Project description:The aim of this study was to assess the gene expression profil of skin chilblain-like lesions that appeared during the COVID-19 pandemic and to compare it with seasonal chilblain and healthy skin
Project description:Chilblain-like lesions (CLL) coinciding with SARS-CoV-2 infection have been described. Previous systematic reviews suggest CLL are associated with younger age, an equal sex ratio, negative testing for SARS-CoV-2, and mild to no extracutaneous symptoms. A systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines on CLL coinciding with SARS-CoV-2 to clarify the demographic characteristics, clinical features, and resolution outcomes of these skin findings. One hundred twenty-eight studies, published between March 2020 and January 2022, met inclusion criteria and were summarized in this review, representing 4,982 cases of CLL. Available data showed a slight female predominance (55%, n = 2,471 of 4,472). The mean age was 25 years, ranging from 0 to 95 years. Most cases were not associated with extracutaneous signs and symptoms (63%, n = 1,649 of 2,636). Overall, 19% (n = 347 of 1,838) of patients tested positive for SARS-CoV-2 using polymerase chain reaction, serology, or tissue biopsy. Clinical course was generally benign with 80% (n = 979 of 1,224) of cases resolving and 47% (n = 204 of 432) resolving without receiving treatment. This review provides a comprehensive summary of CLL associated with SARS-CoV-2. CLL occurred at a mean age of 25 years with a slight female predominance. The majority had negative COVID-19 testing, no extracutaneous signs and symptoms, and resolution without recurrence.
Project description:ACE2 on epithelial cells is the SARS-CoV-2 entry receptor. Single-cell RNA-sequencing data derived from two COVID-19 cohorts revealed that MAP4K3/GLK-positive epithelial cells were increased in patients. SARS-CoV-2-induced GLK overexpression in epithelial cells correlated with COVID-19 severity and vesicle secretion. GLK overexpression induced the epithelial cell-derived exosomes containing ACE2; the GLK-induced exosomes transported ACE2 proteins to recipient cells, facilitating pseudovirus infection. Consistently, ACE2 proteins were increased in the serum exosomes from another COVID-19 cohort. Remarkably, SARS-CoV-2 spike protein stimulated GLK, and GLK stabilized ACE2 in epithelial cells. Mechanistically, GLK phosphorylated ACE2 at two serine residues (Ser776, Ser783), leading to dissociation of ACE2 from its E3 ligase UBR4. Reduction of UBR4-induced Lys48-linked ubiquitination at three lysine residues (Lys26, Lys112, Lys114) of ACE2 prevented its degradation. Furthermore, SARS-CoV-2 pseudovirus or live virus infection in humanized ACE2 mice induced GLK and ACE2 protein levels, as well as ACE2-containing exosomes. Collectively, ACE2 stabilization by SARS-CoV-2-induced MAP4K3/GLK may contribute to the pathogenesis of COVID-19.
Project description:Bat sarbecovirus BANAL-236 is highly related to SARS-CoV-2 and infects human cells, albeit lacking the furin cleavage site in its spike protein. BANAL-236 replicates efficiently and pauci-symptomatically in humanized mice and in macaques, where its tropism is enteric, strongly differing from that of SARS-CoV-2. BANAL-236 infection leads to protection against superinfection by a virulent strain. We find no evidence of antibodies recognizing bat sarbecoviruses in populations in close contact with bats in which the virus was identified, indicating that such spillover infections, if they occur, are rare. Six passages in humanized mice or in human intestinal cells, mimicking putative early spillover events, select adaptive mutations without appearance of a furin cleavage site and no change in virulence. Therefore, acquisition of a furin site in the spike protein is likely a pre-spillover event that did not occur upon replication of a SARS-CoV-2-like bat virus in humans or other animals. Other hypotheses regarding the origin of the SARS-CoV-2 should therefore be evaluated, including the presence of sarbecoviruses carrying a spike with a furin cleavage site in bats.
Project description:To evaluate the gene expression profiling of peripheral leukocytes in different outcomes of SARS-CoV-2 infections, whole blood samples were collected from individuals with positive SARS-CoV-2 nasopharyngeal swab by RT-PCR (54 patients) and healthy uninfected individuals (12 volunteers). Infected patients were classified into mild, moderate, severe and critical groups according to a modified statement in the Novel Coronavirus Pneumonia Diagnosis and Treatment Guideline. Blood were collected into EDTA tubes and the buffy coat samples were stored in TRIzol reagent at -80 °C until use for RNA extraction. Affymetrix Clariom S array was used to perform the high-throughput gene expression profiling. Microarray analyses were performed using APT Affymetrix software, R packages and Bioconductor libraries. This systemic view of SARS-CoV-2 infections through blood transcriptomics will foster the understanding about molecular mechanisms and immunopathological processes involved in COVID-19 disease and its different outcomes.
Project description:SARS-CoV-2 is a virus that is the cause of a serious life-threatening disease known as COVID-19. It was first noted to have occurred in Wuhan, China in November 2019 and the WHO reported the first case on December 31, 2019. The outbreak was declared a global pandemic on March 11, 2020 and by May 30, 2020, a total of 5 899 866 positive cases were registered including 364 891 deaths. SARS-CoV-2 primarily targets the lung and enters the body through ACE2 receptors. Typical symptoms of COVID-19 include fever, cough, shortness of breath and fatigue, yet some atypical symptoms like loss of smell and taste have also been described. 20% require hospital admission due to severe disease, a third of whom need intensive support. Treatment is primarily supportive, however, prognosis is dismal in those who need invasive ventilation. Trials are ongoing to discover effective vaccines and drugs to combat the disease. Preventive strategies aim at reducing the transmission of disease by contact tracing, washing of hands, use of face masks and government-led lockdown of unnecessary activities to reduce the risk of transmission.