Brian J Willett; Sam Scott; Nicola Logan; Matthew K Siggins; Dawid Swieboda; Jasmin K Sidhu; Claudia Efstathiou; Shona C Moore; Chris Davis; Noura Mohamed; Jose Nunag; Clara King; A A Roger Thompson; Sarah L Rowland-Jones; Annemarie B Docherty; James D Chalmers; Ling-Pei Ho; Alexander Horsley; Betty Raman; Krisnah Poinasamy; Michael Marks; Onn Min Kon; Luke Howard; Daniel G Wootton; Susanna Dunachie; Jennifer K Quint; Rachael A Evans; Louise V Wain; Sara Fontanella; Thushan I de Silva; Antonia Ho; Ewen Harrison; J Kenneth Baillie; Malcolm G Semple; Christopher Brightling; Ryan S Thwaites; Lance Turtle; Peter J M Openshaw; ISARIC4C Investigators; Cherie Armour; G. Carson; J. Busby; B. Connolly; J. Cooper; S. Drain; D. Grieve; N. Hart; M. Harvey; L. G. Heaney; J. Hughes; M. G. Jones; N. Magee; A. McArdle; L. McGarvey; C. Mills; J. Mitchell; T. Peto; N. Powell; M. Rowland; M. Sharma; S. Siddiqui

doi:10.1016/j.ebiom.2022.104402

SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination

Felicity Liew, Shubha Talwar, Andy Cross, Brian J Willett, Sam Scott, Nicola Logan, Matthew K Siggins, Dawid Swieboda, Jasmin K Sidhu, Claudia Efstathiou, Shona C Moore, Chris Davis, Noura Mohamed, Jose Nunag, Clara King, A A Roger Thompson, Sarah L Rowland-Jones, Annemarie B Docherty, James D Chalmers, Ling-Pei HoAlexander Horsley, Betty Raman, Krisnah Poinasamy, Michael Marks, Onn Min Kon, Luke Howard, Daniel G Wootton, Susanna Dunachie, Jennifer K Quint, Rachael A Evans, Louise V Wain, Sara Fontanella, Thushan I de Silva, Antonia Ho, Ewen Harrison, J Kenneth Baillie, Malcolm G Semple, Christopher Brightling, Ryan S Thwaites, Lance Turtle, Peter J M Openshaw, ISARIC4C Investigators, Cherie Armour, G. Carson, J. Busby, B. Connolly, J. Cooper, S. Drain, D. Grieve, N. Hart, M. Harvey, L. G. Heaney, J. Hughes, M. G. Jones, N. Magee, A. McArdle, L. McGarvey, C. Mills, J. Mitchell, T. Peto, N. Powell, M. Rowland, M. Sharma, S. Siddiqui

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Abstract

Background
Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced.

Methods
In this follow up study, plasma and nasosorption samples were prospectively collected from 446 adults hospitalised for COVID-19 between February 2020 and March 2021 via the ISARIC4C and PHOSP-COVID consortia. IgA and IgG responses to NP and S of ancestral SARS-CoV-2, Delta and Omicron (BA.1) variants were measured by electrochemiluminescence and compared with plasma neutralisation data.

Findings
Strong and consistent nasal anti-NP and anti-S IgA responses were demonstrated, which remained elevated for nine months (p < 0.0001). Nasal and plasma anti-S IgG remained elevated for at least 12 months (p < 0.0001) with plasma neutralising titres that were raised against all variants compared to controls (p < 0.0001). Of 323 with complete data, 307 were vaccinated between 6 and 12 months; coinciding with rises in nasal and plasma IgA and IgG anti-S titres for all SARS-CoV-2 variants, although the change in nasal IgA was minimal (1.46-fold change after 10 months, p = 0.011) and the median remained below the positive threshold determined by pre-pandemic controls. Samples 12 months after admission showed no association between nasal IgA and plasma IgG anti-S responses (R = 0.05, p = 0.18), indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by vaccination.

