Neurologic manifestations associated with COVID-19: a multicentre registry.

OBJECTIVES: To provide an overview of the spectrum, characteristics and outcomes of neurologic manifestations associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: We conducted a single-centre retrospective study during the French coronavirus disease 2019 (COVID-19) epidemic in March-April 2020. All COVID-19 patients with de novo neurologic manifestations were eligible. RESULTS: We included 222 COVID-19 patients with neurologic manifestations from 46 centres in France. Median (interquartile range, IQR) age was 65 (53-72) years and 136 patients (61.3%) were male. COVID-19 was severe or critical in 102 patients (45.2%). The most common neurologic diseases were COVID-19-associated encephalopathy (67/222, 30.2%), acute ischaemic cerebrovascular syndrome (57/222, 25.7%), encephalitis (21/222, 9.5%) and Guillain-Barré syndrome (15/222, 6.8%). Neurologic manifestations appeared after the first COVID-19 symptoms with a median (IQR) delay of 6 (3-8) days in COVID-19-associated encephalopathy, 7 (5-10) days in encephalitis, 12 (7-18) days in acute ischaemic cerebrovascular syndrome and 18 (15-28) days in Guillain-Barré syndrome. Brain imaging was performed in 192 patients (86.5%), including 157 magnetic resonance imaging (70.7%). Among patients with acute ischaemic cerebrovascular syndrome, 13 (22.8%) of 57 had multiterritory ischaemic strokes, with large vessel thrombosis in 16 (28.1%) of 57. Brain magnetic resonance imaging of encephalitis patients showed heterogeneous acute nonvascular lesions in 14 (66.7%) of 21. Cerebrospinal fluid of 97 patients (43.7%) was analysed, with pleocytosis found in 18 patients (18.6%) and a positive SARS-CoV-2 PCR result in two patients with encephalitis. The median (IQR) follow-up was 24 (17-34) days with a high short-term mortality rate (28/222, 12.6%). CONCLUSIONS: Clinical spectrum and outcomes of neurologic manifestations associated with SARS-CoV-2 infection were broad and heterogeneous, suggesting different underlying pathogenic processes.

Prevalence of post-acute coronavirus disease 2019 symptoms twelve months after hospitalization in participants retained in follow-up: analyses stratified by gender from a large prospective cohort.

OBJECTIVES: Persistent post-acute coronavirus disease 2019 (COVID-19) symptoms (PACSs) have been reported up to 6 months after hospital discharge. Herein we assessed the symptoms that persisted 12 months (M12) after admission for COVID-19 in the longitudinal prospective national French coronavirus disease cohort. METHODS: Hospitalized patients with a confirmed virological diagnosis of COVID-19 were enrolled. Follow-up was planned until M12 after admission. Associations between persistence of ≥3 PACSs at M12 and clinical characteristics at admission were assessed through logistic regression according to gender. RESULTS: We focused on participants enrolled between 24 January 2020 and 15 July 2020, to allow M12 follow-up. The M12 data were available for 737 participants. Median age was 61 years, 475 (64%) were men and 242/647 (37%) were admitted to intensive care units during the acute phase. At M12, 27% (194/710) of the participants had ≥3 persistent PACS, mostly fatigue, dyspnoea and joint pain. Among those who had a professional occupation before the acute phase, 91 out of 339 (27%) were still on sick leave at M12. Presence of ≥3 persistent PACS was associated with female gender, both anxiety and depression, impaired health-related quality of life and Medical Muscle Research Council Scale <57. Compared with men, women more often reported presence of ≥3 persistent PACSs (98/253, 39% vs. 96/457, 21%), depression and anxiety (18/152, 12% vs. 17/268, 6% and 33/156, 21% vs. 26/264, 10%, respectively), impaired physical health-related quality of life (76/141, 54% vs. 120/261, 46%). Women had less often returned to work than men (77/116, 66% vs. 171/223, 77%). CONCLUSIONS: One fourth of the individuals admitted to hospital for COVID-19 still had ≥3 persistent PACSs at M12 post-discharge. Women reported more often ≥3 persistent PACSs, suffered more from anxiety and depression and had less often returned to work than men.

