key: cord-0814143-178f21u7
authors: Hu, Daojun; Li, Li; Shi, Wenjie; Zhang, Li
title: 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
date: 2020-06-27
journal: Clin Chim Acta
DOI: 10.1016/j.cca.2020.06.040
sha: bfd89ba98f7d430ee32944067edf68aec3edeeb7
doc_id: 814143
cord_uid: 178f21u7

This study mainly focused on the very serious COVID-19 epidemic situation at present and provided a new insight for the treatment and monitor of patients with COVID-19. Through this meta-analysis, we could draw a conclusion that less expression of blood CD4(+) and CD8(+) T cells count might reflect the severity of infection and often accompanied by a poor prognosis. Hence, we inferred blood CD4+ and CD8+ T cells count could be a promising biomarker for disease assessment and monitor of patients with COVID-19.

coronavirus 2019) AND (CD4 OR CD8)" without date(i.e. until April 28, 2020) or language restriction. The title, abstract and full text of all potentially studies were reviewed to identify the eligible studies, and disagreement was solved through discussion and consultation by authors. Finally, all the literatures reporting data on patients with severe (defined as needing to enter intensive care unit, using of mechanical ventilation or shock occurrence, etc.) or not-severe COVID-19 were included in our meta-analysis.

Ten studies were finally included in this meta-analysis, consisting of 643 COVID-19 cases, 277 of whom (43.08%) were severe cases. The primary characteristics of included COVID-19 patients was displayed in Table 1 . Due to the large differences in the mean values among the included studies and heterogeneity was observed, so standardized mean difference (SMD) was adopted as the effect quantity in this metaanalysis. In this study, meta-analysis was performed using Comprehensive Meta Analysis Version 3.3 to calculate SMD and the 95% confidence interval (95% CI) of CD4 + , CD8 + T cells count in COVID-19 patients with or without severe diseases.

When the original study could not provide the mean and standard deviation, the mean and standard deviation of CD4 + and CD8 + T cells count were extrapolated according to the sample size, median and quartile range [6] . Eventually, The SMD values and other relevant indexes from ten studies were presented in Figure 1 . The heterogeneity (I 2 statistics) among the ten studies exceeded 50%, so random effect model was adopted. The pooled results revealed the blood CD4 + or CD8 + T cells count (CD4 + : SMD=-2.062, 95%CI=-3.047 to -1.077; CD8 + : SMD=-1.630,95%CI=-2.545 to -0.716) was significantly lower in severe COVID-19 patients compared to non-severe group. Sensitivity analysis by removing one study in turn indicated the pooled result was robust and reliable ( Figure 2 ). The heterogeneity among included studies was high (CD4 + : I 2 =95.186; CD8 + : I 2 =95.002). To search for the source of heterogeneity, a subgroup analysis was conducted. Subgroup analysis pointed that severe COVID-19 patients with hypertension become the important source of heterogeneity. In addition, inherent variability in blood CD4 + and CD8 + T cells count among patients also possibly be a vital cause of heterogeneity. Furthermore, the Begg rank correction test and Egger linear regression did not support the existence of publication bias among the eleven studies (Begg, P = 0.1074; Egger's, P=0.5268).It is well known that CD4 + and CD8 + T cells count are widely involved in the process of immune response, and virus-specific CD4 + and CD8 + T cells often play a critical role in clearing virus by eliminating virus infected cells [7] . As in humans infected with coronavirus, CD4 + T cells can induce a protective immune response via IFN-γ expression and enhancement of CD8 + T cell and antibody responses [8] . SARS-CoV antigen is recognized and [9] .

To our knowledge, this is the first meta-analysis to comprehensively clarify the relationship between the levels of blood CD4 + and CD8 + T cells and the severity of COVID-19. This study suggests that the detection of blood CD4 + and CD8 + T cells count in patients with COVID-19 is helpful to evaluate the severity of COVID-19, and then treat severe patients as soon as possible. In the future, we probably use big data analysis to establish the reference interval of CD4 + and CD8 + T cell count in COVID-19 patients to distinguish between severe and non-severe patients and monitor the therapeutic effect of COVID-19. 

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