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

ISARIC4C Investigators; PHOSP-COVID Collaborative Group; 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

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

ISARIC4C Investigators, PHOSP-COVID Collaborative Group, Felicity Liew (Lead / Corresponding author), 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. DochertyJames 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 (Lead / Corresponding author), Lance Turtle (Lead / Corresponding author), Peter J. M. Openshaw (Lead / Corresponding author)

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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
Number of pages	14
Journal	EBioMedicine
Volume	87
Early online date	16 Dec 2022
DOIs	https://doi.org/10.1016/j.ebiom.2022.104402
Publication status	Published - Jan 2023

Keywords

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

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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10.1016/j.ebiom.2022.104402Licence: CC BY

Final Published VersionFinal published version, 1.92 MBLicence: CC BY

Cite this

ISARIC4C Investigators, PHOSP-COVID Collaborative Group, 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., ... Openshaw, P. J. M. (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{52a35d2075ea4bc384643919244b325c,

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

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.",

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

author = "{ISARIC4C Investigators} and {PHOSP-COVID Collaborative Group} and 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 Jacob George",

note = "Funding Information: This research used data assets made available by Outbreak Data Analysis Platform (ODAP) as part of the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation (grant ref MC_PC_20058). This work is supported by the following grants: The PHOSP-COVD study is jointly funded by UK Research and Innovation and National Institute for Health and Care Research (grant references: MR/V027859/1 and COV0319). ISARIC4C is supported by grants from the National Institute for Health and Care Research (award CO-CIN-01) and the Medical Research Council (grant MC_PC_19059) Liverpool Experimental Cancer Medicine Centre provided infrastructure support for this research (grant reference: C18616/A25153). Other grants which have supported this work include: the UK Coronavirus Immunology Consortium [funder reference:1257927], the Imperial Biomedical Research Centre (NIHR Imperial BRC, grant IS-BRC-1215-20013), the Health Protection Research Unit (HPRU) in Respiratory Infections at Imperial College London and NIHR HPRU in Emerging and Zoonotic Infections at University of Liverpool, both in partnership with Public Health England, [NIHR award 200907], Wellcome Trust and Department for International Development [215091/Z/18/Z], Health Data Research UK (HDR UK) [grant code: 2021.0155], Medical Research Council [grant code: MC_UU_12014/12], and NIHR Clinical Research Network for providing infrastructure support for this research. FL is supported by an MRC clinical training fellowship [award MR/W000970/1]. LPH is supported by Oxford NIHR Biomedical Research Centre. AART is supported by a BHF Intermediate Clinical Fellowship (FS/18/13/33281). SLRJ receives support from UKRI, GCRF, Rosetrees Trust, BHIVA, EDCTP, Globvac. JDC has grants from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Gilead Sciences, Grifols, Novartis and Insmed. RAE holds a NIHR Clinician Scientist Fellowship (CS-2016-16-020). AH is currently supported by UK Research and Innovation. NIHR and NIHR Manchester BRC. BR receives support from BHF Oxford Centre of Research Excellence, NIHR Oxford BRC and MRC. SJD is funded by an NIHR Global Research Professorship [NIHR300791]. DW is supported by an NIHR Advanced Fellowship. AH has received support from MRC and the Coronavirus Immunology Consortium (MR/V028448/1). LVW has received support from UKRI, GSK/Asthma + Lung UK and NIHR for this study. MGS has received support from NIHR UK, MRC UK and Health Protection Research Unit in Emerging & Zoonotic Infections, University of Liverpool. JKB is supported by the Wellcome Trust (223164/Z/21/Z) and UKRI (MC_PC_20004, MC_PC_19025, MC_PC_1905, MRNO2995X/1, and MC_PC_20029). PJMO is supported by a NIHR Senior Investigator Award [award 201385]. LT is supported by the Wellcome Trust [clinical career development fellowship grant number 205228/Z/16/Z], the Centre of Excellence in Infectious Diseases Research (CEIDR) and the Alder Hey Charity. Copyright: {\textcopyright} 2022 The Author(s). Published by Elsevier B.V.",

year = "2023",

month = jan,

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

language = "English",

volume = "87",

journal = "EBioMedicine",

issn = "2352-3964",

publisher = "Elsevier",

}

ISARIC4C Investigators, PHOSP-COVID Collaborative Group, 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 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 - ISARIC4C Investigators

