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Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) impacts multiple anatomical sites. Whether this is due to the virus itself or is a secondary effect caused by the influx and activation of immune cells is not known. Positron emission tomography (PET) with immunoglobulins can provide insights into which sites and cells are activated in a living animal. Our aim is to use two nanobodies as tools to monitor (1) the distribution of antigen presenting cells (APC) by virtue of their Mafa-DR expression profile, (2) virus-infected cells and viral particles using a nanobody against the SARS-CoV-2 spike protein. Two [ 89 Zr]-labeled nanobodies that target the SARS-CoV-2 spike protein and major histocompatability complex (MHC) class II antigens (Mafa-DR), respectively, are used to monitor their distribution during an experimental SARS-CoV-2 infection in a nonhuman primate model. Scans are obtained before infection and on Day 3 and 10 post infection (pi) in two macaques each. The [ 89 Zr]anti-SARS-CoV-2 spike nanobody localized to SARS-CoV-2-associated lung lesions and the nasal mucosa, while the [ 89 Zr]anti-human leukocyte antigen (HLA)-DR nanobody was predominantly found in non-affected lung tissue after infection. We also detected, pi, upregulation of the Mafa-DR signal, indicative of recruitment of professional APCs, in the superior sagittal sinus. [ 89 Zr]-labeled nanobodies show recruitment of macrophages/monocytes in non-lesional lung tissue in cynomolgus macaques after experimental infection with SARS-CoV-2, as well as accumulation of the spike protein in both lung lesions and the nasal mucosa during infection. These results show the possibility of in vivo monitoring the quality and quantity of immune responses during the initial stages of an infection., (© 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.)

Background: The COVID-19 pandemic had a global impact on people life, notably because of lockdown periods. This could particularly affected patients suffering from hip fracture, who could have been more isolated during these periods. We aim at evaluating the impact of the COVID-19 period (including lockdown periods) on quality of life (QOL) in older adult patients 90 days after a surgery for a hip fracture., Subject and Methods: Ancillary study of the prospective randomized controlled HiFIT study. We compared the QOL measured at 90 days after a hip fracture surgery using the EuroQOL-5 dimensions 3 levels (EQ-5D), the Perceived Quality of life (PQOL) and the Instrumental Activities of Daily Living (IADL) in patients included in the Hifit study before and during the COVID-19 pandemic., Results: The characteristics of the 161 patients included before and of the 213 included during the COVID period (including 122 (57%) during COVID with containment periods and 91 (43%) during COVID without containment periods) were similar (mean age 84 ± 10 years; 282 (75%) women). The majority (81%) of the patients alive at 90 days had returned to their previous place of residence in both periods. During the COVID period, EQ-5D showed better patient pain/discomfort and anxiety/depression levels. The PQOL happiness was not different, with around 81% of the patient being "happy" or "very happy" during the two periods and the IADL was also similar during the two periods. In the multivariate analysis odd ratios of having poorer outcomes were increased before COVID for pain/discomfort (OR 2.38, 95%CI [1.41-4.15], p  = 0.001), anxiety (OR 1.89 [1.12-3.21], p  = 0.017) and mobility (1.69 [1.02-2.86], p  = 0.044)., Conclusion: Patient's quality of life measured using different scales was not altered during the COVID period compared to before COVID, 90 days after a hip fracture. Surprisingly, the Pain/Discomfort and Anxiety dimensions of the EQ-5D questionnaires were even better during the COVID period. Clinical trial registration: https://clinicaltrials.gov/ (NCT02972294)., Competing Interests: SL or his institution has received grants, personal fees, and non-financial support from Pharmocosmos, Vifor Pharma, Masimo and Pfizer outside the submitted work. ER received personal fees and non-financial support from Vifor Pharma and Pfizer outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lasocki, Capdevila, Bijok, Lahlou-Casulli, Collange, Grillot, Loupec, Rineau, Léger and the HiFIT Investigators on behalf of the SFAR Research Network.)

The unceasing circulation of SARS-CoV-2 leads to the continuous emergence of novel viral sublineages. Here, we isolate and characterize XBB.1, XBB.1.5, XBB.1.9.1, XBB.1.16.1, EG.5.1.1, EG.5.1.3, XBF, BA.2.86.1 and JN.1 variants, representing >80% of circulating variants in January 2024. The XBB subvariants carry few but recurrent mutations in the spike, whereas BA.2.86.1 and JN.1 harbor >30 additional changes. These variants replicate in IGROV-1 but no longer in Vero E6 and are not markedly fusogenic. They potently infect nasal epithelial cells, with EG.5.1.3 exhibiting the highest fitness. Antivirals remain active. Neutralizing antibody (NAb) responses from vaccinees and BA.1/BA.2-infected individuals are markedly lower compared to BA.1, without major differences between variants. An XBB breakthrough infection enhances NAb responses against both XBB and BA.2.86 variants. JN.1 displays lower affinity to ACE2 and higher immune evasion properties compared to BA.2.86.1. Thus, while distinct, the evolutionary trajectory of these variants combines increased fitness and antibody evasion., (© 2024. The Author(s).)

Background: Epidemiologic studies on coronavirus disease 2019 (COVID-19) in patients with multiple sclerosis (pwMS) have focused on the first waves of the pandemic until early 2021., Objectives: We aimed to extend these data from the onset of the pandemic to the global coverage by vaccination in summer 2022., Methods: This retrospective, multicenter observational study analyzed COVISEP registry data on reported COVID-19 cases in pwMS between January 2020 and July 2022. Severe COVID-19 was defined as hospitalization or higher severity., Results: Among 2584 pwMS with confirmed/highly suspected COVID-19, severe infection rates declined from 14.6% preomicron wave to 5.7% during omicron wave ( p  < 0.001). Multivariate analysis identified age (odds ratio (OR) = 1.43, 95% confidence interval (CI) = [1.25-1.64] per 10 years), male sex (OR = 2.01, 95% CI = [1.51-2.67]), obesity (OR = 2.36, 95% CI = [1.52-3.68]), cardiac comorbidities (OR = 2.36, 95% CI = [1.46-3.83]), higher Expanded Disability Status Scale (EDSS) scores (OR = 2.09, 95% CI = [1.43-3.06] for EDSS 3-5.5 and OR = 4.53, 95% CI = [3.04-6.75] for EDSS ⩾6), and anti-CD20 therapies (OR = 2.67, 95% CI = [1.85-3.87]) as risk factors for COVID-19 severity. Vaccinated individuals experienced less severe COVID-19, whether on (risk ratio (RR) = 0.64, 95% CI = [0.60-0.69]) or off (RR = 0.32, 95% CI = [0.30-0.33]) anti-CD20., Discussion: In pwMS, consistent risk factors were anti-CD20 therapies and neurological disability, emerging as vital drivers of COVID-19 severity regardless of wave, period, or vaccination status., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: L.J. reports no disclosure. E.J. reports no disclosure. P.L. reports no disclosure. E.M. has received research support from Fondation ARSEP and Biogen Idec, travel funding and/or consulting fees from Alexion, Biogen Idec, BMS, Janssen, Merck, Novartis, Roche, Sanofi-Genzyme, and Teva. J.D.S. reports no disclosure. H.Z. has no disclosure related to this manuscript. Unrelated to this manuscript H.Z. received consulting fees from Biogen Idec, Sanofi, Merck, Novartis, Roche, Horizon Therpaeutics, Alexion, BMS, and Grant Research Support from ROCHE. J.P. reports no disclosure. P.K. reports no disclosure. D.B. reports no disclosure. O.H. has received consulting and lecture fees from Bayer Schering, Merck, Teva, Genzyme, Novartis, Almirall, and Biogen Idec, travel grants from Novartis, Teva, Genzyme, Merck Serono, and Biogen Idec, and research support from Roche, Merck, and Novartis. L.G. has received consulting and/or lecture fees and/or travel funding from Novartis, Merck, Sanofi, BMS, and Biogen. C.B. has received consulting honoraria from Alexion, Sanofi, Merck, Biogen, BMS, Novartis, Roche, and Teva. M.T. reports receiving consulting and lecture fees from Merck, Novartis, and Biogen Idec, travel grants from Sanofi, Merck Serono, and Biogen Idec. S.V. has received lecturing fees, travel grants, and research support from Biogen, BMS-Celgene, Janssen, Merck, Novartis, Roche, Sanofi-Genzyme, and Teva. O.C. reports receiving personal fees from Biogen, Roche, Merck, Novartis, Janssen, and Sanofi and nonfinancial support from Roche, Merck, and Novartis outside the submitted work. A.M. reports no disclosure. D.L. reports receiving grants from Roche, Sanofi, the ARSEP Foundation, the EDMUS Foundation, and the National Agency of Research and receiving personal fees from Biogen, Novartis, Alexion, Merck, and MSD outside the submitted work. E.B. has received honoraria and consulting fees from Alexion, Novartis, Sanofi Aventis, Biogen Idec, Genzyme, Merck, Roche, and Teva. C.L-F. reports no disclosure. B.B. serves on scientific advisory board, has received funding for travel and honoraria from Alexion, Biogen, BMS, Janssen, Merck, Novartis, Sanofi, Roche, and Teva. P.B. reports receiving personal fees from Novartis, Biogen, Merck, BMS, Alexion, and Sanofi outside the submitted work. B.S. reports research support from Roche, Sanofi, and Merck and personal fees for lectures or advisory boards from Novartis, Sanofi, Biogen, Janssen, and Merck. P.C. reports receiving personal fees for board participation from Janssen and Novartis and for board participation and travel from Sanofi and Merck outside the submitted work. E.T. reports receiving personal fees from Biogen, BMS, Janssen, Horizon, Merck, Novartis, and Sanofi outside the submitted work. E.M. reports no disclosure. T.M. reports receiving travel grants and fees for advisory boards from Biogen, Roche, Novartis, Sanofi, and Teva outside the submitted work. F.S. reports receiving consulting and/or lecture fees and/or travel funding from Novartis-Pharma, Biogen, Roche, Sanofi, Linde, and LVL. M.Z. reports receiving expert testimony from Alexion and Novartis, and travel grants from Merck, Roche, and Sanofi Aventis France. C.P. reports receiving honoraria and consulting fees from Alexion, Biogen, Merck, Horizon, and Roche outside the submitted work and serving as president of the Francophone Multiple Sclerosis Society from 2021 to 2024. C.L. has received consulting or travel fees from Biogen, Novartis, Roche, Sanofi, Teva, and Merck Serono, and research grant from Biogen.

