Centenarians and extremely old people living with frailty can elicit durable SARS-CoV-2 spike specific IgG antibodies with virus neutralization functions following virus infection as determined by serological study

Mary K. Foley; Samuel D. Searle; Ali Toloue; Ryan Booth; Alec Falkenham; Darryl Falzarano; Salvatore Rubino; Magen E. Francis; Mara McNeil; Christopher Richardson; Jason LeBlanc; Sharon Oldford; Volker Gerdts; Melissa K. Andrew; Shelly A. McNeil; Barry Clarke; Kenneth Rockwood; David J. Kelvin; Alyson A. Kelvin

doi:10.1016/j.eclinm.2021.100975

Centenarians and extremely old people living with frailty can elicit durable SARS-CoV-2 spike specific IgG antibodies with virus neutralization functions following virus infection as determined by serological study

Mary K. Foley, Samuel D. Searle, Ali Toloue, Ryan Booth, Alec Falkenham, Darryl Falzarano, Salvatore Rubino, Magen E. Francis, Mara McNeil, Christopher Richardson, Jason LeBlanc, Sharon Oldford, Volker Gerdts, Melissa K. Andrew, Shelly A. McNeil, Barry Clarke, Kenneth Rockwood, David J. Kelvin, Alyson A. Kelvin

Résultat de recherche: Article › examen par les pairs

6 Citations (Scopus)

Résumé

Background: The SARS-CoV-2 (Severe Acute Respiratory Syndrome coronavirus 2) has led to more than 165 million COVID-19 cases and >3.4 million deaths worldwide. Epidemiological analysis has revealed that the risk of developing severe COVID-19 increases with age. Despite a disproportionate number of older individuals and long-term care facilities being affected by SARS-CoV-2 and COVID-19, very little is understood about the immune responses and development of humoral immunity in the extremely old person after SARS-CoV-2 infection. Here we conducted a serological study to investigate the development of humoral immunity in centenarians following a SARS-CoV-2 outbreak in a long-term care facility. Methods: Extreme aged individuals and centenarians who were residents in a long-term care facility and infected with or exposed to SARS-CoV-2 were investigated between April and June 2020 for the development of antibodies to SARS-CoV-2. Blood samples were collected from positive and bystander individuals 30 and 60 days after original diagnosis of SARS-CoV-2 infection. Plasma was used to quantify IgG, IgA, and IgM isotypes and subsequent subclasses of antibodies specific for SARS-CoV-2 spike protein. The function of anti-spike was then assessed by virus neutralization assays against the native SARS-CoV-2 virus. Findings: Fifteen long-term care residents were investigated for SARS-CoV-2 infection. All individuals had a Clinical Frailty scale score ≥5 and were of extreme older age or were centenarians. Six women with a median age of 98.8 years tested positive for SARS-CoV-2. Anti-spike IgG antibody titers were the highest titers observed in our cohort with all IgG positive individuals having virus neutralization ability. Additionally, 5 out of the 6 positive participants had a robust IgA anti-SARS-CoV-2 response. In all 5, antibodies were detected after 60 days from initial diagnosis.

Langue d'origine	English
Numéro d'article	100975
Journal	EClinicalMedicine
Volume	37
DOI	https://doi.org/10.1016/j.eclinm.2021.100975
Statut de publication	Published - juill. 2021

Note bibliographique

Funding Information:
We wish to thank all of the study participants for their involvement. This article is published with the permission of the Director of VIDO-InterVac with article number 932. The data reported in this manuscript are subject to access restriction to protect patient confidentiality. Inquiries can be made with the corresponding authors. Canadian Institutes of Health Research (CIHR), NIH/NIAID, Genome Atlantic. VIDO receives operational funding from the Canada Foundation for Innovation through the Major Science Initiatives Fund and by Government of Saskatchewan through Innovation Saskatchewan.

