Unravelling the role of secretory Immnuoglobulin-A in COVID-19: a multicentre study in nursing homes during the first wave.
COVID-19
Nursing homes
Secretory Immnuoglobulin-A
Journal
BMC geriatrics
ISSN: 1471-2318
Titre abrégé: BMC Geriatr
Pays: England
ID NLM: 100968548
Informations de publication
Date de publication:
01 Oct 2024
01 Oct 2024
Historique:
received:
26
10
2023
accepted:
24
09
2024
medline:
2
10
2024
pubmed:
2
10
2024
entrez:
1
10
2024
Statut:
epublish
Résumé
The function of mucosal secretory IgA (SIgA) seems to be paramount in the immune response against SARS-CoV-2 however, there are few studies addressing this issue specifically in the institutionalized older population. This study aims to determine the levels of secretory IgA against the S1 domain of the SARS-CoV-2 spike (SIgA-S1) in older people living in nursing homes (NH) and to investigate the differences in baseline characteristics, severity of COVID-19, duration of symptoms, 30-day mortality, and reinfection according to the levels of SIgA-S1. In this multicentre longitudinal study, conducted in two NHs attended in coordination with a hospital-based Geriatric team, 305 residents (87.3 years, 74.4% female) were included. A massive collection of nasopharyngeal samples was carried out after the first wave of COVID-19 in May 2020 and an ELISA analysis of SIgA-S1 was performed on frozen samples in May 2023. Values of SIgA-S1 ≥ 57.6 U/mL ("cut-off point") were considered "induced". Resident medical records were reviewed to assess symptoms, comprehensive geriatric assessment (CGA), reinfection, and overall 30-day mortality. At the time of sample collection, 274 residents (89.8%) exhibited "induced" SIgA-S1 levels (≥ 57.6 U/mL), 46 (15.1%) tested positive for PCR SARS-CoV-2, and 170 (57%) had experienced COVID-19 symptoms. "Induced" SIgA-S1 patients were more likely to be symptomatic (60.3% vs. 29%; p < 0.001) and exhibited upper respiratory tract symptoms more frequently (25.1% vs. 6.5%; p = 0.020) compared to "non-induced" patients. Patients with severe disease and duration of symptoms > 10 days had higher levels of SIgA-S1 than those with mild disease (252 vs.192.6 U/mL; p = 0.012) or duration ≤ 10 days (270.5 vs. 208.1 U/mL; p = 0.043), respectively. No significant differences were observed in age, sex, CGA, duration of symptoms, disease severity, overall 30-day-mortality, or reinfection between "induced" and "non-induced" residents. Levels of SIgA-S1 are associated with the duration and type of COVID-19 symptoms, along with the severity of infection. While these findings shed light on the knowledge of SIgA-S1, further interdisciplinary studies are warranted to better understand the immune response to SARS-CoV-2 infection.
Sections du résumé
BACKGROUND
BACKGROUND
The function of mucosal secretory IgA (SIgA) seems to be paramount in the immune response against SARS-CoV-2 however, there are few studies addressing this issue specifically in the institutionalized older population. This study aims to determine the levels of secretory IgA against the S1 domain of the SARS-CoV-2 spike (SIgA-S1) in older people living in nursing homes (NH) and to investigate the differences in baseline characteristics, severity of COVID-19, duration of symptoms, 30-day mortality, and reinfection according to the levels of SIgA-S1.
METHODS
METHODS
In this multicentre longitudinal study, conducted in two NHs attended in coordination with a hospital-based Geriatric team, 305 residents (87.3 years, 74.4% female) were included. A massive collection of nasopharyngeal samples was carried out after the first wave of COVID-19 in May 2020 and an ELISA analysis of SIgA-S1 was performed on frozen samples in May 2023. Values of SIgA-S1 ≥ 57.6 U/mL ("cut-off point") were considered "induced". Resident medical records were reviewed to assess symptoms, comprehensive geriatric assessment (CGA), reinfection, and overall 30-day mortality.
RESULTS
RESULTS
At the time of sample collection, 274 residents (89.8%) exhibited "induced" SIgA-S1 levels (≥ 57.6 U/mL), 46 (15.1%) tested positive for PCR SARS-CoV-2, and 170 (57%) had experienced COVID-19 symptoms. "Induced" SIgA-S1 patients were more likely to be symptomatic (60.3% vs. 29%; p < 0.001) and exhibited upper respiratory tract symptoms more frequently (25.1% vs. 6.5%; p = 0.020) compared to "non-induced" patients. Patients with severe disease and duration of symptoms > 10 days had higher levels of SIgA-S1 than those with mild disease (252 vs.192.6 U/mL; p = 0.012) or duration ≤ 10 days (270.5 vs. 208.1 U/mL; p = 0.043), respectively. No significant differences were observed in age, sex, CGA, duration of symptoms, disease severity, overall 30-day-mortality, or reinfection between "induced" and "non-induced" residents.