Interpretation
The decline in nasal IgA responses 9 months after infection and minimal impact of subsequent vaccination may explain the lack of long-lasting nasal defence against reinfection and the limited effects of vaccination on transmission. These findings highlight the need to develop vaccines that enhance nasal immunity.

Original language	English
Article number	104402
Journal	EBioMedicine
Volume	87
DOIs	https://doi.org/10.1016/j.ebiom.2022.104402
Publication status	Published - 16 Jan 2023

Keywords

Convalescent
COVID-19
Mucosal immunity
Nasal antibody
SARS-CoV-2 immunity
SARS-CoV-2 variants
Vaccination

ASJC Scopus subject areas

General Biochemistry,Genetics and Molecular Biology

UN SDGs

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

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SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination
Copyright 2022 The Authors. This is an open access article published under a Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
Final published version, 1.92 MBLicence: CC BY

Cite this

Liew, F., Talwar, S., Cross, A., Willett, B. J., Scott, S., Logan, N., Siggins, M. K., Swieboda, D., Sidhu, J. K., Efstathiou, C., Moore, S. C., Davis, C., Mohamed, N., Nunag, J., King, C., Thompson, A. A. R., Rowland-Jones, S. L., Docherty, A. B., Chalmers, J. D., ... Siddiqui, S. (2023). SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination. EBioMedicine, 87, Article 104402. https://doi.org/10.1016/j.ebiom.2022.104402

@article{196e1ee747cf4704bfe83336310d75a9,

title = "SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination",

abstract = "BackgroundMost studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced.MethodsIn this follow up study, plasma and nasosorption samples were prospectively collected from 446 adults hospitalised for COVID-19 between February 2020 and March 2021 via the ISARIC4C and PHOSP-COVID consortia. IgA and IgG responses to NP and S of ancestral SARS-CoV-2, Delta and Omicron (BA.1) variants were measured by electrochemiluminescence and compared with plasma neutralisation data.FindingsStrong and consistent nasal anti-NP and anti-S IgA responses were demonstrated, which remained elevated for nine months (p < 0.0001). Nasal and plasma anti-S IgG remained elevated for at least 12 months (p < 0.0001) with plasma neutralising titres that were raised against all variants compared to controls (p < 0.0001). Of 323 with complete data, 307 were vaccinated between 6 and 12 months; coinciding with rises in nasal and plasma IgA and IgG anti-S titres for all SARS-CoV-2 variants, although the change in nasal IgA was minimal (1.46-fold change after 10 months, p = 0.011) and the median remained below the positive threshold determined by pre-pandemic controls. Samples 12 months after admission showed no association between nasal IgA and plasma IgG anti-S responses (R = 0.05, p = 0.18), indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by vaccination.InterpretationThe decline in nasal IgA responses 9 months after infection and minimal impact of subsequent vaccination may explain the lack of long-lasting nasal defence against reinfection and the limited effects of vaccination on transmission. These findings highlight the need to develop vaccines that enhance nasal immunity.",

keywords = "Convalescent, COVID-19, Mucosal immunity, Nasal antibody, SARS-CoV-2 immunity, SARS-CoV-2 variants, Vaccination",

author = "Felicity Liew and Shubha Talwar and Andy Cross and Willett, {Brian J} and Sam Scott and Nicola Logan and Siggins, {Matthew K} and Dawid Swieboda and Sidhu, {Jasmin K} and Claudia Efstathiou and Moore, {Shona C} and Chris Davis and Noura Mohamed and Jose Nunag and Clara King and Thompson, {A A Roger} and Rowland-Jones, {Sarah L} and Docherty, {Annemarie B} and Chalmers, {James D} and Ling-Pei Ho and Alexander Horsley and Betty Raman and Krisnah Poinasamy and Michael Marks and Kon, {Onn Min} and Luke Howard and Wootton, {Daniel G} and Susanna Dunachie and Quint, {Jennifer K} and Evans, {Rachael A} and Wain, {Louise V} and Sara Fontanella and {de Silva}, {Thushan I} and Antonia Ho and Ewen Harrison and Baillie, {J Kenneth} and Semple, {Malcolm G} and Christopher Brightling and Thwaites, {Ryan S} and Lance Turtle and Openshaw, {Peter J M} and {ISARIC4C Investigators} and Cherie Armour and G. Carson and J. Busby and B. Connolly and J. Cooper and S. Drain and D. Grieve and N. Hart and M. Harvey and Heaney, {L. G.} and J. Hughes and Jones, {M. G.} and N. Magee and A. McArdle and L. McGarvey and C. Mills and J. Mitchell and T. Peto and N. Powell and M. Rowland and M. Sharma and S. Siddiqui",

