The association between comorbid conditions and CD4+ T-cell counts with in-hospital mortality of patients with moderate to critical COVID-19 disease

Authors

  • C L de Swardt Department of Internal Medicine, Kalafong Hospital, University of Pretoria, South Africa
  • M de Villiers Department of Internal Medicine, Kalafong Hospital, University of Pretoria, South Africa
  • D Van Zyl Department of Internal Medicine, Kalafong Hospital, University of Pretoria, South Africa

DOI:

https://doi.org/10.7196/SAMJ.2025.v115i10.2793

Keywords:

COVID-19, CD4+ T-cell, Human Immunodeficiency Virus, Mortality, Comorbidity, Predictor

Abstract

Background. COVID‑19 presents with variable severity, and identifying accessible prognostic markers is critical in resource-limited settings such as South Africa (SA), where the prevalence of HIV may influence immune response and outcomes.

Objectives. To assess the association between CD4+ T-cell count and in-hospital mortality among patients with moderate to severe COVID‑19 infection in SA, with a focus on specific comorbid conditions.

Methods. This cross-sectional analytical study analysed data from the first COVID‑19 wave, using an electronic database compiled during the first wave of the epidemic as well as clinical records. During this period, 336 patients with moderate to critical COVID‑19 were admitted to Kalafong Provincial Tertiary Hospital in Pretoria, SA. The analysis included only those patients in whom CD4+ T-cell counts (n=270) were done. Mean CD4+ T-cell counts were compared between survivors and non-survivors using non-parametric statistics. Logistic regression was performed to adjust for confounders, with survival status as the outcome variable.

Results. Sixty-nine of the 270 patients (26%) died. Mortality rates by severity of COVID were moderate (7/49, 14.3%), severe (55/211, 26.1%) and critical (7/10, 70%) (p=0.001). Patients who were positive for HIV had significantly higher mortality (19/52, 36.5%) than HIV‑negative patients (50/218, 22.9%) (p=0.0436). Non-survivors had significantly lower CD4+ T-cell counts (p<0.001). After adjusting for age, hypertension, diabetes, pre-diabetes, renal disease, critical COVID‑19 disease and HIV status, the CD4+ T-cell count remained significantly lower in non-survivors (p<0.001).

Conclusion. In patients with moderate to critical COVID‑19 disease, lower CD4+ T-cell counts were significantly associated with mortality, suggesting that this may serve as a useful marker for predicting outcomes.

 

References

1. National Institute for Communicable Diseases. COVID‑19. Johannesburg: NICD, 2024. https://www.

nicd.ac.za/diseases-a-z-index/disease-index-covid-19/ (accessed 14 July 2024).

2. World Health Organization. Weekly epidemiological update on COVID‑19. Geneva: WHO, 2024.

https://www.who.int/publications/m/item/covid-19-epidemiological-update-edition-167 (accessed 14

July 2024).

3. Worldometer. Coronavirus tracker: South Africa. Worldometer, 2024. https://www.worldometers.info/

coronavirus/country/south-africa/ (accessed 26 May 2024).

4. Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019

(COVID‑19) outbreak in China: Summary of a report of 72 314 cases from the Chinese Center for Disease

Control and Prevention. JAMA 2020;323(13):1239-1242. https://doi.org/10.1001/jama.2020.2648

5. Booth A, Reed AB, Ponzo S, et al. Population risk factors for severe disease and mortality in COVID‑19:

A global systematic review and meta-analysis. PLoS ONE 2021;16(3):e0247461. https://doi.org/10.1371/

journal.pone.0247461

6. Centers for Disease Control and Prevention. Assessing risk factors for severe covid-19 illness. Atlanta:

CDC, 2024. https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-medicalconditions.

html (accessed 14 July 2024).