AU - PHOSP-COVID Collaborative Group

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 - George, Jacob

N1 - Funding Information: This research used data assets made available by Outbreak Data Analysis Platform (ODAP) as part of the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation (grant ref MC_PC_20058). This work is supported by the following grants: The PHOSP-COVD study is jointly funded by UK Research and Innovation and National Institute for Health and Care Research (grant references: MR/V027859/1 and COV0319). ISARIC4C is supported by grants from the National Institute for Health and Care Research (award CO-CIN-01) and the Medical Research Council (grant MC_PC_19059) Liverpool Experimental Cancer Medicine Centre provided infrastructure support for this research (grant reference: C18616/A25153). Other grants which have supported this work include: the UK Coronavirus Immunology Consortium [funder reference:1257927], the Imperial Biomedical Research Centre (NIHR Imperial BRC, grant IS-BRC-1215-20013), the Health Protection Research Unit (HPRU) in Respiratory Infections at Imperial College London and NIHR HPRU in Emerging and Zoonotic Infections at University of Liverpool, both in partnership with Public Health England, [NIHR award 200907], Wellcome Trust and Department for International Development [215091/Z/18/Z], Health Data Research UK (HDR UK) [grant code: 2021.0155], Medical Research Council [grant code: MC_UU_12014/12], and NIHR Clinical Research Network for providing infrastructure support for this research. FL is supported by an MRC clinical training fellowship [award MR/W000970/1]. LPH is supported by Oxford NIHR Biomedical Research Centre. AART is supported by a BHF Intermediate Clinical Fellowship (FS/18/13/33281). SLRJ receives support from UKRI, GCRF, Rosetrees Trust, BHIVA, EDCTP, Globvac. JDC has grants from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Gilead Sciences, Grifols, Novartis and Insmed. RAE holds a NIHR Clinician Scientist Fellowship (CS-2016-16-020). AH is currently supported by UK Research and Innovation. NIHR and NIHR Manchester BRC. BR receives support from BHF Oxford Centre of Research Excellence, NIHR Oxford BRC and MRC. SJD is funded by an NIHR Global Research Professorship [NIHR300791]. DW is supported by an NIHR Advanced Fellowship. AH has received support from MRC and the Coronavirus Immunology Consortium (MR/V028448/1). LVW has received support from UKRI, GSK/Asthma + Lung UK and NIHR for this study. MGS has received support from NIHR UK, MRC UK and Health Protection Research Unit in Emerging & Zoonotic Infections, University of Liverpool. JKB is supported by the Wellcome Trust (223164/Z/21/Z) and UKRI (MC_PC_20004, MC_PC_19025, MC_PC_1905, MRNO2995X/1, and MC_PC_20029). PJMO is supported by a NIHR Senior Investigator Award [award 201385]. LT is supported by the Wellcome Trust [clinical career development fellowship grant number 205228/Z/16/Z], the Centre of Excellence in Infectious Diseases Research (CEIDR) and the Alder Hey Charity. Copyright: © 2022 The Author(s). Published by Elsevier B.V.

PY - 2023/1

Y1 - 2023/1

N2 - 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.

AB - 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.

KW - COVID-19

KW - SARS-CoV-2 immunity

KW - Convalescent

KW - Nasal antibody

KW - Mucosal immunity

KW - Vaccination

KW - SARS-CoV-2 variants

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U2 - 10.1016/j.ebiom.2022.104402

DO - 10.1016/j.ebiom.2022.104402

M3 - Article

C2 - 36543718

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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PHOS-COVID (Joint with University of Leicester)

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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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Projects

PHOS-COVID (Joint with University of Leicester)

Cite this