Funding Information:
Kenneth Rockwood – Dr. Rockwood reports personal fees from Clinical Cardio Day – Cape Breton University, personal fees from CRUIGM-Montreal, from Speaker at Jackson Lab, Bar Harbor MA, personal fees from Speaker at MouseAge Rome Italy, personal fees from Frontemporal Dementia Study Group, personal fees from SunLife Insurance Japan, outside the submitted work and Kenneth Rockwood is President and Co-founder of Ardea Outcomes, which in the last three years (as DGI Clinical) has contracts with pharma and device manufacturers (Shire, Hollister, Nutricia, Roche, Otsuka) on individualized outcome measurement. Otherwise any personal fees are for invited guest lectures and academic symposia, received directly from event organizers, chiefly for presentations on frailty. He is Associate Director of the Canadian Consortium on Neurodegeneration in Aging, which is funded by the Canadian Institutes of Health Research, and with additional funding from the Alzheimer Society of Canada and several other charities. He receives career support from the Dalhousie Medical Research Foundation as the Kathryn Allen Weldon Professor of Alzheimer Research, and research support from the Canadian Institutes of Health Research, The Canadian Frailty Network, the QEII Health Science centre Foundation, the Nova Scotia Health Research Fund and the Fountain Family Innovation Fund of the QEII Health Science centre Foundation.

Funding Information:
Melissa K. Andrew – Dr. Andrew reports grants from Sanofi, grants from GSK, grants from Pfizer, grants from Canadian Frailty Network, grants from CIHR, grans from Public Health Agency of Canada, personal fees from Sanofi, from Pfizer, personal fees from Seqirus, outside the submitted work.

Funding Information:
Samuel D. Searle - Dr. Searle received PhD and fellowship funding from the Canadian Frailty Network, Dalhousie Medical Research Foundation, Dalhousie University Internal Medicine Research Foundation and the QE II Innovation Fund.

Funding Information:
Canadian Institutes of Health Research (CIHR), NIH/NIAID, Genome Atlantic. VIDO receives operational funding from the Canada Foundation for Innovation through the Major Science Initiatives Fund and by Government of Saskatchewan through Innovation Saskatchewan.

Publisher Copyright:
© 2021 The Authors

ASJC Scopus Subject Areas

General Medicine

PubMed: MeSH publication types

Journal Article

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10.1016/j.eclinm.2021.100975

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Foley, M. K., Searle, S. D., Toloue, A., Booth, R., Falkenham, A., Falzarano, D., Rubino, S., Francis, M. E., McNeil, M., Richardson, C., LeBlanc, J., Oldford, S., Gerdts, V., Andrew, M. K., McNeil, S. A., Clarke, B., Rockwood, K., Kelvin, D. J., & Kelvin, A. A. (2021). Centenarians and extremely old people living with frailty can elicit durable SARS-CoV-2 spike specific IgG antibodies with virus neutralization functions following virus infection as determined by serological study. EClinicalMedicine, 37, Article 100975. https://doi.org/10.1016/j.eclinm.2021.100975

Centenarians and extremely old people living with frailty can elicit durable SARS-CoV-2 spike specific IgG antibodies with virus neutralization functions following virus infection as determined by serological study. / Foley, Mary K.; Searle, Samuel D.; Toloue, Ali et al.
Dans: EClinicalMedicine, Vol. 37, 100975, 07.2021.

Résultat de recherche: Article › examen par les pairs

Foley, MK, Searle, SD, Toloue, A, Booth, R, Falkenham, A, Falzarano, D, Rubino, S, Francis, ME, McNeil, M, Richardson, C, LeBlanc, J, Oldford, S, Gerdts, V, Andrew, MK, McNeil, SA, Clarke, B, Rockwood, K , Kelvin, DJ & Kelvin, AA 2021, 'Centenarians and extremely old people living with frailty can elicit durable SARS-CoV-2 spike specific IgG antibodies with virus neutralization functions following virus infection as determined by serological study', EClinicalMedicine, vol. 37, 100975. https://doi.org/10.1016/j.eclinm.2021.100975

