Azvudine reduces the mortality rate of patients with Coronavirus disease 2019: a single-center retrospective analysis study (preprint)

Background: Several therapeutic drugs have been authorized for the treatment of patients with Coronavirus disease 2019 (COVID-19). However, further research on the mechanisms of action, efficacy, and target populations of these novel therapeutic drugs are necessary. Hence, this study aimed to investigate the effectiveness of azvudine in hospitalized patients with COVID-19. Methods: We conducted a retrospective cohort study of patients with COVID-19 admitted to our hospital from December 1, 2022, to March 31, 2023. Patients were divided into retrospective cohorts receiving azvudine antiviral therapy and standard treatment, and were followed-up for up to 28 days. Results: Prior to data processing, azvudine treatment was associated with reduced mortality rates at 7 days (1.09/1000 persons vs.5.06/1000 persons, p<0.001)and 14 days (3.35/1000 persons vs. 5.65/1000 persons, p=0.001). After propensity score matching, a decrease in mortality rates at 7 days (0.08/1000 persons vs.6.29/1000 persons, p<0.001), 14 days (3.42/1000 persons vs. 7.26/1000 persons, p<0.001), and 28 days (4.33/1000 persons vs. 7.29/1000 persons, p=0.003) were observed following azvudine treatment. After inverse probability of treatment weighting adjustment, the results were consistent with propensity score matching. In the clinical subgroup analysis, for hospitalized severe and critical patients with COVID-19, azvudine treatment intervention significantly reduced patient mortality rates. Conclusions: The study suggests that in hospitalized patients with COVID-19, azvudine treatment significantly reduces patient mortality rates in hospitalized COVID-19 infections, wherein the effects are more pronounced in severe and critical patients.

Characterization and Evaluation of the Pathogenicity of a Natural Gene-Deleted Transmissible Gastroenteritis Virus in China

Porcine transmissible gastroenteritis virus is the major pathogen that causes fatal diarrhea in newborn piglets. In this study, a TGEV strain was isolated from the small intestine of diarrhea piglets in Sichuan Province, China, and designated SC2021. The complete genomic sequence of TGEV SC2021 was 28561 bp, revealing a new natural deletion TGEV strain. Based on phylogenetic analyses, TGEV SC2021 belonged to the Miller cluster and was closely related to CN strains. The newborn piglets orally challenged with TGEV SC2021 showed typical watery diarrhea. In addition, macro and micropathological changes in the lungs and intestines were observed. In conclusion, we isolated a new natural deletion virus strain and confirmed that the virus strain has high pathogenicity in newborn piglets. Moreover, macroscopic and microscopic lesions were observed in the lungs and intestines of all TGEV SC2021-infected piglets. In summary, we isolated a new natural deletion TGEV strain and demonstrated that the natural deletion strain showed high pathogenicity in newborn piglets. These data enrich the diversity of TGEV strains and help us to understand the genetic evolution and molecular pathogenesis of TGEV.

Postpartum extracorporeal membrane oxygenation of a woman with COVID-19-related acute respiratory distress syndrome: A case report.

INTRODUCTION: Patients with coronavirus disease (COVID-19) may develop acute respiratory distress syndrome (ARDS). There have been few reports of postpartum woman with ARDS secondary to COVID-19 who required respiratory support using veno-venous extracorporeal membrane oxygenation (ECMO). We present the case of a 31-year-old woman who was admitted to hospital at 35 weeks gestation with ARDS secondary to COVID-19 and required ECMO during the postpartum period. PATIENT CONCERNS: The patient had obvious dyspnea, accompanied by chills and fever. Her dyspnea worsened and her arterial oxygen saturation decreased rapidly. DIAGNOSIS: ARDS secondary to COVID-19. INTERVENTIONS: Emergency bedside cesarean section. Medications included immunotherapy (thymosin α 1), antivirals (lopinavir/ritonavir and ribavirin), antibiotics (imipenem-cilastatin sodium and vancomycin), and methylprednisolone. Ventilatory support was provided using invasive mechanical ventilation. This was replaced by venous-venous ECMO 5 days postpartum. ECMO management focused on blood volume control, coagulation function adjustment, and airway management. OUTCOMES: The patient was successfully weaned for ECMO and the ventilator and made a good recovery. CONCLUSION: Special care, including blood volume control, coagulation function adjustment, and airway management, should be provided to postpartum patients with ARDS secondary to COVID-19 who require ECMO support.