Transmission of SARS-CoV-2 during indoor clubbing events: A clustered randomized, controlled, multicentre trial protocol

Introduction The SARS-CoV-2 pandemic led to the implementation of several non-pharmaceutical interventions (NPIs), from closings of bars and restaurants to curfews and lockdowns. Vaccination campaigns started hoping it could efficiently alleviate NPI. The primary objective of the “Indoor Transmission of COVID-19” (ITOC) study is to determine among a fully vaccinated population the relative risk of SARS-CoV-2 transmission during one indoor clubbing event. Secondary objectives are to assess the transmission of other respiratory viruses, risk exposure, and attitudes toward COVID-19 vaccination, health pass, and psychological impact of indoor club closing. Methods and analysis Four thousand four hundred healthy volunteers aged 18–49 years and fully vaccinated will be included in Paris region. The intervention is an 8-hour indoor clubbing event with no masks, no social distance, maximum room capacity, and ventilation. A reservation group of up to 10 people will recruit participants, who will be randomized 1:1 to either the experimental group (2,200 volunteers in two venues with capacities of 1,000 people each) or the control group (2,200 volunteers asked not to go to the club). All participants will provide a salivary sample on the day of the experiment and 7 days later. They also will answer several questionnaires. Virological analyses include polymerase chain reaction (PCR) of salivary samples and air of the venue, investigating SARS-CoV-2 and 18 respiratory viruses. Ethics and dissemination Ethical clearance was first obtained in France from the institutional review board (Comité de Protection des Personnes Ile de France VII - CPP), and the trial received clearance from the French National Agency for Medicines and Health Products (Agence National de Sécurité du Médicament - ANSM). The trial is supported and approved by The Agence Nationale Recherche sur le SIDA, les hépatites et maladies émergences (ANRS-MIE). Positive, negative, and inconclusive results will be published in peer-reviewed scientific journals. Trial registration number IDR-CB 2021-A01473-38. Clinicaltrial.gov, identifier: NCT05311865.

Prevalence of post-acute COVID-19 symptoms twelve months after hospitalisation in participants retained in follow-up: analyses stratified by gender from a large prospective cohort

Objectives Persistent post-acute COVID-19 symptom (PACS) have been reported up to 6-months (M6) after hospital discharge. Here we assessed, in the longitudinal prospective national French COVID cohort, symptoms that persisted 12-months (M12) after admission for COVID-19. Methods Hospitalized patients with a virologically-confirmed COVID-19 were enrolled. Follow-up was planned until M12 post-admission. Associations between persistence of ≥3 PACS at M12 and clinical characteristics at admission were assessed through logistic regression according to gender. Results We focused on participants enrolled between January 24th and July 15th 2020, in order to allow M12 follow-up. M12 data were available for 737 participants. Median age was 61 years, 475 (64%) were men and 242/647 (37%) were admitted to ICU during the acute phase. At M12, 194/710 (27%) of participants had ≥3 persistent PACS, mostly fatigue, dyspnea and joint pain. Among those who had a professional occupation before the acute phase 91/339 (27%) were still on sick leave at M12. Presence of ≥3 persistent PACS was associated with female gender, both anxiety and depression, impaired health-related quality of life (HRQL) and mMRC scale <57. Compared to men, women more often reported presence of >3 persistent PACS (98/253, 39% vs 96/457, 21%), depression and anxiety (18/152, 12% vs 17/268, 6% and 33/156, 21% vs 26/264, 10%, respectively), impaired physical HRQL (76/141, 54% vs 120/261, 46%). Women had less often returned to work than men (77/116, 66% vs 171/223, 77%). Conclusions A fourth of individuals admitted to hospital for COVID-19 still had ≥3 persistent PACS at M12 post-discharge. Women reported more often ≥3 persistent PACS, suffered more from anxiety and depression, and had less often returned to work than men.

Facteurs de risque de contamination professionnelle des soignants par le SARS-CoV-2 : enquête par TDR et sérologies au CHU de Rennes

