Ethnic differences in cellular and humoral immune responses to SARS-CoV-2 vaccination in UK healthcare workers: a cross-sectional analysis

Christopher A Martin; Joshua Nazareth; Amar Jarkhi; Daniel Pan; Mrinal Das; Nicola Logan; Sam Scott; Luke Bryant; Neha Abeywickrama; Oluwatobi Adeoye; Aleem Ahmed; Aqua Asif; Srini Bandi; Nisha George; Marjan Gohar; Laura J Gray; Ross Kaszuba; Jitendra Mangwani; Marianne Martin; Arumugam Moorthy; Valerie Renals; Lucy Teece; Denny Vail; Kamlesh Khunti; Paul Moss; Andrea Tattersall; Bassam Hallis; Ashley D Otter; Cathy Rowe; Brian J Willett; Pranab Haldar; Andrea Cooper; Manish Pareek

doi:10.1016/j.eclinm.2023.101926

Ethnic differences in cellular and humoral immune responses to SARS-CoV-2 vaccination in UK healthcare workers: a cross-sectional analysis

Christopher A Martin, Joshua Nazareth, Amar Jarkhi, Daniel Pan, Mrinal Das, Nicola Logan, Sam Scott, Luke Bryant, Neha Abeywickrama, Oluwatobi Adeoye, Aleem Ahmed, Aqua Asif, Srini Bandi, Nisha George, Marjan Gohar, Laura J Gray, Ross Kaszuba, Jitendra Mangwani, Marianne Martin, Arumugam MoorthyValerie Renals, Lucy Teece, Denny Vail, Kamlesh Khunti, Paul Moss, Andrea Tattersall, Bassam Hallis, Ashley D Otter, Cathy Rowe, Brian J Willett, Pranab Haldar, Andrea Cooper, Manish Pareek^*

^*Corresponding author for this work

Medical and Dental Sciences

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Abstract

BACKGROUND: Few studies have compared SARS-CoV-2 vaccine immunogenicity by ethnic group. We sought to establish whether cellular and humoral immune responses to SARS-CoV-2 vaccination differ according to ethnicity in UK Healthcare workers (HCWs).

METHODS: In this cross-sectional analysis, we used baseline data from two immunological cohort studies conducted in HCWs in Leicester, UK. Blood samples were collected between March 3, and September 16, 2021. We excluded HCW who had not received two doses of SARS-CoV-2 vaccine at the time of sampling and those who had serological evidence of previous SARS-CoV-2 infection. Outcome measures were SARS-CoV-2 spike-specific total antibody titre, neutralising antibody titre and ELISpot count. We compared our outcome measures by ethnic group using univariable (t tests and rank-sum tests depending on distribution) and multivariable (linear regression for antibody titres and negative binomial regression for ELISpot counts) tests. Multivariable analyses were adjusted for age, sex, vaccine type, length of interval between vaccine doses and time between vaccine administration and sample collection and expressed as adjusted geometric mean ratios (aGMRs) or adjusted incidence rate ratios (aIRRs). To assess differences in the early immune response to vaccination we also conducted analyses in a subcohort who provided samples between 14 and 50 days after their second dose of vaccine.

FINDINGS: The total number of HCWs in each analysis were 401 for anti-spike antibody titres, 345 for neutralising antibody titres and 191 for ELISpot. Overall, 25.4% (19.7% South Asian and 5.7% Black/Mixed/Other) were from ethnic minority groups. In analyses including the whole cohort, neutralising antibody titres were higher in South Asian HCWs than White HCWs (aGMR 1.47, 95% CI [1.06-2.06], P = 0.02) as were T cell responses to SARS-CoV-2 S1 peptides (aIRR 1.75, 95% CI [1.05-2.89], P = 0.03). In a subcohort sampled between 14 and 50 days after second vaccine dose, SARS-CoV-2 spike-specific antibody and neutralising antibody geometric mean titre (GMT) was higher in South Asian HCWs compared to White HCWs (9616 binding antibody units (BAU)/ml, 95% CI [7178-12,852] vs 5888 BAU/ml [5023-6902], P = 0.008 and 2851 95% CI [1811-4487] vs 1199 [984-1462], P < 0.001 respectively), increments which persisted after adjustment (aGMR 1.26, 95% CI [1.01-1.58], P = 0.04 and aGMR 2.01, 95% CI [1.34-3.01], P = 0.001). SARS-CoV-2 ELISpot responses to S1 and whole spike peptides (S1 + S2 response) were higher in HCWs from South Asian ethnic groups than those from White groups (S1: aIRR 2.33, 95% CI [1.09-4.94], P = 0.03; spike: aIRR, 2.04, 95% CI [1.02-4.08]).