Multi-omics integrated analysis reveals a specific phenotype of CD8+ T cell may contribute to immunothromosis via Th17 response in severe and critical COVID-19 (preprint)

T lymphocyte reduction and immunosenescence frequently occur in severe and critical coronavirus disease 2019 (COVID-19) patients, which may cause immunothrombosis and numerous sequelae. This study integrated analyzed multi-omics data from healthy donors, pneumonia, COVID-19 patients (mild & moderate, severe, and critical), and convalescences, including clinical, laboratory test, PBMC bulk RNA-seq, PBMC scRNA-seq and TCR-seq, BAL scRNA-seq, and lung proteome. We revealed that there are certain associations among T lymphocyte reduction, CD8+ T cell senescence, Th17 immune activation, and immunothrombosis. A specific phenotype (S. P.) CD8+ T cells were identified in severe and critical COVID-19 patients in both PBMC and BAL scRNA-seq, which showed highly TCR homology with terminal effector CD8+ T cells and senescent CD8+ T cells. Pseudotime analysis showed that the S. P. CD8+ T cells were located in the transition trajectory from mild to severe disease. Which may be activated by terminal effector CD8+ T cells or senescent CD8+ T cells, thereby promoting Th17 cell differentiation. This phenomenon was absent in healthy donors, mild and moderate COVID-19 patients, or convalescences. Our findings are an important reference for avoiding the conversion of patients with mild to severe diseases and provide insight into the future prevention and control of COVID-19 and its variants.

Immunogenicity and safety of the CoronaVac inactivated SARS-CoV-2 vaccine in people with underlying medical conditions in China: a retrospective study (preprint)

People living with chronic disease, particularly seniors older than 60 years old, are lagging behind in the national COVID-19 vaccination campaign in China due to the uncertainty of vaccine safety and effectiveness. However, this special population made up of most severe symptom and death cases among SARS-CoV-2 infected patients and should be prioritized in vaccination program. Thus, safety and immunogenicity data of COVID-19 vaccines in people with underlying medical conditions are needed to address the vaccine hesitancy in this special population. Here, we report a retrospective cohort study evaluating the immunogenicity and safety of the inactivated COVID-19 vaccine, CoronaVac, in people with at least one of the six common diseases, focusing on seniors (N = 969). We found that CoronaVac is as safe in people with chronic diseases as that in healthy control, without serious adverse event reported in this study. By day 14-28 post vaccination, we observed no significant difference for the antibody responses between disease groups and healthy control, except for the coronary artery disease (p=0.03) and chronic respiratory disease group (p=0.04) showing moderate reduction. Such difference diminished by day 90 and 180, as neutralizing antibodies significantly reduced in all participants. Most people showed detectable SARS-CoV-2-specific T cell response at day 90 and day 180 without significant difference between disease groups and healthy control. Overall, our results highlight the comparable safety, immunogenicity and cellular immunity memory of CoronaVac in seniors and people living with chronic diseases, addressing vaccine hesitancy for this special population.

Clinicopathological and Immunological Features of Patients With New Onset Kidney Disease After Inactivated SARS-CoV-2 Vaccination: An Observational Cohort Study (preprint)

Background: The onset of various kidney diseases have been reported after COVID-19 vaccination. However, detailed clinical and pathological examination of kidney injury in patients receiving inactivated vaccines are lacking.Methods: We screened and analyzed patients with newly diagnosed kidney diseases after inactivated SARS-CoV-2 vaccination in Peking University First Hospital from January 2021 to August 2021. We obtained samples of blood, urine, and renal biopsy tissues. Clinical and laboratory information, as well as light microscopy, immunostaining and ultrastructural observation were described. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike protein and Nucleoprotein were stained using immune-fluorescence technique in the kidney biopsy samples. SARS-CoV-2 specific antibodies were tested using magnetic particle chemiluminescence immunoassay.Findings: The study group included 17 patients, including immune complex mediated kidney diseases (IgA nephropathy, membranous nephropathy and lupus nephritis), podocytopathy (minimal change disease and focal segmental glomerulosclerosis) and others (antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, anti-GBM nephritis, acute tubulointerstitial nephritis, and thrombotic microangiopathy). Seven patients (41.18%) developed renal disease after the first dose and 10 (58.82%) after the second dose. We found no definitive evidence of SARS-CoV-2 Spike protein or Nucleoprotein deposition in the kidney biopsy samples. Serological markers implicated abnormal immune responses in predisposed individuals. Treatment and follow-up (median = 86 days) showed that biopsy diagnosis informed treatment and prognosis in all patients.Interpretation: We observed various kidney diseases following inactivated SARS-CoV-2 vaccine administration. Our findings provide an evidence against direct vaccine protein deposition as the major pathomechanism, but implicate abnormal immune responses in predisposed individuals. These findings expand our understanding of inactivated SARS-CoV-2 vaccine renal safety.Funding: This study was funded by National Natural Science Foundation of China (91742205, 82170711, 81800636, 82070733, 81625004), Clinical Medicine Plus X—Young Scholars Project of Peking University (PKU2021LCXQ017), the Fundamental Research Funds for the Central Universities, CAMS Innovation Fund for Medical Sciences (2019-I2M-5-046), Yunnan Provincial Science and Technology Department (202102AA100051 and 202003AC100010, China), and Beijing Young Scientist Program (BJJWZYJH01201910001006).Declaration of Interest: The authors declare no competing interests.Ethical Approval: This study was approved by the institutional review board of Peking University First Hospital (2021-352) and the Committee on Human Subject Research and Ethics of Yunnan University (CHSRE2021020). Written Informed Consent Form was obtained from each participant.