Background: Vaccination in patients with multiple sclerosis (MS) treated with immunosuppressive drugs is highly recommended. Regarding COVID-19 vaccination, no specific concern has been raised., Objectives: We aimed to evaluate if COVID-19 vaccination or infection increased the risk of disease activity, either radiological or clinical, with conversion to MS in a cohort of people with a radiologically isolated syndrome (RIS)., Methods: This multicentric observational study analyzed patients in the RIS Consortium cohort during the pandemic between January 2020 and December 2022. We compared the occurrence of disease activity in patients according to their vaccination status. The same analysis was conducted by comparing patients' history of COVID-19 infection., Results: No difference was found concerning clinical conversion to MS in the vaccinated versus unvaccinated group (6.7% vs 8.5%, p > 0.9). The rate of disease activity was not statistically different (13.6% and 7.4%, respectively, p = 0.54). The clinical conversion rate to MS was not significantly different in patients with a documented COVID-19 infection versus non-infected patients., Conclusion: Our study suggests that COVID-19 infection or immunization in RIS individuals does not increase the risk of disease activity. Our results support that COVID-19 vaccination can be safely proposed and repeated for these subjects.

Importance: In patients with multiple sclerosis (MS), factors associated with severe COVID-19 include anti-CD20 therapies and neurologic disability, but it is still unclear whether these 2 variables are independently associated with severe COVID-19 or whether the association depends on MS clinical course., Objective: To assess the association between anti-CD20 therapies and COVID-19 severity in patients with relapsing-remitting MS (RRMS) and progressive MS (PMS)., Design, Setting, and Participants: This multicenter, retrospective cohort study used data from the COVISEP study, which included patients with MS and COVID-19 from February 1, 2020, to June 30, 2022, at 46 French MS expert centers, general hospitals, and private neurology practices. Eligible patients with RRMS were those treated with high-efficacy MS therapy (ie, anti-CD20, fingolimod, or natalizumab), and eligible patients with PMS were those younger than 70 years with an Expanded Disability Status Scale (EDSS) score of 8 or lower. Patients were monitored from COVID-19 symptom onset until recovery or death., Exposures: Current anti-CD20 therapy (ocrelizumab or rituximab)., Main Outcomes and Measures: The main outcome was severe COVID-19 (ie, hospitalization with any mode of oxygenation or death). All analyses were conducted separately in patients with RRMS and PMS using propensity score-weighted logistic regression. Subgroup analyses were performed according to COVID-19 vaccine status, sex, EDSS score, and age., Results: A total of 1400 patients, 971 with RRMS (median age, 39.14 years [IQR, 31.38-46.80 years]; 737 [76.1%] female) and 429 with PMS (median age, 54.21 years [IQR, 48.42-60.14 years]; 250 [58.3%] female) were included in the study. A total of 418 patients with RRMS (43.0%) and 226 with PMS (52.7%) were treated with anti-CD20 therapies. In weighted analysis, 13.4% and 2.9% of patients with RRMS treated and not treated with anti-CD20 had severe COVID-19, respectively, and anti-CD20 treatment was associated with increased risk of severe COVID-19 (odds ratio [OR], 5.20; 95% CI, 2.78-9.71); this association persisted among vaccinated patients (7.0% vs 0.9%; OR, 8.85; 95% CI, 1.26-62.12). Among patients with PMS, 19.0% and 15.5% of patients treated and not treated with anti-CD20 had severe COVID-19, respectively, and there was no association between anti-CD20 treatment and severe COVID-19 (OR, 1.28; 95% CI, 0.76-2.16). In PMS subgroup analysis, anti-CD20 exposure interacted negatively with EDSS score (P = .009 for interaction) and age (P = .03 for interaction); anti-CD20 therapies were associated with risk of severe COVID-19 only in patients with less neurologic disability and younger patients with PMS., Conclusions and Relevance: In this cohort study, risk of severe COVID-19 was higher in patients with PMS than in those with RRMS. Use of anti-CD20 therapies was associated with an increased risk of severe COVID-19 among patients with RRMS. In patients with PMS, there was no association between anti-CD20 therapies and risk of severe COVID-19.

Introduction: In case of COVID-19 related scarcity of critical care resources, an early French triage algorithm categorized critically ill patients by probability of survival based on medical history and severity, with four priority levels for initiation or continuation of critical care: P1 -high priority, P2 -intermediate priority, P3 -not needed, P4 -not appropriate. This retrospective multi-center study aimed to assess its classification performance and its ability to help saving lives under capacity saturation., Methods: ICU patients admitted for severe COVID-19 without triage in spring 2020 were retrospectively included from three hospitals. Demographic data, medical history and severity items were collected. Priority levels were retrospectively allocated at ICU admission and on ICU day 7-10. Mortality rate, cumulative incidence of death and of alive ICU discharge, length of ICU stay and of mechanical ventilation were compared between priority levels. Calculated mortality and survival were compared between full simulated triage and no triage., Results: 225 patients were included, aged 63.1±11.9 years. Median SAPS2 was 40 (IQR 29-49). At the end of follow-up, 61 (27%) had died, 26 were still in ICU, and 138 had been discharged. Following retrospective initial priority allocation, mortality rate was 53% among P4 patients (95CI 34-72%) versus 23% among all P1 to P3 patients (95CI 17-30%, chi-squared p = 5.2e-4). The cumulative incidence of death consistently increased in the order P3, P1, P2 and P4 both at admission (Gray's test p = 3.1e-5) and at reassessment (p = 8e-5), and conversely for that of alive ICU discharge. Reassessment strengthened consistency. Simulation under saturation showed that this two-step triage protocol could have saved 28 to 40 more lives than no triage., Conclusion: Although it cannot eliminate potentially avoidable deaths, this triage protocol proved able to adequately prioritize critical care for patients with highest probability of survival, hence to save more lives if applied., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Donat et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

No Abstract Available.

