Metabolic Benefit of Teleconsultation for Diabetes Management During the COVID-19 Pandemic: A French Observational Prospective Study.

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/m2 versus 30 ± 5.8 kg/m2, 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.

Cerebral perfusion using ASL in patients with COVID-19 and neurological manifestations: A retrospective multicenter observational study.

BACKGROUND AND PURPOSE: Cerebral hypoperfusion has been reported in patients with COVID-19 and neurological manifestations in small cohorts. We aimed to systematically assess changes in cerebral perfusion in a cohort of 59 of these patients, with or without abnormalities on morphological MRI sequences. METHODS: Patients with biologically-confirmed COVID-19 and neurological manifestations undergoing a brain MRI with technically adequate arterial spin labeling (ASL) perfusion were included in this retrospective multicenter study. ASL maps were jointly reviewed by two readers blinded to clinical data. They assessed abnormal perfusion in four regions of interest in each brain hemisphere: frontal lobe, parietal lobe, posterior temporal lobe, and temporal pole extended to the amygdalo-hippocampal complex. RESULTS: Fifty-nine patients (44 men (75%), mean age 61.2 years) were included. Most patients had a severe COVID-19, 57 (97%) needed oxygen therapy and 43 (73%) were hospitalized in intensive care unit at the time of MRI. Morphological brain MRI was abnormal in 44 (75%) patients. ASL perfusion was abnormal in 53 (90%) patients, and particularly in all patients with normal morphological MRI. Hypoperfusion occurred in 48 (81%) patients, mostly in temporal poles (52 (44%)) and frontal lobes (40 (34%)). Hyperperfusion occurred in 9 (15%) patients and was closely associated with post-contrast FLAIR leptomeningeal enhancement (100% [66.4%-100%] of hyperperfusion with enhancement versus 28.6% [16.6%-43.2%] without, p = 0.002). Studied clinical parameters (especially sedation) and other morphological MRI anomalies had no significant impact on perfusion anomalies. CONCLUSION: Brain ASL perfusion showed hypoperfusion in more than 80% of patients with severe COVID-19, with or without visible lesion on conventional MRI abnormalities.

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.

Étude d’un algorithme adapté de gestion de la fièvre chez les patients traités par dabrafénib+tramétinib en adjuvant : premiers résultats de la cohorte française de COMBI-APlus

Introduction L’intérêt de dabrafénib tramétinib (dab+tram) en adjuvant chez les patients (pts) ayant un mélanome BRAF V600E/K muté de stade III réséqué a été démontré dans l’étude COMBI-AD. Dans COMBI-AD, les effets indésirables (EI) ont conduit à l’arrêt définitif de dab+tram chez 26 % des pts, principalement en raison de la fièvre (9 %). L’objectif de COMBI-APlus (NCT03551626) est d’évaluer un nouvel algorithme de gestion de la fièvre pour réduire les grades 3/4 et ses conséquences (arrêt du traitement, hospitalisation). Matériel et méthodes COMBI-APlus est un essai ouvert de phase IIIb évaluant un algorithme de gestion de la fièvre chez des pts ayant un mélanome réséqué de stade III BRAF V600E/K-muté traités en adjuvant par dab+tram pendant 12 mois. L’algorithme prévoit l’interruption de dab+tram dès apparition d’une température≥38°C et la reprise à la même dose dès disparition des symptômes depuis 24h. En cas de suspicion de fièvre récurrente et en présence d’un syndrome fébrile (frissons, raideurs, sueurs nocturnes, symptômes grippaux sans fièvre) le traitement peut être interrompu à la discrétion de l’investigateur. Le critère d’évaluation principal est le taux composite de fièvre (grades 3/4, hospitalisation ou arrêt définitif du traitement dus à la fièvre) comparé aux données historiques de COMBI-AD (20 % ;IC95 % : 16,3 %–24,1 %). Les critères secondaires incluent la survie sans rechute (SSR) et l’innocuité. Résultats Cent soixante-seize pts ont été inclus en France sur un total de 552 pts avec un suivi médian de 18,14 mois. COMBI-APlus a atteint son critère principal d’amélioration significative du taux composite de fièvre par rapport au témoin historique COMBI-AD. Il est de 7,4 % (IC95 % : 4,0 %–12,3 %) avec des taux de 4,0 % pour les grades 3/4, de 2,8 % pour les hospitalisations et de 3,4 % pour les arrêts définitifs de traitement dus à la fièvre. Le taux de SSR estimé à 12 mois est de 90,9 % (IC95 % : 85,4 %–94,4 %). Les principaux EI≥20 % sont : fièvre (67,0 %), asthénie (48,9 %), céphalées (40,9 %), diarrhée (34,7 %), augmentation de la créatine phosphokinase sanguine (31,8 %), frissons (31,3 %), nausées (26,7 %), arthralgies (25,6 %), fatigue (22,2 %). L’ensemble des EI a conduit à l’arrêt définitif de dab+tram chez 14,2 % des pts versus 26 % dans COMBI-AD. Discussion Cette analyse suggère que ce nouvel algorithme simplifié de gestion de la fièvre est efficace pour réduire le taux composite de fièvre (grades 3/4, hospitalisation, arrêt de traitement) chez les pts recevant dab+tram en adjuvant. Les premiers résultats d’efficacité semblent correspondre à ceux observés dans COMBI-AD. Cet algorithme peut réduire le besoin d’hospitalisation ou de consultation liées à la fièvre, ce qui est souhaitable dans le contexte actuel de pandémie du COVID-19. Ainsi plus de pts peuvent rester sous traitement et en tirer un bénéfice clinique.