Introduction Depuis décembre 2019, et l’apparition de l’épidémie par SARS-CoV-2, de nombreux soignants ont été contaminés par ce virus au cours de leur exercice professionnel. La transmission du virus peut en effet se faire par voie cutanée, par voie respiratoire, en particulier par les gouttelettes émises par les malades lors de toux, et enfin par aérosol. Toutefois, les circonstances exactes ne sont pas connues avec précision, alors même que ces éléments sont indispensables à la prévention. L’objectif de cette étude est de rechercher l’existence de gestes professionnels à risque associés à une plus grande prévalence de contamination par ce virus. Méthodes Entre le 29 mai et le 10 juillet 2020, l’ensemble du personnel du CHU de Rennes a été convié à participer à une enquête séro-épidémiologique. Dix équipes de 3 personnes sont ainsi passées systématiquement dans tous les services du CHU à plusieurs reprises. Tous les personnels volontaires ont rempli un questionnaire standardisé sur la présence de symptômes compatibles avec la COVID-19 et leurs activités durant l’épidémie (février à juin 2020). Ils bénéficiaient dans le même temps d’un test rapide (TDR) de Ng Biotech®, approuvé par le CNR. Un échantillon de sujets tirés au sort selon leurs activités dans un service ayant accueilli ou non des patients COVID-19 positifs a rempli un questionnaire complémentaire sur les gestes réalisés ainsi que l’utilisation d’équipements de protection individuelle (masques, gants, charlottes, blouses, …). Les sujets ayant eu une RT-PCR durant l’épidémie ont également été inclus dans cet échantillon. Les TDR positifs ont fait l’objet d’une confirmation sérologique par au moins un test ELISA sur la base du volontariat. Résultats Plus de 7000 personnels du CHU ont participé au dépistage, dont 3500 à l’étude ancillaire. Le taux de positivité du TDR ou de la sérologie est de 3,78 %. L’analyse préliminaire montre que le risque d’un TDR ou d’une sérologie positive associé à la prise en charge d’un patient COVID-19 positif est de 1,15 (0,74–1,78), de 2,00 (1,33–3,01) lors du contact avec un professionnel lui-même positif et de 2,06 (1,31–3,26) lors de la présence dans la vie personnelle d’un sujet identifié comme COVID-19 certain ou possible. En analyse univariée, certains gestes paraissent plus à risque de contamination chez les soignants (examen clinique, ophtalmologique, respiratoire). Les résultats plus complets seront présentés au Congrès. Conclusion Le risque de contamination professionnelle par le SARS-CoV-2 semble être surtout lié aux contacts entre professionnels, à l’environnement privé et à certains gestes professionnels. Le respect des mesures de prévention doit être systématisé dans toutes les circonstances professionnelles, y compris hors soins.

Incidence and characteristics of COVID-19 in French professional football players during the 2020-2021 season.

OBJECTIVES: To describe the epidemiology of COVID-19 in French professional football players, and to compare the infection incidence with the general population across the first three waves. METHODS: During the 2020-2021 season, all professional football players (n = 1217) in the two primary French leagues underwent weekly testing for SARS-CoV-2 infection by nasopharyngeal PCR, in combination with rigorous infection control measures. RESULTS: Among all players, 572 (47%) tested positive at least once, with no COVID-19-related death or hospital admission. Monthly incidence estimates in players ranged from 1486 to 6731 per 100,000 individuals, i.e. 2-17 times higher than incidence estimates in the general population in France during the study period. CONCLUSION: Almost 50% of professional football players developed SARS-CoV-2 infection during the 2020-2021 season in France, with no severe complication.

Delay between COVID-19 complete vaccination and SARS-CoV-2 infection among healthcare workers.

OBJECTIVES: Healthcare workers (HCWs), at increased risk of coronavirus disease 2019 (COVID-19) were among the primary targets for vaccination, which became mandatory for them on September 15th, 2021 in France. In November they were confronted to the fifth COVID-19 wave despite excellent vaccine coverage. We aimed to estimate the incidence of SARS-CoV-2 infection after complete vaccination among HCWs with different vaccination schemes, and its determinants. METHODS: We enrolled all HCWs in the university hospital of Rennes, France who had received complete vaccination (two doses of COVID-19 vaccine). The delay from last vaccination dose to SARS-CoV-2 infection was computed.Fitted mixed Cox survival model with a random effect applied to exposure risk periods to account for epidemic variation was used to estimate the determinants of SARS-CoV-2 infection after complete vaccination. RESULTS: Of the 6674 (82%) HCWs who received complete vaccination (36% BNT162b2, 29% mRNA-1273, and 34% mixed with ChAdOx1 nCoV-19) and were prospectively followed-up for a median of 7.0 [6.3-8.0] months, 160 (2.4%) tested positive for SARS-CoV-2 by RT-PCR. Incidence density of SARS-CoV-2 infection after complete vaccination was 3.39 [2.89-3.96] infections per 1000 person-month. Median time from vaccine completion to SARS-CoV-2 infection was 5.5 [3.2-6.6] months. Using fitted mixed Cox regression with the delay as a time-dependent variable and random effect applied to exposure risk periods, age (P < 0.001) was independently associated with the incidence of SARS-CoV-2 infection. Vaccine schemes were not associated with SARS-CoV-2 infection (P = 0.068). A period effect was significantly associated with the incidence of SARS-CoV-2 infection (P < 0.001). CONCLUSIONS: In this real-world study, incidence of SARS-CoV-2 infection increases with time in fully vaccinated HCWs with no differences according to the vaccination scheme. The short delay between complete vaccination and incident SARS-CoV-2 infection highlights the need for sustained barrier measures even in fully vaccinated HCWs.