Aim: To investigate the impact of teleconsultation on glycemic control in patients with diabetes during the COVID-19 pandemic. Methods: In this observational prospective study, the main outcome was the comparison of glycated hemoglobin (HbA1c) between patients with or without teleconsultation at 6-month follow-up. Results: From March 17 to May 31, 2020, 610 patients were included, 456 were followed-up using Teleconsultation présent (TC+) and 154 not using No Teleconsultation (TC-). Patients of TC+ Group were younger, 57 ± 17 versus 65 ± 15.5 years ( p < 0.001), with a lower body mass index, 28 ± 6.2 kg/m 2 versus 30 ± 5.8 kg/m 2 , compared to those of TC- Group ( p < 0.001). HbA1c were comparable between the two groups: 7.35 ± 0.27% for TC+ versus 7.48 ± 0.22% for TC- Group. At 6-month follow-up, HbA1c was lower in TC+ versus TC- Group: 7.21 ± 0.15% versus 7.6 ± 0.18% ( p  = 0.004). Conclusion: Our findings point toward the feasibility and usefulness of teleconsultation for the follow-up of patients with diabetes in such exceptional circumstances.

Massive efforts on both vaccine development and antiviral research were launched to combat the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We contributed, amongst others, by the development of a high-throughput screening (HTS) antiviral assay against SARS-CoV-2 using a fully automated, high-containment robot system. Here, we describe the development of this novel, convenient and phenotypic dual-reporter virus-cell-based high-content imaging assay using the A549+hACE2+TMPRSS2&#95;mCherry reporter lung carcinoma cell line and an ancestral SARS-CoV-2&#95;Wuhan&#95;mNeonGreen reporter virus. Briefly, by means of clonal selection, a host cell subclone was selected that (i) efficiently supports replication of the reporter virus with high expression, upon infection, of the NeonGreen fluorescent reporter protein, (ii) that is not affected by virus-induced cytopathogenic effects and, (iii) that expresses a strong fluorescent mCherry signal in the nucleus. The selected clone matched these criteria with an infection rate on average of 75% with limited cell death. The average (R)Z'-factors of the assay plates were all >0.8, which indicates a robust assay suitable for HTS purposes. A selection of reference compounds that inhibits SARS-CoV-2 replication in vitro were used to validate this novel dual-reporter assay and confirms the data reported in the literature. This assay is a convenient and powerful tool for HTS of large compound libraries against SARS-CoV-2., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: The prognostic significance of the thrombin generation assay (TGA) with a thrombomodulin (TM) challenge in patients entering hospital with severe COVID-19 is uncertain., Methods: We prospectively evaluated an automated TGA (aTGA) using the ST-ThromboScreen® assay and ST-Genesia® analyser in 179 patients with severe COVID-19 during their admission to 2 university hospitals. The primary outcome was early survival at Day 28 (D28). Secondary outcomes were late survival at Day 90 (D90), later transfer to an intensive care unit (ICU), and occurrence of any thrombotic complications during hospitalisation., Results: Among the 174 patients, 50 were initially admitted to ICUs. Forty-two were transferred to ICUs before D28. Fourteen patients, all in ICUs, died before D28, and 20 before D90, all but 1 in ICUs. None of the aTGA-derived results were associated with vital status either at D28 or D90. Nine patients had a thrombotic event with no association with the aTGA results. Later transfer to the ICU was associated with higher velocity index, thrombin peak height and endogenous thrombin potential (ETP) values of the aTGA performed with TM, and mainly with a lower TM-induced decrease in ETP (odds ratio 15.5 (2.15-132), p = 0.009)., Conclusions: aTGA, a global assay supposed to evidence coagulopathy, could predict neither early or late survival, nor thrombotic events, in hospitalised COVID-19 patients. Its clinical justification in that setting is thus unlikely. A relative resistance of the ETP to TM was associated with later transfer to the ICU and deserves further investigation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

We extracted items to create a brief version of the COVID-19 Stress Scale (i.e., CSS-B) and examined its psychometric properties in young adults. A sample of 1318 first- and second-year undergraduates from five Canadian universities (mean [SD] age = 19.27 [1.35] years; 77.6% women) completed an online cross-sectional survey that included the CSS-B as well as validated measures of anxiety and depression. The 18-item CSS-B fit well on both a 5-factor and a hierarchical model indicating that the five CSS-B dimensions may be factors of the same over-arching construct. The CSS-B factor structure displayed lower-order and higher-order configural and metric invariance across sites but not scalar invariance indicating that the intercepts/means were not consistent across sites. The CSS dimensions were positively related to measures of general anxiety and depression but not so strongly as to indicate that they are measuring the same construct. The CSS-B scale is a valid measure of COVID-19 stress among young adults. It is recommended that this shorter version of the scale be considered for use in longer surveys to avoid participant fatigue., (© 2022 John Wiley & Sons Ltd.)

Objectives: Prone positioning and venovenous extracorporeal membrane oxygenation (ECMO) are both useful interventions in acute respiratory distress syndrome (ARDS). Combining the two therapies is feasible and safe, but the effectiveness is not known. Our objective was to evaluate the potential survival benefit of prone positioning in venovenous ECMO patients cannulated for COVID-19-related ARDS., Design: Retrospective analysis of a multicenter cohort., Patients: Patients on venovenous ECMO who tested positive for severe acute respiratory syndrome coronavirus 2 by reverse transcriptase polymerase chain reaction or with a diagnosis on chest CT were eligible., Interventions: None., Measurements and Main Results: All patients on venovenous ECMO for respiratory failure in whom prone position status while on ECMO and in-hospital mortality were known were included. Of 647 patients in 41 centers, 517 were included. Median age was 55 (47-61), 78% were male and 95% were proned before cannulation. After cannulation, 364 patients (70%) were proned and 153 (30%) remained in the supine position for the whole ECMO run. There were 194 (53%) and 92 (60%) deaths in the prone and the supine groups, respectively. Prone position on ECMO was independently associated with lower in-hospital mortality (odds ratio = 0.49 [0.29-0.84]; p = 0.010). In 153 propensity score-matched pairs, mortality rate was 49.7% in the prone position group versus 60.1% in the supine position group (p = 0.085). Considering only patients alive at decannulation, propensity-matched proned patients had a significantly lower mortality rate (22.4% vs 37.8%; p = 0.029) than nonproned patients., Conclusions: Prone position may be beneficial in patients supported by venovenous ECMO for COVID-19-related ARDS but more data are needed to draw definitive conclusions., Competing Interests: Dr. Guervilly received consultancy fees from Xenios FMC. Dr. Schmidt received consultancy fees from Getinge, Xenios FMC, and Drager. Dr. Lebreton reports lecture fees from Livanova and Abiomed. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Biofilm (BF) growth is believed to play a major role in the development of ventilator-associated pneumonia (VAP) in the intensive care unit. Despite concerted efforts to understand the potential implication of endotracheal tube (ETT)-BF dispersal, clinically relevant data are lacking to better characterize the impact of its mesostructure and microbiological singularity on the occurrence of VAP. We conducted a multicenter, retrospective observational study during the third wave of the COVID-19 pandemic, between March and May 2021. In total, 64 ETTs collected from 61 patients were included in the present BIOPAVIR study. Confocal microscopy acquisitions revealed two main morphological aspects of ETT-deposited BF: (1) a thin, continuous ribbon-shaped aspect, less likely monobacterial and predominantly associated with Enterobacter spp., Streptococcus pneumoniae or Viridans streptococci, and (2) a thicker, discontinuous, mushroom-shaped appearance, more likely characterized by the association of bacterial and fungal species in respiratory samples. The microbiological characterization of ETT-deposited BF found higher acquired resistance in more than 80% of analyzed BF phenotypes, compared to other colonization sites from the patient's environment. These findings reveal BF as a singular microbiological compartment, and are of added clinical value, with a view to future ETT-deposited BF-based antimicrobial stewardship in critically ill patients. Trial registration NCT04926493. Retrospectively registered 15 June 2021., (© 2022. The Author(s).)

