Background There have been reports of procoagulant activity in patients with COVID‐19. Whether there is an association between pulmonary embolism (PE) and COVID‐19 in the emergency department (ED) is unknown. The aim of this study was to assess whether COVID‐19 is associated with PE in ED patients who underwent a computed tomographic pulmonary angiogram (CTPA). Methods A retrospective study in 26 EDs from six countries. ED patients in whom a CTPA was performed for suspected PE during a 2‐month period covering the pandemic peak. The primary endpoint was the occurrence of a PE on CTPA. COVID‐19 was diagnosed in the ED either on CT or reverse transcriptase–polymerase chain reaction. A multivariable binary logistic regression was built to adjust with other variables known to be associated with PE. A sensitivity analysis was performed in patients included during the pandemic period. Results A total of 3,358 patients were included, of whom 105 were excluded because COVID‐19 status was unknown, leaving 3,253 for analysis. Among them, 974 (30%) were diagnosed with COVID‐19. Mean (±SD) age was 61 (±19) years and 52% were women. A PE was diagnosed on CTPA in 500 patients (15%). The risk of PE was similar between COVID‐19 patients and others (15% in both groups). In the multivariable binary logistic regression model, COVID‐19 was not associated with higher risk of PE (adjusted odds ratio = 0.98, 95% confidence interval = 0.76 to 1.26). There was no association when limited to patients in the pandemic period. Conclusion In ED patients who underwent CTPA for suspected PE, COVID‐19 was not associated with an increased probability of PE diagnosis. These results were also valid when limited to the pandemic period. However, these results may not apply to patients with suspected COVID‐19 in general.

Background We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10−8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10−5). Conclusions Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.

We thank « John Doe » et al. for their interest and comments on our paper “Association between Pulmonary Embolism and COVID‐19 in ED patients: the PEPCOV international retrospective study”. The authors raised the important issue of a possible bias, because we only analyzed patients that were tested for pulmonary embolism (PE) with computed tomography pulmonary angiogram (CTPA). We acknowledge that this is a limitation, and accordingly highlighted in our manuscript that whether these results apply to the general population is unknown.

Depuis décembre 2019 le monde a dû faire face à une nouvelle maladie nommée : Covid-19. Sa dissémination rapide a imposé à l’Organisation mondiale de la santé de déclarer le statut de pandémie mondiale. La réponse des services d’urgence français à cette catastrophe sanitaire était cruciale. Elle a dû intégrer la notion d’urgence inhérente à la multiplication des nouveaux cas, mais également la nécessité d’une réponse organisée et d’une modulation continuelle de celle-ci sur une période jusqu’alors inconnue. Nous présentons dans cet article un schéma d’organisation et un retour d’expérience, d’un service d’urgence de centre hospitalier universitaire (CHU), établissement de santé de référence (ESR) pour le risque épidémique et biologique pour faire face à l’épidémie. Nous exposons les grandes lignes d’une réorganisation structurelle de notre service, la modification du circuit patient en amont de la filière des urgences et en aval, mais également la modification de nos pratiques de soins. Cette réorganisation a dû prendre en compte la notion de contagiosité avec la nécessité d’une séparation précoce en deux filières de soins, effectuée grâce à un processus de prétriage et de triage en amont de la filière. L’un des points clés de cette organisation a été l’évolutivité des définitions des cas suspects au cours du temps et au gré de l’évolution de la connaissance de ce virus et de sa dissémination. Cela a nécessité une adaptabilité de notre filière et une réévaluation quasi quotidienne de cette organisation associée à une information, une formation et un entraînement du personnel de cette structure.

Introduction Seizures are one of the most common neurological reasons for emergency department (ED) visits. The benefit of ED‐initiated, short‐course outpatient benzodiazepine (BZD) treatment to prevent early recurrent seizure is unknown. This study assesses the risk of early seizure recurrence in patients who were or were not started with outpatient BZD in the ED. Methods This was a multicenter retrospective study conducted in eight French EDs between January 1 and December 31, 2019. All patients admitted for seizure were retrospectively screened and those discharged home from the ED were included. Patients with a history of chronic alcohol intoxication or chronic BZD therapy were excluded. Baseline characteristics, type of seizure, and 30‐day outcome were retrospectively collected from the electronic health records. The primary endpoint was a return visit for seizure recurrence within 30 days. Independent factors associated with a seizure recurrence were identified using a multivariable binary logistic regression. Results A total of 2,218 patients were included and 1,820 were analyzed. The median age was 39 years and 60% were men. Among them 82% of patients had a generalized tonic–clonic seizure and 47% of seizures were idiopathic. BZD treatment was started in 773 (42%) patients. A total of 154 (8%) patients had an early recurrence at 30 days: 68 (9%) in patients who were treated with BZD versus 86 (8%) in patients who were not (odds ratio [OR] = 1.07, 95% confidence interval [CI] = 0.71 to 1.43). In multivariable analysis, two factors were independently associated with the primary endpoint: chronic epileptic treatment (adjusted OR = 2.58, 95% CI = 1.55 to 4.37) and having had a focal seizure (adjusted OR = 2.16, 95% CI = 1.56 to 4.37). Conclusion BZD therapy was started in 42% of patients who were discharged home after ED visit for a seizure. This treatment was not an independent factor associated with the risk of return visit for seizure recurrence at 30 days.

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