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

<p><strong>Background</strong> 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 f...

Full description

Bibliographic Details
Main Authors: 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
Other Authors: ISARIC4C Investigators
Format: Journal article
Language:English
Published: Elsevier 2022
_version_ 1797109527655481344
author 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
author2 ISARIC4C Investigators
author_facet ISARIC4C Investigators
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
author_sort Liew, F
collection OXFORD
description <p><strong>Background</strong> 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.</p> <p><strong>Methods</strong> 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.</p> <p><strong>Findings</strong> Strong and consistent nasal anti-NP and anti-S IgA responses were demonstrated, which remained elevated for nine months (<i>p</i> < 0.0001). Nasal and plasma anti-S IgG remained elevated for at least 12 months (<i>p</i> < 0.0001) with plasma neutralising titres that were raised against all variants compared to controls (<i>p</i> < 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, <i>p</i> = 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 (<i>R</i> = 0.05, <i>p</i> = 0.18), indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by vaccination.</p> <p><strong>Interpretation</strong> 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.</p> <p><strong>Funding</strong> This study has been supported by ISARIC4C and PHOSP-COVID consortia. ISARIC4C is supported by grants from the National Institute for Health and Care Research and the Medical Research Council. Liverpool Experimental Cancer Medicine Centre provided infrastructure support for this research. The PHOSP-COVD study is jointly funded by UK Research and Innovation and National Institute of Health and Care Research. The funders were not involved in the study design, interpretation of data or the writing of this manuscript.</p>
first_indexed 2024-03-07T07:43:00Z
format Journal article
id oxford-uuid:c27b6b38-6b9f-4364-a5f4-7728a98b3f11
institution University of Oxford
language English
last_indexed 2024-03-07T07:43:00Z
publishDate 2022
publisher Elsevier
record_format dspace
spelling oxford-uuid:c27b6b38-6b9f-4364-a5f4-7728a98b3f112023-05-04T11:44:46ZSARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccinationJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:c27b6b38-6b9f-4364-a5f4-7728a98b3f11EnglishSymplectic ElementsElsevier2022Liew, FTalwar, SCross, AWillett, BJScott, SLogan, NSiggins, MKSwieboda, DSidhu, JKEfstathiou, CMoore, SCDavis, CMohamed, NNunag, JKing, CThompson, AARRowland-Jones, SLDocherty, ABChalmers, JDHo, L-PHorsley, ARaman, BPoinasamy, KMarks, MKon, OMHoward, LWootton, DGDunachie, SQuint, JKEvans, RAWain, LVFontanella, Sde Silva, TIHo, AHarrison, EBaillie, JKSemple, MGBrightling, CThwaites, RSTurtle, LOpenshaw, PJMISARIC4C InvestigatorsPHOSP-COVID collaborative groupSigfrid, L<p><strong>Background</strong> 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.</p> <p><strong>Methods</strong> 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.</p> <p><strong>Findings</strong> Strong and consistent nasal anti-NP and anti-S IgA responses were demonstrated, which remained elevated for nine months (<i>p</i> < 0.0001). Nasal and plasma anti-S IgG remained elevated for at least 12 months (<i>p</i> < 0.0001) with plasma neutralising titres that were raised against all variants compared to controls (<i>p</i> < 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, <i>p</i> = 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 (<i>R</i> = 0.05, <i>p</i> = 0.18), indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by vaccination.</p> <p><strong>Interpretation</strong> 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.</p> <p><strong>Funding</strong> This study has been supported by ISARIC4C and PHOSP-COVID consortia. ISARIC4C is supported by grants from the National Institute for Health and Care Research and the Medical Research Council. Liverpool Experimental Cancer Medicine Centre provided infrastructure support for this research. The PHOSP-COVD study is jointly funded by UK Research and Innovation and National Institute of Health and Care Research. The funders were not involved in the study design, interpretation of data or the writing of this manuscript.</p>
spellingShingle 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
SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination
title SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination
title_full SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination
title_fullStr SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination
title_full_unstemmed SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination
title_short SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination
