Impact of lockdown on cardiovascular disease hospitalizations in a Zero-COVID-19 country.

OBJECTIVES: There are concerns about the potential effect of social distancing used to control COVID-19 on the incidence of cardiovascular diseases (CVD). STUDY DESIGN: Retrospective cohort study. METHODS: We examined the association between lockdown and CVD incidence in a Zero-COVID country, New Caledonia. Inclusion criteria were defined by a positive troponin sample during hospitalization. The study period lasted for 2 months, starting March 20, 2020 (strict lockdown: first month; loose lockdown: second month) compared with the same period of the three previous years to calculate incidence ratio (IR). Demographic characteristics and main CVD diagnoses were collected. The primary endpoint was the change in incidence of hospital admission with CVD during lockdown compared with the historical counterpart. The secondary endpoint included influence of strict lockdown, change in incidence of the primary endpoint by disease, and outcome incidences (intubation or death) analyzed with inverse probability weighting method. RESULTS: A total of 1215 patients were included: 264 in 2020 vs 317 (average of the historical period). CVD hospitalizations were reduced during strict lockdown (IR 0.71 [0.58-0.88]), but not during loose lockdown (IR 0.94 [0.78-1.12]). The incidence of acute coronary syndromes was similar in both periods. The incidence of acute decompensated heart failure was reduced during strict lockdown (IR 0.42 [0.24-0.73]), followed by a rebound (IR 1.42 [1-1.98]). There was no association between lockdown and short-term outcomes. CONCLUSIONS: Our study showed that lockdown was associated with a striking reduction in CVD hospitalizations, independently from viral spread, and a rebound of acute decompensated heart failure hospitalizations during looser lockdown.

Risk factors associated with COVID-19-associated pulmonary aspergillosis in ICU patients: a French multicentric retrospective cohort

OBJECTIVES: The main objective of this study was to determine the incidence of invasive pulmonary aspergillosis (IPA) in patients with coronavirus disease 2019 (COVID-19) admitted to the intensive care unit (ICU), and to describe the patient characteristics associated with IPA occurrence and to evaluate its impact on prognosis. METHODS: We conducted a retrospective cohort study including all successive COVID-19 patients, hospitalized in four ICUs, with secondary deterioration and one or more respiratory samples sent to the mycology department. We used a strengthened IPA testing strategy including seven mycological criteria. Patients were classified as probable IPA according to the European Organization for Research and Treatment of Cancer (EORTC)/Mycoses Study Group Education and Research Consortium (MSGERC) classification if immunocompromised, and according to the recent COVID-19-associated IPA classification otherwise. RESULTS: Probable IPA was diagnosed in 21 out of the 366 COVID-19 patients (5.7%) admitted to the ICU and in the 108 patients (19.4%) who underwent respiratory sampling for deterioration. No significant differences were observed between patients with and without IPA regarding age, gender, medical history and severity on admission and during hospitalization. Treatment with azithromycin for >=3 days was associated with the diagnosis of probable IPA (odds ratio 3.1, 95% confidence interval 1.1-8.5, p = 0.02). A trend was observed with high-dose dexamethasone and the occurrence of IPA. Overall mortality was higher in the IPA patients (15/21, 71.4% versus 32/87, 36.8%, p < 0.01). CONCLUSION: IPA is a relatively frequent complication in severe COVID-19 patients and is responsible for increased mortality. Azithromycin, known to have immunomodulatory properties, may contribute to increase COVID-19 patient's susceptibility to IPA.

Imbalance between procoagulant factors and natural coagulation inhibitors contributes to hypercoagulability in the critically ill COVID-19 patient: clinical implications.

OBJECTIVE: Coronavirus Disease-2019 (COVID-19) predisposes patients to thrombosis which underlying mechanisms are still incompletely understood. We sought to investigate the balance between procoagulant factors and natural coagulation inhibitors in the critically ill COVID-19 patient and to evaluate the usefulness of hemostasis parameters to identify patients at risk of venous thromboembolic event (VTE). PATIENTS AND METHODS: We conducted an observational study recording VTEs defined as deep vein thrombosis or pulmonary embolism using lower limb ultrasound (92% of the patients), computed tomography pulmonary angiography (6%) and both tests (2%). We developed a comprehensive analysis of hemostasis. RESULTS: Ninety-two consecutive mechanically ventilated COVID-19 patients (age, 62 years [53-69] (median [25th-75th percentiles]); M/F sex ratio, 2.5; body-mass index, 28 kg/m2 [25-32]; past hypertension (52%) and diabetes mellitus (30%)) admitted to the Intensive Care Unit (ICU) from 03/11/2020 to 5/05/2020, were included. When tested, patients were receiving prophylactic (74%) or therapeutic (26%) anticoagulation. Forty patients (43%) were diagnosed with VTE. Patients displayed inflammatory and prothrombotic profile including markedly elevated plasma fibrinogen (7.7 g/L [6.1-8.6]), D-dimer (3,360 ng/mL [1668-7575]), factor V (166 IU/dL [136-195]) and factor VIII activities (294 IU/dL [223-362]). We evidenced significant discrepant protein C anticoagulant and chromogenic activities, combined with slightly decreased protein S activity. Plasma D-dimer >3,300 ng/mL predicted VTE presence with 78% (95%-confidence interval (95% CI), 62-89) sensitivity, 69% (95% CI, 55-81) specificity, 66% (95% CI, 51-79) positive predictive value and 80% (95% CI, 65-90) negative predictive value [area under the ROC curve, 0.779 (95%CI, 0.681-0.859), p=0.0001]. CONCLUSIONS: Mechanically ventilated COVID-19 patients present with an imbalance between markedly increased factor V/VIII activity and overwhelmed protein C/S pathway. Plasma D-dimer may be a useful biomarker at the bedside for suspicion of VTE.