7. Akbari H, Tabrizi R, Lankarani KB, et al. The role of cytokine profile and lymphocyte subsets in the

severity of coronavirus disease 2019 (COVID‑19): A systematic review and meta-analysis. Life Sci

2020;258:118167. https://doi.org/10.1016/j.lfs.2020.118167

8. Belaid B, Lamara Mahammad L, Mihi B, et al. T-cell counts and IL‐6 concentration in blood of North

African COVID‐19 patients are two independent prognostic factors for severe disease and death. J

Leukoc Biol 2022;111(1):269-281. https://doi.org/10.1002/JLB.4COVA1020-703R

9. Fu YQ, Sun YL, Lu SW, Yang Y, Wang Y, Xu F. Effect of blood analysis and immune function on the

prognosis of patients with COVID‑19. PLoS ONE 2020;15(10):e0240751. https://doi.org/10.1371/

journal.pone.0240751

10. Hu D, Li L, Shi W, Zhang L. Less expression of CD4(+) and CD8(+) T-cells might reflect the severity of

infection and predict worse prognosis in patients with COVID‑19: Evidence from a pooled analysis. Clin

Chim Acta 2020;510:1-4. https://doi.org/10.1016/j.cca.2020.06.040

11. Jesenak M, Brndiarova M, Urbancikova I, et al. Immune parameters and COVID‑19 infection –

associations with clinical severity and disease prognosis. Front Cell Infect Microbiol 2020;10:364. https://

doi.org/10.3389/fcimb.2020.00364

12. Li M, Guo W, Dong Y, et al. Elevated exhaustion levels of NK and CD8(+) T cells as indicators

for progression and prognosis of COVID‑19 disease. Front Immunol 2020;11:580237. https://doi.

org/10.3389/fimmu.2020.580237

13. Luo M, Liu J, Jiang W, Yue S, Liu H, Wei S. IL-6 and CD8+ T-cell counts combined are an early predictor

of in-hospital mortality of patients with COVID‑19. JCI Insight 2020;5(13):e139024. https://doi.

org/10.1172/jci.insight.139024

14. Zhang P, Du W, Yang T, et al. Lymphocyte subsets as a predictor of severity and prognosis in

COVID‑19 patients. Int J Immunopathol Pharmacol 2021;35:20587384211048567. https://doi.

org/10.1177/20587384211048567

15. Zhang X, Tan Y, Ling Y, et al. Viral and host factors related to the clinical outcome of COVID‑19. Nature

2020;583(7816):437-440. https://doi.org/10.1038/s41586-020-2355-0

16. Zhao Z, Xie J, Yin M, et al. Interleukin-6 and severity of COVID‑19 patients in Hefei, China. Med Mal

Infect 2020;50(7):629-631. https://doi.org/10.1016/j.medmal.2020.06.005

17. Bivona G, Agnello L, Ciaccio M. Biomarkers for prognosis and treatment response in COVID‑19

patients. Ann Lab Med 2021;41(6):540-548. https://doi.org/10.3343/alm.2021.41.6.540

18. Coomes EA, Haghbayan H. Interleukin-6 in Covid-19: A systematic review and meta-analysis. Rev Med

Virol 2020;30(6):1-9. https://doi.org/10.1002/rmv.2141

19. Hariyanto TI, Japar KV, Kwenandar F, et al. Inflammatory and hematologic markers as predictors of

severe outcomes in COVID‑19 infection: A systematic review and meta-analysis. Am J Emerg Med

2021;41:110-119. https://doi.org/10.1016/j.ajem.2020.12.076

20. Li Q, Xu W, Li W, Huang C, et al. Dynamic differences of immunological parameters between severe and

non-severe COVID‑19 patients. Discov Med 2021;31(163):79-87.

21. Malik P, Patel U, Mehta D, et al. Biomarkers and outcomes of COVID‑19 hospitalisations: Systematic

review and meta-analysis. BMJ Evid Based Med 2021;26(3):107-108. https://doi.org/10.1136/

bmjebm-2020-111536

22. Wang F, Nie J, Wang H, et al. Characteristics of peripheral lymphocyte subset alteration in COVID‑19

pneumonia. J Infect Dis 2020;221(11):1762-1769. https://doi.org/10.1093/infdis/jiaa150

23. Xiang G, Xie L, Chen Z, et al. Clinical risk factors for mortality of hospitalised patients with COVID‑19:

Systematic review and meta-analysis. Ann Palliat Med 2021;10(3):2723-2735. https://doi.org/10.21037/

apm-20-1278

24. Zeng F, Huang Y, Guo Y, et al. Association of inflammatory markers with the severity of COVID‑19:

A meta-analysis. Int J Infect Dis 2020;96:467-474. https://doi.org/10.1016/j.ijid.2020.05.055

