Background: An outbreak of pneumonia associated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan city and then to other city. It is very urgent to delineate the epidemiological and clinical characteristics of these affected patients. Methods: To investigate the epidemiological characteristics of the COVID-19, we describe a case series of 459 patients with con rmed COVID-19 in WZ of China from January 27 to February 12, 2020. Results: The median age of all patients was 48.0 years, and 46.8% were females. 37.5% of patients had a history of residence in Wuhan. Fever (72.1%) and cough (43.6%) were the most frequent symptoms. In addition, three kinds of unconventional cases were observed, in which included 4.4% con rmed virus carrier who were asymptomatic, 7.8% con rmed patients who had no link to Wuhan city but contact with individuals from Wuhan without any symptoms at the time of contact, and 10.7% con rmed patients who had no link to Wuhan city nor a history of intimate contact with patients or individuals from Wuhan without any symptoms, respectively. Conclusion: Our ndings presented the possibility of asymptomatic carriers affected with SARS-CoV-2, and this phenomenon suggested that chances of uncontrollable transmission in the larger population might be higher than formerly estimated, and transmission by these three kinds of unconventional patients in WZ may be one of the characteristics of infection in other Chinese cities outside the Wuhan epidemic area.

Inflammatory caspases (caspases 1, 4, 5 and 11) are activated in response to microbial infection and danger signals. When activated, they cleave mouse and human gasdermin D (GSDMD) after Asp276 and Asp275, respectively, to generate an N-terminal cleavage product (GSDMD-NT) that triggers inflammatory death (pyroptosis) and release of inflammatory cytokines such as interleukin-1β1,2. Cleavage removes the C-terminal fragment (GSDMD-CT), which is thought to fold back on GSDMD-NT to inhibit its activation. However, how GSDMD-NT causes cell death is unknown. Here we show that GSDMD-NT oligomerizes in membranes to form pores that are visible by electron microscopy. GSDMD-NT binds to phosphatidylinositol phosphates and phosphatidylserine (restricted to the cell membrane inner leaflet) and cardiolipin (present in the inner and outer leaflets of bacterial membranes). Mutation of four evolutionarily conserved basic residues blocks GSDMD-NT oligomerization, membrane binding, pore formation and pyroptosis. Because of its lipid-binding preferences, GSDMD-NT kills from within the cell, but does not harm neighbouring mammalian cells when it is released during pyroptosis. GSDMD-NT also kills cell-free bacteria in vitro and may have a direct bactericidal effect within the cytosol of host cells, but the importance of direct bacterial killing in controlling in vivo infection remains to be determined.

Cleavage of the gasdermins to produce a pore-forming N-terminal fragment causes inflammatory death (pyroptosis) 1 . Caspase-3 cleaves gasdermin E (GSDME, also known as DFNA5), mutated in familial aging-related hearing loss 2 , which converts noninflammatory apoptosis to pyroptosis in GSDME-expressing cells 3 – 5 . GSDME expression is suppressed in many cancers and reduced GSDME is associated with decreased breast cancer survival 2 , 6 , suggesting GSDME might be a tumor suppressor. Here we show reduced GSDME function of 20 of 22 tested cancer-associated mutations. Gsdme knockout in GSDME-expressing tumors enhances, while ectopic expression in Gsdme -repressed tumors inhibits, tumor growth. Tumor suppression is mediated by cytotoxic lymphocyte killing since it is abrogated in perforin-deficient or killer lymphocyte-depleted mice. GSDME expression enhances tumor-associated macrophage phagocytosis and the number and functions of tumor-infiltrating NK and CD8 + T lymphocytes. Killer cell granzyme B also activates caspase-independent pyroptosis in target cells by directly cleaving GSDME at the same site as caspase-3. Non-cleavable or pore-defective GSDME are not tumor suppressive. Thus, tumor GSDME is a tumor suppressor by activating pyroptosis, which enhances anti-tumor immunity.