Unusual arterial thrombotic events in Covid-19 patients.

INTRODUCTION: COVID-19 infection is commonly complicated with pro-thrombotic state and endothelial dysfunction. While several studies reported a high incidence of venous thromboembolic events. The occurrence of arterial thromboses are yet rarely described and could be underestimated. OBJECTIVES: To describe the clinical and biological characteristics of COVID-19 patients presenting with an associated arterial thromboembolic event. MATERIAL AND METHODS: We performed a retrospective multicentric study in 3 centers between France and Italy. All patients with a confirmed SARS-CoV-2 infection and arterial thromboembolic events were included in the analysis. RESULTS: From March 8th to April 25th 2020, we identified 20 patients (24 events) with arterial thromboembolic events over 209 admitted patients (9.6%) with severe COVID-19 infection. Arterial thrombotic events included acute coronary occlusions (n = 9), stroke (n = 6), limb ischemia (n = 3), splenic infarcts (n = 3), aortic thrombosis (n = 2) and occlusive mesenteric ischemia (n = 1). At the time of the event, 10/20 (50%) of patients received thromboprohylaxis, 2/20 (10%) were receiving treatment dose anticoagulation and 5/20 (25%) were receiving antiplatelet therapy. CONCLUSION: Our observations suggest that serious arterial thrombotic events might occur in Covid-19 patients. However, the exact incidence of such events and the best way to prevent them yet remains to be investigated.

Infections fongiques invasives chez le patient admis en réanimation avec le COVID-19 : une cohorte rétrospective

Introduction Les infections fongiques invasives (IFIs) surviennent habituellement chez le sujet immunodéprimé. Des formes d’aspergillose pulmonaires invasives (API) ont été décrites chez le sujet atteint de grippe sévère et attribué à l’association de dommages de l’épithélium respiratoire, d’anomalie de la clairance muco-ciliaire et d’une paralysie immunitaire transitoire. Les formes sévères de COVID-19 combinent également ces facteurs physiopathologiques clés. Les critères diagnostiques des IFIs chez le patient en réanimation et particulièrement dans les cas de COVID-19 ne sont pas complètement validés et leur interprétation peut mésestimer l’incidence de ces infections/colonisations. L’objectif est d’évaluer l’incidence des IFIs chez les patients hospitalisés en réanimation pour COVID-19 et de discuter l’utilisation des différents marqueurs et critères mycologiques disponibles. Matériels et méthodes Cent trois patients hospitalisés dans 4 réanimations du 15 mars au 30 avril 2020 pour détresse respiratoire avec une RT-PCR SARS-CoV-2 positive et pour qui≥1 prélèvement respiratoire a été reçu au laboratoire de mycologie ont été inclus. Sur chaque prélèvement : – une culture ;– une PCR Aspergillus ;– une PCR Pneumocystis ;– le dosage du galactomannane (GM) (LBA uniquement) était réalisé. Les marqueurs sériques ß-D-glucanes (BDG), GM, ADN aspergillaire ont été testés en parallèle. Les patients ont été classés en IFI selon la classification EORTC si des facteurs d’hôte étaient présents et selon la récente classification proposée des aspergilloses invasives associées au COVID-19 (AIAC). Résultats Un total de 27 patients présentait des critères mycologiques d’aspergillose concordant avec une API probable (n=22) selon les critères AIAC (n=20/22) et EORTC (n=2/22), une colonisation aspergillaire (n=2) ou uniquement des BDG isolés (n=3). Parmi les API probables, la culture était positive dans 88,1 % (18/22) des cas. La PCR aspergillaire et le GM (≥ 1) sur le prélèvement respiratoire était positifs dans 50,0 % (11/22) (Ct moyen=29,5) et 21,4 % (3/14) respectivement. La PCR aspergillaire, BDG (≥80pg/mL) et GM (≥ 0,5) sérique étaient positifs dans 11,8 % (3/19), 52,6 % (10/19) et 15,8 % (3/19) respectivement. La mortalité était plus important dans le groupe API probable (68,1 % vs 34,5 %, p<0,01) et s’élève à 90,0 % dans le groupe avec un BDG≥80pg/mL. La PCR Pneumocystis dans les prélèvements respiratoires était positive chez 9 patients avec des Ct moyen de 32,8 (±2,6) témoin d’une charge fongique faible-intermédiaire. Conclusion Nous retrouvons une prévalence importante de patients COVID-19 sévère présentant une co-infection aspergillaire (21,4 %), un portage de Pneumocystis (8,7 %) ou les deux (3,8 %). La performance des marqueurs est variable et peu étudiée dans cette population et nécessite plus d’investigations. Le BDG pourraient être utiles dans la différenciation infection versus colonisation. L’analyse détaillée des données cliniques est en cours afin d’évaluer les facteurs de risque de développer une AIAC chez les patients COVID-19.