Purpose: Little evidence of increased thrombotic risk is available in COVID-19 patients. Our purpose was to assess thrombotic risk in severe forms of SARS-CoV-2 infection. Methods:All patients referred to 4 intensive care units (ICUs) from two centers of a French tertiary hospital for acute respiratory distress syndrome (ARDS) due to COVID-19 between March 3rd and 31st 2020 were included. Medical history, symptoms, biological data and imaging were prospectively collected. Propensity score matching was performed to analyze the occurrence of thromboembolic events between non-COVID-19 ARDS and COVID-19 ARDS patients.Results: 150 COVID-19 patients were included (122 men, median age 63 [53; 71] years, SAPSII 49 [37; 64] points). Sixty-four clinically relevant thrombotic complications were diagnosed in 150 patients, mainly pulmonary embolisms (16.7%). 28/29 patients (96.6%) receiving continuous renal replacement therapy experienced circuit clotting. Three thrombotic occlusions (in 2 patients) of centrifugal pump occurred in 12 patients (8%) supported by ECMO. Most patients (> 95%) had elevated D-dimer and fibrinogen. No patient developed disseminated intravascular coagulation. Von Willebrand (vWF) activity, vWF antigen and FVIII were considerably increased, and 50/57 tested patients (87.7%) had positive lupus anticoagulant. Comparison with non-COVID-19 ARDS patients (n = 145) confirmed that COVID-19 ARDS patients (n = 77) developed significantly more thrombotic complications, mainly pulmonary embolisms (11.7 vs. 2.1%, p < 0.008). Coagulation parameters significantly differed between the two groups. Conclusion:Despite anticoagulation, a high number of patients with ARDS secondary to COVID-19 developed life-threatening thrombotic complications. Higher anticoagulation targets than in usual critically ill patients should therefore probably be suggested.

To the Editor: We report the neurologic features in an observational series of 58 of 64 consecutive patients admitted to the hospital because of acute respiratory distress syndrome (ARDS) due to Covid-19. The patients received similar evaluations by intensivists in two intensive care units (ICUs) in Strasbourg, France, between March 3 and April 3, 2020.Six patients were excluded because of paralytic neuromuscular blockade when neurologic data were collected or because they had died without a neurologic examination having been performed. In all 58 patients, reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assays of nasopharyngeal samples were positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The median age of the patients was 63 years, and the median Simplified Acute Physiology Score II at the time of neurologic examination was 52 (interquartile range, 37 to 65, on a scale ranging from 0 to 163, with higher scores indicating greater severity of illness). Seven patients had had previous neurologic disorders, including transient ischemic attack, partial epilepsy, and mild cognitive impairment.The neurologic findings were recorded in 8 of the 58 patients (14%) on admission to the ICU (before treatment) and in 39 patients (67%) when sedation and a neuromuscular blocker were withheld. Agitation was present in 40 patients (69%) when neuromuscular blockade was discontinued (Table 1). A total of 26 of 40 patients were noted to have confusion according to the Confusion Assessment Method for the ICU; those patients could be evaluated when they were responsive (i.e., they had a score of −1 to 1 on the Richmond Agitation and Sedation Scale, on a scale of −5 [unresponsive] to +4 [combative]). Diffuse corticospinal tract signs with enhanced tendon reflexes, ankle clonus, and bilateral extensor plantar reflexes were present in 39 patients (67%). Of the patients who had been discharged at the time of this writing, 15 of 45 (33%) had had a dysexecutive syndrome consisting of inattention, disorientation, or poorly organized movements in response to command.