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title = "Centenarians and extremely old people living with frailty can elicit durable SARS-CoV-2 spike specific IgG antibodies with virus neutralization functions following virus infection as determined by serological study",

abstract = "Background: The SARS-CoV-2 (Severe Acute Respiratory Syndrome coronavirus 2) has led to more than 165 million COVID-19 cases and >3.4 million deaths worldwide. Epidemiological analysis has revealed that the risk of developing severe COVID-19 increases with age. Despite a disproportionate number of older individuals and long-term care facilities being affected by SARS-CoV-2 and COVID-19, very little is understood about the immune responses and development of humoral immunity in the extremely old person after SARS-CoV-2 infection. Here we conducted a serological study to investigate the development of humoral immunity in centenarians following a SARS-CoV-2 outbreak in a long-term care facility. Methods: Extreme aged individuals and centenarians who were residents in a long-term care facility and infected with or exposed to SARS-CoV-2 were investigated between April and June 2020 for the development of antibodies to SARS-CoV-2. Blood samples were collected from positive and bystander individuals 30 and 60 days after original diagnosis of SARS-CoV-2 infection. Plasma was used to quantify IgG, IgA, and IgM isotypes and subsequent subclasses of antibodies specific for SARS-CoV-2 spike protein. The function of anti-spike was then assessed by virus neutralization assays against the native SARS-CoV-2 virus. Findings: Fifteen long-term care residents were investigated for SARS-CoV-2 infection. All individuals had a Clinical Frailty scale score ≥5 and were of extreme older age or were centenarians. Six women with a median age of 98.8 years tested positive for SARS-CoV-2. Anti-spike IgG antibody titers were the highest titers observed in our cohort with all IgG positive individuals having virus neutralization ability. Additionally, 5 out of the 6 positive participants had a robust IgA anti-SARS-CoV-2 response. In all 5, antibodies were detected after 60 days from initial diagnosis.",

author = "Foley, {Mary K.} and Searle, {Samuel D.} and Ali Toloue and Ryan Booth and Alec Falkenham and Darryl Falzarano and Salvatore Rubino and Francis, {Magen E.} and Mara McNeil and Christopher Richardson and Jason LeBlanc and Sharon Oldford and Volker Gerdts and Andrew, {Melissa K.} and McNeil, {Shelly A.} and Barry Clarke and Kenneth Rockwood and Kelvin, {David J.} and Kelvin, {Alyson A.}",

note = "Funding Information: We wish to thank all of the study participants for their involvement. This article is published with the permission of the Director of VIDO-InterVac with article number 932. The data reported in this manuscript are subject to access restriction to protect patient confidentiality. Inquiries can be made with the corresponding authors. Canadian Institutes of Health Research (CIHR), NIH/NIAID, Genome Atlantic. VIDO receives operational funding from the Canada Foundation for Innovation through the Major Science Initiatives Fund and by Government of Saskatchewan through Innovation Saskatchewan. Funding Information: Kenneth Rockwood – Dr. Rockwood reports personal fees from Clinical Cardio Day – Cape Breton University, personal fees from CRUIGM-Montreal, from Speaker at Jackson Lab, Bar Harbor MA, personal fees from Speaker at MouseAge Rome Italy, personal fees from Frontemporal Dementia Study Group, personal fees from SunLife Insurance Japan, outside the submitted work and Kenneth Rockwood is President and Co-founder of Ardea Outcomes, which in the last three years (as DGI Clinical) has contracts with pharma and device manufacturers (Shire, Hollister, Nutricia, Roche, Otsuka) on individualized outcome measurement. Otherwise any personal fees are for invited guest lectures and academic symposia, received directly from event organizers, chiefly for presentations on frailty. He is Associate Director of the Canadian Consortium on Neurodegeneration in Aging, which is funded by the Canadian Institutes of Health Research, and with additional funding from the Alzheimer Society of Canada and several other charities. He receives career support from the Dalhousie Medical Research Foundation as the Kathryn Allen Weldon Professor of Alzheimer Research, and research support from the Canadian Institutes of Health Research, The Canadian Frailty Network, the QEII Health Science centre Foundation, the Nova Scotia Health Research Fund and the Fountain Family Innovation Fund of the QEII Health Science centre Foundation. Funding Information: Melissa K. Andrew – Dr. Andrew reports grants from Sanofi, grants from GSK, grants from Pfizer, grants from Canadian Frailty Network, grants from CIHR, grans from Public Health Agency of Canada, personal fees from Sanofi, from Pfizer, personal fees from Seqirus, outside the submitted work. Funding Information: Samuel D. Searle - Dr. Searle received PhD and fellowship funding from the Canadian Frailty Network, Dalhousie Medical Research Foundation, Dalhousie University Internal Medicine Research Foundation and the QE II Innovation Fund. Funding Information: Canadian Institutes of Health Research (CIHR), NIH/NIAID, Genome Atlantic. VIDO receives operational funding from the Canada Foundation for Innovation through the Major Science Initiatives Fund and by Government of Saskatchewan through Innovation Saskatchewan. Publisher Copyright: {\textcopyright} 2021 The Authors",