INTERPRETATION: This study provides evidence that, in an infection naïve cohort, humoral and cellular immune responses to SARS-CoV-2 vaccination are stronger in South Asian HCWs than White HCWs. These differences are most clearly seen in the early period following vaccination. Further research is required to understand the underlying mechanisms, whether differences persist with further exposure to vaccine or virus, and the potential impact on vaccine effectiveness.

FUNDING: DIRECT and BELIEVE have received funding from UK Research and Innovation (UKRI) through the COVID-19 National Core Studies Immunity (NCSi) programme (MC_PC_20060).

Original language	English
Article number	101926
Number of pages	16
Journal	EClinicalMedicine
Volume	58
DOIs	https://doi.org/10.1016/j.eclinm.2023.101926
Publication status	Published - 4 Apr 2023

Bibliographical note

Acknowledgements:
We would like to thank all the participants who have taken part in this study when the NHS is under immense pressure. We would also like to thank all the staff in the Research Space at Leicester Royal Infirmary, without whom this work would not have been possible. LJG and KK are supported by the National Institute for Health and Care Research (NIHR) Applied Research Collaboration East Midlands (ARC EM) and Leicester NIHR Biomedical Research Centre (BRC). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. DIRECT and BELIEVE have received funding from UK Research and Innovation (UKRI) through the COVID-19 National Core Studies Immunity (NCSi) programme (MC_PC_20060). BELIEVE was originally established as an influenza study funded by Sanofi. JN is an NIHR Academic Clinical Fellow. DP is an NIHR doctoral fellow. MP is funded by a NIHR Development and Skills Enhancement Award.

Copyright:
© 2023 The Author(s).

Keywords

SARS-CoV-2
COVID-19
Vaccine
Ethnicity
Heathcare worker

UN SDGs

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

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Cite this

Martin, C. A., Nazareth, J., Jarkhi, A., Pan, D., Das, M., Logan, N., Scott, S., Bryant, L., Abeywickrama, N., Adeoye, O., Ahmed, A., Asif, A., Bandi, S., George, N., Gohar, M., Gray, L. J., Kaszuba, R., Mangwani, J., Martin, M., ... Pareek, M. (2023). Ethnic differences in cellular and humoral immune responses to SARS-CoV-2 vaccination in UK healthcare workers: a cross-sectional analysis. EClinicalMedicine, 58, Article 101926. https://doi.org/10.1016/j.eclinm.2023.101926

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title = "Ethnic differences in cellular and humoral immune responses to SARS-CoV-2 vaccination in UK healthcare workers: a cross-sectional analysis",

abstract = "BACKGROUND: Few studies have compared SARS-CoV-2 vaccine immunogenicity by ethnic group. We sought to establish whether cellular and humoral immune responses to SARS-CoV-2 vaccination differ according to ethnicity in UK Healthcare workers (HCWs).METHODS: In this cross-sectional analysis, we used baseline data from two immunological cohort studies conducted in HCWs in Leicester, UK. Blood samples were collected between March 3, and September 16, 2021. We excluded HCW who had not received two doses of SARS-CoV-2 vaccine at the time of sampling and those who had serological evidence of previous SARS-CoV-2 infection. Outcome measures were SARS-CoV-2 spike-specific total antibody titre, neutralising antibody titre and ELISpot count. We compared our outcome measures by ethnic group using univariable (t tests and rank-sum tests depending on distribution) and multivariable (linear regression for antibody titres and negative binomial regression for ELISpot counts) tests. Multivariable analyses were adjusted for age, sex, vaccine type, length of interval between vaccine doses and time between vaccine administration and sample collection and expressed as adjusted geometric mean ratios (aGMRs) or adjusted incidence rate ratios (aIRRs). To assess differences in the early immune response to vaccination we also conducted analyses in a subcohort who provided samples between 14 and 50 days after their second dose of vaccine. FINDINGS: The total number of HCWs in each analysis were 401 for anti-spike antibody titres, 345 for neutralising antibody titres and 191 for ELISpot. Overall, 25.4% (19.7% South Asian and 5.7% Black/Mixed/Other) were from ethnic minority groups. In analyses including the whole cohort, neutralising antibody titres were higher in South Asian HCWs than White HCWs (aGMR 1.47, 95% CI [1.06-2.06], P = 0.02) as were T cell responses to SARS-CoV-2 S1 peptides (aIRR 1.75, 95% CI [1.05-2.89], P = 0.03). In a subcohort sampled between 14 and 50 days after second vaccine dose, SARS-CoV-2 spike-specific antibody and neutralising antibody geometric mean titre (GMT) was higher in South Asian HCWs compared to White HCWs (9616 binding antibody units (BAU)/ml, 95% CI [7178-12,852] vs 5888 BAU/ml [5023-6902], P = 0.008 and 2851 95% CI [1811-4487] vs 1199 [984-1462], P < 0.001 respectively), increments which persisted after adjustment (aGMR 1.26, 95% CI [1.01-1.58], P = 0.04 and aGMR 2.01, 95% CI [1.34-3.01], P = 0.001). SARS-CoV-2 ELISpot responses to S1 and whole spike peptides (S1 + S2 response) were higher in HCWs from South Asian ethnic groups than those from White groups (S1: aIRR 2.33, 95% CI [1.09-4.94], P = 0.03; spike: aIRR, 2.04, 95% CI [1.02-4.08]).INTERPRETATION: This study provides evidence that, in an infection na{\"i}ve cohort, humoral and cellular immune responses to SARS-CoV-2 vaccination are stronger in South Asian HCWs than White HCWs. These differences are most clearly seen in the early period following vaccination. Further research is required to understand the underlying mechanisms, whether differences persist with further exposure to vaccine or virus, and the potential impact on vaccine effectiveness.FUNDING: DIRECT and BELIEVE have received funding from UK Research and Innovation (UKRI) through the COVID-19 National Core Studies Immunity (NCSi) programme (MC_PC_20060).",

