The efficacy of therapeutic plasma exchange in COVID-19 patients on endothelial tightness in vitro is hindered by platelet activation.

Coronavirus disease (COVID)-19 is characterised in particular by vascular inflammation with platelet activation and endothelial dysfunction. During the pandemic, therapeutic plasma exchange (TPE) was used to reduce the cytokine storm in the circulation and delay or prevent ICU admissions. This procedure consists in replacing the inflammatory plasma by fresh frozen plasma from healthy donors and is often used to remove pathogenic molecules from plasma (autoantibodies, immune complexes, toxins, etc.). This study uses an in vitro model of platelet-endothelial cell interactions to assess changes in these interactions by plasma from COVID-19 patients and to determine the extent to which TPE reduces such changes. We noted that exposure of an endothelial monolayer to plasmas from COVID-19 patients post-TPE induced less endothelial permeability compared to COVID-19 control plasmas. Yet, when endothelial cells were co-cultured with healthy platelets and exposed to the plasma, the beneficial effect of TPE on endothelial permeability was somewhat reduced. This was linked to platelet and endothelial phenotypical activation but not with inflammatory molecule secretion. Our work shows that, in parallel to the beneficial removal of inflammatory factors from the circulation, TPE triggers cellular activation which may partly explain the reduction in efficacy in terms of endothelial dysfunction. These findings provide new insights for improving the efficacy of TPE using supporting treatments targeting platelet activation, for instance.

Les virus dans l'environnement, considérations virologiques et exemples de leur impact en santé humaine Viruses present in the environment: virological considerations and examples of their impact on human health

Résumé Les virus animaux sont présents dans la plupart des environnements humains. Leur viabilité dans ces milieux est très variable et l'élément le plus important qui conditionne cette viabilité est l'existence ou non d'une enveloppe de nature phospholipidique autour de la nucléocapside. Après quelques considérations générales sur la structure des virus, leur cycle de multiplication et leur résistance à différents agents physico-chimiques, seront proposés quelques exemples de l'impact des virus animaux présents dans l'environnement sur la santé humaine. Les situations présentées sont en relation avec l'actualité épidémiologique récente : circulation de poliovirus de type 2 dérivés de la souche vaccinale Sabin dans les eaux usées de New York, de Londres et de Jérusalem, risque de transmission du Sars-CoV-2 lors de l'épandage sur les terres agricoles de boues provenant de stations d'épuration à l'ère de la pandémie de Covid-19, « nouvelles » formes de toxi-infections alimentaires d'origine virale (hépatite E, encéphalite à tique, infection à virus Nipah), contaminations par des virus épidémiques des téléphones portables utilisés par les pédiatres, rôle des fomites dans la propagation des orthopoxviroses (variole, cowpox, monkeypox). Le risque attaché aux virus animaux présents dans l'environnement doit être évalué de façon mesurée sans surestimation ni sous-estimation de leurs conséquences potentielles en santé humaine.

[Viruses present in the environment: virological considerations and examples of their impact on human health]. / Les virus dans l'environnement, considérations virologiques et exemples de leur impact en santé humaine.

Animal viruses are present in most human environments. Their viability in these media is very variable and the most important element that conditions this viability is the existence or not of a phospholipid envelope surrounding the nucleocapsid. After some general considerations on the structure of viruses, their multiplication cycle and their resistance to different physico-chemical agents, some examples of the impact of animal viruses present in the environment on human health will be presented. The situations that are related concern recent epidemiological events: circulation of type 2 polioviruses derived from the Sabin vaccine strain in the wastewater of New York, London and Jerusalem; risk of transmission of Sars-CoV-2 during the spreading of sludge from wastewater treatment plants on agricultural land in the era of the Covid-19 pandemic; « new ¼ forms of food-borne poisoning of viral origin (hepatitis E, tick-borne encephalitis, Nipah virus infection); contamination by epidemic viruses of mobile phones used by pediatricians; role of fomites in the spread of orthopoxvirus infections (smallpox, cowpox, monkeypox). The risk attached to animal viruses present in the environment must be assessed in a measured way without overestimating or underestimating their potential consequences for human health.

Development and Validation of the COVID-19 Knowledges and Behavior Questionnaire in a French Population (CoVQuest-CC).