year = "2021",

month = jul,

doi = "10.1016/j.eclinm.2021.100975",

language = "English",

volume = "37",

journal = "EClinicalMedicine",

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TY - JOUR

T1 - Centenarians and extremely old people living with frailty can elicit durable SARS-CoV-2 spike specific IgG antibodies with virus neutralization functions following virus infection as determined by serological study

AU - Foley, Mary K.

AU - Searle, Samuel D.

AU - Toloue, Ali

AU - Booth, Ryan

AU - Falkenham, Alec

AU - Falzarano, Darryl

AU - Rubino, Salvatore

AU - Francis, Magen E.

AU - McNeil, Mara

AU - Richardson, Christopher

AU - LeBlanc, Jason

AU - Oldford, Sharon

AU - Gerdts, Volker

AU - Andrew, Melissa K.

AU - McNeil, Shelly A.

AU - Clarke, Barry

AU - Rockwood, Kenneth

AU - Kelvin, David J.

AU - Kelvin, Alyson A.

N1 - Funding Information: We wish to thank all of the study participants for their involvement. This article is published with the permission of the Director of VIDO-InterVac with article number 932. The data reported in this manuscript are subject to access restriction to protect patient confidentiality. Inquiries can be made with the corresponding authors. Canadian Institutes of Health Research (CIHR), NIH/NIAID, Genome Atlantic. VIDO receives operational funding from the Canada Foundation for Innovation through the Major Science Initiatives Fund and by Government of Saskatchewan through Innovation Saskatchewan. Funding Information: Kenneth Rockwood – Dr. Rockwood reports personal fees from Clinical Cardio Day – Cape Breton University, personal fees from CRUIGM-Montreal, from Speaker at Jackson Lab, Bar Harbor MA, personal fees from Speaker at MouseAge Rome Italy, personal fees from Frontemporal Dementia Study Group, personal fees from SunLife Insurance Japan, outside the submitted work and Kenneth Rockwood is President and Co-founder of Ardea Outcomes, which in the last three years (as DGI Clinical) has contracts with pharma and device manufacturers (Shire, Hollister, Nutricia, Roche, Otsuka) on individualized outcome measurement. Otherwise any personal fees are for invited guest lectures and academic symposia, received directly from event organizers, chiefly for presentations on frailty. He is Associate Director of the Canadian Consortium on Neurodegeneration in Aging, which is funded by the Canadian Institutes of Health Research, and with additional funding from the Alzheimer Society of Canada and several other charities. He receives career support from the Dalhousie Medical Research Foundation as the Kathryn Allen Weldon Professor of Alzheimer Research, and research support from the Canadian Institutes of Health Research, The Canadian Frailty Network, the QEII Health Science centre Foundation, the Nova Scotia Health Research Fund and the Fountain Family Innovation Fund of the QEII Health Science centre Foundation. Funding Information: Melissa K. Andrew – Dr. Andrew reports grants from Sanofi, grants from GSK, grants from Pfizer, grants from Canadian Frailty Network, grants from CIHR, grans from Public Health Agency of Canada, personal fees from Sanofi, from Pfizer, personal fees from Seqirus, outside the submitted work. Funding Information: Samuel D. Searle - Dr. Searle received PhD and fellowship funding from the Canadian Frailty Network, Dalhousie Medical Research Foundation, Dalhousie University Internal Medicine Research Foundation and the QE II Innovation Fund. Funding Information: Canadian Institutes of Health Research (CIHR), NIH/NIAID, Genome Atlantic. VIDO receives operational funding from the Canada Foundation for Innovation through the Major Science Initiatives Fund and by Government of Saskatchewan through Innovation Saskatchewan. Publisher Copyright: © 2021 The Authors