25. Chen G, Wu D, Guo W, et al. Clinical and immunological features of severe and moderate coronavirus

disease 2019. J Clin Invest 2020;130(5):2620-2629. https://doi.org/10.1172/jci137244

26. Giamarellos-Bourboulis EJ, Netea MG, Rovina N, et al. Complex immune dysregulation in COVID‑19

patients with severe respiratory failure. Cell Host Microbe 2020;27(6):992-1000. https://doi.org/10.1016/j.

chom.2020.04.009

27. Qin C, Zhou L, Hu Z, et al. Dysregulation of immune response in patients with coronavirus 2019

(COVID‑19) in Wuhan, China. Clin Infect Dis 2020;71(15):762-768. https://doi.org/10.1093/cid/ciaa248

28. He R, Lu Z, Zhang L, et al. The clinical course and its correlated immune status in COVID‑19 pneumonia.

J Clin Virol 2020;127:104361. https://doi.org/10.3389/fcimb.2020.00364

29. Hedayati-Ch M, Ebrahim-Saraie HS, Bakhshi A. Clinical and immunological comparison of COVID‑19

disease between critical and non-critical courses: A systematic review and meta-analysis. Front Immunol

2024;15:1341168. https://doi.org/10.3389/fimmu.2024.1341168

30. Iwamura APD, Tavares da Silva MR, Hümmelgen AL, et al. Immunity and inflammatory biomarkers

in COVID‑19: A systematic review. Rev Med Virol 2021;31(4):e2199. https://doi.org/10.1002/rmv.2199

31. Zahornacky O, Rovnakova A, Surimova M, Porubcin S, Jarcuska P. Identifying mortality predictors in

hospitalised COVID‑19 patients: Insights from a single-center retrospective study at a university hospital.

Microorganisms 2024;12(5):1032. https://doi.org/10.3390/microorganisms12051032

32. Venturas J, Zamparini J, Shaddock E, et al. Comparison of outcomes in HIV-positive and HIV-negative

patients with COVID‑19. J Infect 2021;83(2):217-227. https://doi.org/10.1016/j.jinf.2021.05.020

33. Western Cape Department of Health in collaboration with the National Institute for Communicable

Diseases SA. Risk factors for coronavirus disease 2019 (COVID‑19) death in a population cohort study

from the Western Cape Province, South Africa. Clin Infect Dis 2020;73(7):e2005-e2015. https://doi.

org/10.1093/cid/ciaa1198

34. National Institutes of Health. Clinical spectrum of SARS-CoV-2 infection. Bethesda: NIH, 2024. https://

www.covid19treatmentguidelines.nih.gov/overview/clinical-spectrum/ (accessed 14 July 2024).

35. Pillay-van Wyk V, Bradshaw D, Groenewald P, et al. COVID deaths in South Africa: 99 days since

South Africa’s first death. S Afr Med J 2020;110(11):1093-1099. https://doi.org/10.7196/samj.2020.

v110i11.15249

36. Jassat W, Cohen C, Tempia S, et al. A national cohort study of COVID‑19 in-hospital mortality in South

Africa: The intersection of communicable and non-communicable chronic diseases in a high HIV

prevalence setting. medRxiv 2021. https://doi.org/10.1101/2020.12.21.20248409

37. Favara G, Barchitta M, Maugeri A, Faro G, Agodi A. HIV infection does not affect the risk of death of

COVID‑19 patients: A systematic review and meta-analysis of epidemiological studies. J Glob Health

2022;12:05036. https://doi.org/10.7189/jogh.12.05036

Downloads

Published

2025-11-04

Issue

Section

Research

Categories

How to Cite

1.
de Swardt CL, de Villiers M, Van Zyl D. The association between comorbid conditions and CD4+ T-cell counts with in-hospital mortality of patients with moderate to critical COVID-19 disease. S Afr Med J [Internet]. 2025 Nov. 4 [cited 2025 Nov. 13];115(10):e2793. Available from: https://samajournals.co.za/index.php/samj/article/view/2793