Background: Persistent COVID-19 sequelae could have global, public health ramifications. We therefore aimed to describe sequelae presenting more than 180 days after COVID-19-focussing on several organ systems, general health, and laboratory parameters-in non-hospitalised, unvaccinated, young adults., Methods: We did a longitudinal cohort study of all army bases in Switzerland. Eligible participants were personnel of the Swiss Armed Forces (SAF) who were aged 18-30 years with a positive or negative RT-PCR test for SARS-CoV-2 during their service between March 1, 2020, and Dec 31, 2020. Exclusion criteria were unwillingness to participate in testing. Females or men with a known reproductive anomaly were excluded from the optional component of male fertility testing. COVID-19 was defined as a positive diagnostic RT-PCR test result for SARS-CoV-2 with concurrent symptoms compatible with COVID-19. Participants were subdivided into four groups: control group (ie, serologically negative), asymptomatic infection group (ie, serologically positive but with no symptoms), non-recent COVID-19 group (>180 days since positive PCR test), and recent COVID-19 group (≤180 days since positive PCR test). Outcomes of interest were part of a comprehensive, intensive test battery that was administered during a single day. The test battery quantified the effect of SARS-CoV-2 infection on cardiovascular, pulmonary, neurological, renal, ophthalmological, male reproductive, psychological, general health, and laboratory parameters. This study was registered with ClinicalTrials.gov, number NCT04942249., Findings: Between May 20, 2021, and Nov 26, 2021, we enrolled 501 participants. 29 (6%) of 501 were female and 464 (93%) were male, and the median age was 21 years (IQR 21-23). Eight (2%) of 501 had incomplete data and were not included into the study groups. 177 participants had previous COVID-19 that was more than 180 days (mean 340 days) since diagnosis (ie, the non-recent COVID-19 group) compared with 251 serologically negative individuals (ie, the control group). We included 19 participants in the recent COVID-19 group and 46 in the asymptomatic infection group. We found a significant trend towards metabolic disorders in participants of the non-recent COVID-19 group compared with those in the control group: higher BMI (median 24·0 kg/m 2 [IQR 22·0-25·8] vs 23·2 kg/m 2 [27·1-25·0]; p=0·035), lower aerobic threshold (39% [36-43] vs 41% [37-46]; p=0·012), and higher blood cholesterol (4·2 μM [3·7-4·7] vs 3·9 μM [3·5-4·5]; p<0·0001) and LDL concentrations (2·4 μM [1·9-2·9] vs 2·2 μM [1·7-2·7]; p=0·001). The only significant psychosocial difference was found in the results of the Chalder Fatigue scale with the non-recent COVID-19 group reporting higher fatigue scores than the control group (median 12 points [IQR 11-15] vs 11 [9-14]; p=0·027). No significant differences in other psychosocial questionnaire scores, ophthalmological outcomes, and sperm quality or motility were reported between the control group and non-recent COVID-19 group., Interpretation: Young, previously healthy, individuals largely recover from SARS-CoV-2 infection. However, the constellation of higher BMI, dyslipidaemia, and lower physical endurance 180 days after COVID-19 is suggestive of a higher risk of developing metabolic disorders and possible cardiovascular complications. These findings will guide future investigations and follow-up management., Funding: Swiss Armed Forces., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: As circulating DNA (cirDNA) is mainly detected as mononucleosome-associated circulating DNA (mono-N cirDNA) in blood, apoptosis has until now been considered as the main source of cirDNA. The mechanism of cirDNA release into the circulation, however, is still not fully understood. This work addresses that knowledge gap, working from the postulate that neutrophil extracellular traps (NET) may be a source of cirDNA, and by investigating whether NET may directly produce mono-N cirDNA., Methods: We studied (1) the in vitro kinetics of cell derived genomic high molecular weight (gHMW) DNA degradation in serum; (2) the production of extracellular DNA and NET markers such as neutrophil elastase (NE) and myeloperoxidase (MPO) by ex vivo activated neutrophils; and (3) the in vitro NET degradation in serum; for this, we exploited the synergistic analytical information provided by specifically quantifying DNA by qPCR, and used shallow WGS and capillary electrophoresis to perform fragment size analysis. We also performed an in vivo study in knockout mice, and an in vitro study of gHMW DNA degradation, to elucidate the role of NE and MPO in effecting DNA degradation and fragmentation. We then compared the NET-associated markers and fragmentation size profiles of cirDNA in plasma obtained from patients with inflammatory diseases found to be associated with NET formation and high levels of cirDNA (COVID-19, N = 28; systemic lupus erythematosus, N = 10; metastatic colorectal cancer, N = 10; and from healthy individuals, N = 114)., Results: Our studies reveal that gHMW DNA degradation in serum results in the accumulation of mono-N DNA (81.3% of the remaining DNA following 24 h incubation in serum corresponded to mono-N DNA); "ex vivo" NET formation, as demonstrated by a concurrent 5-, 5-, and 35-fold increase of NE, MPO, and cell-free DNA (cfDNA) concentration in PMA-activated neutrophil culture supernatant, leads to the release of high molecular weight DNA that degrades down to mono-N in serum; NET mainly in the form of gHMW DNA generate mono-N cirDNA (2 and 41% of the remaining DNA after 2 h in serum corresponded to 1-10 kbp fragments and mono-N, respectively) independent of any cellular process when degraded in serum; NE and MPO may contribute synergistically to NET autocatabolism, resulting in a 25-fold decrease in total DNA concentration and a DNA fragment size profile similar to that observed from cirDNA following 8 h incubation with both NE and MPO; the cirDNA size profile of NE KO mice significantly differed from that of the WT, suggesting NE involvement in DNA degradation; and a significant increase in the levels of NE, MPO, and cirDNA was detected in plasma samples from lupus, COVID-19, and mCRC, showing a high correlation with these inflammatory diseases, while no correlation of NE and MPO with cirDNA was found in HI., Conclusions: Our work describes the mechanisms by which NET and cirDNA are linked. In doing so, we demonstrate that NET are a major source of mono-N cirDNA independent of apoptosis and establish a new paradigm of the mechanisms of cirDNA release in normal and pathological conditions. We also demonstrate a link between immune response and cirDNA., (© 2022. The Author(s).)

Numerous studies reported a significant decline in physical activity level in adolescents as a result of the COVID-19 lockdown. Physical fitness is recognized as a powerful marker of health in youth. The aim of this study was to evaluate the impact of the COVID-19 pandemic lockdown on health-related physical fitness in French adolescents. Two cross-sectional studies were performed comparing two different groups of French adolescents, before (sample 1) and after the first lockdown (sample 2). A total of 1231 adolescents (aged to 16.5 ± 1.5 years) participated in the two cross-sectional studies. Complete data for physical fitness and anthropometrics data were obtained. Adolescents from sample 2 showed lower physical fitness levels compared to adolescents from sample 1. Regarding physical fitness for boys and girls, physical fitness levels were significantly lower in both sex between adolescents from the sample 1 and adolescents from the sample 2, except for cardiorespiratory fitness and flexibility for boys and girls, respectively. The physical fitness global score was also significantly lower between adolescents from the sample 1 and 2 for boys (-9.8%, p < 0.01) and girls (-16.2%; p < 0.01), respectively. Overall, the higher difference was found for performance in the speed body displacement test (-30%). A difference of 12.8% and 25% was observed for boys and girls, respectively.   Conclusion: COVID-19 pandemic lockdown had a negative impact on physical fitness in French youth. This study highlights the need to develop, in a near future, prevention programmes in order to improve the physical fitness in youth. What is Known: • COVID-19 pandemic deeply impacted lifestyle habits. A worrying decrease of physical activity, associated to a dramatic increase of time spent in sedentary behaviors was found in many coutries. What is New: • Our study bring first data on the health-related physical fitness consequences due to lockdown in French adolescents. Our study demonstrate the negative impact of COVID-19 pandemic lockdown on health-related physical fitness in French adolescents., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Competing Interests: The authors have disclosed no conflicts of interest.

Background: Even though COVID-19 clinical features, pathogenesis, complications, and therapeutic options have been largely described in the literature, long-term consequences in patients remain poorly known., Methods: The French, multicentre, non-interventional SISCOVID study evaluated lung impairment three (M3) and six months (M6) after hospital discharge in patients recovered from COVID-19. Evaluation was based on clinical examination, pulmonary function tests, and chest computed tomography (CT-scan)., Results: Of the 320 included patients (mean age: 61 years; men: 64.1%), 205 had had a severe form of COVID-19, being hospitalised in an intensive care unit (ICU), and requiring high flow nasal cannula, non-invasive ventilation, or invasive mechanical ventilation. At M6, 54.1% of included patients had persistent dyspnoea (mMRC score ≥1), 20.1% severe impairment in gas diffusing capacity (DL CO <60% pred.), 21.6% restrictive ventilatory pattern (total lung capacity <80% pred.), and 40% a fibrotic-like pattern at CT-scan. Fibrotic-like pattern and restrictive ventilatory pattern were significantly more frequent in patients recovered from severe than non-severe COVID-19. Improved functional and radiological outcomes were observed between M3 and M6. At M6, age was an independent risk factor for severe DLco impairment and fibrotic-like pattern and severe COVID-19 form was independent risk factor for restrictive ventilatory profile and fibrotic-like pattern., Conclusion: Six months after discharge, patients hospitalised for COVID-19, especially those recovered from a severe form of COVID-19, frequently presented persistent dyspnoea, lung function impairment, and persistent fibrotic-like pattern, confirming the need for long-term post-discharge follow-up in these patients and for further studies to better understand long-term COVID-19 lung impairment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 SPLF and Elsevier Masson SAS. All rights reserved.)