keywords = "SARS-CoV-2, COVID-19, Vaccine, Ethnicity, Heathcare worker",

author = "Martin, {Christopher A} and Joshua Nazareth and Amar Jarkhi and Daniel Pan and Mrinal Das and Nicola Logan and Sam Scott and Luke Bryant and Neha Abeywickrama and Oluwatobi Adeoye and Aleem Ahmed and Aqua Asif and Srini Bandi and Nisha George and Marjan Gohar and Gray, {Laura J} and Ross Kaszuba and Jitendra Mangwani and Marianne Martin and Arumugam Moorthy and Valerie Renals and Lucy Teece and Denny Vail and Kamlesh Khunti and Paul Moss and Andrea Tattersall and Bassam Hallis and Otter, {Ashley D} and Cathy Rowe and Willett, {Brian J} and Pranab Haldar and Andrea Cooper and Manish Pareek",

note = "Acknowledgements: We would like to thank all the participants who have taken part in this study when the NHS is under immense pressure. We would also like to thank all the staff in the Research Space at Leicester Royal Infirmary, without whom this work would not have been possible. LJG and KK are supported by the National Institute for Health and Care Research (NIHR) Applied Research Collaboration East Midlands (ARC EM) and Leicester NIHR Biomedical Research Centre (BRC). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. DIRECT and BELIEVE have received funding from UK Research and Innovation (UKRI) through the COVID-19 National Core Studies Immunity (NCSi) programme (MC_PC_20060). BELIEVE was originally established as an influenza study funded by Sanofi. JN is an NIHR Academic Clinical Fellow. DP is an NIHR doctoral fellow. MP is funded by a NIHR Development and Skills Enhancement Award. Copyright: {\textcopyright} 2023 The Author(s).",

year = "2023",

month = apr,

day = "4",

doi = "10.1016/j.eclinm.2023.101926",

language = "English",

volume = "58",

journal = "EClinicalMedicine",

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Martin, CA, Nazareth, J, Jarkhi, A, Pan, D, Das, M, Logan, N, Scott, S, Bryant, L, Abeywickrama, N, Adeoye, O, Ahmed, A, Asif, A, Bandi, S, George, N, Gohar, M, Gray, LJ, Kaszuba, R, Mangwani, J, Martin, M, Moorthy, A, Renals, V, Teece, L, Vail, D, Khunti, K, Moss, P, Tattersall, A, Hallis, B, Otter, AD, Rowe, C, Willett, BJ, Haldar, P, Cooper, A & Pareek, M 2023, 'Ethnic differences in cellular and humoral immune responses to SARS-CoV-2 vaccination in UK healthcare workers: a cross-sectional analysis', EClinicalMedicine, vol. 58, 101926. https://doi.org/10.1016/j.eclinm.2023.101926

TY - JOUR

T1 - Ethnic differences in cellular and humoral immune responses to SARS-CoV-2 vaccination in UK healthcare workers

