COVID-19 exposure in SARS-CoV-2-seropositive hospital staff members during the first pandemic wave at Strasbourg University Hospital, France.

OBJECTIVES: Strasbourg University Hospital faced an important COVID-19 first wave from early March 2020. We performed a longitudinal prospective cohort study to describe clinical and virological data, exposure history to COVID-19, and adherence to strict hygiene standards during the first pandemic wave in 1497 workers undergoing a SARS-CoV-2 serological test at our hospital, with a follow up of serology result three months later. PATIENTS AND METHODS: A total of 1497 patients were enrolled from April 6 to May 7, 2020. Antibody response to SARS-CoV-2 was measured, and COVID-19 exposure routes were analyzed according to SARS-CoV-2 serological status. RESULTS: A total of 515 patients (34.4%) were seropositive, mainly medical students (13.2%) and assistant nurses (12.0%). A history of COVID-19 exposure in a professional and/or private setting was mentioned by 83.1% of seropositive subjects (P<0.05; odds ratio [OR]: 2.5; 95% confidence interval [CI]: 1.8-3.4). COVID-19 exposure factors associated with seropositive status were non-professional exposure (OR: 1.9, 95% CI: 1.3-2.7), especially outside the immediate family circle (OR: 2.2, 95% CI: 1.2-3.9) and contact with a COVID-19 patient (OR: 1.6; 95% CI: 1.1-2.2). Among professionally exposed workers, systematic adherence to strict hygiene standards was well observed, except for the use of a surgical mask (P<0.05, OR: 1.9, 95% CI: 1.3-2.8). Of those who reported occasionally or never wearing a surgical mask, nurses (25.7%), assistant nurses (16.2%), and medical students (11.7%) were predominant. CONCLUSION: Infection of staff members during the first pandemic wave in our hospital occurred after both professional and private COVID-19 exposure, underlining the importance of continuous training in strict hygiene standards.

[POCT-management during the first wave of Covid-19 in France. Results of a national survey leaded by the SFBC-POCT Working Group]. / Gestion de la biologie délocalisée lors de la première vague de Covid-19 en France. Résultats de l'enquête nationale menée par le groupe de travail des EBMD de la SFBC.

During the first wave of Covid-19 in France, in spring 2020, healthcare institution's laboratory had to adapt itself quickly to the growing demand for emergency biology, in particular by reorganizing their POCT analyzers: redeployment of analyzers and/or new installations. In order to analyze this management, a subgroup of 15 hospital biologists from the SFBC Working Group "Biochemical markers of Covid-19" sent, in fall 2020, an on-line survey to French hospital laboratories using POCT. Answers analysis (n = 86) shows a territorial disparity related to the severity of the first wave: increased activity essentially in red zones, management of unexpected situations, training of additional nursing staff for 40 % of the laboratories... The survey also showed simplification of aspects related to accreditation those periods of health crisis. An additional survey, carried out in the spring of 2021, showed good overall satisfaction of the healthcare services (n = 139) concerning the services provided by biology in the POCT sector. Because of their great adaptation capacity, the laboratories and their POCT-teams have played a key role in the management of the first wave of Covid-19 in France. However, the success of these organizations requires an essential collaboration between laboratories and healthcare services. The results of this survey are fundamental in the context of the prolongation of the pandemia throughout the world with a POCT sector appearing to be growing.

Evolution of antibody responses up to 13 months after SARS-CoV-2 infection and risk of reinfection.

BACKGROUND: Assessment of the kinetics of SARS-CoV-2 antibodies is essential in predicting risk of reinfection and durability of vaccine protection. METHODS: This is a prospective, monocentric, longitudinal, cohort clinical study. Healthcare workers (HCW) from Strasbourg University Hospital were enrolled between April 6th and May 7th, 2020 and followed up to 422 days. Serial serum samples were tested for antibodies against the Receptor Binding Domain (RBD) of the spike protein and nucleocapsid protein (N) to characterize the kinetics of SARS-CoV-2 antibodies and the incidence of reinfection. Live-neutralization assays were performed for a subset of samples before and after vaccination to analyze sensitivity to SARS-CoV-2 variants. FINDINGS: A total of 4290 samples from 393 convalescent COVID-19 and 916 COVID-19 negative individuals were analyzed. In convalescent individuals, SARS-CoV-2 antibodies followed a triphasic kinetic model with half-lives at month (M) 11-13 of 283 days (95% CI 231-349) for anti-N and 725 days (95% CI 623-921) for anti-RBD IgG, which stabilized at a median of 1.54 log BAU/mL (95% CI 1.42-1.67). The incidence of SARS-CoV-2 infections was 12.22 and 0.40 per 100 person-years in COVID-19-negative and COVID-19-positive HCW, respectively, indicating a relative reduction in the incidence of SARS-CoV-2 reinfection of 96.7%. Live-virus neutralization assay revealed that after one year, variants D614G and B.1.1.7, but less so B.1.351, were sensitive to anti-RBD antibodies at 1.4 log BAU/mL, while IgG ≥ 2.0 log BAU/mL strongly neutralized all three variants. These latter anti-RBD IgG titers were reached by all vaccinated HCW regardless of pre-vaccination IgG levels and type of vaccine. INTERPRETATION: Our study demonstrates a long-term persistence of anti-RBD antibodies that may reduce risk of reinfection. By significantly increasing cross-neutralizing antibody titers, a single-dose vaccination strengthens protection against variants. FUN1DING: None.

