Clinical characteristics and predictive value of lower CD4+T cell level in patients with moderate and severe COVID-19: a multicenter retrospective study

Abstract

Background: In December 2019, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, Hubei, China. Moreover, it has become a global pandemic. This is of great value in describing the clinical symptoms of COVID-19 patients in detail and looking for markers which are significant to predict the prognosis of COVID-19 patients.

Methods: In this multicenter, retrospective study, 476 patients with COVID-19 were enrolled from a consecutive series. After screening, a total of 395 patients were included in this study. All-cause death was the primary endpoint. All patients were followed up from admission till discharge or death.

Results: The main symptoms observed in the study included fever on admission, cough, fatigue, and shortness of breath. The most common comorbidities were hypertension and diabetes mellitus. Patients with lower CD4+T cell level were older and more often male compared to those with higher CD4+T cell level. Reduced CD8+T cell level was an indicator of the severity of COVID-19. Both decreased CD4+T [HR:13.659; 95%CI: 3.235-57.671] and CD8+T [HR: 10.883; 95%CI: 3.277-36.145] cell levels were associated with in-hospital death in COVID-19 patients, but only the decrease of CD4+T cell level was an independent predictor of in-hospital death in COVID-19 patients.

Conclusions: Reductions in lymphocytes and lymphocyte subsets were common in COVID-19 patients, especially in severe cases of COVID-19. It was the CD8+T cell level, not the CD4+T cell level, that reflected the severity of the patient's disease. Only reduced CD4+T cell level was independently associated with increased in-hospital death in COVID-19 patients.

Trial registration: Prognostic Factors of Patients With COVID-19, NCT04292964 . Registered 03 March 2020. Retrospectively registered.

Keywords: CD4+T cells; COVID-19; In-hospital death; SARS-CoV-2.

Conflict of interest statement

All authors declare no conflict of interest.

Figures

Fig. 1

Flow diagram of Patient Recruitment

Fig. 2

a: The histogram shows the proportion of moderate and severe COVID-19 patients with lymphocyte, CD4+T and CD8+T cell levels below the lower limit of normal count; b: The histogram shows the number of CD4+T cells and CD8+T cells in moderate and severe COVID-19 patients

Fig. 3

Kaplan-Meier plots shows the survival rate of COVID-19 patients who were stratified into two groups according to CD4+T cell level. (green line, higher CD4+T cell level group; blue line, lower CD4+T cell level group)

Fig. 4

Forest plots of multivariate Cox proportional-hazards regression analyze the effect of baseline variables on in-hospital death in all patients with COVID-19. Mode1: adjusted sex, age, and temperature; Mode2: adjusted hypertension, diabetes, and shortness of breath; Mode3: adjusted white blood cell, platelet, and Creatinine; Mode4: adjusted hypersensitive C-reactive protein, procalcitonin, and D-dimer; Mode5: adjusted the group with lower CD8+T cell level, CD4/CD8 ratio, and the group with lower lymphocyte level; Mode6: adjusted age, hypertension, shortness of breath, white blood cell, platelet, D-dimer, and CD4/CD8 ratio