the french enterovirus Myocarditis Study Group (feMSG) * Major 5′terminally deleted (5′TD) group-B enterovirus (EV-B) populations were identified in heart biopsies of patients with fulminant myocarditis or dilated cardiomyopathy suggesting that these 5′TD forms are key drivers of host-cell interaction in EV cardiac infections. To date, early emergence of EV-B 5′TD forms and its impact on type 1 IFN response during acute myocarditis remains unknown. Using quantitative RACE-PCR assay, we identified major EV-B 5′tD RnA populations in plasma or heart samples of acute myocarditis cases. Deletions identified within the 5′ non-coding region of EV-B populations only affected secondary-structural elements of genomic RNA domain I and were distinguished in two major groups based on the extent of RnA structural deletions. proportions of these two respective EV-B 5′tD population groups were positively or negatively correlated with IFN-β levels in plasma samples of myocarditis patients. Transfection of synthetic CVB3/28 RNAs harboring various 5′terminal full-length or deleted sequences into human cultured cardiomyocytes demonstrated that viral genomic RnA domain i possessed essential immunomodulatory secondarystructural elements responsible for IFN-β pathway induction. Overall, our results highlight the early emergence of major EVB-TD populations which deletions affecting secondary-structures of RNA domain i can modulate innate immune sensing mechanisms in cardiomyocytes of patients with acute myocarditis. Group-B Enteroviruses (EV-B) belong to the Picornaviridae family and are recognized as major causes of aseptic meningitis, upper or lower respiratory tract infections and acute myocarditis cases diagnosed in neonates, infants and young adults 1,2. Between 10-20% of acute myocarditis cases will evolve into chronic myocarditis as well as dilated cardiomyopathy (DCM, prevalence = 7 cases / 100,000, second leading cause of heart transplantation worldwide after ischemic heart disease) 1. EV-B RNA genome is approximately 7,400 nucleotides (nt) in length and is flanked at the 5′ end by a highly conserved non-coding region (5′NCR) that is crucial for the initiation of the viral replication and translation activities 3. A study in 2008 of heart tissue from a patient who died of fulminant myocarditis demonstrated the presence of a group B Coxsackie virus type 2 (CVB-2) population with partial deletions at the 5′ terminus and proceeding inward 4. Similar findings had been described following CVB-3 replication in cell cultures and in mice 5,6. Bouin et al.7 identified EV-B populations characterized by 5′NCR RNA deletions ranging from 15 to 48 nt

Differential kinetics of RNA loads and infectious viral levels in the upper respiratory tract between asymptomatic and symptomatic SARS-CoV-2 infected adult outpatients remain unclear limiting recommendations that may guide clinical management, infection control measures and occupational health decisions. In the present investigation, 496 (2.8%) of 17,911 French adult outpatients were positive for an upper respiratory tract SARS-CoV-2 RNA detection by a quantitative RT-PCR assay, of which 180 (36.3%) were COVID-19 asymptomatic. Of these adult asymptomatic viral shedders, 75% had mean to high RNA viral loads (Ct values < 30) which median value was significantly higher than that observed in symptomatic subjects (P = 0.029), and 50.6% were positive by cell culture assays of their upper respiratory tract specimens. Our findings indicate that COVID-19 asymptomatic adult outpatients are significant viable SARS-CoV-2 shedders in their upper respiratory tract playing a major potential role as SARS-CoV-2 transmitters in various epidemiological transmission chains, promoting COVID-19 resurgence in populations.

Group-B enteroviruses (EV-B) are ubiquitous naked single-stranded positive RNA viral pathogens that are responsible for common acute or persistent human infections. Their genome is composed in the 5′ end by a non-coding region, which is crucial for the initiation of the viral replication and translation processes. RNA domain-I secondary structures can interact with viral or cellular proteins to form viral ribonucleoprotein (RNP) complexes regulating viral genomic replication, whereas RNA domains-II to -VII (internal ribosome entry site, IRES) are known to interact with cellular ribosomal subunits to initiate the viral translation process. Natural 5′ terminally deleted viral forms lacking some genomic RNA domain-I secondary structures have been described in EV-B induced murine or human infections. Recent in vitro studies have evidenced that the loss of some viral RNP complexes in the RNA domain-I can modulate the viral replication and infectivity levels in EV-B infections. Moreover, the disruption of secondary structures of RNA domain-I could impair viral RNA sensing by RIG-I (Retinoic acid inducible gene I) or MDA5 (melanoma differentiation-associated protein 5) receptors, a way to overcome antiviral innate immune response. Overall, natural 5′ terminally deleted viral genomes resulting in the loss of various structures in the RNA domain-I could be major key players of host–cell interactions driving the development of acute or persistent EV-B infections.

Background Understanding patterns of environmental contamination by SARS-CoV-2 is essential for infection prevention policies. Methods We screened surfaces and air samples from single bed ICU rooms of COVID-19 adult patients for SARS-CoV-2 RNA and viable viruses. Results and discussion We evidenced viral RNA environmental contamination in 76% of 100 surfaces samples and in 30% of 40 air samples without any viable virus detection by cell culture assays. No significant differences of viral RNA levels on surfaces and in ambient air were observed between rooms of patients with assisted mechanical ventilation and those of patients with high-flow nasal cannula system. Using an original experimental SARS-CoV-2 infection model of surfaces, we assessed that infectious viruses might have been present on benches within 15 hours before the time of sampling in patient rooms. Conclusions We observed that SARS-CoV-2 environmental contamination around COVID-19 patients hospitalized in single ICU rooms was extensive and that a high-flow nasal cannula system did not generate more viral aerosolization than a mechanical ventilation system in COVID-19 patients. Despite an absence of SARS-CoV-2 viable particles in study samples, our experimental model confirmed the need to apply strict environmental disinfection procedures and classical standard and droplet precautions in ICU wards.

We assessed relationships between early peripheral blood type I interferons (IFN) levels, clinical new early warning scores (NEWS), and clinical outcomes in hospitalized coronavirus disease‐19 (COVID‐19) adult patients. Early IFN‐β levels were lower among patients who further required intensive care unit (ICU) admission than those measured in patients who did not require an ICU admission during severe acute respiratory syndrome coronavirus type 2 infection. IFN‐β levels were inversely correlated with NEWS only in the subgroup of patients who further required ICU admission. To assess whether peripheral blood IFN‐β levels could be a potential relevant biomarker to predict further need for ICU admission, we performed receiver operating characteristic (ROC) curve analyses that showed for all study patients an area under ROC curve of 0.77 growing to 0.86 (p = 0.003) when the analysis was restricted to a subset of patients with NEWS ≥5 at the time of hospital admission. Overall, our findings indicated that early peripheral blood IFN‐β levels might be a relevant predictive marker of further need for an ICU admission in hospitalized COVID‐19 adult patients, specifically when clinical score (NEWS) was graded as upper than 5 at the time of hospital admission.