CONCLUSIONS
CONCLUSIONS
Levels of SIgA-S1 are associated with the duration and type of COVID-19 symptoms, along with the severity of infection. While these findings shed light on the knowledge of SIgA-S1, further interdisciplinary studies are warranted to better understand the immune response to SARS-CoV-2 infection.
Identifiants
pubmed: 39354348
doi: 10.1186/s12877-024-05402-6
pii: 10.1186/s12877-024-05402-6
doi:
Substances chimiques
Immunoglobulin A, Secretory
0
Spike Glycoprotein, Coronavirus
0
spike protein, SARS-CoV-2
0
Types de publication
Journal Article
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
804Informations de copyright
© 2024. The Author(s).
Références
Comas-Herrera A, Zalakain J. Mortality associated with COVID-19 outbreaks in care homes: early international evidence. Resour to Support community institutional Long-Term Care responses to COVID-19. 2020;(April):1–6. https://www.ontario.ca/page/how-ontario-is-responding-covid-19#section-1%0ALTCcovid.org
Abrams HR, Loomer L, Gandhi A, Grabowski DC. Characteristics of U.S. nursing Homes with COVID -19 cases. J Am Geriatr Soc. 2020.
Sette A, Crotty S. Adaptive immunity to SARS-CoV-2 and COVID-19. Cell. 2021 Feb 18 [cited 2023 Aug 31];184(4):861–80. https://pubmed.ncbi.nlm.nih.gov/33497610/
Diamond MS, Kanneganti TD. Innate immunity: the first line of defense against SARS-CoV-2. Nat Immunol. 2022 Feb 1 [cited 2023 Aug 31];23(2):165–76. https://pubmed.ncbi.nlm.nih.gov/35105981/
Khoury DS, Cromer D, Reynaldi A, Schlub TE, Wheatley AK, Juno JA et al. Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection. Nat Med. 2021 Jul 1 [cited 2023 Aug 31];27(7):1205–11. https://pubmed.ncbi.nlm.nih.gov/34002089/
Garcia-Beltran WF, Lam EC, Astudillo MG, Yang D, Miller TE, Feldman J et al. COVID-19-neutralizing antibodies predict disease severity and survival. Cell. 2021 Jan 21 [cited 2023 Aug 31];184(2):476–488.e11. https://pubmed.ncbi.nlm.nih.gov/33412089/
Russell MW, Moldoveanu Z, Ogra PL, Mestecky J. Mucosal Immunity in COVID-19: A Neglected but Critical Aspect of SARS-CoV-2 Infection. Front Immunol. 2020 Nov 30 [cited 2023 Aug 31];11. https://pubmed.ncbi.nlm.nih.gov/33329607/
Pilette C, Ouadrhiri Y, Godding V, Vaerman JP, Sibille Y. Lung mucosal immunity: immunoglobulin-A revisited. Eur Respir J. 2001 [cited 2023 Aug 31];18(3):571–88. https://pubmed.ncbi.nlm.nih.gov/11589357/
Brandtzaeg P. Mucosal and Glandular Distribution of Immunoglobulin Components: Differential localization of free and bound SC in secretory epithelial cells. J Immunol. 1974;112(4):1553–9.
doi: 10.4049/jimmunol.112.4.1553
pubmed: 4205532
Wang Z, Lorenzi JCC, Muecksch F, Finkin S, Viant C, Gaebler C et al. Enhanced SARS-CoV-2 neutralization by dimeric IgA. Sci Transl Med. 2021 Jan 20 [cited 2023 Aug 31];13(577). https://pubmed.ncbi.nlm.nih.gov/33288661/
Stokes CR, Soothill JF, Turner MW. Immune exclusion is a function of IgA. Nature. 1975 [cited 2023 Aug 31];255(5511):745–6. https://pubmed.ncbi.nlm.nih.gov/1169692/
Santos J, de MB CP, Monteiro FR, Mello R, Amaral JB do, Aguiar AS et al. In Nasal Mucosal Secretions, Distinct IFN and IgA Responses Are Found in Severe and Mild SARS-CoV-2 Infection. Front Immunol. 2021;12(February):1–11.
