key: cord-0850920-h7wwq8he authors: Liu, Dafeng; Lan, Lijuan; Luo, Dongxia; Zhao, Bennan; Wei, Guo; He, Yinsheng; Zhang, Renqing; Liu, Yalin title: Lymphocyte subsets with the lowest decline at baselineand the slow lowest rise during recovery in COVID-19 critical illnesspatients with diabetes mellitus date: 2020-07-22 journal: Diabetes Res Clin Pract DOI: 10.1016/j.diabres.2020.108341 sha: 653828533375b5fc17966e64edfa82cb76b02efe doc_id: 850920 cord_uid: h7wwq8he Abstract Background Host dysregulation of immune response was highly involved in thepathological process of Coronavirus disease 2019 (COVID-19), especially COVID-19severe cases with DM. Aim In this study we aimed at the dynamic changeof peripheral lymphocyte and subsets during COVID-19covery. Methods The peripheral lymphocyte and subsetsof 95 confirmed cases with COVID-19from baseline to four weeks were compared between critical illness and non-critical illness cases with or without DM. Results The dynamic characteristics oflymphocyteand subsets in COVID-19patients was that it reduced significantly at one week, rapidlyelevated to the peak at two weeks after onset, then gradually declined during recovery. The COVID-19 critical illnesspatients with DM had the lowest decline at one week and the slow lowest rise at two weeks after onset, while COVID-19 non-critical illnesspatients with DMhad therapid highest rise at two weeks after onset, both of them had similar lymphocyte and subsets at five weeks after onset and lower than those patients without DM. Conclusions These findings provide a reference for cliniciansthat for COVID-19patients withDM and the lowest decline of lymphocyte and subsets, immunomodulatory therapy as soon as possiblemight avoid or slow downdisease progression; moreover for COVID-19 critical illness patients with or without DM and non-critical illnesspatients with DM, continuous immunomodulatory therapy in later stages of disease might speed up virus clearance, shorten hospital stay, improve disease prognosisin COVID-19 critical illness patientswith DM. The outbreak of novel coronavirus(2019-nCOV) infection namedas coronavirus disease 2019 is widespreadin the world [1] [2] [3] [4] .As ofApril18, 2020, cases were reported in China and the whole world, a total of cumulative confirmed and death cases were 2,160,207 and 146,088 cases in the whole world [5] ,82,735 and 4,632 cases in China [6],respectively. Those COVID-19patients who is the elderly and those with chronic underlying diseasehave a poor prognosis. Diabetes mellitus is one of the common underlying diseases [7] .Host dysregulation of immune response was highly involved in thepathological process of COVID- 19 [8] .Our previous research found that the COVID-19severe cases with diabetes mellitus(DM) had overall decreased lymphocytes and subsets which can affect the diseaseseverity, disease progression, viral negative conversion and prognosis [9] .Thedynamic changes of lymphocyte and subsets between critical illness case and non-critical illness case of COVID-19 with or without DMare unknown and worth studyingin this article. 95 patients with COVID-19 was retrospectively recruited from January 16, 2020 to The participants were divided in two subgroups according to clinical typing: the noncriticalillnesssubgroup(including light and common type)and critical illnesssubgroup (including severe and critically illness type). Dataincluding underline disease history, demographic information(age and sex), lymphocyte subsets at baseline, one week and 4 weeks,clinical data and glucose metabolic parameters[FPGlevelsand hemoglobin A1c(HbA1c) levels]were obtained from the hospital electronic medical record system of the Public and Health Clinic Centre of Chengdu[9]. According to the needs of the research databases were established bytwo researchers simultaneously collecting and entering, 30% of that data was randomly selected by the researchers to assess data integrity, authenticity, and accuracy. . The Statistical Package for the Social Sciences software version 17.0(IBM Inc., Armonk, NY, the USA) and GraphPad Prism 8(GraphPad, CA, the USA) software were used for statistical analysis. The measurement data were expressed as x±SD, and a multigroup comparison was performed using ANOVA. Further comparison between the two groups was conducted using Student-Newman-Keuls(SNK) analysis. The two groups were compared using an independent-sample t-test. Chi-square test was used for the enumeration data. A p value of <0.05 was considered statistically significant. Patients in non-critical illness non-DM subgroup were significantly younger than those in the other three subgroups, but similar age was found in latter three subgroups and similar male percentage was foundin four subgroups (Table 1 ). FPG levels and HbA1c level in DM group were obviously higher than that in non-DM group (Table 1) . But there was no significant difference between each intra-group ( At baseline in COVID-19 critical illness patients with DM except B(CD19+) count level( Figure 3a )was obviously lower than that in COVID-19 critical illness patient without DM, the difference was significant, no statistical difference of the otherlymphocytes subsetswas found between the same disease severity with and without DM subgroups. During recovery in COVID-19 patients whether critical illness or non-critical illness, whether with or without DM, lymphocyte count level and percentage value ( At 4 weeks COVID-19 patients without DM had higher lymphocyte and subsets than those with DM, but the lymphocyte and subsets was similar between critical illness cases and non-critical illness cases whether with or without DM. Pearson correlation analysisshowed that B(CD19+) count leveland percentage value at five weeks were negatively related to viral negative conversion time ( CoV [15] .CD4+ T cells are more susceptible to SARS-COV infection, resulting in itself reduction or even depletion, which reduces the recruitment of lymphocytes in the lungs and the neutralization of antibody and cytokine production, resulting in strong immune-mediated interstitial pneumonia and delay the clearance of SARS-COV in the lungs. But the depletion of CD8+ T cells does not affect or delay viral replication [16] [17] [18] . From this we speculate that for COVID-19patients with DM in early stage of disease, the rapid highest rise of lymphocyte and subsets in somepatientsavoid disease progression to critical illness cases or slow down disease progression, while the slow lowest rise of lymphocyte and subsets in the others promote disease progression to critical illness cases. Additionally, T helper cells produce proinflammatory cytokines via the NF-kB signalingpathway [19] . A Novel Coronavirus from Patients with Pneumonia in China Outbreak of Pneumonia of Unknown Etiology in Wuhan China: the Mystery and the Miracle Cross-species transmission of the newly identified coronavirus 2019-nCoV Responding to COVID-19 -A Once-in-a-Century Pandemic? 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Expert review of respiratory medicine Th17 Cells and the IL-23/IL-17 axis in the pathogenesis of periodontitis and immune-mediated inflammatory diseases T helper 17 cells as pathogenic drivers of periodontitis Bcl-xL inhibits T-cell apoptosis induced by expression of SARS coronavirus E protein in the absence of growth factors Middle East respiratory syndrome coronavirus (MERS-CoV): infection, immunological response, and vaccine development Thanks to Dr. Hong Chen,Ling Zhang,Min yang,Xiu Li(the Public and Health Clinic Centre of Chengdu, one ward, two wardof hospital isolation ward,respectively). The authors declare that they have no competing interests.