The CD4 cell level as a predictive factor for the outcome severity and prognosis of patients with COVID-19

Keshtkar Rajabi, Shahin; Divsalar, Farshad; Montazer, Fatemeh; Motamed-gorji, Nogol; Azh, Nima; Abbasi, Mohammad Amin

doi:10.61186/rabms.11.1.11

Volume 11, Issue 1 (1-2025) Journal of Research in Applied and Basic Medical Sciences 2025, 11(1): 11-18 | Back to browse issues page

‎ 10.61186/rabms.11.1.11

Ethics code: IR.IUMS.REC.1399.007

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Keshtkar Rajabi S, Divsalar F, Montazer F, Motamed-gorji N, Azh N, Abbasi M A. The CD4 cell level as a predictive factor for the outcome severity and prognosis of patients with COVID-19. Journal of Research in Applied and Basic Medical Sciences 2025; 11 (1) :11-18
URL: http://ijrabms.umsu.ac.ir/article-1-353-en.html

The CD4 cell level as a predictive factor for the outcome severity and prognosis of patients with COVID-19

Shahin Keshtkar Rajabi

, Farshad Divsalar

, Fatemeh Montazer

, Nogol Motamed-gorji

, Nima Azh

, Mohammad Amin Abbasi ^*

Firoozabadi clinical research development unit (FCRDU), School of Medicine, Iran University of Medical Sciences (IUMS), Tehran, Iran , amin.abbasi1314@gmail.com

Abstract: (449 Views)

Background & Aims: Coronavirus disease 2019 (COVID-19) leads to the activation of immune cells, especially in patients developing severe disease, and induces lymphopenia, primarily affecting the cluster of differentiation 4 T-cell (CD4+ T) subset. The presence of lymphopenia and cytokine storm may play a major role in the pathogenesis of COVID-19. This prospective single-center study aimed to assess the association between CD4 cell levels and the severity and prognosis of COVID-19 pneumonia, comparing the differences in lymphocyte subsets and inflammatory biomarkers between severe and non-severe cases using flow cytometry.
Materials & Methods: Between March 1 and June 30, 2020, a cohort of 122 RT-PCR-confirmed COVID-19 patients was enrolled in this prospective study. CD4 levels and other laboratory data were measured at the beginning of hospitalization.
Results: Of the 122 patients, 56 were admitted to the respiratory ward and 66 to the ICU. ICU patients had significantly lower CD4 counts (368.93 cells/μL) compared to non-ICU patients (562.24 cells/μL) (P = 0.001). Serum C-reactive protein (CRP) levels were significantly higher in ICU patients (85.06 ± 41.85 mg/dL) than in non-ICU patients (57.29 ± 27.51 mg/dL) (P = 0.01), and a negative correlation was observed between CRP and CD4 levels (P = 0.03). Mortality was significantly higher in ICU patients (40.9%) compared to non-ICU patients (19.6%) (Odds Ratio = 2.83, P = 0.006).
Conclusion: Our study demonstrates that lower CD4+ T-cell counts on admission are strongly associated with increased disease severity and poor prognosis in COVID-19 patients. The correlation between lower CD4 levels and higher CRP suggests that CD4+ T cell depletion may be a critical marker for predicting clinical outcomes. These findings highlight the potential role of CD4+ T-cell monitoring in managing severe COVID-19 cases and improving prognostic assessments.

Keywords: COVID-19, CD4 cell, Immune response, Inflammatory biomarkers, Lymphopenia

Full-Text [PDF 331 kb] (144 Downloads)

Type of Study: orginal article | Subject: Virology

References

1. Opal SM, DePalo VA. Anti-inflammatory cytokines. Chest. 2000;117(4):1162-72. [DOI:10.1378/chest.117.4.1162] [PMID]

2. Aoshi T, Koyama S, Kobiyama K, Akira S, Ishii KJ. Innate and adaptive immune responses to viral infection and vaccination. Current opinion in virology. Curr Opin Virol 2011;1(4):226-32. [DOI:10.1016/j.coviro.2011.07.002] [PMID]

3. Sefik E, Qu R, Junqueira C, Kaffe E, Mirza H, Zhao J, et al. Inflammasome activation in infected macrophages drives COVID-19 pathology. Nature 2022;606(7914):585-93. [DOI:10.1038/s41586-022-04802-1] [PMID] [PMCID]

4. Channappanavar R, Perlman S. Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Semin. Immunopathol 2017;39(5):529-39. [DOI:10.1007/s00281-017-0629-x] [PMID] [PMCID]

5. Schultze JL, Aschenbrenner AC. COVID-19 and the human innate immune system. Cell 2021;184(7):1671-92. [DOI:10.1016/j.cell.2021.02.029] [PMID] [PMCID]

6. 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(11):1061-9. [DOI:10.1001/jama.2020.1585] [PMID] [PMCID]

7. Huang Z, Fu Z, Huang W, Huang K. Prognostic value of neutrophil-to-lymphocyte ratio in sepsis: A meta-analysis. Am. J. Emerg. Med 2020;38(3):641-7. [DOI:10.1016/j.ajem.2019.10.023] [PMID]

8. Templeton AJ, McNamara MG, Šeruga B, Vera-Badillo FE, Aneja P, Ocaña A, et al. Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. J. Natl. Cancer Inst 2014;106(6):dju124. [DOI:10.1093/jnci/dju124]