BACKGROUND: The SARS-CoV-2 pandemic has led most countries to take restrictive measures affecting social activities and individual freedoms to limit viral transmission. It was shown that practical, motivational and social barriers impact on adherence to the isolation and social distancing measures advocated by the health authorities. The purpose of this study was to develop and validate a COVID-19 Knowledges and Behavior Questionnaire adapted to a teenager and adult French population. METHODS: CoVQuest-CC was developed by a multidisciplinary team made of infectious diseases physicians, medical virologist, specialists of infectious control, experts of the questionnaires methodology, experts in public health and prevention, and statisticians. CoVQuest-CC was responded to by a big cohort from the general population during their participation in a massive SARS-CoV-2 screening campaign in 2021 in Saint-Etienne, France. RESULTS: The confirmatory factorial analysis yielded good results (CFI = 0.94, TLI = 0.94, RMSEA = 0.04), and confirmed the five-dimensional structure of the questionnaire. Each dimension had a satisfying internal consistency, with Cronbach alphas of 0.83, 0.71, 0.65, 0.72 and 0.83 for transmission knowledge, barrier gesture respect, tests acceptability, home isolation possibility and test practicability, respectively. CONCLUSIONS: According to our knowledge, CoVQuest-CC is the first validated, consistent and reliable self-administrated French-specific questionnaire investigating the general population's knowledge and attitudes towards COVID-19. It shows acceptable psychometric properties and can be use by Public Health teams or caregivers for public health and research purposes. TRIAL REGISTRATION: The study protocol was approved by the IRB ILE-DE-FRANCE 1 (No. IRB: I ORG0009918). All participants were given written and verbal information about the study and gave informed consent to participate. CLINICALTRIALS: gov identifier (NCT number): NCT04859023.

Factors Associated with Psychological Distress in French Medical Students during the COVID-19 Health Crisis: A Cross-Sectional Study.

BACKGROUND: The purpose of this study was to assess the prevalence of psychological distress in medical students during the COVID-19 health crisis and to identify factors associated with psychological distress. METHODS: A cross-sectional observational study was presented to 1814 medical students (from first to sixth year) in a French university hospital center. Sociodemographic, occupational and medical information (psychological distress measured on the French GHQ12 scale) were collected via an online anonymous self-administered questionnaire. Variables associated with psychological distress were investigated using univariate analysis and multivariate analysis (modified Poisson regression). RESULTS: In total, 832 medical students responded (46%) and 699 completed the questionnaire in full (39%); 625 (75%) showed signs of psychological distress and 109 (15%) reported suicidal ideation. Female gender, psychological trauma during the COVID-19 health crisis, change in alcohol consumption, and difficulties with online learning emerged as risk factors for psychological distress, whereas a paid activity, a feeling of mutual aid and cooperation within the studies framework, and recognition of work appeared to be protective factors. CONCLUSIONS: Mental health care or suicide prevention should be provided to students at risk in the aftermath of the pandemic. Knowing the educational and medical factors associated with psychological distress enables areas for prevention to be identified.

Platelet Innate Immune Receptors and TLRs: A Double-Edged Sword.

Platelets are hematopoietic cells whose main function has for a long time been considered to be the maintenance of vascular integrity. They have an essential role in the hemostatic response, but they also have functional capabilities that go far beyond it. This review will provide an overview of platelet functions. Indeed, stress signals may induce platelet apoptosis through proapoptotis or hemostasis receptors, necrosis, and even autophagy. Platelets also interact with immune cells and modulate immune responses in terms of activation, maturation, recruitment and cytokine secretion. This review will also show that platelets, thanks to their wide range of innate immune receptors, and in particular toll-like receptors, and can be considered sentinels actively participating in the immuno-surveillance of the body. We will discuss the diversity of platelet responses following the engagement of these receptors as well as the signaling pathways involved. Finally, we will show that while platelets contribute significantly, via their TLRs, to immune response and inflammation, these receptors also participate in the pathophysiological processes associated with various pathogens and diseases, including cancer and atherosclerosis.

A longitudinal study of SARS-CoV-2-infected patients reveals a high correlation between neutralizing antibodies and COVID-19 severity.

