Down-regulated gene expression spectrum and immune responses changed during the disease progression in COVID-19 patients

Title: Down-regulated Summary : Suppressed T cell immune response and decreased T cells in COVID-19 patients related to down-regulated gene expression involved in T cell activation and differentiation Abstract Background: WHO characterizes novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as a pandemic. Here, we investigated the clinical, cytokine levels, T cell proportion and related gene expression occurring in COVID-19 patients on admission and after intial treatment. Methods: 11 patients diagnosed as COVID-19 with similar initial treatment regimen were enrolled in the hospital. Plasma cytokines, CyTOF and microfluidic qPCR for gene expression were conducted. Results: 5 mild and 6 severe patients were included. Cough and fever were the top symptoms in the 11 COVID-2019 cases. The elder age, more neutrophils numbers and higher C-reactive protein level were found in severe cases. IL-10 level was significantly varied with disease progression and treatment. The decreased T cell proportions were observed in COVID-19 patients especially in severe cases, and all elevated to normal in mild patiens after initial treatment but only CD4+T cells return to normal in severe cases. The number of DEGs increased with the disease progress, and decreased after initial treatment. All down-regulated DEGs in severe cases mainly involved in Th17 cell differentiation, cytokine-mediated signaling pathway and T cell activation. After initial treatmen in severe cases, MAP2K7 and SOS1 were upregulated relative to that on admission. Conclusions: Our findings show a decreased T cell proportion with down-regulated gene expression related to T cell activation and differentiation were occurred in COVID-19 severe patients, which may help to provide effective treatment strategies for COVID-19 . reported clinical and plasma cytokines features of COVID-19, only limited information is available on the host innate immune status of SARS-CoV-2 infected patients. The changes of immune-related gene expression levels during SARS-CoV-2 infection were still unclear. Here, we comprehensively evaluated the characteristics of 11 patients with COVID-19 admitted to Beijing Youan Hospital. We aimed to compare the clinical, cytokine levels and immune related gene expression characteristics between different clinical stages. Our data provide basic information to understand the role of immune responses on the disease process of COVID-19. Results of microfluidic qPCR and following bioinformatics analysis demonstrated that SARS-CoV-2 infection could affect the mRNA expression level related with immune functions in COVID-19 cases. Our study revealed the number of misregulated genes increased as the disease progressed when compared to normal. A more DEGs were found in severe cases. Both DEGs of severe and mild patients are participated in such as Th17 cell differentiation, cytokine-mediated signaling pathway, sa mmp cytokine connection, natural killer cell mediated cytotoxicity and T cell activation. While DEGs specific to severe cases were mainly responsible for CD8 TCR pathway, EPO pathway, signaling by Interleukins, TNF signaling pathway, entry into host cell and regulation of T cell proliferation enrichment terms. These results indicated SARS-CoV-2 infection may resulting inspecific Th1/Th17 inactivation and impaired inflammatory responses, which may related to the decreased proportion of T cells expecially in COVID-19 severe patients. 14 key genes related with immune functions in COVID-19 cases were screened, which revealed FC down-regulated more in group A1 than that in group B1 both relative to the NC group. Like influenza viruses, CoVs such as SARS-CoV and MERS-CoV also use a combination of ways to achieve host shut-off both at the transcriptional and the translational levels [7]. Innate and adaptive immune responses to viral infection during infection. Coronaviruses (CoVs) infects macrophages and presents CoV antigens to T cells, which process could results in T cell activation and differentiation that including the production of cytokines associated with different T cell subpopulations, and subsequent large release of cytokines for immune response expansion in the severe COVID-19 patients before treatment we demonstrated the changed immune response in COVID-19 patients through down-regulated at the transcriptional levels involved in T cell activation and differentiation especially in severe patients. Although clinical blood laboratory findings did not show significantly differences after intinal treatment, IL-10 level, T cells proportions and related mRNA expression level changed with the disease progression. These findings will help us extend our understanding of the SARS-CoV-2 infection mechanism, may help elucidate the COVID-19 infection and provide a basis for future novel immune therapeutic strategies.