title_sort sars cov 2 specific nasal iga wanes 9 months after hospitalisation with covid 19 and is not induced by subsequent vaccination
work_keys_str_mv AT liewf sarscov2specificnasaligawanes9monthsafterhospitalisationwithcovid19andisnotinducedbysubsequentvaccination
AT talwars sarscov2specificnasaligawanes9monthsafterhospitalisationwithcovid19andisnotinducedbysubsequentvaccination
AT crossa sarscov2specificnasaligawanes9monthsafterhospitalisationwithcovid19andisnotinducedbysubsequentvaccination
AT willettbj sarscov2specificnasaligawanes9monthsafterhospitalisationwithcovid19andisnotinducedbysubsequentvaccination
AT scotts sarscov2specificnasaligawanes9monthsafterhospitalisationwithcovid19andisnotinducedbysubsequentvaccination
AT logann sarscov2specificnasaligawanes9monthsafterhospitalisationwithcovid19andisnotinducedbysubsequentvaccination
AT sigginsmk sarscov2specificnasaligawanes9monthsafterhospitalisationwithcovid19andisnotinducedbysubsequentvaccination
AT swiebodad sarscov2specificnasaligawanes9monthsafterhospitalisationwithcovid19andisnotinducedbysubsequentvaccination
AT sidhujk sarscov2specificnasaligawanes9monthsafterhospitalisationwithcovid19andisnotinducedbysubsequentvaccination
AT efstathiouc sarscov2specificnasaligawanes9monthsafterhospitalisationwithcovid19andisnotinducedbysubsequentvaccination
AT mooresc sarscov2specificnasaligawanes9monthsafterhospitalisationwithcovid19andisnotinducedbysubsequentvaccination
AT davisc sarscov2specificnasaligawanes9monthsafterhospitalisationwithcovid19andisnotinducedbysubsequentvaccination
AT mohamedn sarscov2specificnasaligawanes9monthsafterhospitalisationwithcovid19andisnotinducedbysubsequentvaccination
AT nunagj sarscov2specificnasaligawanes9monthsafterhospitalisationwithcovid19andisnotinducedbysubsequentvaccination
AT kingc sarscov2specificnasaligawanes9monthsafterhospitalisationwithcovid19andisnotinducedbysubsequentvaccination
AT thompsonaar sarscov2specificnasaligawanes9monthsafterhospitalisationwithcovid19andisnotinducedbysubsequentvaccination
AT rowlandjonessl sarscov2specificnasaligawanes9monthsafterhospitalisationwithcovid19andisnotinducedbysubsequentvaccination
AT dochertyab sarscov2specificnasaligawanes9monthsafterhospitalisationwithcovid19andisnotinducedbysubsequentvaccination
AT chalmersjd sarscov2specificnasaligawanes9monthsafterhospitalisationwithcovid19andisnotinducedbysubsequentvaccination
AT holp sarscov2specificnasaligawanes9monthsafterhospitalisationwithcovid19andisnotinducedbysubsequentvaccination
AT horsleya sarscov2specificnasaligawanes9monthsafterhospitalisationwithcovid19andisnotinducedbysubsequentvaccination
AT ramanb sarscov2specificnasaligawanes9monthsafterhospitalisationwithcovid19andisnotinducedbysubsequentvaccination
AT poinasamyk sarscov2specificnasaligawanes9monthsafterhospitalisationwithcovid19andisnotinducedbysubsequentvaccination
AT marksm sarscov2specificnasaligawanes9monthsafterhospitalisationwithcovid19andisnotinducedbysubsequentvaccination
AT konom sarscov2specificnasaligawanes9monthsafterhospitalisationwithcovid19andisnotinducedbysubsequentvaccination
AT howardl sarscov2specificnasaligawanes9monthsafterhospitalisationwithcovid19andisnotinducedbysubsequentvaccination
AT woottondg sarscov2specificnasaligawanes9monthsafterhospitalisationwithcovid19andisnotinducedbysubsequentvaccination
AT dunachies sarscov2specificnasaligawanes9monthsafterhospitalisationwithcovid19andisnotinducedbysubsequentvaccination
AT quintjk sarscov2specificnasaligawanes9monthsafterhospitalisationwithcovid19andisnotinducedbysubsequentvaccination
AT evansra sarscov2specificnasaligawanes9monthsafterhospitalisationwithcovid19andisnotinducedbysubsequentvaccination
AT wainlv sarscov2specificnasaligawanes9monthsafterhospitalisationwithcovid19andisnotinducedbysubsequentvaccination
AT fontanellas sarscov2specificnasaligawanes9monthsafterhospitalisationwithcovid19andisnotinducedbysubsequentvaccination
AT desilvati sarscov2specificnasaligawanes9monthsafterhospitalisationwithcovid19andisnotinducedbysubsequentvaccination
AT hoa sarscov2specificnasaligawanes9monthsafterhospitalisationwithcovid19andisnotinducedbysubsequentvaccination
AT harrisone sarscov2specificnasaligawanes9monthsafterhospitalisationwithcovid19andisnotinducedbysubsequentvaccination
AT bailliejk sarscov2specificnasaligawanes9monthsafterhospitalisationwithcovid19andisnotinducedbysubsequentvaccination
AT semplemg sarscov2specificnasaligawanes9monthsafterhospitalisationwithcovid19andisnotinducedbysubsequentvaccination
AT brightlingc sarscov2specificnasaligawanes9monthsafterhospitalisationwithcovid19andisnotinducedbysubsequentvaccination
AT thwaitesrs sarscov2specificnasaligawanes9monthsafterhospitalisationwithcovid19andisnotinducedbysubsequentvaccination
AT turtlel sarscov2specificnasaligawanes9monthsafterhospitalisationwithcovid19andisnotinducedbysubsequentvaccination
AT openshawpjm sarscov2specificnasaligawanes9monthsafterhospitalisationwithcovid19andisnotinducedbysubsequentvaccination