Sex Differences in the Evolution of Neutralizing Antibodies to Severe Acute Respiratory Syndrome Coronavirus 2.

We measured anti-spike (S), nucleoprotein (N), and neutralizing antibodies in sera from 308 healthcare workers with a positive reverse-transcription quantitative polymerase chain reaction result for severe acute respiratory syndrome coronavirus 2 and with mild disease, collected at 2 timepoints up to 6 months after symptom onset. At month 1, anti-S and -N antibody levels were higher in male participants aged >50 years and participants with a body mass index (BMI) >25 kg/m2. At months 3-6, anti-S and anti-N antibodies were detected in 99% and 59% of individuals, respectively. Anti-S antibodies and neutralizing antibodies declined faster in men than in women, independent of age and BMI, suggesting an association of sex with evolution of the humoral response.

Impact of intravenous lidocaine on clinical outcomes of patients with ARDS during COVID-19 pandemia (LidoCovid): A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: The main objective of this study is to evaluate the effect of intravenous lidocaine on gas exchange and inflammation in acute respiratory distress syndrome due or not to Covid-19 pneumonia. TRIAL DESIGN: This is a prospective monocentric, randomized, quadruple-blinded and placebo-controlled superiority trial. This phase 3 clinical study is based on two parallel groups received either intravenous lidocaine 2% or intravenous NaCl 0.9%. PARTICIPANTS: This study has been conducted at the University Hospitals of Strasbourg (medical and surgical Intensive Care Units in Hautepierre Hospital) since the 4th November 2020. The participants are 18 years-old and older, hospitalized in ICU for a moderate to severe ARDS according to the Berlin definition; they have to be intubated and sedated for mechanical protective ventilation. All participants are affiliated to the French Social security system and a dosage of beta HCG has to be negative for women of child bearing age . For the Covid-19 subgroup, the SARS-CoV2 infection is proved by RT-PCR <7 days before admission and/or another approved diagnostic technique and/or typical CT appearance pneumonia. The data are prospectively collected in e-Case Report Forms and extracted from clinical files. INTERVENTION AND COMPARATOR: The participants are randomised in two parallel groups with a 1:1 ratio. In the experimental group, patients receive intravenous lidocaine 2% (20mg/mL) (from FRESENIUS KABI France); the infusion protocol provide a bolus of 1 mg/kg (ideal weight), followed by 3 mg/kg/h for the first hour, 1.5 mg/kg/h for the second hour, 0.72 mg/kg/h for the next 22 hours and then 0.6 mg/kg/h for 14 days at most or 24 hours after extubation or ventilator-weaning. The patients in the control group receive intravenous NaCl 0.9% (9 mg/mL) (from Aguettant, France) as placebo comparator; the infusion protocol provide a bolus of 0.05 mL/kg (ideal weight), followed by 0.15 mL/kg/h for the first hour, 0.075 mL/kg/h for the second hour, 0.036 mL/kg/h for the next 22 hours, and the 0.03 mL/kg/h for up to 14 days or 24 hours after extubation or ventilator-weaning. Lidocaine level is assessed at H4, D2, D7 and D14 to prevent local anesthetics systemic toxicity. Clinical data and biological samples are collected to assess disease progression. MAIN OUTCOMES: The primary outcome is the evolution of alveolar-capillary gas exchange measured by the PaO2/FiO2 ratio after two days of treatment. The secondary endpoints of the study include the following: Evolution of PaO2/FiO2 ratio at admission and after 21 days of treatment Number of ventilator-free days Anti-inflammatory effects by dosing inflammatory markers at different timepoints (ferritin, bicarbonate, CRP, PCT, LDH, IL-6, Troponin HS, triglycerides, complete blood count, lymphocytes) Anti-thrombotic effects by dosing platelets, aPTT, fibrinogen, D-dimers, viscoelastic testing and identification of all thromboembolic events up to 4 weeks. Plasmatic concentration of lidocaine and albumin Incidence of adverse events like cardiac rhythm disorders, need of vasopressors, any modification of the QRS, QTc or PR intervals every day Ileus recovery time Consumption of hypnotics, opioids, neuromuscular blockers. Lengths of stay in the ICU, incidence of reintubation and complications due to intensive care unit care (mortality until 90 days, pneumothorax, bacterial pneumopathy, bronchospasm, cardiogenic shock, acute renal failure, need of renal dialysis, delirium, atrial fibrillation, stroke (CAM-ICU score), tetraplegia (MCR score)). Incidence of cough and sore throat at extubation or ventilator-weaning and within 24 hours. All these outcomes will be evaluated according to positivity to Sars-Cov-2. RANDOMISATION: The participants who meet the inclusion criteria and have signed written informed consent will be randomly allocated using a computer-generated random number to either intervention group or control group. The distribution ratio of the two groups will be 1:1, with a stratification according to positivity to Sars-Cov-2. BLINDING (MASKING): All participants, care providers, investigator and outcomes assessor are blinded. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): We planned to randomize fifty participants in each group, 100 participants total. TRIAL STATUS: The amended protocol version 2.1 was approved by the Ethics Committee "Comité de Protection des Personnes Sud-Méditerranée II on January 8, 2021 and by the Commission Nationale de l'Informatique et des Libertés (CNIL) on November 10, 2020. The study is currently recruiting participants; the recruitment started in November 2020 and the planned recruitment period is three years. TRIAL REGISTRATION: The trial was registered on clinicaltrials.gov on October 30, 2020 and identified by number NCT04609865 . FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.