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.

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.

Bedside Renal Doppler Ultrasonography and Acute Kidney Injury after TAVR.

Acute kidney injury (AKI) following transcatheter aortic valve replacement (TAVR) is associated with a dismal prognosis. Elevated renal resistive index (RRI), through renal Doppler ultrasound (RDU) evaluation, has been associated with AKI development and increased systemic arterial stiffness. Our pilot study aimed to investigate the performance of Doppler based RRI to predict AKI and outcomes in TAVR patients. From May 2018 to May 2019, 100 patients with severe aortic stenosis were prospectively enrolled for TAVR and concomitant RDU evaluation at our institution (Nouvel Hôpital Civil, Strasbourg University, France). AKI by serum Creatinine (sCr-AKI) was defined according to the VARC-2 definition and AKI by serum Cystatin C (sCyC-AKI) was defined as an sCyC increase of greater than 15% with baseline value. Concomitant RRI measurements as well as renal and systemic hemodynamic parameters were recorded before, one day, and three days after TAVR. It was found that 10% of patients presented with AKIsCr and AKIsCyC. The whole cohort showed higher baseline RRI values (0.76 ± 0.7) compared to normal known and accepted values. AKIsCyC had significant higher post-procedural RRI one day (Day 1) after TAVR (0.83 ± 0.1 vs. 0.77 ± 0.6, CI 95%, p = 0.005). AUC for AKIsCyC was 0.766 and a RRI cut-off value of ≥ 0.795 had the most optimal sensitivity/specificity (80/62%) combination. By univariate Cox analysis, Mehran Risk Score, higher baseline right atrial pressure at baseline > 0.8 RRI values one day after TAVR (HR 6.5 (95% CI 1.3-32.9; p = 0.021) but not RRI at baseline were significant predictors of AKIsCyC. Importantly, no significant impact of baseline biological parameters, renal or systemic parameters could be demonstrated. Doppler-based RRI can be helpful for the non-invasive assessment of AKI development after TAVR.

Functional evidence for a role of GABA receptors in modulating nerve activities of circular smooth muscle from rat colon in vitro.

In the enteric nervous system, activation of neuronal GABA(A)- and GABA(B)-receptors has been shown to modulate neuronal activity. The consequences of this modulation depend on the location in the gastrointestinal tract or the animal species studied. These data illustrate the complexity of GABA-induced effects. Furthermore, the GABA(C)-receptor has been identified in a neuroendocrine cell line suggesting a modulating role of this third type of GABA receptor in intestinal functions. Therefore, the modulating role of GABA-receptor agonists was determined in circular preparations of rat distal colon during electrical nerve stimulation (NS) in vitro. Mechanical response to NS was characterized by a relaxation followed at the end of the stimulation by an off-contraction. In normal Krebs solution (basal conditions), muscimol and baclofen, respectively GABA(A)- and GABA(B)-agonists, induced a significant increase of the electrically induced off-contraction. The GABA(C) agonist, CACA, showed no significant effect on the response to NS. Excitatory effects of muscimol on the off-contraction were abolished in the presence of atropine. Furthermore, in the presence of atropine, muscimol increased the amplitude of the electrically induced relaxation; similarly the baclofen-induced increase of off-contraction amplitude was significantly lower than that observed in control conditions. Baclofen and muscimol effects on the off-contraction were abolished in the presence of hexamethonium or guanethidine. Furthermore, muscimol and baclofen did not induce any significant change on the response to NS in the presence of L-NAME and apamin together. Thus, it seems that in rat distal colon, GABA regulates significantly both excitatory (through GABA(A)- and GABA(B)-receptors) and inhibitory (through GABA(A)-receptors) neuronal activities. We also gave evidence for a possible interplay between GABAergic intrinsic neurons and adrenergic nerve terminals. Finally, it is shown for the first time the presence of the GABA vesicular transporter (VIAAT) around myenteric ganglia of rat colon.