9. Erre GL, Paliogiannis P, Castagna F, Mangoni AA, Carru C, Passiu G, et al. Meta‐analysis of neutrophil‐to‐lymphocyte and platelet‐to‐lymphocyte ratio in rheumatoid arthritis. Eur. J. Clin. Invest 2019;49(1):e13037. [DOI:10.1111/eci.13037] [PMID]

10. Miyahara R, Piyaworawong S, Naranbhai V, Prachamat P, Kriengwatanapong P, Tsuchiya N, et al. Predicting the risk of pulmonary tuberculosis based on the neutrophil-to-lymphocyte ratio at TB screening in HIV-infected individuals. BMC Infect. Dis 2019;19:1-9. [DOI:10.1186/s12879-019-4292-9] [PMID] [PMCID]

11. Mahallawi WH, Khabour OF, Zhang Q, Makhdoum HM, Suliman BA. MERS-CoV infection in humans is associated with a pro-inflammatory Th1 and Th17 cytokine profile. Cytokine. 2018;104:8-13. [DOI:10.1016/j.cyto.2018.01.025] [PMID] [PMCID]

12. Pena NM, Santana LC, Hunter JR, Blum VF, Vergara T, Gouvea C, et al. T cell-mediated Immune response and correlates of inflammation and their relationship with COVID-19 clinical severity: not an intuitive guess. BMC Infect. Dis 2024;24(1):612. [DOI:10.1186/s12879-024-09490-y] [PMID] [PMCID]

13. Koblischke M, Traugott MT, Medits I, Spitzer FS, Zoufaly A, Weseslindtner L, et al. Dynamics of CD4 T cell and antibody responses in COVID-19 patients with different disease severity. Front. Med. (Lausanne) 2020;7:592629. [DOI:10.3389/fmed.2020.592629] [PMID] [PMCID]

14. Grifoni A, Weiskopf D, Ramirez SI, Mateus J, Dan JM, Moderbacher CR, et al. Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals. Cell 2020;181(7):1489-501.e15. [DOI:10.1016/j.cell.2020.05.015] [PMID] [PMCID]

15. Shi X, Qin L, Yang L, Bai W, Jing L, Mei K. Value of interleukin-6 and CD4+ T-lymphocytopenia in assessing the severity and prognosis of coronavirus disease 2019. Zhonghua wei Zhong Bing ji jiu yi xue. 2020;32(10):1165-70. [Google Scholar]

16. Yan S, Wu G. Is lymphopenia different between SARS and COVID‐19 patients? FASEB J 2021;35(2):e21245. [DOI:10.1096/fj.202002512]

17. Fathi N, Rezaei N. Lymphopenia in COVID‐19: Therapeutic opportunities. Cell Biol. Int 2020;44(9):1792-7. [DOI:10.1002/cbin.11403] [PMID] [PMCID]

18. Montiel-Cervantes LA, Medina G, Pérez-Tapia S, Jiménez-Martínez M, Arrieta-Oliva H, Carballo-Uicab G, et al. Poor survival in COVID-19 associated with lymphopenia and higher neutrophile-lymphocyte ratio. Isr. Med. Assoc. J IMAJ. 2021;23(3):153-9. [Google Scholar]

19. Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020;46(5):846-8. [DOI:10.1007/s00134-020-05991-x] [PMID] [PMCID]

20. 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. [DOI:10.3389/fimmu.2020.00827] [PMID] [PMCID]

21. Jeffery LE, Burke F, Mura M, Zheng Y, Qureshi OS, Hewison M, et al. 1, 25-Dihydroxyvitamin D3 and IL-2 combine to inhibit T cell production of inflammatory cytokines and promote development of regulatory T cells expressing CTLA-4 and FoxP3. J. Immunol 2009;183(9):5458-67. [DOI:10.4049/jimmunol.0803217] [PMID] [PMCID]

22. Oh SM, Skendelas JP, Macdonald E, Bergamini M, Goel S, Choi J, et al. On-admission anemia predicts mortality in COVID-19 patients: A single center, retrospective cohort study. Am. J. Emerg. Med 2021;48:140-7. [DOI:10.1016/j.ajem.2021.03.083] [PMID] [PMCID]

23. Pan F, Yang L, Li Y, Liang B, Li L, Ye T, et al. Factors associated with death outcome in patients with severe coronavirus disease-19 (COVID-19): a case-control study. Int. J. Med. Sci 2020;17(9):1281. [DOI:10.7150/ijms.46614] [PMID] [PMCID]

24. Battaglini D, Lopes-Pacheco M, Castro-Faria-Neto HC, Pelosi P, Rocco PRM. Laboratory Biomarkers for Diagnosis and Prognosis in COVID-19. Front. Immunol 2022;13:857573. [DOI:10.3389/fimmu.2022.857573] [PMID] [PMCID]

25. Kazancioglu S, Yilmaz FM, Bastug A, Sakallı A, Ozbay BO, Buyuktarakci C, et al. Lymphocyte subset alteration and monocyte CD4 expression reduction in patients with severe COVID-19. Viral Immunol 2021;34(5):342-51. [DOI:10.1089/vim.2020.0166] [PMID]