Interactions between Severe Acute Respiratory Syndrome Coronavirus 2 Replication and Major Respiratory Viruses in Human nasal Epithelium.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), along with extensive non-pharmacological interventions, have profoundly altered the epidemiology of major respiratory viruses. Some studies have described virus-virus interactions, particularly manifested by viral interference mechanisms at different scales. Still, our knowledge of the mutual interactions between SARS-CoV-2 and other respiratory viruses remains incomplete. Here, we studied the interactions between SARS-CoV-2 and several respiratory viruses (influenza, RSV, hMPV, and hRV) in a reconstituted human epithelial airway model, exploring different scenarios affecting the sequence and timing of co-infections. We show that the virus type and the sequence of infections are key parameters of virus-virus interactions, having the impact of primary infections on the regulation of the immune response a determinant role in the outcome of secondary infections.

Role of interfering substances in the survival of coronaviruses on surfaces and their impact on the efficiency of hand and surface disinfection (preprint)

Contaminated environmental surfaces are considered to represent a significant vector for hospital-acquired viral infections. In this study, we have evaluated the impact of interfering substances on SARS-CoV-2 surface stability and virucidal efficiency of hand sanitizers and surface disinfectant. To this end, surface stability of SARS-CoV-2 was measured on stainless steel in different experimental conditions, with or without an artificial mucus/saliva mixture and compared against that of human coronavirus HCoV-229E and feline coronavirus FCoV. The impact of the mucus/saliva mixture on the virucidal efficiency of 3 commercial alcohol hand sanitizers and 1 surface chemical disinfectant against SARS-CoV-2, HCoV-229E and FCoV was then measured. Our results indicate that mucus/saliva mixture did not demonstrate a beneficial effect on the surface survival of tested viruses, with temperature being an important parameter. In addition, we demonstrated that interfering substances may play an important role in the virucidal efficacy of hand sanitizers and disinfectants, highlighting the need for adapted testing protocols that better reflect current - real life -conditions of use.

Transcriptional profiling of immune and inflammatory responses in the context of SARS-CoV-2 fungal superinfection in a human airway epithelial model (preprint)

Superinfections of bacterial/fungal origin are known to affect the course and severity of respiratory viral infections. An increasing number of evidence indicate a relatively high prevalence of superinfections associated with COVID-19, including invasive aspergillosis, but the underlying mechanisms remain to be characterized. In the present study, to better understand the biological impact of superinfection we sought to determine and compare the host transcriptional response to SARS-CoV-2 versus Aspergillus superinfection, using a model of reconstituted humain airway epithelium. Our analyses reveal that both simple infection and superinfection induce a strong deregulation of core components of innate immune and inflammatory responses, with a stronger response to superinfection in the bronchial epithelial model compared to its nasal counterpart. Our results also highlight unique transcriptional footprints of SARS-CoV-2 Aspergillus superinfection, such as an imbalanced type I/type III IFN, and an induction of several monocyte- and neutrophil associated chemokines, that could be useful for the understanding of Aspergillus-associated COVID-19 and but also management of severe forms of aspergillosis in this specific context.

Characterization and treatment of SARS-CoV-2 in nasal and bronchial human airway epithelia (preprint)

In the current COVID-19 pandemic context, proposing and validating effective treatments represents a major challenge. However, the lack of biologically relevant pre-clinical experimental models of SARS-CoV-2 infection as a complement of classic cell lines represents a major barrier for scientific and medical progress. Here, we advantageously used human reconstituted airway epithelial models of nasal or bronchial origin to characterize viral infection kinetics, tissue-level remodeling of the cellular ultrastructure and transcriptional immune signatures induced by SARS-CoV-2. Our results underline the relevance of this model for the preclinical evaluation of antiviral candidates. Foremost, we provide evidence on the antiviral efficacy of remdesivir and the therapeutic potential of the remdesivir-diltiazem combination as a rapidly available option to respond to the current unmet medical need imposed by COVID-19. One Sentence SummaryNew insights on SARS-CoV-2 biology and drug combination therapies against COVID-19.