year = "2023",

month = jan,

day = "16",

doi = "10.1016/j.ebiom.2022.104402",

language = "English",

volume = "87",

journal = "EBioMedicine",

issn = "2352-3964",

publisher = "Elsevier B.V.",

}

Liew, F, Talwar, S, Cross, A, Willett, BJ, Scott, S, Logan, N, Siggins, MK, Swieboda, D, Sidhu, JK, Efstathiou, C, Moore, SC, Davis, C, Mohamed, N, Nunag, J, King, C, Thompson, AAR, Rowland-Jones, SL, Docherty, AB, Chalmers, JD, Ho, L-P, Horsley, A, Raman, B, Poinasamy, K, Marks, M, Kon, OM, Howard, L, Wootton, DG, Dunachie, S, Quint, JK, Evans, RA, Wain, LV, Fontanella, S, de Silva, TI, Ho, A, Harrison, E, Baillie, JK, Semple, MG, Brightling, C, Thwaites, RS, Turtle, L, Openshaw, PJM, ISARIC4C Investigators, Armour, C , Carson, G , Busby, J , Connolly, B, Cooper, J, Drain, S, Grieve, D, Hart, N, Harvey, M, Heaney, LG, Hughes, J, Jones, MG, Magee, N, McArdle, A , McGarvey, L , Mills, C , Mitchell, J , Peto, T, Powell, N, Rowland, M, Sharma, M & Siddiqui, S 2023, 'SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination', EBioMedicine, vol. 87, 104402. https://doi.org/10.1016/j.ebiom.2022.104402

TY - JOUR

T1 - SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination

AU - Liew, Felicity

AU - Talwar, Shubha

AU - Cross, Andy

AU - Willett, Brian J

AU - Scott, Sam

AU - Logan, Nicola

AU - Siggins, Matthew K

AU - Swieboda, Dawid

AU - Sidhu, Jasmin K

AU - Efstathiou, Claudia

AU - Moore, Shona C

AU - Davis, Chris

AU - Mohamed, Noura

AU - Nunag, Jose

AU - King, Clara

AU - Thompson, A A Roger

AU - Rowland-Jones, Sarah L

AU - Docherty, Annemarie B

AU - Chalmers, James D

AU - Ho, Ling-Pei

AU - Horsley, Alexander

AU - Raman, Betty

AU - Poinasamy, Krisnah

AU - Marks, Michael

AU - Kon, Onn Min

AU - Howard, Luke

AU - Wootton, Daniel G

AU - Dunachie, Susanna

AU - Quint, Jennifer K

AU - Evans, Rachael A

AU - Wain, Louise V

AU - Fontanella, Sara

AU - de Silva, Thushan I

AU - Ho, Antonia

AU - Harrison, Ewen

AU - Baillie, J Kenneth

AU - Semple, Malcolm G

AU - Brightling, Christopher

AU - Thwaites, Ryan S

AU - Turtle, Lance

AU - Openshaw, Peter J M

AU - ISARIC4C Investigators

AU - Armour, Cherie

AU - Carson, G.

AU - Busby, J.

AU - Connolly, B.

AU - Cooper, J.

AU - Drain, S.

AU - Grieve, D.

AU - Hart, N.