Severity of self-reported symptoms and psychological burden 6-months after hospital admission for COVID-19: a prospective cohort study.

OBJECTIVES: Few studies have reported clinical COVID-19 sequelae six months (M6) after hospital discharge, but none has studied symptom severity. METHODS: Prevalence and severity of 7 symptoms were estimated until M6 using the self-administered influenza severity scale in COVID-19 hospitalized patients enrolled in the French COVID cohort. Factors associated with severity were assessed by logistic regression. Anxiety, depression and health-related quality of life (HRQL) were also assessed. RESULTS: At M6, among the 324 patients (median age 61 years, 63% men, 19% admitted to intensive care during the acute phase), 187/324 (58%) reported at least one symptom, mostly fatigue (47%) and myalgia (23%). Symptom severity was scored, at most, mild in 125 (67%), moderate in 44 (23%) and severe in 18 (10%). Female gender was the sole factor associated with moderate/severe symptom reporting (OR = 1.98, 95%CI=1.13-3.47). Among the 225 patients with psychological assessment, 24 (11%) had anxiety, 18 (8%) depressive symptoms, and their physical HRQL was significantly poorer than the general population (p=0.0005). CONCLUSION: Even if 58% of patients reported ≥1 symptom at M6, less than 7% rated any symptom as severe. Assessing symptoms severity could be helpful to identify patients requiring appropriate medical care. Women may require special attention.

Risk factors for SARS-CoV-2 infection among health care workers.

BACKGROUND: Health care workers (HCWs) are on the front line for COVID-19. Better knowledge of risk factors for SARS-CoV-2 infection is crucial for their protection. We aimed to identify these risk factors with a focus on care activities. METHODS: We conducted a seroprevalence survey among HCWs in a French referral hospital. Data on COVID-19 exposures, care activities, and protective equipment were collected on a standardized questionnaire. Multivariate logistic regressions were used to assess risk factors for SARS-CoV-2 IgG adjusted on potential confounding. FINDINGS: Among the 3,234 HCWs enrolled, the prevalence of SARS-CoV-2 IgG was 3.8%. Risk factors included contact with relatives or HCWs with COVID-19 (odds ratio [OR] 2.20 [1.40-3.45] and 2.16 [1.46-3.18], respectively), but not contact with COVID-19 patients. In multivariate analyses, suboptimal use of protective equipment during nasopharyngeal sampling (OR 3.46 [1.15-10.40]), mobilisation of patients in bed (OR 3.30 [1.51-7.25]), clinical examination (OR 2.51 [1.16-5.43]), and eye examination (OR 2.90 [1.01-8.35]) were associated with SARS-CoV-2 infection. Patients washing and dressing and aerosol-generating procedures were additional risk factors, with or without appropriate use of protective equipment (OR 1.37 [1.04-1.81] and 1.74 [1.05-2.88]). CONCLUSIONS: Risk factors for SARS-CoV-2 infection among HCWs are (1) contact with relatives or HCWs with COVID-19, (2) close or prolonged contact with patients, (3) aerosol-generating procedures. Enhanced protective measures during the two latter care-activities may be warranted.

Vaccine effectiveness against COVID-19 hospitalization in adults in France: A test negative case control study.

BACKGROUND: Measuring vaccine effectiveness (VE) using real-life data is critical to confirm the effectiveness of licensed vaccine, which could strengthen vaccination adherence. METHODS: We measured VE against adult COVID-19 hospitalization in five hospitals in France using a test negative design. We compared the odds of vaccinated patients hospitalized with COVID-19 with the odds of vaccinated patients hospitalized for the same symptoms with a negative test. RESULTS: A total of 853 patients (463 cases and 390 controls) were included, with a total of 170 patients vaccinated (104 with one dose, 65 with two doses, and one with three doses). There were four cases of breakthrough infections, all in immunocompromised patients. The VE was 84.0% (CI0.95=[72.6; 90.6]) for one dose and 96.2% (CI0.95=[86.8; 98.9]) for two doses. CONCLUSION: Our results confirm the high VE of COVID-19 vaccine in France to prevent hospitalizations due to the alpha variant.