Background: COVID-19 infection is associated not only with venous thromboses but also with arterial thromboses (COV-ATs) in relation with an endothelial dysfunction, a coagulopathy and rhythm disorders. The incidence, the topography, and the prognosis of COV-ATs remain poorly known. The objective of this study was to report the overall experience of the Greater Paris University Hospitals (Assistance Publique - Hopitaux de Paris, AP-HP) during the first pandemic wave of COVID-19 infection., Methods: After approval by the ethics committee, a study using the AP-HP clinical data warehouse was carried out between March and May 2020. Overall, 124,609 patients had a polymerase chain reaction for COVID-19 in our hospitals, of which 25,345 were positive. From 20,710 exploitable stays, patients tested positive for COVID who presented an episode of acute COV-AT (except coronary and intracranial arteries) were selected on the basis of the French medical classification for clinical procedures codes. The data are presented as absolute values with percentages and/or means with standard deviation., Results: Over the studied period, 60 patients (aged 71±14 years, 42 men) presented a COV-AT at the time of their hospitalization, an incidence of 0.2%. The arterial complication occurred 3±7 days after the COVID infection and was inaugural in 30% of the cases (n = 18). The sites of COV-AT were the lower extremities (n = 35%, 58%), the abdominal aorta (n = 10%, 17%), the thoracic aorta (n = 7%, 12%), the upper limbs (n = 7%, 12%), the cerebral arteries (n = 7%, 12%), the digestive arteries (n = 6%, 10%), the renal arteries (n = 2%, 3%), and the ophthalmic artery (n = 1%, 2%). Multiple COV-ATs were observed in 13 patients (22%). At the time of diagnosis, 20 (33%) patients were in intensive care, including six (10%) patients who were intubated. On computed tomography angiography, COVID lesions were classified as moderate and severe in 25 (42%) and 21 (35%) cases, respectively. Revascularization was attempted in 27 patients (45%), by open surgery in 16 cases, using endovascular techniques in 8 cases and with a hybrid approach in three cases. Six patients (22%) required reinterventions. The duration of hospitalization was 12±9 days. Early mortality (in-hospital or at 30 days) was 30% (n = 18). Nine (15%) patients presented severe nonlethal ischemic complications., Conclusions: Arterial involvement is rare during COVID-19 infection. The aorta and the arteries of the limbs are the privileged sites. The morbi-mortality of these patients is high. Future studies will have to determine if the systematization of anticoagulation therapy decreases the incidence and the severity of the condition., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: This study aimed to identify markers of disease worsening in patients hospitalized for SARS-Cov2 infection., Patients and Methods: Patients hospitalized for severe recent-onset (<1 week) SARS-Cov2 infection were prospectively included. The percentage of T-cell subsets and plasma IL-6 at admission (before any steroid therapy) were compared between patients who progressed to a critical infection and those who did not., Results: Thirty-seven patients (18 men, 19 women) were included; 11 (30%) progressed to critical infection. At admission, the critical infection patients were older (P = 0.021), had higher creatinine levels (P = 0.003), and decreased percentages of circulating B cells (P = 0.04), T cells (P = 0.009), and CD4+ T cells (P = 0.004) than those with a favorable course. Among T cell subsets, there was no significant difference between the two groups except for the percentage of Th17 cells, which was two-fold higher in patients who progressed to critical infection (P = 0.028). Plasma IL-6 at admission was also higher in this group (P = 0.018). In multivariate analysis, the percentage of circulating Th17 cells at admission was the only variable associated with higher risk of progression to critical SARS-Cov2 infection (P = 0.021)., Conclusion: This study suggests that an elevated percentage of Th17 cells in patients hospitalized for SARS-Cov2 infection is associated with an increased risk of progression to critical disease. If these data are confirmed in a larger study, this marker could be used to better target the population of patients in whom tocilizumab could decrease the risk of progression to critical COVID-19., (Copyright © 2022. Published by Elsevier B.V.)

COVID-19 has strongly impacted the elderly population with a particularly high mortality rate due to several reasons: sometimes difficult and delayed diagnosis, multimorbidity, immunosenescence, frailty, which seems to be a better prognostic marker than age. Treatment includes both therapies specifically directed against SARS CoV-2 (monoclonal antibodies, systemic corticosteroids, tocilizumab, remdesivir) and symptomatic and palliative treatments. Vaccination, especially the booster, is essential to reduce the risk of infection and severe forms. The emergence of variants is a challenge because of their impact on vaccine and treatment efficacy. Specific studies in the elderly are needed to improve their management., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Introduction: The coronavirus disease 2019 (COVID-19) led to the worldwide closure of dental practices or reduction of dental services. By the end of April 2020, governments and professional organisations were publishing recommendations or guidance for the reopening/restructuring of dental services. The aim of this study was to assess how dental aerosol-generating procedures (AGPs) were defined in international dental guidelines, what mitigation processes were advised, and whether they were linked to COVID-19 epidemiology., Methods: Electronic searches of a broad range of databases, along with grey literature searches, without language restriction were conducted up to 13 July 2020. Recommendations for the use of face masks and fallow times with patients without COVID-19 were assessed against the deaths per 1 million population in the included countries and country income level using Pearson Chi-squared statistics., Results: Sixty-three guidance documents were included. Most (98%) indicated that AGPs can be performed with patients without COVID-19 with caveats, including advice to restrict AGPs where possible, with 21% only recommending AGPs for dental emergencies. Face masks were recommended by most documents (94%), with 91% also specifying the use of goggles or face shields. Fallow periods for patients without COVID-19 were mentioned in 48% of documents, ranging from 2 to 180 minutes. There were no significant differences in recommendations for face masks or fallow time in patients without COVID-19 by country death rate (P = .463 and P = .901) or World Bank status (P = .504 and P = .835). Most documents recommended procedural or environmental mitigations such as preprocedural mouthwash (82%) and general ventilation (52%). Few documents provided underpinning evidence for their recommendations., Conclusions: While the amount of high-quality direct evidence related to dentistry and COVID-19 remains limited, it is important to be explicit about the considered judgements for recommendations as well as generate new evidence to face this challenge., Competing Interests: Conflicts of interest None disclosed., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: We aimed to investigate the impact of the first COVID-19 lockdown on medication adherence, physician access, lifestyle behaviours, and mental health in patients with chronic conditions. Methods: A cross-sectional phone survey was conducted in 1274 housebound adults recruited from 8 regional chronic disease cohorts (CLEO CD study: NCT04390126). Results: Medication adherence was 97%; 305 (41%) patients declared that at least one scheduled visit with a physician was missed during the first lockdown. The main changes in lifestyle behaviours were deterioration in sleep time (duration and/or quality; 71%), increase in screen time (46%), and decrease in physical activity (46%). Nineteen percent experienced psychological distress (Kessler-6 score ≥ 5). An urban living place (OR, 1.76 vs. rural; 95% CI, 1.32−2.33; p = 10−4), worse self-reported mental health (OR, 1.62 vs. about the same or better; 95% CI, 1.17−2.25; p = 0.003), and a K6 score ≥ 5 (OR, 1.52 vs. <5; 95% CI, 1.05−2.21; p = 0.03) were independent factors associated with at least one unhealthy behaviour. Conclusions: Encouraging results were observed in terms of medication adherence. Caution is needed in chronic disease patients living in urban places as well as those presenting psychological distress and worse self-reported mental health to reduce unhealthy behaviours.