T2 - a cross-sectional analysis

AU - Martin, Christopher A

AU - Nazareth, Joshua

AU - Jarkhi, Amar

AU - Pan, Daniel

AU - Das, Mrinal

AU - Logan, Nicola

AU - Scott, Sam

AU - Bryant, Luke

AU - Abeywickrama, Neha

AU - Adeoye, Oluwatobi

AU - Ahmed, Aleem

AU - Asif, Aqua

AU - Bandi, Srini

AU - George, Nisha

AU - Gohar, Marjan

AU - Gray, Laura J

AU - Kaszuba, Ross

AU - Mangwani, Jitendra

AU - Martin, Marianne

AU - Moorthy, Arumugam

AU - Renals, Valerie

AU - Teece, Lucy

AU - Vail, Denny

AU - Khunti, Kamlesh

AU - Moss, Paul

AU - Tattersall, Andrea

AU - Hallis, Bassam

AU - Otter, Ashley D

AU - Rowe, Cathy

AU - Willett, Brian J

AU - Haldar, Pranab

AU - Cooper, Andrea

AU - Pareek, Manish

N1 - Acknowledgements: We would like to thank all the participants who have taken part in this study when the NHS is under immense pressure. We would also like to thank all the staff in the Research Space at Leicester Royal Infirmary, without whom this work would not have been possible. LJG and KK are supported by the National Institute for Health and Care Research (NIHR) Applied Research Collaboration East Midlands (ARC EM) and Leicester NIHR Biomedical Research Centre (BRC). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. DIRECT and BELIEVE have received funding from UK Research and Innovation (UKRI) through the COVID-19 National Core Studies Immunity (NCSi) programme (MC_PC_20060). BELIEVE was originally established as an influenza study funded by Sanofi. JN is an NIHR Academic Clinical Fellow. DP is an NIHR doctoral fellow. MP is funded by a NIHR Development and Skills Enhancement Award. Copyright: © 2023 The Author(s).

PY - 2023/4/4

Y1 - 2023/4/4

N2 - BACKGROUND: Few studies have compared SARS-CoV-2 vaccine immunogenicity by ethnic group. We sought to establish whether cellular and humoral immune responses to SARS-CoV-2 vaccination differ according to ethnicity in UK Healthcare workers (HCWs).METHODS: In this cross-sectional analysis, we used baseline data from two immunological cohort studies conducted in HCWs in Leicester, UK. Blood samples were collected between March 3, and September 16, 2021. We excluded HCW who had not received two doses of SARS-CoV-2 vaccine at the time of sampling and those who had serological evidence of previous SARS-CoV-2 infection. Outcome measures were SARS-CoV-2 spike-specific total antibody titre, neutralising antibody titre and ELISpot count. We compared our outcome measures by ethnic group using univariable (t tests and rank-sum tests depending on distribution) and multivariable (linear regression for antibody titres and negative binomial regression for ELISpot counts) tests. Multivariable analyses were adjusted for age, sex, vaccine type, length of interval between vaccine doses and time between vaccine administration and sample collection and expressed as adjusted geometric mean ratios (aGMRs) or adjusted incidence rate ratios (aIRRs). To assess differences in the early immune response to vaccination we also conducted analyses in a subcohort who provided samples between 14 and 50 days after their second dose of vaccine. FINDINGS: The total number of HCWs in each analysis were 401 for anti-spike antibody titres, 345 for neutralising antibody titres and 191 for ELISpot. Overall, 25.4% (19.7% South Asian and 5.7% Black/Mixed/Other) were from ethnic minority groups. In analyses including the whole cohort, neutralising antibody titres were higher in South Asian HCWs than White HCWs (aGMR 1.47, 95% CI [1.06-2.06], P = 0.02) as were T cell responses to SARS-CoV-2 S1 peptides (aIRR 1.75, 95% CI [1.05-2.89], P = 0.03). In a subcohort sampled between 14 and 50 days after second vaccine dose, SARS-CoV-2 spike-specific antibody and neutralising antibody geometric mean titre (GMT) was higher in South Asian HCWs compared to White HCWs (9616 binding antibody units (BAU)/ml, 95% CI [7178-12,852] vs 5888 BAU/ml [5023-6902], P = 0.008 and 2851 95% CI [1811-4487] vs 1199 [984-1462], P < 0.001 respectively), increments which persisted after adjustment (aGMR 1.26, 95% CI [1.01-1.58], P = 0.04 and aGMR 2.01, 95% CI [1.34-3.01], P = 0.001). SARS-CoV-2 ELISpot responses to S1 and whole spike peptides (S1 + S2 response) were higher in HCWs from South Asian ethnic groups than those from White groups (S1: aIRR 2.33, 95% CI [1.09-4.94], P = 0.03; spike: aIRR, 2.04, 95% CI [1.02-4.08]).INTERPRETATION: This study provides evidence that, in an infection naïve cohort, humoral and cellular immune responses to SARS-CoV-2 vaccination are stronger in South Asian HCWs than White HCWs. These differences are most clearly seen in the early period following vaccination. Further research is required to understand the underlying mechanisms, whether differences persist with further exposure to vaccine or virus, and the potential impact on vaccine effectiveness.FUNDING: DIRECT and BELIEVE have received funding from UK Research and Innovation (UKRI) through the COVID-19 National Core Studies Immunity (NCSi) programme (MC_PC_20060).