Partial oral antibiotic treatment for bacterial brain abscess: an open-label randomized non-inferiority trial (ORAL).

BACKGROUND: The advised standard treatment for bacterial brain abscess following surgery is 6 to 8 weeks of intravenous (IV) antibiotic treatment, but an early switch to oral antibiotic treatment has been suggested to be equally effective. METHODS: This investigator-initiated, international, multi-center, parallel group, open-label, randomized (1:1 allocation) controlled trial will examine if oral treatment after 2 weeks of IV antibiotic therapy is non-inferior to standard 6-8 weeks of IV antibiotics for bacterial brain abscess in adults (≥ 18 years of age). The study will be conducted at hospitals across Denmark, the Netherlands, France, Australia, and Sweden. Exclusion criteria are severe immunocompromise or impaired gastro-intestinal absorption, pregnancy, device-related brain abscesses, and brain abscess caused by nocardia, tuberculosis, or Pseudomonas spp. The primary objective is a composite endpoint at 6 months after randomization consisting of all-cause mortality, intraventricular rupture of brain abscess, unplanned re-aspiration or excision of brain abscess, relapse, or recurrence. The primary endpoint will be adjudicated by an independent blinded endpoint committee. Secondary outcomes include extended Glasgow Outcome Scale scores and all-cause mortality at end of treatment as well as 3, 6, and 12 months since randomization, completion of assigned treatment, IV catheter associated complications, durations of admission and antibiotic treatment, severe adverse events, quality of life scores, and cognitive evaluations. The planned sample size is 450 patients for a one-sided alpha of 0.025 and a power of 90% to exclude a difference in favor of standard treatment of more than 10%. Date of initiation of first study center was November 3, 2020, with active recruitment for 3 years and follow-up for 1 year of all patients. DISCUSSION: The results of this study may guide future recommendations for treatment of bacterial brain abscess. If early transition to oral antibiotics proves non-inferior to standard IV treatment, this will provide considerable health and costs benefits. TRIAL REGISTRATION: ClinicalTrials.gov NCT04140903, first registered 28.10.2019. EudraCT number: 2019-002845-39, first registered 03.07.2019.

Effectiveness of mRNA-BNT162b2, mRNA-1273, and ChAdOx1 nCoV-19 vaccines against COVID-19 in healthcare workers: an observational study using surveillance data.

OBJECTIVES: Healthcare workers (HCWs) at increased risk of coronavirus disease 2019 (COVID-19) were among the primary targets for vaccine campaigns. We aimed to estimate the protective efficacy of the first three COVID-19 vaccines available in Western Europe. METHODS: We merged two prospective databases that systematically recorded, in our institution: (a) HCWs positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by RT-PCR on nasopharyngeal samples, and (b) HCWs who received at least one dose of COVID-19 vaccine. We excluded HCWs with SARS-CoV-2 infection during the 6 months prior to the study. HCWs were categorized as non-vaccinated if they received no vaccine and until the first injection +13 days, partially vaccinated from the first injection +14 days to the second injection +13 days, and fully vaccinated thereafter. RESULTS: Of the 8165 HCWs employed in our institution, 360 (4.4%) tested positive for SARS-CoV-2 by RT-PCR during the study period (4th January to 17th May 2021). Incidence was 9.1% (8.2-10.0) in non-vaccinated HCWs, 1.2% (0.7-1.9) after one dose of ChAdOx1 nCoV-19, 1.4% (0.6-2.3) and 0.5% (0.1-1.0) after one and two doses of mRNA BNT162b2, 0.7% (0.1-1.9) and 0% after one and two doses of mRNA-1273 (p < 0.0001). Vaccine effectiveness (Cox model) was estimated at, respectively, 86.2% (76.5-91.0), 38.2% (6.3-59.2), and 49.2% (19.1-68.1) 14 days after the first dose for ChAdOx1 nCoV-19, mRNA-1273, and mRNA-BNT162b2, and 100% (ND) and 94.6% (61.0-99.2) 14 days after the second dose for mRNA-1273 and mRNA-BNT162b2. CONCLUSIONS: In this real-world study, the observed effectiveness of COVID-19 vaccines in HCWs was in line with the efficacy reported in pivotal randomized trials.