PY - 2021/7

Y1 - 2021/7

N2 - Background: The SARS-CoV-2 (Severe Acute Respiratory Syndrome coronavirus 2) has led to more than 165 million COVID-19 cases and >3.4 million deaths worldwide. Epidemiological analysis has revealed that the risk of developing severe COVID-19 increases with age. Despite a disproportionate number of older individuals and long-term care facilities being affected by SARS-CoV-2 and COVID-19, very little is understood about the immune responses and development of humoral immunity in the extremely old person after SARS-CoV-2 infection. Here we conducted a serological study to investigate the development of humoral immunity in centenarians following a SARS-CoV-2 outbreak in a long-term care facility. Methods: Extreme aged individuals and centenarians who were residents in a long-term care facility and infected with or exposed to SARS-CoV-2 were investigated between April and June 2020 for the development of antibodies to SARS-CoV-2. Blood samples were collected from positive and bystander individuals 30 and 60 days after original diagnosis of SARS-CoV-2 infection. Plasma was used to quantify IgG, IgA, and IgM isotypes and subsequent subclasses of antibodies specific for SARS-CoV-2 spike protein. The function of anti-spike was then assessed by virus neutralization assays against the native SARS-CoV-2 virus. Findings: Fifteen long-term care residents were investigated for SARS-CoV-2 infection. All individuals had a Clinical Frailty scale score ≥5 and were of extreme older age or were centenarians. Six women with a median age of 98.8 years tested positive for SARS-CoV-2. Anti-spike IgG antibody titers were the highest titers observed in our cohort with all IgG positive individuals having virus neutralization ability. Additionally, 5 out of the 6 positive participants had a robust IgA anti-SARS-CoV-2 response. In all 5, antibodies were detected after 60 days from initial diagnosis.

AB - Background: The SARS-CoV-2 (Severe Acute Respiratory Syndrome coronavirus 2) has led to more than 165 million COVID-19 cases and >3.4 million deaths worldwide. Epidemiological analysis has revealed that the risk of developing severe COVID-19 increases with age. Despite a disproportionate number of older individuals and long-term care facilities being affected by SARS-CoV-2 and COVID-19, very little is understood about the immune responses and development of humoral immunity in the extremely old person after SARS-CoV-2 infection. Here we conducted a serological study to investigate the development of humoral immunity in centenarians following a SARS-CoV-2 outbreak in a long-term care facility. Methods: Extreme aged individuals and centenarians who were residents in a long-term care facility and infected with or exposed to SARS-CoV-2 were investigated between April and June 2020 for the development of antibodies to SARS-CoV-2. Blood samples were collected from positive and bystander individuals 30 and 60 days after original diagnosis of SARS-CoV-2 infection. Plasma was used to quantify IgG, IgA, and IgM isotypes and subsequent subclasses of antibodies specific for SARS-CoV-2 spike protein. The function of anti-spike was then assessed by virus neutralization assays against the native SARS-CoV-2 virus. Findings: Fifteen long-term care residents were investigated for SARS-CoV-2 infection. All individuals had a Clinical Frailty scale score ≥5 and were of extreme older age or were centenarians. Six women with a median age of 98.8 years tested positive for SARS-CoV-2. Anti-spike IgG antibody titers were the highest titers observed in our cohort with all IgG positive individuals having virus neutralization ability. Additionally, 5 out of the 6 positive participants had a robust IgA anti-SARS-CoV-2 response. In all 5, antibodies were detected after 60 days from initial diagnosis.

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