Impact of age and gender on lymphocyte subset counts in patients with COVID-19.
COVID-19
SARS-CoV-2
age-related
gender-related
lymphocytopenia
Journal
Cytometry. Part A : the journal of the International Society for Analytical Cytology
ISSN: 1552-4930
Titre abrégé: Cytometry A
Pays: United States
ID NLM: 101235694
Informations de publication
Date de publication:
02 2023
02 2023
Historique:
revised:
05
05
2021
received:
30
03
2021
accepted:
25
05
2021
pubmed:
15
6
2021
medline:
15
2
2023
entrez:
14
6
2021
Statut:
ppublish
Résumé
In symptomatic patients with acute Coronavirus disease 2019 (COVID-19), lymphocytopenia is one of the most prominent laboratory findings. However, to date age and gender have not been considered in assessment of COVID-19-related cell count alterations. In this study, the impact of COVID-19 as well as age and gender on a large variety of lymphocyte subsets was analyzed in 33 COVID-19 patients and compared with cell counts in 50 healthy humans. We confirm that cell counts of total lymphocytes, B, NK, cytotoxic and helper T cells are reduced in patients with severe COVID-19, and this tendency was observed in patients with moderate COVID-19. Decreased cell counts were also found in all subsets of these cell types, except for CD4+ and CD8+ effector memory RA+ (EMRA) and terminal effector CD8+ cells. In multivariate analysis however, we show that in addition to COVID-19, there is an age-dependent reduction of total, central memory (CM), and early CD8+ cell subsets, as well as naïve, CM, and regulatory CD4+ cell subsets. Remarkably, reduced naïve CD8+ cell counts could be attributed to age alone, and not to COVID-19. By contrast, decreases in other subsets could be largely attributed to COVID-19, and only partly to age. In addition to COVID-19, male gender was a major factor influencing lower counts of CD3+ and CD4+ lymphocyte numbers. Our study confirms that cell counts of lymphocytes and their subsets are reduced in patients with COVID-19, but that age and gender must be considered when interpreting the altered cell counts.
Identifiants
pubmed: 34125495
doi: 10.1002/cyto.a.24470
pmc: PMC8426831
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
127-135Informations de copyright
© 2021 The Authors. Cytometry Part A published by Wiley Periodicals LLC on behalf of International Society for Advancement of Cytometry.
Références
Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020;382:727-33.
Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020;323:1061-9.
Schaller T, Hirschbuhl K, Burkhardt K, Braun G, Trepel M, Markl B, et al. Postmortem examination of patients with COVID-19. JAMA. 2020;323:2518-20.
Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395:1054-62.
Vabret N, Britton GJ, Gruber C, Hegde S, Kim J, Kuksin M, et al. Immunology of COVID-19: current state of the science. Immunity. 2020;52:910-41.
Henry BM, de Oliveira MHS, Benoit S, Plebani M, Lippi G. Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): a meta-analysis. Clin Chem Lab Med. 2020;58:1021-8.
Chen G, Wu D, Guo W, Cao Y, Huang D, Wang H, et al. Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest. 2020;130:2620-9.
Huang W, Berube J, McNamara M, Saksena S, Hartman M, Arshad T, et al. Lymphocyte subset counts in COVID-19 patients: a meta-analysis. Cytometry A. 2020;97:772-6.
Kverneland AH, Streitz M, Geissler E, Hutchinson J, Vogt K, Boes D, et al. Age and gender leucocytes variances and references values generated using the standardized ONE-study protocol. Cytometry A. 2016;89:543-64.
Andreu-Ballester JC, Garcia-Ballesteros C, Benet-Campos C, Amigo V, Almela-Quilis A, Mayans J, et al. Values for alphabeta and gammadelta T-lymphocytes and CD4+, CD8+, and CD56+ subsets in healthy adult subjects: assessment by age and gender. Cytometry B Clin Cytom. 2012;82:238-44.
WHO. Clinical management of severe acute respiratory infection when COVID-19 is suspected. Interim guidance. 13 March 2020. 2020.
Rank A, Lohr P, Hoffmann R, Ebigbo A, Grutzner S, Schmid C, et al. Sustained cellular immunity in adults recovered from mild COVID-19. Cytometry A. 2021;99:429-34.