A new SARS-CoV-2 variant with high lethality poorly detected by RT-PCR on nasopharyngeal samples: an observational study.

OBJECTIVES: In early January 2021 an outbreak of nosocomial cases of coronavirus disease 2019 (COVID-19) emerged in Western France; RT-PCR tests were repeatedly negative on nasopharyngeal samples but positive on lower respiratory tract samples. Whole-genome sequencing (WGS) revealed a new variant, currently defining a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage B.1.616. In March, the WHO classified this as a 'variant under investigation' (VUI). We analysed the characteristics and outcomes of COVID-19 cases related to this new variant. METHODS: Clinical, virological, and radiological data were retrospectively collected from medical charts in the two hospitals involved. We enrolled those inpatients with: (a) positive SARS-CoV-2 RT-PCR on a respiratory sample, (b) seroconversion with anti-SARS-CoV-2 IgG/IgM, or (c) suggestive symptoms and typical features of COVID-19 on a chest CT scan. Cases were categorized as B.1.616, a variant of concern (VOC), or unknown. RESULTS: From 1st January to 24th March 2021, 114 patients fulfilled the inclusion criteria: B.1.616 (n = 39), VOC (n = 32), and unknown (n = 43). B.1.616-related cases were older than VOC-related cases (81 years, interquartile range (IQR) 73-88 versus 73 years, IQR 67-82, p < 0.05) and their first RT-PCR tests were rarely positive (6/39, 15% versus 31/32, 97%, p < 0.05). The B.1.616 variant was independently associated with severe disease (multivariable Cox model HR 4.0, 95%CI 1.5-10.9) and increased lethality (28-day mortality 18/39 (46%) for B.1.616 versus 5/32 (16%) for VOC, p = 0.006). CONCLUSION: We report a nosocomial outbreak of COVID-19 cases related to a new variant, B.1.616, which is poorly detected by RT-PCR on nasopharyngeal samples and is associated with high lethality.

Chilblains during lockdown are associated with household exposure to SARS-CoV-2: a multicentre case-control study.

OBJECTIVES: During the COVID-19 pandemic, numerous cases of chilblains have been reported. However, in most cases, RT-PCR or serology did not confirm SARS-CoV-2 infection. Hypotheses have been raised about an interferon-mediated immunological response to SARS-CoV-2, leading to effective clearance of the SARS-CoV-2 without the involvement of humoral immunity. Our objective was to explore the association between chilblains and exposure to SARS-CoV-2. METHODS: In this multicentre case-control study, cases were the 102 individuals referred to five referral hospitals for chilblains occurring during the first lockdown (March to May 2020). Controls were recruited from healthy volunteers' files held by the same hospitals. All members of their households were included, resulting in 77 case households (262 individuals) and 74 control households (230 individuals). Household exposure to SARS-CoV-2 during the first lockdown was categorized as high, intermediate or low, using a pre-established algorithm based on individual data on symptoms, high-risk contacts, activities outside the home and RT-PCR testing. Participants were offered a SARS-CoV-2 serological test. RESULTS: After adjustment for age, the association between chilblains and viral exposure was estimated at OR 3.3, 95% CI (1.4-7.3) for an intermediate household exposure, and 6.9 (2.5-19.5) for a high household exposure to SARS-CoV-2. Out of 57 case households tested, six (11%) had positive serology for SARS-CoV-2, whereas all control households tested (n = 50) were seronegative (p = 0.03). The effect of potential misclassification on exposure has been assessed in a bias analysis. DISCUSSION: This case-control study demonstrates the association between chilblains occurring during the lockdown and household exposure to SARS-CoV-2.

COVID-19 vaccine hesitancy among healthcare workers.

OBJECTIVE: To characterize healthcare workers' (HCWs) intention to receive the COVID-19 vaccine by the beginning of the vaccine campaign in France. METHODS: Data were collected on a self-administered questionnaire through the website of a tertiary care center (February 9-18, 2021). RESULTS: Among 1,965 respondents, 1,436 (73.1%), 453 (23.1%), and 76 (3.9%) declared themselves in favor, hesitant, or against the COVID-19 vaccine: <60% of auxiliary nurses and technicians intended to be vaccinated, as compared to 60-79% of nurses and support staff, and>80% of medical staff. On multivariate analysis, age, occupation, flu vaccine history, and controversy over the AstraZeneca vaccine tolerability were independently associated with COVID-19 vaccine intention. CONCLUSIONS: Patterns of vaccine hesitancy related to the COVID-19 and influenza vaccines are similar among HCWs. Media communication on vaccine side effects have a dramatic effect on vaccine hesitancy. Efforts are requested to inform HCWs about the risk/benefit balance of COVID-19 vaccines.