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.

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.

The BAS2IC Score: A Useful Tool to Identify Patients at High Risk of Early Progression to Severe Coronavirus Disease 2019.

We developed a score, with easily accessible data (age, sex, body mass index, dyspnea, inflammatory parameters), to predict the risk of rapid progression to severe coronavirus disease 2019. Using a cutoff of >6 points, the negative predictive value was 87%.

A novel, automated, quantification of abnormal lung parenchyma in patients with COVID-19 infection: Initial description of feasibility and association with clinical outcome.

OBJECTIVE: Ground-glass opacities are the most frequent radiologic features of COVID-19 patients. We aimed to determine the feasibility of automated lung volume measurements, including ground-glass volumes, on the CT of suspected COVID-19 patients. Our goal was to create an automated and quantitative measure of ground-glass opacities from lung CT images that could be used clinically for diagnosis, triage and research. DESIGN: Single centre, retrospective, observational study. MEASUREMENTS: Demographic data, respiratory support treatment (synthetised in the maximal respiratory severity score) and CT-images were collected. Volume of abnormal lung parenchyma was measured with conventional semi-automatic software and with a novel automated algorithm based on voxels X-Ray attenuation. We looked for the relationship between the automated and semi-automated evaluations. The association between the ground-glass opacities volume and the maximal respiratory severity score was assessed. MAIN RESULTS: Thirty-seven patients were included in the main outcome analysis. The mean duration of automated and semi-automated volume measurement process were 15 (2) and 93 (41) min, respectively (p=8.05*10-8). The intraclass correlation coefficient between the semi-automated and automated measurement of ground-glass opacities and restricted normally aerated lung were both superior to 0.99. The association between the automated measured lung volume and the maximal clinical severity score was statistically significant for the restricted normally aerated (p=0.0097, effect-size: -385mL) volumes and for the ratio of ground-glass opacities/restricted normally aerated volumes (p=0.027, effect-size: 3.3). CONCLUSION: The feasibility and preliminary validity of automated impaired lung volume measurements in a high-density COVID-19 cluster was confirmed by our results.

Critical illness-associated cerebral microbleeds for patients with severe COVID-19: etiologic hypotheses.

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 FiO2 (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.

Serologic responses to SARS-CoV-2 infection among hospital staff with mild disease in eastern France.

BACKGROUND: The serologic response of individuals with mild forms of SARS-CoV-2 infection is poorly characterized. METHODS: Hospital staff who had recovered from mild forms of PCR-confirmed SARS-CoV-2 infection were tested for anti-SARS-CoV-2 antibodies using two assays: a rapid immunodiagnostic test (99.4% specificity) and the S-Flow assay (~99% specificity). The neutralizing activity of the sera was tested with a pseudovirus-based assay. FINDINGS: Of 162 hospital staff who participated in the investigation, 160 reported SARS-CoV-2 infection that had not required hospital admission and were included in these analyses. The median time from symptom onset to blood sample collection was 24 days (IQR: 21-28, range 13-39). The rapid immunodiagnostic test detected antibodies in 153 (95.6%) of the samples and the S-Flow assay in 159 (99.4%), failing to detect antibodies in one sample collected 18 days after symptom onset (the rapid test did not detect antibodies in that patient). Neutralizing antibodies (NAbs) were detected in 79%, 92% and 98% of samples collected 13-20, 21-27 and 28-41 days after symptom onset, respectively (P = 0.02). INTERPRETATION: Antibodies against SARS-CoV-2 were detected in virtually all hospital staff sampled from 13 days after the onset of COVID-19 symptoms. This finding supports the use of serologic testing for the diagnosis of individuals who have recovered from SARS-CoV-2 infection. The neutralizing activity of the antibodies increased overtime. Future studies will help assess the persistence of the humoral response and its associated neutralization capacity in recovered patients. FUNDINGS: The funders had no role in study design, data collection, interpretation, or the decision to submit the work for publication.