ABSTRACT
Patients with severe COVID-19 often suffer from lymphopenia, which is linked to T-cell sequestration, cytokine storm, and mortality. However, it remains largely unknown how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces lymphopenia. Here, we studied the transcriptomic profile and epigenomic alterations involved in cytokine production by SARS-CoV-2-infected cells. We adopted a reverse time-order gene coexpression network approach to analyze time-series RNA-sequencing data, revealing epigenetic modifications at the late stage of viral egress. Furthermore, we identified SARS-CoV-2-activated nuclear factor-κB (NF-κB) and interferon regulatory factor 1 (IRF1) pathways contributing to viral infection and COVID-19 severity through epigenetic analysis of H3K4me3 chromatin immunoprecipitation sequencing. Cross-referencing our transcriptomic and epigenomic data sets revealed that coupling NF-κB and IRF1 pathways mediate programmed death ligand-1 (PD-L1) immunosuppressive programs. Interestingly, we observed higher PD-L1 expression in Omicron-infected cells than SARS-CoV-2 infected cells. Blocking PD-L1 at an early stage of virally-infected AAV-hACE2 mice significantly recovered lymphocyte counts and lowered inflammatory cytokine levels. Our findings indicate that targeting the SARS-CoV-2-mediated NF-κB and IRF1-PD-L1 axis may represent an alternative strategy to reduce COVID-19 severity.
Subject(s)
COVID-19 , Lymphopenia , Animals , Mice , SARS-CoV-2/metabolism , B7-H1 Antigen , Immune Evasion , NF-kappa B/metabolism , Up-Regulation , Cytokines/metabolismABSTRACT
Coronavirus disease 2019 (COVID-19) is an acute respiratory infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and it has become a public health concern worldwide. In addition to respiratory symptoms, some COVID19 patients also show various gastrointestinal symptoms and even consider gastrointestinal symptoms to be the first manifestation. A large amount of evidence has shown that SARS-CoV-2 infection could disrupt the gut microbiota balance, and disorders of the gut microbiota could aggravate the condition of COVID-19 patients. Therefore, maintaining the gut microbiota balance is expected to become a potential new therapeutic target for treating COVID-19. Traditional Chinese medicine (TCM) has significant effects in all stages of the prevention and treatment of COVID-19. It can adjust the gut microbiota and is an ideal intestinal microecological regulator. This review summarizes the advantages and clinical efficacy of TCM in the treatment of COVID-19 and expounds on the relationship between TCM and the gut microbiota, the relationship between COVID-19 and the gut microbiota, the mechanism of gut microbiota disorders induced by SARS-CoV-2, the relationship between cytokine storms and the gut microbiota, and the role and mechanism of TCM in preventing and treating COVID-19 by regulating the gut microbiota to provide new research ideas for TCM in the prevention and treatment of COVID-19.
Subject(s)
COVID-19 , Gastrointestinal Microbiome , Cytokine Release Syndrome , Gastrointestinal Microbiome/physiology , Humans , Medicine, Chinese Traditional , SARS-CoV-2ABSTRACT
BACKGROUND: Since the outbreak of COVID-19, the number of COVID-19 patients has been on the rise. With the improvement of diagnosis and treatment level in various countries, more and more patients have recovered. Baduanjin exercise is a traditional Chinese health care method with a long history, easy-to-learn, and remarkable effect. It is not subject to the constraints of the field and can be practiced at any time. It can be used as an alternative therapy for COVID-19 rehabilitation patients. At present, there are no relevant articles for systematic review. METHODS: We will retrieve a randomized controlled trial of Baduanjin exercise for COVID-19 from the beginning to July 2020. The following databases are areas of concern: Published randomized Cochrane Central Register of Controlled Trials (Central), PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and Wan-fang Database-controlled trials in Chinese and English related to Baduanjin exercise and COVID-19 were included. The main result was the effect of Baduanjin exercise on the quality of life in patients recovering from COVID-19. Secondary results to accompany symptoms (such as muscle pain, cough, sputum, runny nose, sore throat, chest tightness, shortness of breath, difficulty breathing, fatigue, headache, nausea, vomiting, anorexia, diarrhea), disappearance rate, 2 consecutive (not on the same day) COVID-19 negative rate of nucleic acid test results, the quality of life improved, improve CT images, the average hospitalization time, severe form of common clinical cure rate and mortality. RESULTS: The results of this study will provide researchers in the field of COVID-19 with a current synthesis of high-quality evidence. CONCLUSION: The conclusion of this study will provide evidence for judging whether Baduanjin exercise is an effective intervention for the quality of life of rehabilitative patients. PROSPERO REGISTRATION NUMBER: CRD42020199443.