Diao B, Wang C, Tan Y, Chen X, Liu Y, Ning L, et al. Reduction and functional exhaustion of T cells in patients with coronavirus disease 2019 (COVID-19). Front Immunol. 2020;11:827.
Qin C, Zhou L, Hu Z, Zhang S, Yang S, Tao Y, et al. Dysregulation of immune response in patients with coronavirus 2019 (COVID-19) in Wuhan, China. Clin Infect Dis. 2020;71:762-8.
He Z, Zhao C, Dong Q, Zhuang H, Song S, Peng G, et al. Effects of severe acute respiratory syndrome (SARS) coronavirus infection on peripheral blood lymphocytes and their subsets. Int J Infect Dis. 2005;9:323-30.
Gratama JW, Kardol M, Naipal AM, Slats J, Den Ouden A, Stijnen T, et al. The influence of cytomegalovirus carrier status on lymphocyte subsets and natural immunity. Clin Exp Immunol. 1987;69:16-24.
Niu MT, Stein DS, Schnittman SM. Primary human immunodeficiency virus type 1 infection: review of pathogenesis and early treatment intervention in humans and animal retrovirus infections. J Infect Dis. 1993;168:1490-501.
Callan MF. The evolution of antigen-specific CD8+ T cell responses after natural primary infection of humans with Epstein-Barr virus. Viral Immunol. 2003;16:3-16.
Zitzow LA, Rowe T, Morken T, Shieh WJ, Zaki S, Katz JM. Pathogenesis of avian influenza A (H5N1) viruses in ferrets. J Virol. 2002;76:4420-9.
O'Donnell DR, Carrington D. Peripheral blood lymphopenia and neutrophilia in children with severe respiratory syncytial virus disease. Pediatr Pulmonol. 2002;34:128-30.
Bautista EM, Ferman GS, Golde WT. Induction of lymphopenia and inhibition of T cell function during acute infection of swine with foot and mouth disease virus (FMDV). Vet Immunol Immunopathol. 2003;92:61-73.
Li T, Qiu Z, Zhang L, Han Y, He W, Liu Z, et al. Significant changes of peripheral T lymphocyte subsets in patients with severe acute respiratory syndrome. J Infect Dis. 2004;189:648-51.
Wang F, Nie J, Wang H, Zhao Q, Xiong Y, Deng L, et al. Characteristics of peripheral lymphocyte subset alteration in COVID-19 pneumonia. J Infect Dis. 2020;221:1762-9.
Liao M, Liu Y, Yuan J, Wen Y, Xu G, Zhao J, et al. Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19. Nat Med. 2020;26:842-4.
Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020;8:420-2.
Li M, Yao D, Zeng X, Kasakovski D, Zhang Y, Chen S, et al. Age related human T cell subset evolution and senescence. Immun Ageing. 2019;16:24.
Saule P, Trauet J, Dutriez V, Lekeux V, Dessaint JP, Labalette M. Accumulation of memory T cells from childhood to old age: central and effector memory cells in CD4(+) versus effector memory and terminally differentiated memory cells in CD8(+) compartment. Mech Ageing Dev. 2006;127:274-81.
Goronzy JJ, Fang F, Cavanagh MM, Qi Q, Weyand CM. Naive T cell maintenance and function in human aging. J Immunol. 2015;194:4073-80.
Chinn IK, Blackburn CC, Manley NR, Sempowski GD. Changes in primary lymphoid organs with aging. Semin Immunol. 2012;24:309-20.
Farber DL, Yudanin NA, Restifo NP. Human memory T cells: generation, compartmentalization and homeostasis. Nat Rev Immunol. 2014;14:24-35.
Palmer DB. The effect of age on thymic function. Front Immunol. 2013;4:316.
Song C-Y, Xu J, He J-Q, Lu Y-Q. COVID-19 early warning score: a multi-parameter screening tool to identify highly suspected patients. medRxiv. 2020;2020.03.05.20031906.
Zheng M, Gao Y, Wang G, Song G, Liu S, Sun D, et al. Functional exhaustion of antiviral lymphocytes in COVID-19 patients. Cell Mol Immunol. 2020;17:533-5.
National Research Project for SARS BG. The involvement of natural killer cells in the pathogenesis of severe acute respiratory syndrome. Am J Clin Pathol. 2004;121:507-11.