Résumé
For exploring the histopathological changes of intestinal tissues and the mechanism of porcine deltacoronavirus(PDCo V) replication and leading to inflammatory lesions of piglets intestine which induced by PDCo V infection, 10-day-old piglets were infected by PDCo V strain TJ1 which isolated from Tianjin through oral route in this study. The piglets were necropsied at 4 days post-infection. Through histopathological observation, the main lesions of jejunum, ileum, colon and cecum were investigated. The diffuse inflammatory cell infiltration was found in mesenchyme, lamina propria and submucosa of intestinal mucosa, and the mucosal villi atrophy occurred in response to local tissues. The m RNA expression level of PDCo V M gene, innate immune genes including IFN-a, IFN-beta, DDX58 and STAT2 as well as the inflammatory cytoines including TNF-a and IL-6 in intestinal tissues were examined. The results showed that PDCo V replication was achieved by inhibiting host cell innate immune response, and the occurrence of inflammatory lesions in jejunum, ileum and colon were promoted through the enhancement of TNF-a and IL-6 expression. This study can provide a theoretical basis for the pathogenic mechanism study of porcine deltacoronavirus.
Résumé
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of Coronavirus disease 2019 (COVID-19). However, the microbial composition of the respiratory tract and other infected tissues as well as their possible pathogenic contributions to varying degrees of disease severity in COVID-19 patients remain unclear. Between 27 January and 26 February 2020, serial clinical specimens (sputum, nasal and throat swab, anal swab and feces) were collected from a cohort of hospitalized COVID-19 patients, including 8 mildly and 15 severely ill patients in Guangdong province, China. Total RNA was extracted and ultra-deep metatranscriptomic sequencing was performed in combination with laboratory diagnostic assays. We identified distinct signatures of microbial dysbiosis among severely ill COVID-19 patients on broad spectrum antimicrobial therapy. Co-detection of other human respiratory viruses (including human alphaherpesvirus 1, rhinovirus B, and human orthopneumovirus) was demonstrated in 30.8% (4/13) of the severely ill patients, but not in any of the mildly affected patients. Notably, the predominant respiratory microbial taxa of severely ill patients were Burkholderia cepacia complex (BCC), Staphylococcus epidermidis, or Mycoplasma spp. (including M. hominis and M. orale). The presence of the former two bacterial taxa was also confirmed by clinical cultures of respiratory specimens (expectorated sputum or nasal secretions) in 23.1% (3/13) of the severe cases. Finally, a time-dependent, secondary infection of B. cenocepacia with expressions of multiple virulence genes was demonstrated in one severely ill patient, which might accelerate his disease deterioration and death occurring one month after ICU admission. Our findings point to SARS-CoV-2-related microbial dysbiosis and various antibiotic-resistant respiratory microbes/pathogens in hospitalized COVID-19 patients in relation to disease severity. Detection and tracking strategies are needed to prevent the spread of antimicrobial resistance, improve the treatment regimen and clinical outcomes of hospitalized, severely ill COVID-19 patients.
Résumé
The emergence of the novel human coronavirus, SARS-CoV-2, causes a global COVID-19 (coronavirus disease 2019) pandemic. Here, we have characterized and compared viral populations of SARS-CoV-2 among COVID-19 patients within and across households. Our work showed an active viral replication activity in the human respiratory tract and the co-existence of genetically distinct viruses within the same host. The inter-host comparison among viral populations further revealed a narrow transmission bottleneck between patients from the same households, suggesting a dominated role of stochastic dynamics in both inter-host and intra-host evolutions.