Background: Vaccines are critical cost-effective tools to control the coronavirus disease 2019 (COVID-19) pandemic. However, the emergence of variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may threaten the global impact of mass vaccination campaigns., Aims: The objective of this study was to provide an up-to-date comparative analysis of the characteristics, adverse events, efficacy, effectiveness and impact of the variants of concern for 19 COVID-19 vaccines., Sources: References for this review were identified through searches of PubMed, Google Scholar, BioRxiv, MedRxiv, regulatory drug agencies and pharmaceutical companies' websites up to 22nd September 2021., Content: Overall, all COVID-19 vaccines had a high efficacy against the original strain and the variants of concern, and were well tolerated. BNT162b2, mRNA-1273 and Sputnik V after two doses had the highest efficacy (>90%) in preventing symptomatic cases in phase III trials. mRNA vaccines, AZD1222, and CoronaVac were effective in preventing symptomatic COVID-19 and severe infections against Alpha, Beta, Gamma or Delta variants. Regarding observational real-life data, full immunization with mRNA vaccines and AZD1222 seems to effectively prevent SARS-CoV-2 infection against the original strain and Alpha and Beta variants but with reduced effectiveness against the Delta strain. A decline in infection protection was observed at 6 months for BNT162b2 and AZD1222. Serious adverse event rates were rare for mRNA vaccines-anaphylaxis 2.5-4.7 cases per million doses, myocarditis 3.5 cases per million doses-and were similarly rare for all other vaccines. Prices for the different vaccines varied from $2.15 to $29.75 per dose., Implications: All vaccines appear to be safe and effective tools to prevent severe COVID-19, hospitalization, and death against all variants of concern, but the quality of evidence greatly varies depending on the vaccines considered. Questions remain regarding a booster dose and waning immunity, the duration of immunity, and heterologous vaccination. The benefits of COVID-19 vaccination outweigh the risks, despite rare serious adverse effects., (Copyright © 2021 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Following severe adverse reactions to the AstraZeneca ChAdOx1-S-nCoV-19 vaccine 1,2 , European health authorities recommended that patients under the age of 55 years who received one dose of ChAdOx1-S-nCoV-19 receive a second dose of the Pfizer BNT162b2 vaccine as a booster. However, the effectiveness and the immunogenicity of this vaccination regimen have not been formally tested. Here we show that the heterologous ChAdOx1-S-nCoV-19 and BNT162b2 combination confers better protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection than the homologous BNT162b2 and BNT162b2 combination in a real-world observational study of healthcare workers (n = 13,121). To understand the underlying mechanism, we conducted a longitudinal survey of the anti-spike immunity conferred by each vaccine combination. Both combinations induced strong anti-spike antibody responses, but sera from heterologous vaccinated individuals displayed a stronger neutralizing activity regardless of the SARS-CoV-2 variant. This enhanced neutralizing potential correlated with increased frequencies of switched and activated memory B cells that recognize the SARS-CoV-2 receptor binding domain. The ChAdOx1-S-nCoV-19 vaccine induced a weaker IgG response but a stronger T cell response than the BNT162b2 vaccine after the priming dose, which could explain the complementarity of both vaccines when used in combination. The heterologous vaccination regimen could therefore be particularly suitable for immunocompromised individuals., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

In the early steps of an emerging infectious disease epidemic such as Covid-19, uncertainties about the nature of the disease, its spread and impact can lead to emotional distress. In addition, the studies on confinement during an epidemic have shown a psychological impact of this measure on the feelings of anxiety and depression in the general population., Method: We assessed the psychological health of 550 patients followed up in outpatient psychiatry, via a pandemic-related teleconsultation during the first confinement period between March and June 2020. Patients were assessed at the beginning and at the end of the confinement on their personal situation, social relationships, professional activity, anxiety and mood. We also evaluated patients' symptomatology and their quality of life., Results: Patients were well informed about Covid-19 via the media and complied with the confinement and barrier procedures. They appreciated the phone-calls and the teleconsultation follow-up. A small proportion of patients were completely socially isolated mainly at the beginning of the confinement (10%). There was no difference between the beginning and the end of the confinement in terms of depressive and anxiety symptoms or quality of life. The women were more anxious and depressed than men. Only smoking was significantly increased during this period., Conclusion: The expected and feared health catastrophe in psychiatry during this first phase of the pandemic in 2020 did not occur. Will the psychiatric wave appear in the "post- pandemic", the future will tell., (Copyright © 2021. Published by Elsevier B.V.)

Objectives: We conducted a systematic literature review and meta-analysis of observational studies to investigate the association between diabetes, hypertension, body mass index (BMI) or smoking with the risk of death in patients with COVID-19 and to estimate the proportion of deaths attributable to these conditions., Methods: Relevant observational studies were identified by searches in the PubMed, Cochrane library and Embase databases through 14 November 2020. Random-effects models were used to estimate summary relative risks (SRRs) and 95% CIs. Certainty of evidence was assessed using the Cochrane methods and the Grading of Recommendations, Assessment, Development and Evaluations framework., Results: A total of 186 studies representing 210 447 deaths among 1 304 587 patients with COVID-19 were included in this analysis. The SRR for death in patients with COVID-19 was 1.54 (95% CI 1.44 to 1.64, I 2 =92%, n=145, low certainty) for diabetes and 1.42 (95% CI 1.30 to 1.54, I 2 =90%, n=127, low certainty) for hypertension compared with patients without each of these comorbidities. Regarding obesity, the SSR was 1.45 (95% CI 1.31 to 1.61, I 2 =91%, n=54, high certainty) for patients with BMI ≥30 kg/m 2 compared with those with BMI <30 kg/m 2 and 1.12 (95% CI 1.07 to 1.17, I 2 =68%, n=25) per 5 kg/m 2 increase in BMI. There was evidence of a J-shaped non-linear dose-response relationship between BMI and mortality from COVID-19, with the nadir of the curve at a BMI of around 22-24, and a 1.5-2-fold increase in COVID-19 mortality with extreme obesity (BMI of 40-45). The SRR was 1.28 (95% CI 1.17 to 1.40, I 2 =74%, n=28, low certainty) for ever, 1.29 (95% CI 1.03 to 1.62, I 2 =84%, n=19) for current and 1.25 (95% CI 1.11 to 1.42, I 2 =75%, n=14) for former smokers compared with never smokers. The absolute risk of COVID-19 death was increased by 14%, 11%, 12% and 7% for diabetes, hypertension, obesity and smoking, respectively. The proportion of deaths attributable to diabetes, hypertension, obesity and smoking was 8%, 7%, 11% and 2%, respectively., Conclusion: Our findings suggest that diabetes, hypertension, obesity and smoking were associated with higher COVID-19 mortality, contributing to nearly 30% of COVID-19 deaths., Trial Registration Number: CRD42020218115., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The Hospitalization or Outpatient Management of Patients With SARS-CoV-2 Infection (HOME-CoV) rule is a checklist of eligibility criteria for home treatment of patients with COVID-19, defined using a Delphi method., Research Question: Is the HOME-CoV rule reliable for identifying a subgroup of COVID-19 patients with a low risk of adverse outcomes who can be treated at home safely?, Study Design and Methods: We aimed to validate the HOME-CoV rule in a prospective, multicenter study before and after trial of patients with probable or confirmed COVID-19 who sought treatment at the ED of 34 hospitals. The main outcome was an adverse evolution, that is, invasive ventilation or death, occurring within the 7 days after patient admission. The performance of the rule was assessed by the false-negative rate. The impact of the rule implementation was assessed by the absolute differences in the rate of patients who required invasive ventilation or who died and in the rate of patients treated at home, between an observational and an interventional period after implementation of the HOME-CoV rule, with propensity score adjustment., Results: Among 3,000 prospectively enrolled patients, 1,239 (41.3%) demonstrated a negative HOME-CoV rule finding. The false-negative rate of the HOME-CoV rule was 4 in 1,239 (0.32%; 95% CI, 0.13%-0.84%), and its area under the receiver operating characteristic curve was 80.9 (95% CI, 76.5-85.2). On the adjusted populations, 25 of 1,274 patients (1.95%) experienced an adverse evolution during the observational period vs 12 of 1,274 patients (0.95%) during the interventional period: -1.00 (95% CI, -1.86 to -0.15). During the observational period, 858 patients (67.35%) were treated at home vs 871 patients (68.37%) during the interventional period: -1.02 (95% CI, -4.46 to 2.26)., Interpretation: A large proportion of patients treated in the ED with probable or confirmed COVID-19 have a negative HOME-CoV rule finding and can be treated safely at home with a very low risk of complications., Trial Registry: ClinicalTrials.gov; No.: NCT04338841; URL: www.clinicaltrials.gov., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Critically ill patients with coronavirus disease 2019 (COVID-19) are prone to developing macrothrombosis and microthrombosis. COVID-19 has been reported to be rarely associated with thrombotic microangiopathies. A disintegrin and metalloprotease with thrombospondin type I repeats, member 13 (ADAMTS13) severe deficiency, the hallmark of thrombotic thrombocytopenic purpura (TTP), induces the formation of platelet, unusually large von Willebrand factor (VWF) multimer microthrombi. In immune-mediated TTP, ADAMTS13 adopts specifically an open conformation. The VWF/ADAMTS13 couple may contribute to the microthrombi formation in pulmonary alveolar capillaries in COVID-19., Objective: To investigate clinical features, hemostatic laboratory parameters, VWF/ADAMTS13 axis, and ADAMTS13 conformation in critically ill COVID-19 patients at admission., Methods: Fifty three critically ill COVID-19 patients were enrolled between March 18 and May 9 2020 in a monocentric hospital., Results: The median age was 59 years and the male-to-female ratio was 2.8/1. We reported seven pulmonary embolisms and 15 deaths. Biological investigations showed increased fibrinogen and factor V levels, and strongly increased D-dimers correlated with mortality. No patient presented severe thrombocytopenia nor microangiopathic hemolytic anemia. An imbalance between high VWF antigen levels and normal or slightly decreased ADAMTS13 activity levels (strongly elevated VWF/ADAMTS13 ratio) was correlated with mortality. Three patients had a partial quantitative deficiency in ADAMTS13. We also reported a closed conformation of ADAMTS13 in all patients, reinforcing the specificity of an open conformation of ADAMTS13 as a hallmark of TTP., Conclusion: We suggest that slightly decreased or normal ADAMTS13 activity and highly elevated VWF are rather biomarkers reflecting both the strong inflammation and the endothelial damage rather than drivers of the thrombotic process of COVID-19., (© 2021 International Society on Thrombosis and Haemostasis.)