To explore the material basis and mechanism of Lianhua Qingwen Prescription against COVID-19 based on network pharmacology

Objective: In the treatment of COVID-19, the application of Lianhua Qingwen Prescription has become growingly widespread, however, the mechanism of action is still unclear. To explore the material basis and mechanism of Lianhua Qingwen Prescription against SARS-CoV-2, to provide a reference for the treatment of COVID-19. Methods: Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), SwissTargetPrediction, and Similarity Ensemble Approach (SEA) database were used to search the chemical constituents and targets of Lianhua Qingwen Prescription. The targets of COVID-19 were screened by GeneCards, Therapeutic Target Database (TTD), and Comparative Toxicogenomics Database (CTD). Cytoscape software was used to construct a “drug-component-target” network diagram and the mechanism of action was predicted by enrichment analysis. Results: Two hundred and twenty four active components, 246 drug therapeutic targets, and 16,611 potential targets of Lianhua Qingwen Prescription were mined out. Moreover, 163 common targets were obtained, including PTGS2, IL6, CASP3, mapk1, EGFR, ACE2, etc. Thirty seven items were obtained by Gene Ontology (GO) enrichment analysis, mainly involving T-cell activation, virus receptor, and inflammatory reaction, etc. One hundred and forty items were obtained by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enriched analysis, including TNF signaling pathway, MAPK signaling pathway, and IL-17 signaling pathway. Conclusion: Compounds such as quercetin and kaempferol play an important role in anti-COVID-19 through the TNF signaling pathway and MAPK signaling pathway.

Extracorporeal membrane oxygenation for coronavirus disease 2019-associated acute respiratory distress syndrome: Report of two cases and review of the literature.

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2, is a worldwide pandemic. Some COVID-19 patients develop severe acute respiratory distress syndrome and progress to respiratory failure. In such cases, extracorporeal membrane oxygenation (ECMO) treatment is a necessary life-saving procedure. CASE SUMMARY: Two special COVID-19 cases-one full-term pregnant woman and one elderly (72-year-old) man-were treated by veno-venous (VV)-ECMO in the Second People's Hospital of Zhongshan, Zhongshan City, Guangdong Province, China. Both patients had developed refractory hypoxemia shortly after hospital admission, despite conventional support, and were therefore managed by VV-ECMO. Although both experienced multiple ECMO-related complications on top of the COVID-19 disease, their conditions improved gradually. Both patients were weaned successfully from the ECMO therapy. At the time of writing of this report, the woman has recovered completely and been discharged from hospital to home; the man remains on mechanical ventilation, due to respiratory muscle weakness and suspected lung fibrosis. As ECMO itself is associated with various complications, it is very important to understand and treat these complications to achieve optimal outcome. CONCLUSION: VV-ECMO can provide sufficient gas exchange for COVID-19 patients with acute respiratory distress syndrome. However, it is crucial to understand and treat ECMO-related complications.

A Case Report of Sedation Strategy for a Patient With Coronavirus Disease 2019 Supported by Extracorporeal Membrane Oxygenation After Cesarean Section.

Pneumonia caused by coronavirus disease 2019 (COVID-19) is a highly contagious disease. Unfortunately, research on extracorporeal membrane oxygenation (ECMO) assisted treatments for patients with COVID-19 infection is limited. In this case study, a patient who was in late pregnancy (35+2 weeks of pregnancy) and suffering from severe COVID-19 was extremely irritable during ECMO-assisted treatment after she underwent a cesarean section. Her Richmond Agitation Sedation Scale (RASS) score reached +3. Nevertheless, the patient successfully was treated with a continuous single/combined application of propofol, midazolam, dexmedetomidine, hibernation mixture, and other drugs for several days (maintaining RASS -2 to -4) and provided with anti-infection, mechanical ventilation, nutritional support, fluid balance under hemodynamic monitoring, liver support, and other organ function support treatments. ECMO-assisted sedation strategy for patients was introduced and discussed in this case to provide a certain reference for the clinical diagnosis and treatment of such patients.