Cervia C, Nilsson J, Zurbuchen Y, Valaperti A, Schreiner J, Wolfensberger A et al. Systemic and mucosal antibody responses specific to SARS-CoV-2 during mild versus severe COVID-19. J Allergy Clin Immunol. 2021 Feb 1 [cited 2023 Aug 31];147(2):545–557.e9. https://pubmed.ncbi.nlm.nih.gov/33221383/
Takamatsu Y, Omata K, Shimizu Y, Kinoshita-Iwamoto N, Terada M, Suzuki T et al. SARS-CoV-2-Neutralizing Humoral IgA Response Occurs Earlier but Is Modest and Diminishes Faster than IgG Response. Microbiol Spectr. 2022 Dec 21 [cited 2023 Aug 31];10(6). https://pubmed.ncbi.nlm.nih.gov/36219096/
Sterlin D, Mathian A, Miyara M, Mohr A, Anna F, Claër L et al. IgA dominates the early neutralizing antibody response to SARS-CoV-2. Sci Transl Med. 2021 Jan 20 [cited 2023 Aug 31];13(577). https://pubmed.ncbi.nlm.nih.gov/33288662/
Fröberg J, Gillard J, Philipsen R, Lanke K, Rust J, van Tuijl D et al. SARS-CoV-2 mucosal antibody development and persistence and their relation to viral load and COVID-19 symptoms. Nat Commun. 2021 Dec 1 [cited 2023 Aug 31];12(1). https://pubmed.ncbi.nlm.nih.gov/34556667/
Classen DC, Morningstar JM, Shanley JD. Detection of antibody to murine cytomegalovirus by enzyme-linked immunosorbent and indirect immunofluorescence assays. J Clin Microbiol. 1987;25(4):600–4.
doi: 10.1128/jcm.25.4.600-604.1987
pubmed: 3033015
pmcid: 266042
Killick R, Eckley IA. changepoint: An R Package for Changepoint Analysis. J Stat Softw. 2014 Jun 25 [cited 2023 Sep 6];58(3):1–19. https://www.jstatsoft.org/index.php/jss/article/view/v058i03
Lardeux F, Torrico G, Aliaga C. Calculation of the ELISA’s cut-off based on the change-point analysis method for detection of Trypanosoma cruzi infection in Bolivian dogs in the absence of controls. Mem Inst Oswaldo Cruz. 2016 Aug 1 [cited 2023 Sep 6];111(8):501–4. https://pubmed.ncbi.nlm.nih.gov/27384081/
Page E. Continuous inspection schemes. Biometrika. 1954 Jun 1 [cited 2023 Sep 6];41(1–2):100–15. https://doi.org/10.1093/biomet/41.1-2.100
Wu Z, McGoogan JM. Characteristics of and important lessons from the Coronavirus Disease 2019 (COVID-19) outbreak in China: Summary of a report of 72314 cases from the Chinese Center for Disease Control and Prevention. JAMA - J Am Med Assoc. 2020;323(13):1239–42.
doi: 10.1001/jama.2020.2648
Who W. Clinical guidance of severe SARS when Covid19 disease is suspectef. Who. 2020;2019(December 2019):1–19.
Rangel-Ramírez VV, Macías-Piña KA, Servin-Garrido RR, de Alba-Aguayo DR, Moreno-Fierros L, Rubio-Infante N. A systematic review and meta-analysis of the IgA seroprevalence in COVID-19 patients: is there a role for IgA in COVID-19 diagnosis or severity? Microbiol Res. 2022;263(June).
Wians FH. Clinical laboratory tests: which, why, and what do the results mean? Lab Med. 2009;40(2):105–13.
doi: 10.1309/LM404L0HHUTWWUDD
Bielza R, Sanz J, Zambrana F, Arias E, Malmierca E, Portillo L et al. Clinical Characteristics, Frailty, and Mortality of Residents With COVID-19 in Nursing Homes of a Region of Madrid. J Am Med Dir Assoc. 2021;22(2):245–252.e2. https://doi.org/10.1016/j.jamda.2020.12.003
Zervou FN, Louie P, Stachel A, Zacharioudakis IM, Ortiz-Mendez Y, Thomas K, et al. SARS-CoV-2 antibodies: IgA correlates with severity of disease in early COVID-19 infection. J Med Virol. 2021;93(9):5409–15.
doi: 10.1002/jmv.27058
pubmed: 33932299
pmcid: 8242647
Mullins MO, Smith M, Maboreke H, Nel AJM, Ntusi NAB, Burgers WA, et al. Epitope Coverage of Anti-SARS-CoV-2 Nucleocapsid IgA and IgG antibodies correlates with Protection against Re-infection by New variants in subsequent waves of the COVID-19 pandemic. Viruses. 2023;15(2):1–11.
doi: 10.3390/v15020584
Fox T, Geppert J, Dinnes J, Scandrett K, Bigio J, Sulis G et al. Antibody tests for identification of current and past infection with SARS-CoV-2. Cochrane database Syst Rev. 2022 Nov 17 [cited 2023 Sep 4];11(11). https://pubmed.ncbi.nlm.nih.gov/36394900/
Liew F, Talwar S, Cross A, Willett BJ, Scott S, Logan N, et al. SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination. eBioMedicine. 2023;87:1–14.
doi: 10.1016/j.ebiom.2022.104402