S Protein of SARS-CoV-2: research progress and challenges

SARS-CoV-2, which caused a pandemic, is a new coronavirus pathogen that can spread rapidly from person to person. The spike protein (S) on the surface of coronavirus plays an important role in determining the host specificity. pathogenicity and interspecies transmission of the virus. S protein is the most studied SARS - CoV-2 protein after the outbreak of SARS-CoV-2. S protein is also the most important antigenic protein for the development of SAES - CoV -2 vaccine and the important target of antiviral drugs. Here the latest research progress of SARS-CoV-2 S protein was reviewed, and the problems and challenges in current research were discussed. .

Single-Cell Analysis Reveals Macrophage-Driven T Cell Dysfunction in Severe COVID-19 Patients (preprint)

The vastly spreading COVID-19 pneumonia is caused by SARS-CoV-2. Lymphopenia and cytokine levels are tightly associated with disease severity. However, virus-induced immune dysregulation at cellular and molecular levels remains largely undefined. Here, the leukocytes in the pleural effusion, sputum, and peripheral blood biopsies from severe and mild patients were analyzed at single-cell resolution. Drastic T cell hyperactivation accompanying elevated T cell exhaustion was observed, predominantly in pleural effusion. The mechanistic investigation identified a group of CD14+ monocytes and macrophages highly expressing CD163 and MRC1 in the biopsies from severe patients, suggesting M2 macrophage polarization. These M2-like cells exhibited up-regulated IL10, CCL18, APOE, CSF1 (M-CSF), and CCL2 signaling pathways. Further, SARS-CoV-2-specific T cells were observed in pleural effusion earlier than in peripheral blood. Together, our results suggest that severe SARS-CoV-2 infection causes immune dysregulation by inducing M2 polarization and subsequent T cell exhaustion. This study improves our understanding of COVID-19 pathogenesis.

Single-cell atlas of a non-human primate reveals new pathogenic mechanisms of COVID-19 (preprint)

Stopping COVID-19 is a priority worldwide. Understanding which cell types are targeted by SARS-CoV-2 virus, whether interspecies differences exist, and how variations in cell state influence viral entry is fundamental for accelerating therapeutic and preventative approaches. In this endeavor, we profiled the transcriptome of nine tissues from a Macaca fascicularis monkey at single-cell resolution. The distribution of SARS-CoV-2 facilitators, ACE2 and TMRPSS2, in different cell subtypes showed substantial heterogeneity across lung, kidney, and liver. Through co-expression analysis, we identified immunomodulatory proteins such as IDO2 and ANPEP as potential SARS-CoV-2 targets responsible for immune cell exhaustion. Furthermore, single-cell chromatin accessibility analysis of the kidney unveiled a plausible link between IL6-mediated innate immune responses aiming to protect tissue and enhanced ACE2 expression that could promote viral entry. Our work constitutes a unique resource for understanding the physiology and pathophysiology of two phylogenetically close species, which might guide in the development of therapeutic approaches in humans. Bullet pointsO_LIWe generated a single-cell transcriptome atlas of 9 monkey tissues to study COVID-19. C_LIO_LIACE2+TMPRSS2+ epithelial cells of lung, kidney and liver are targets for SARS-CoV-2. C_LIO_LIACE2 correlation analysis shows IDO2 and ANPEP as potential therapeutic opportunities. C_LIO_LIWe unveil a link between IL6, STAT transcription factors and boosted SARS-CoV-2 entry. C_LI

Cases Report of Cured Novel Coronavirus-infected Pneumonia Patients with Viral Nucleic Acid Test Positive in Fecal Specimens (preprint)

Background: The outbreak of the novel coronavirus in China (COVID-19) represents a significant and urgent threat to global health. We report here five cases of COVID-19 infection patients in our clinical practices who are medically stable and presumed to successfully “cleared” the virus after antiviral treatments. Case presentation: The clinical evaluation depends on the viral nucleic acid test in respiratory specimens by real-time PCR reverse transcription (RT-PCR) assays according to the authorized guidance. We found that the stool samples of these cured patients remain positive in RT-PCR assay while the virus is undetectable in respiratory specimens. RT-PCR molecular diagnostic assay was designed to specifically detect the presence of viral RNA. Thus, the positive result in the fecal specimens implies the existence of viable virions with the patients. Conclusions: This highlights the importance to look closely at the assessment standard of medical treatment, as well as the need for reevaluation of the criteria for the initial screening, prevention, and care of patients with this emerging infection.