Prevalence and characteristics of persistent symptoms after non-severe COVID-19: a prospective cohort study.

We performed a prospective cohort study of 311 outpatients with non-severe COVID-19 (187 women, median age 39 years). Of the 214 (68.8%) who completed the 6-week follow-up questionnaire, 115 (53.7%) had recovered. Others mostly reported dyspnea (n = 86, 40.2%), weight loss (n = 83, 38.8%), sleep disorders (n = 68, 31.8%), and anxiety (n = 56, 26.2%). Of those who developed ageusia and anosmia, these symptoms were still present at week 6 in, respectively, 11/111 (9.9%) and 19/114 (16.7%). Chest CT scan and lung function tests found no explanation in the most disabled patients (n = 23). This study confirms the high prevalence of persistent symptoms after non-severe COVID-19.

Modeling SARS-CoV-2 viral kinetics and association with mortality in hospitalized patients from the French COVID cohort.

The characterization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral kinetics in hospitalized patients and its association with mortality is unknown. We analyzed death and nasopharyngeal viral kinetics in 655 hospitalized patients from the prospective French COVID cohort. The model predicted a median peak viral load that coincided with symptom onset. Patients with age ≥65 y had a smaller loss rate of infected cells, leading to a delayed median time to viral clearance occurring 16 d after symptom onset as compared to 13 d in younger patients (P < 10-4). In multivariate analysis, the risk factors associated with mortality were age ≥65 y, male gender, and presence of chronic pulmonary disease (hazard ratio [HR] > 2.0). Using a joint model, viral dynamics after hospital admission was an independent predictor of mortality (HR = 1.31, P < 10-3). Finally, we used our model to simulate the effects of effective pharmacological interventions on time to viral clearance and mortality. A treatment able to reduce viral production by 90% upon hospital admission would shorten the time to viral clearance by 2.0 and 2.9 d in patients of age <65 y and ≥65 y, respectively. Assuming that the association between viral dynamics and mortality would remain similar to that observed in our population, this could translate into a reduction of mortality from 19 to 14% in patients of age ≥65 y with risk factors. Our results show that viral dynamics is associated with mortality in hospitalized patients. Strategies aiming to reduce viral load could have an effect on mortality rate in this population.

SARS-CoV-2-Induced ARDS Associates with MDSC Expansion, Lymphocyte Dysfunction, and Arginine Shortage.

PURPOSE: The SARS-CoV-2 infection can lead to a severe acute respiratory distress syndrome (ARDS) with prolonged mechanical ventilation and high mortality rate. Interestingly, COVID-19-associated ARDS share biological and clinical features with sepsis-associated immunosuppression since lymphopenia and acquired infections associated with late mortality are frequently encountered. Mechanisms responsible for COVID-19-associated lymphopenia need to be explored since they could be responsible for delayed virus clearance and increased mortality rate among intensive care unit (ICU) patients. METHODS: A series of 26 clinically annotated COVID-19 patients were analyzed by thorough phenotypic and functional investigations at days 0, 4, and 7 after ICU admission. RESULTS: We revealed that, in the absence of any difference in demographic parameters nor medical history between the two groups, ARDS patients presented with an increased number of myeloid-derived suppressor cells (MDSC) and a decreased number of CD8pos effector memory cell compared to patients hospitalized for COVID-19 moderate pneumonia. Interestingly, COVID-19-related MDSC expansion was directly correlated to lymphopenia and enhanced arginase activity. Lastly, T cell proliferative capacity in vitro was significantly reduced among COVID-19 patients and could be restored through arginine supplementation. CONCLUSIONS: The present study reports a critical role for MDSC in COVID-19-associated ARDS. Our findings open the possibility of arginine supplementation as an adjuvant therapy for these ICU patients, aiming to reduce immunosuppression and help virus clearance, thereby decreasing the duration of mechanical ventilation, nosocomial infection acquisition, and mortality.