During an epidemic period, we compared patients hospitalized for initial suspicion of COVID-19 but for whom an alternative diagnosis was finally retained (n = 152) with those who had COVID-19 (n = 222). Most common diagnoses were another infectious disease and heart failure. COVID-19-negative patients were more often active smokers had less often cough, fever, and digestive symptoms, as compared to the 222 COVID-19-positive patients. They had higher median neutrophil and lymphocyte counts and lower CRP level. In multivariate analysis, no current smoking, neurocognitive disorder, myalgia, and fibrinogen ≥4g/L were independently associated with a final diagnosis of COVID-19., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: The health crisis linked to the COVID-19 epidemic has required lockdown measures in France and changes in practices in dialysis centers. The objective was to assess the depressive and anxiety symptoms during lockdown in hemodialysis patients and their caregivers., Methods: We sent, during lockdown period, between April and May 2020, self-questionnaires to voluntary subjects (patients and caregivers), treated by hemodialysis or who worked in hemodialysis in one of the 14 participating centers in France. We analyzed their perception of dialysis sessions (beneficial or worrying), their stress level (VAS rated from 0 to 10), their anxiety and depressive symptoms (Hospital anxiety and depression scale). Factors associated with stress, anxiety and depression were analyzed with multiple linear regression models., Results: 669 patients and 325 caregivers agreed to participate. 70 % of participants found it beneficial to come to dialysis during confinement. The proportions of subjects with a stress level ≥ 6 linked to the epidemic, confinement, fear of contracting COVID-19 and fear of infecting a loved one were respectively 23.9%, 26.2%, 33.4% and 42%. 39.2% presented with certain (13.7%) or doubtful (19.2%) anxious symptoms. 21.2% presented a certain (7.9%) or doubtful (13.3%) depressive symptomatology. Age, gender, history of psychological disorders and perception of dialysis sessions were associated with levels of stress, anxiety and depression., Conclusion: During the lockdown period, in France, the majority of hemodialysis patients and caregivers found it beneficial to come to dialysis. One in three subjects had anxiety symptoms and one in five subjects had depressive symptoms., (Copyright © 2021. Published by Elsevier Masson SAS.)

We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR = 2.05, 95%CI = 1.39-3.02, p < 0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR = 0.42, 95%CI = 0.18-0.99, p = 0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon., (© 2021 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Aim: Describing acute respiratory distress syndrome patterns, therapeutics management, and outcomes of ICU COVID-19 patients and indentifying risk factors of 28-day mortality., Methods: Prospective multicentre, cohort study conducted in 29 French ICUs. Baseline characteristics, comorbidities, adjunctive therapies, ventilatory support at ICU admission and survival data were collected., Results: From March to July 2020, 966 patients were enrolled with a median age of 66 (interquartile range 58-73) years and a median SAPS II of 37 (29-48). During the first 24 h of ICU admission, COVID-19 patients received one of the following respiratory supports: mechanical ventilation for 559 (58%), standard oxygen therapy for 228 (24%) and high-flow nasal cannula (HFNC) for 179 (19%) patients. Overall, 721 (75%) patients were mechanically ventilated during their ICU stay. Prone positioning and neuromuscular blocking agents were used in 494 (51%) and 460 (48%) patients, respectively. Bacterial co-infections and ventilator-associated pneumonia were diagnosed in 79 (3%) and 411 (43%) patients, respectively. The overall 28-day mortality was 18%. Age, pre-existing comorbidities, severity of respiratory failure and the absence of antiviral therapy on admission were identified as independent predictors of 28-day outcome., Conclusion: Severity of hypoxaemia on admission, older age (> 70 years), cardiovascular and renal comorbidities were associated with worse outcome in COVID-19 patients. Antiviral treatment on admission was identified as a protective factor for 28-day mortality. Ascertaining the outcomes of critically ill COVID-19 patients is crucial to optimise hospital and ICU resources and provide the appropriate intensity level of care., (Copyright © 2021 Société française d'anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.)

Background and Purpose: During the COVID-19 outbreak, the presence of extensive white matter microhemorrhages was detected by brain MRIs. The goal of this study was to investigate the origin of this atypical hemorrhagic complication., Methods: Between March 17 and May 18, 2020, 80 patients with severe COVID-19 infections were admitted for acute respiratory distress syndrome to intensive care units at the University Hospitals of Strasbourg for whom a brain MRI for neurologic manifestations was performed. 19 patients (24%) with diffuse microhemorrhages were compared to 18 control patients with COVID-19 and normal brain MRI., Results: The first hypothesis was hypoxemia. The latter seemed very likely since respiratory failure was longer and more pronounced in patients with microhemorrhages (prolonged endotracheal intubation (p = 0.0002), higher FiO 2  (p = 0.03), increased use of extracorporeal membrane oxygenation (p = 0.04)). A relevant hypothesis, the role of microangiopathy, was also considered, since patients with microhemorrhages presented a higher increase of the D-Dimers (p = 0.01) and a tendency to more frequent thrombotic events (p = 0.12). Another hypothesis tested was the role of kidney failure, which was more severe in the group with diffuse microhemorrhages (higher creatinine level [median of 293 µmol/L versus 112 µmol/L, p = 0.04] and more dialysis were introduced in this group during ICU stay [12 versus 5 patients, p = 0.04])., Conclusions: Blood-brain barrier dysfunction secondary to hypoxemia and high concentration of uremic toxins seems to be the main mechanism leading to critical illness-associated cerebral microbleeds, and this complication remains to be frequently described in severe COVID-19 patients., (© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.)