AB - BACKGROUND: Few studies have compared SARS-CoV-2 vaccine immunogenicity by ethnic group. We sought to establish whether cellular and humoral immune responses to SARS-CoV-2 vaccination differ according to ethnicity in UK Healthcare workers (HCWs).METHODS: In this cross-sectional analysis, we used baseline data from two immunological cohort studies conducted in HCWs in Leicester, UK. Blood samples were collected between March 3, and September 16, 2021. We excluded HCW who had not received two doses of SARS-CoV-2 vaccine at the time of sampling and those who had serological evidence of previous SARS-CoV-2 infection. Outcome measures were SARS-CoV-2 spike-specific total antibody titre, neutralising antibody titre and ELISpot count. We compared our outcome measures by ethnic group using univariable (t tests and rank-sum tests depending on distribution) and multivariable (linear regression for antibody titres and negative binomial regression for ELISpot counts) tests. Multivariable analyses were adjusted for age, sex, vaccine type, length of interval between vaccine doses and time between vaccine administration and sample collection and expressed as adjusted geometric mean ratios (aGMRs) or adjusted incidence rate ratios (aIRRs). To assess differences in the early immune response to vaccination we also conducted analyses in a subcohort who provided samples between 14 and 50 days after their second dose of vaccine. FINDINGS: The total number of HCWs in each analysis were 401 for anti-spike antibody titres, 345 for neutralising antibody titres and 191 for ELISpot. Overall, 25.4% (19.7% South Asian and 5.7% Black/Mixed/Other) were from ethnic minority groups. In analyses including the whole cohort, neutralising antibody titres were higher in South Asian HCWs than White HCWs (aGMR 1.47, 95% CI [1.06-2.06], P = 0.02) as were T cell responses to SARS-CoV-2 S1 peptides (aIRR 1.75, 95% CI [1.05-2.89], P = 0.03). In a subcohort sampled between 14 and 50 days after second vaccine dose, SARS-CoV-2 spike-specific antibody and neutralising antibody geometric mean titre (GMT) was higher in South Asian HCWs compared to White HCWs (9616 binding antibody units (BAU)/ml, 95% CI [7178-12,852] vs 5888 BAU/ml [5023-6902], P = 0.008 and 2851 95% CI [1811-4487] vs 1199 [984-1462], P < 0.001 respectively), increments which persisted after adjustment (aGMR 1.26, 95% CI [1.01-1.58], P = 0.04 and aGMR 2.01, 95% CI [1.34-3.01], P = 0.001). SARS-CoV-2 ELISpot responses to S1 and whole spike peptides (S1 + S2 response) were higher in HCWs from South Asian ethnic groups than those from White groups (S1: aIRR 2.33, 95% CI [1.09-4.94], P = 0.03; spike: aIRR, 2.04, 95% CI [1.02-4.08]).INTERPRETATION: This study provides evidence that, in an infection naïve cohort, humoral and cellular immune responses to SARS-CoV-2 vaccination are stronger in South Asian HCWs than White HCWs. These differences are most clearly seen in the early period following vaccination. Further research is required to understand the underlying mechanisms, whether differences persist with further exposure to vaccine or virus, and the potential impact on vaccine effectiveness.FUNDING: DIRECT and BELIEVE have received funding from UK Research and Innovation (UKRI) through the COVID-19 National Core Studies Immunity (NCSi) programme (MC_PC_20060).

KW - SARS-CoV-2

KW - COVID-19

KW - Vaccine

KW - Ethnicity

KW - Heathcare worker

U2 - 10.1016/j.eclinm.2023.101926

DO - 10.1016/j.eclinm.2023.101926

M3 - Article

C2 - 37034357

SN - 2589-5370

VL - 58

JO - EClinicalMedicine

JF - EClinicalMedicine

M1 - 101926

ER -