Résumé
Introduction: One of the major challenges of the SARS-CoV2 pandemic is to identify people most at risk of developing severe COVID-19. Patients with cystic fibrosis (CF) and COPD are at higher risk as alteration of their bronchial epithelium is a major target of SARS-CoV2 in triggering excessive inflammation. Aims and objectives: We aim to know whether the pathophysiological status of bronchial epithelium from CF and COPD patients could lead to specific responses to SARS-CoV2 infection. Method(s): Differentiated bronchial epithelium from controls, CF and COPD patients (N=4/group) were infected with SARS-CoV2 (24, 48 and 72h) as we previously described (Pizzorno, A. et al. Cell Rep Med, 2020). We compared its effect on epithelial integrity (transepithelial resistance), global gene expression (RNA sequencing) and inflammation (multiplex analysis). Result(s): SARS-CoV2 induces a stronger impairment of bronchial epithelial integrity and a greater number of deregulated genes in controls, compared to CF or COPD subjects. We identified specific transcriptomic signatures for each group, further characterized using in silico functional enrichment approaches. Although the magnitude of the responses differed, we identified common genes induced 72h post infection, including SOCS1, ZBP1 and CXCL10 (IP-10). Differential induction of CXCL10 was further validated at the protein level. Conclusion(s): We defined a common core signature of the bronchial epithelium response to SARS-CoV2, as well as specific differences according to the pathological context. This study may allow a better understanding of the underlying mechanisms related to COVID-19 severity and for identifying potential markers of interest.
Résumé
Several reviews and models have suggested that indirect contact transmission involving contaminated surfaces could be the predominant transmission route for certain respiratory viruses. Indeed, contaminated environmental surfaces are considered to represent a significant vector for hospital-acquired viral infections. For any environmental contamination to be relevant, a virus should not only remain infectious on the recipient surface but also persist at a sufficient concentration to enable it to reach the respiratory tract via finger contamination. In general terms, the potential of a fomite to spread a given infectious agent is directly related to the capacity of the agent to survive on that surface. The surface stability of viruses is generally influenced by the type of surface, environmental factors such as relative humidity and temperature, and the presence of body fluid secretions (respiratory excretions, feces, blood.). We investigated the influence of such parameters on the stability of several alpha and betacoronaviruses, including 3 variants of SARS-CoV-2 (SARS-CoV-2 variant 2020, SARS-CoV-2 variant UK and SARS-CoV2 variant delta), on stainless steel discs and porous surface corresponding to borosilicate discs. Assays were done at 7 °C and 25 °C with a relative humidity of 65%. Artificial mucus/saliva or BSA/yeast extract mixtures were used as fluid mimetics for respiratory and enteric viruses, respectively. Our results showed significant variable stability of the viruses depending on both the porous/non-porous nature of the surfaces and the temperature. Beneficial or negative impacts of the body fluids were also observed. This study characterizes for the first time the behaviour of human and animal coronaviruses, including highly pathogenic betacoronaviruses, on several surfaces with fixed environmental parameters.