Understanding the immune responses elicited by SARS-CoV-2 infection is critical in terms of protection against reinfection and, thus, for public health policy and vaccine development for COVID-19. In this study, using either live SARS-CoV-2 particles or retroviruses pseudotyped with the SARS-CoV-2 S viral surface protein (Spike), we studied the neutralizing antibody (nAb) response in serum samples from a cohort of 140 SARS-CoV-2 qPCR-confirmed infections, including patients with mild symptoms and also more severe forms, including those that required intensive care. We show that nAb titers correlated strongly with disease severity and with anti-spike IgG levels. Indeed, patients from intensive care units exhibited high nAb titers; conversely, patients with milder disease symptoms had heterogeneous nAb titers, and asymptomatic or exclusive outpatient-care patients had no or low nAbs. We found that nAb activity in SARS-CoV-2-infected patients displayed a relatively rapid decline after recovery compared to individuals infected with other coronaviruses. Moreover, we found an absence of cross-neutralization between endemic coronaviruses and SARS-CoV-2, indicating that previous infection by human coronaviruses may not generate protective nAbs against SARS-CoV-2. Finally, we found that the D614G mutation in the spike protein, which has recently been identified as the current major variant in Europe, does not allow neutralization escape. Altogether, our results contribute to our understanding of the immune correlates of SARS-CoV-2-induced disease, and rapid evaluation of the role of the humoral response in the pathogenesis of SARS-CoV-2 is warranted.

COVID-19 in health-care workers: lessons from SARS and MERS epidemics and perspectives for chemoprophylaxis and vaccines.

Introduction: The world is now facing the COVID-19 pandemic. Experience with SARS-CoV and MERS-CoV, and early reports about SARS-CoV-2 infection suggest that health-care settings and health-care workers (HCWs) are vulnerable in the context of the emergence of a new coronavirus. Areas covered: To highlight the need for prophylactic strategies particularly for HCWs, we identified SARS-CoV, MERS-CoV, and SARS-CoV-2 outbreaks in health-care settings and the incidence of infections in HCWs by a search on MEDLINE and MEDxRIV (for SARS-Cov-2). To identify prophylactic strategies against, we conducted a search on MEDLINE and clinicaltrials.gov about studies involving SARS-CoV, MERS-CoV, and SARS-CoV-2. Expert opinion: HCWs account for a great part of SARS, MERS, and SARS-CoV-2 infections, they may also contribute to the spread of the disease, particularly in health-care settings, and contribute to nosocomial outbreaks. Some preventive strategies were evaluated in previous emerging coronavirus epidemics, particularly in MERS-CoV. For COVID-19 prevention, different chemoprophylaxis with drug repositioning and new agents are under evaluation, and different vaccine candidates entered clinical development, with clinical trials. HCWs are a crucial target population for pre-exposure and post-exposure prophylaxis.

Cluster of Coronavirus Disease 2019 (COVID-19) in the French Alps, February 2020.

BACKGROUND: On 7 February 2020, French Health authorities were informed of a confirmed case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in an Englishman infected in Singapore who had recently stayed in a chalet in the French Alps. We conducted an investigation to identify secondary cases and interrupt transmission. METHODS: We defined as a confirmed case a person linked to the chalet with a positive reverse-transcription polymerase chain reaction sample for SARS-CoV-2. RESULTS: The index case stayed 4 days in the chalet with 10 English tourists and a family of 5 French residents; SARS-CoV-2 was detected in 5 individuals in France, 6 in England (including the index case), and 1 in Spain (overall attack rate in the chalet: 75%). One pediatric case, with picornavirus and influenza A coinfection, visited 3 different schools while symptomatic. One case was asymptomatic, with similar viral load as that of a symptomatic case. Seven days after the first cases were diagnosed, 1 tertiary case was detected in a symptomatic patient with from the chalet a positive endotracheal aspirate; all previous and concurrent nasopharyngeal specimens were negative. Additionally, 172 contacts were monitored; all contacts tested for SARS-CoV-2 (N = 73) were negative. CONCLUSIONS: The occurrence in this cluster of 1 asymptomatic case with similar viral load as a symptomatic patient suggests transmission potential of asymptomatic individuals. The fact that an infected child did not transmit the disease despite close interactions within schools suggests potential different transmission dynamics in children. Finally, the dissociation between upper and lower respiratory tract results underscores the need for close monitoring of the clinical evolution of suspected cases of coronavirus disease 2019.