key: cord-0836594-v3pxb997 authors: Zhang, Haipeng; Wu, Ti title: CD4+T, CD8+T counts and severe COVID-19: A meta-analysis date: 2020-06-20 journal: J Infect DOI: 10.1016/j.jinf.2020.06.036 sha: 08ae4e797209326671acfbd5123ee806c914ccab doc_id: 836594 cord_uid: v3pxb997 nan Key Words: CD4+T, CD8+T, CD4/CD8 ratio, COVID-19, meta-analysis To the editor: We read an interesting study in your journal. A retrospective study by Liu et al was conducted to investigate the associated between lymphocyte subset counts and severe COVID-19 [1] . They found low counts of CD4+T and CD8+T were more common in patients with severe COVID-19. And CD4/CD8 ratio showed no significant difference between non-severe and severe COVID-19 groups. CD4+T and CD8+T play a vital role in maintaining immune function and viral clearance in the body. It has been reported that CD4+T and CD8+T counts significantly decreased in COVID-19 patients [2] . However, whether their status were correlated with the clinical type of COVID-19 patients has not reached consistent conclusions. Therefore, we conducted this meta-analysis to investigate the relationship between CD4+T counts, CD8+T counts, CD4/CD8 ratio and the severity of COVID-19 patients. We searched PubMed, EMBASE and Web of Sciences, using the keywords as "CD4", "CD8", "COVID-19", "Severe 2019-nCoV", and "SARS-CoV-2" without date (until Jun 2, 2020) or language restrictions. Trials providing data of counts of CD4+T, CD8+T or CD4/CD8 ratio in patients with non-severe or severe COVID-19 were included. According to Guidelines for the Diagnosis and Treatment of COVID-19 [3] , COVID-19 is classified as mild, moderate, severe, and critical pneumonia. We categorized severe and critical pneumonia into the severe group, mild and moderate pneumonia into the non-severe group. We independently screened every article and extracted the data. Any disagreement were resolved by discussion and consensus. Mean difference (MD) with 95% confidence intervals (95% CI) was calculated in this meta-analysis using Review Manager 5.3 software. Study heterogeneity was assessed using I 2 statistic, when I 2 <50%, a fixed-effects model was used, otherwise a random-effects model was chosen. Sensitivity analysis were performed by sequential removal of each trial. 13 studies included a total number of 1647 patients were considered in our meta-analysis.(Supplementary Material) All the studies, except for 1 in Spain [4] , were conducted in China. 10 studies distinguished non-severe and severe groups, 2 studies only reported ICU and non-ICU groups [4 5] , and 1 study only reported decease and survivor groups [6] . Data of CD4+T, CD8+T counts and CD4/CD8 ratio were provided in 13, 12 and 8 studies, respectively. Both CD4+T and CD8+T counts significantly reduced in severe COVID-19 group compared with non-severe group [CD4+T (MD: -0.22×10 9 /L, 95%CI: -0.27 to -0.17×10 9 /L, I 2 =89%); CD8+T (MD: difference between two groups in CD4/CD8 ratio (MD: 0.17, 95%CI: -0.12 to 0.46, ).The details of our meta-analysis are presented in Figure 1 . COVID-19 is an acute inflammatory infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 has a genome sequence 79.6% identical to the SARS-CoV [7] . Similar clinical features, such as fever, dry cough, dyspnoea, and bilateral ground-glass opacities on chest CT scans, were found between COVID-19 and severe acute respiratory syndrome (SARS) [8] . It has been reported that low counts of CD4+T and CD8+T were associated with adverse outcome in patients with SARS, and the counts would rise dramatically when clinical symptoms improved [9] . As Wang et al. reported, after 1 week of COVID-19 treatment, CD8+T counts increased only in patients with attenuated symptoms or improved radiological abnormalities, while no similar change of CD4+T counts was found [10] . It appears that, unlike SARS, CD8+T may be a more sensitive predictor of clinical outcome than CD4+T in COVID-19 patients. However, both CD4+T and Lymphocyte subset (CD4+, CD8+) counts reflect the severity of infection and predict the clinical outcomes in patients with COVID-19 T cell subset counts in peripheral blood can be used as discriminatory biomarkers for diagnosis and severity prediction of COVID-19 National Health Commission of the People's Republic of China. Guidelines for the Diagnosis and Treatment of COVID-19 989/files/ce3e6945832a438eaae415350a8ce964 Selective CD8 cell reduction by SARS-CoV-2 is associated with a worse prognosis and systemic inflammation in COVID-19 patients Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID-19) Predictors of mortality for patients with COVID-19 pneumonia caused by SARS-CoV-2: a prospective cohort study A pneumonia outbreak associated with a new coronavirus of probable bat origin Clinical features of patients infected with 2019 novel coronavirus in Wuhan Haematological manifestations in patients with severe acute respiratory syndrome: retrospective analysis Characteristics of Peripheral Lymphocyte Subset Alteration in COVID-19 Pneumonia