Aim: Our objective was to describe the impact of hyponatremia on the outcomes of COVID-19 patients [outcomes selected: intensive care unit (ICU) admission, mechanical ventilation or death]., Methods: Two groups of COVID-19 patients were retrospectively screened on the basis of plasma sodium level at admission: hyponatremic (sodium < 135 mM, n = 92) or normonatremic (sodium ≥ 135 mM, n = 198) patients. Pearson's chi- 2 (qualitative variables) and Student's T tests (quantitative variables) were used to compare the two groups. A multiple logistic regression model was used to explore the association between patients' clinical data and outcomes., Results: Hyponatremia was frequent but generally mild. There were more male patients in the hyponatremic group (p = 0.014). Pulmonary lesions on the first thoracic CT-scan performed during hospitalization were significantly more extensive in the hyponatremic group (p = 0.010). ICU admission, mechanical ventilation or death were significantly more frequent in hyponatremic compared to normonatremic patients (37 versus 14%; p < 0.001; 17 versus 6%; p = 0.003; 18 versus 9%, p = 0.042, respectively). Hyponatremia was an independent predictor of adverse outcomes (adjusted Odds-ratio: 2.77 [1.26-6.15, p = 0.011])., Conclusions: Our study showed an independent relationship between hyponatremia at admission and transfer to ICU, use of mechanical ventilation or death in COVID-19 patients. Hyponatremia may reflect the severity of underlying pulmonary lesions. Our results support the use of sodium levels as a simple bedside screening tool for the early identification of SARS-CoV-2 infected patients at high risk of poor outcome., (© 2021. Italian Society of Nephrology.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to an unprecedented global health crisis, resulting in a critical need for effective vaccines that generate protective antibodies. Protein subunit vaccines represent a promising approach but often lack the immunogenicity required for strong immune stimulation. To overcome this challenge, it is first demonstrated that advanced biomaterials can be leveraged to boost the effectiveness of SARS-CoV-2 protein subunit vaccines. Additionally, it is reported that oxygen is a powerful immunological co-adjuvant and has an ability to further potentiate vaccine potency. In preclinical studies, mice immunized with an oxygen-generating coronavirus disease 2019 (COVID-19) cryogel-based vaccine (O 2 -Cryogel VAX ) exhibit a robust Th1 and Th2 immune response, leading to a sustained production of highly effective neutralizing antibodies against the virus. Even with a single immunization, O 2 -Cryogel VAX achieves high antibody titers within 21 days, and both binding and neutralizing antibody levels are further increased after a second dose. Engineering a potent vaccine system that generates sufficient neutralizing antibodies after one dose is a preferred strategy amid vaccine shortage. The data suggest that this platform is a promising technology to reinforce vaccine-driven immunostimulation and is applicable to current and emerging infectious diseases., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Background: Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection causes direct lung damage, overwhelming endothelial activation, and inflammatory reaction, leading to acute respiratory failure and multi-organ dysfunction. Ongoing clinical trials are evaluating targeted therapies to hinder this exaggerated inflammatory response. Critically ill coronavirus disease 2019 (COVID-19) patients have shown heterogeneous severity trajectories, suggesting that response to therapies is likely to vary across patients., Research Question: Are critically ill COVID-19 patients biologically and immunologically dissociable based on profiling of currently evaluated therapeutic targets?, Study Design and Methods: We did a single-center, prospective study in an ICU department in France. Ninety-six critically ill adult patients admitted with a documented SARS-CoV-2 infection were enrolled. We conducted principal components analysis and hierarchical clustering on a vast array of immunologic variables measured on the day of ICU admission., Results: We found that patients were distributed in three clusters bearing distinct immunologic features and associated with different ICU outcomes. Cluster 1 had a "humoral immunodeficiency" phenotype with predominant B-lymphocyte defect, relative hypogammaglobulinemia, and moderate inflammation. Cluster 2 had a "hyperinflammatory" phenotype, with high cytokine levels (IL-6, IL-1β, IL-8, tumor necrosis factor-alpha [TNF⍺]) associated with CD4+ and CD8+ T-lymphocyte defects. Cluster 3 had a "complement-dependent" phenotype with terminal complement activation markers (elevated C3 and sC5b-9)., Interpretation: Patients with severe COVID-19 exhibiting cytokine release marks, complement activation, or B-lymphocyte defects are distinct from each other. Such immunologic variability argues in favor of targeting different mediators in different groups of patients and could serve as a basis for patient identification and clinical trial eligibility., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Systems of care have been challenged to control progression of the COVID-19 pandemic. Whether this has been associated with delayed reperfusion and worse outcomes in French patients with ST-segment elevation myocardial infarction (STEMI) is unknown., Aim: To compare the rate of STEMI admissions, treatment delays, and outcomes between the first peak of the COVID-19 pandemic in France and the equivalent period in 2019., Methods: In this nationwide French survey, data from consecutive STEMI patients from 65 centres referred for urgent revascularization between 1 March and 31 May 2020, and between 1 March and 31 May 2019, were analysed. The primary outcome was a composite of in-hospital death or non-fatal mechanical complications of acute myocardial infarction., Results: A total of 6306 patients were included. During the pandemic peak, a 13.9±6.6% (P=0.003) decrease in STEMI admissions per week was observed. Delays between symptom onset and percutaneous coronary intervention were longer in 2020 versus 2019 (270 [interquartile range 150-705] vs 245 [140-646]min; P=0.013), driven by the increase in time from symptom onset to first medical contact (121 [60-360] vs 150 [62-420]min; P=0.002). During 2020, a greater number of mechanical complications was observed (0.9% vs 1.7%; P=0.029) leading to a significant difference in the primary outcome (112 patients [5.6%] in 2019 vs 129 [7.6%] in 2020; P=0.018). No significant difference was observed in rates of orotracheal intubation, in-hospital cardiac arrest, ventricular arrhythmias and cardiogenic shock., Conclusions: During the first peak of the COVID-19 pandemic in France, there was a decrease in STEMI admissions, associated with longer ischaemic time, exclusively driven by an increase in patient-related delays and an increase in mechanical complications. These findings suggest the need to encourage the population to seek medical help in case of symptoms., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Background and Purpose: Cerebral complications related to COVID-19 were recently reported, and the underlying mechanisms of brain damage remain uncertain, probably multifactorial. Among various hypotheses suggested, a possible vasculitis was issued but never confirmed. Herein, we aimed to describe brain MRIs focused on the intracranial vessel wall in a population of COVID-19 patients with neurologic manifestations., Materials and Methods: Between March 1 and May 31, 2020, 69 consecutive COVID-19 patients with neurologic manifestations underwent a brain MRI allowing the study of the intracranial vessel wall at Strasbourg University hospitals and were retrospectively included. During the same period, 25 consecutive patients, without suspicion of SARS-CoV-2 infection, underwent a brain MRI urgently, with the same imaging protocols. A vasculitis seemed likely when imaging demonstrated vessel wall thickening with homogeneous and concentric enhancement., Results: Among the 69 COVID-19 patients included, 11 (16%) presented arterial vessel wall thickening with homogeneous and concentric enhancement, compatible with cerebral vasculitis. These neuroimaging findings were not found among the 25 patients without SARS-CoV-2 infection, and the difference was statistically significant (p = 0.03). Middle cerebral arteries, basilar artery, and posterior cerebral arteries were the most frequent vessels involved. For nine of them, imaging demonstrated ischemic or hemorrhagic complications., Conclusion: Cerebral vasculitis of medium-sized vessels seems to be one of the mechanisms at the origin of brain damage related to COVID-19., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Background: Coronavirus disease 2019 (COVID-19) has been associated with coagulation disorders, in particular high concentrations of D-dimer, and increased frequency of venous thromboembolism., Aim: To explore the association between D-dimer at admission and in-hospital mortality in patients hospitalised for COVID-19, with or without symptomatic venous thromboembolism., Methods: From 26 February to 20 April 2020, D-dimer concentration at admission and outcomes (in-hospital mortality and venous thromboembolism) of patients hospitalised for COVID-19 in medical wards were retrospectively analysed in a multicenter study in 24 French hospitals., Results: Among 2878 patients enrolled in the study, 1154 (40.1%) patients had D-dimer measurement at admission. Receiver operating characteristic curve analysis identified a D-dimer concentration>1128ng/mL as the best cut-off value for in-hospital mortality (area under the curve 64.9%, 95% confidence interval [CI] 60-69), with a sensitivity of 71.1% (95% CI 62-78) and a specificity of 55.6% (95% CI 52-58), which did not differ in the subgroup of patients with venous thromboembolism during hospitalisation. Among 545 (47.2%) patients with D-dimer concentration>1128ng/mL at admission, 86 (15.8%) deaths occurred during hospitalisation. After adjustment, in Cox proportional hazards and logistic regression models, D-dimer concentration>1128ng/mL at admission was also associated with a worse prognosis, with an odds ratio of 3.07 (95% CI 2.05-4.69; P<0.001) and an adjusted hazard ratio of 2.11 (95% CI 1.31-3.4; P<0.01)., Conclusions: D-dimer concentration>1128ng/mL is a relevant predictive factor for in-hospital mortality in patients hospitalised for COVID-19 in a medical ward, regardless of the occurrence of venous thromboembolism during hospitalisation., (Copyright © 2021. Published by Elsevier Masson SAS.)