AU - Harvey, M.

AU - Heaney, L. G.

AU - Hughes, J.

AU - Jones, M. G.

AU - Magee, N.

AU - McArdle, A.

AU - McGarvey, L.

AU - Mills, C.

AU - Mitchell, J.

AU - Peto, T.

AU - Powell, N.

AU - Rowland, M.

AU - Sharma, M.

AU - Siddiqui, S.

PY - 2023/1/16

Y1 - 2023/1/16

N2 - BackgroundMost studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced.MethodsIn this follow up study, plasma and nasosorption samples were prospectively collected from 446 adults hospitalised for COVID-19 between February 2020 and March 2021 via the ISARIC4C and PHOSP-COVID consortia. IgA and IgG responses to NP and S of ancestral SARS-CoV-2, Delta and Omicron (BA.1) variants were measured by electrochemiluminescence and compared with plasma neutralisation data.FindingsStrong and consistent nasal anti-NP and anti-S IgA responses were demonstrated, which remained elevated for nine months (p < 0.0001). Nasal and plasma anti-S IgG remained elevated for at least 12 months (p < 0.0001) with plasma neutralising titres that were raised against all variants compared to controls (p < 0.0001). Of 323 with complete data, 307 were vaccinated between 6 and 12 months; coinciding with rises in nasal and plasma IgA and IgG anti-S titres for all SARS-CoV-2 variants, although the change in nasal IgA was minimal (1.46-fold change after 10 months, p = 0.011) and the median remained below the positive threshold determined by pre-pandemic controls. Samples 12 months after admission showed no association between nasal IgA and plasma IgG anti-S responses (R = 0.05, p = 0.18), indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by vaccination.InterpretationThe decline in nasal IgA responses 9 months after infection and minimal impact of subsequent vaccination may explain the lack of long-lasting nasal defence against reinfection and the limited effects of vaccination on transmission. These findings highlight the need to develop vaccines that enhance nasal immunity.

AB - BackgroundMost studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced.MethodsIn this follow up study, plasma and nasosorption samples were prospectively collected from 446 adults hospitalised for COVID-19 between February 2020 and March 2021 via the ISARIC4C and PHOSP-COVID consortia. IgA and IgG responses to NP and S of ancestral SARS-CoV-2, Delta and Omicron (BA.1) variants were measured by electrochemiluminescence and compared with plasma neutralisation data.FindingsStrong and consistent nasal anti-NP and anti-S IgA responses were demonstrated, which remained elevated for nine months (p < 0.0001). Nasal and plasma anti-S IgG remained elevated for at least 12 months (p < 0.0001) with plasma neutralising titres that were raised against all variants compared to controls (p < 0.0001). Of 323 with complete data, 307 were vaccinated between 6 and 12 months; coinciding with rises in nasal and plasma IgA and IgG anti-S titres for all SARS-CoV-2 variants, although the change in nasal IgA was minimal (1.46-fold change after 10 months, p = 0.011) and the median remained below the positive threshold determined by pre-pandemic controls. Samples 12 months after admission showed no association between nasal IgA and plasma IgG anti-S responses (R = 0.05, p = 0.18), indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by vaccination.InterpretationThe decline in nasal IgA responses 9 months after infection and minimal impact of subsequent vaccination may explain the lack of long-lasting nasal defence against reinfection and the limited effects of vaccination on transmission. These findings highlight the need to develop vaccines that enhance nasal immunity.

KW - Convalescent

KW - COVID-19

KW - Mucosal immunity

KW - Nasal antibody

KW - SARS-CoV-2 immunity

KW - SARS-CoV-2 variants

KW - Vaccination

U2 - 10.1016/j.ebiom.2022.104402

DO - 10.1016/j.ebiom.2022.104402

M3 - Article

C2 - 36543718

AN - SCOPUS:85146269668

SN - 2352-3964

VL - 87

JO - EBioMedicine

JF - EBioMedicine

M1 - 104402

ER -

SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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