Background Neurotropism of SARS-CoV-2 and its neurological manifestations have now been confirmed. We aimed at describing delirium and neurological symptoms of COVID-19 in ICU patients. Methods We conducted a bicentric cohort study in two French ICUs of Strasbourg University Hospital. All the 150 patients referred for acute respiratory distress syndrome due to SARS-CoV-2 between March 3 and May 5, 2020, were included at their admission. Ten patients (6.7%) were excluded because they remained under neuromuscular blockers during their entire ICU stay. Neurological examination, including CAM-ICU, and cerebrospinal fluid analysis, electroencephalography, and magnetic resonance imaging (MRI) were performed in some of the patients with delirium and/or abnormal neurological examination. The primary endpoint was to describe the incidence of delirium and/or abnormal neurological examination. The secondary endpoints were to describe the characteristics of delirium, to compare the duration of invasive mechanical ventilation and ICU length of stay in patients with and without delirium and/or abnormal neurological symptoms. Results The 140 patients were aged in median of 62 [IQR 52; 70] years old, with a median SAPSII of 49 [IQR 37; 64] points. Neurological examination was normal in 22 patients (15.7%). One hundred eighteen patients (84.3%) developed a delirium with a combination of acute attention, awareness, and cognition disturbances. Eighty-eight patients (69.3%) presented an unexpected state of agitation despite high infusion rates of sedative treatments and neuroleptics, and 89 (63.6%) patients had corticospinal tract signs. Brain MRI performed in 28 patients demonstrated enhancement of subarachnoid spaces in 17/28 patients (60.7%), intraparenchymal, predominantly white matter abnormalities in 8 patients, and perfusion abnormalities in 17/26 patients (65.4%). The 42 electroencephalograms mostly revealed unspecific abnormalities or diffuse, especially bifrontal, slow activity. Cerebrospinal fluid examination revealed inflammatory disturbances in 18/28 patients, including oligoclonal bands with mirror pattern and elevated IL-6. The CSF RT-PCR SARS-CoV-2 was positive in one patient. The delirium/neurological symptoms in COVID-19 patients were responsible for longer mechanical ventilation compared to the patients without delirium/neurological symptoms. Delirium/neurological symptoms could be secondary to systemic inflammatory reaction to SARS-CoV-2. Conclusions and relevance Delirium/neurological symptoms in COVID-19 patients are a major issue in ICUs, especially in the context of insufficient human and material resources. Trial registration NA.

Background Ilio-psoas hematoma is a potentially lethal condition that can arise during hospital stay. However, neither the incidence nor the prognosis of patients whose stay in intensive care units (ICU) is complicated by a iatrogenic ilio-psoas hematoma is known. Methods A bicentric retrospective study was conducted to compile the patients who developed an ilio-psoas hematoma while they were hospitalized in ICU between January 2009 and December 2016. Their biometric characteristics, pre-existing conditions, the circumstances in which the hematoma was diagnosed, the treatments they received and their prognosis were recorded. Results Forty patients were diagnosed with an ilio-psoas hematoma during their ICU stay. The incidence of this complication was 3.8 cases for 1000 admissions, taking into account only patients who stayed more than three days in ICU. The median age of patients was 74 years old and the median time between admission and the diagnosis of ilio-psoas hematoma was 12.6 days. A large proportion of them was obese (42.5%) and/or under dialysis (50%) prior to developing their hematoma. Ninety-five percent of the patients had heparin at prophylactic or therapeutic doses. Only 10% of them were above the therapeutic range of anticoagulation. The ICU mortality rate was of 50% following this complication (versus a general mortality rate of 22% for the patients without IPH over the same period of time). Patients with IPH that were complicated by disseminated intravascular coagulopathy had a significantly higher mortality rate than those with IPH and no disseminated intravascular coagulopathy (OR 6.91, 95% CI [1.28; 58.8], p = 0.04). Conclusion Age, anticoagulation, a high body mass index and dialysis seem to be risk factors of developing an ilio-psoas hematoma in ICU. Iatrogenic ilio-psoas hematomas complicated by disseminated intravascular coagulopathies are more at risk of leading to death. It is noteworthy that activated partial thromboplastin time above the therapeutic range was not a good predictor of developing a hematoma for patients who received unfractioned heparin therapy.

Background: COVID-19 acute respiratory distress syndrome (ARDS) shares the common histological hallmarks with other forms of ARDS. However, the chronology of the histological lesions has not been well established. Objective: To describe the chronological histopathological alterations in the lungs of patients with COVID-19 related ARDS. Design: A prospective cohort study was carried out. Setting: Intensive Care Unit of a tertiary hospital. Patients: The first 22 consecutive COVID-19 deaths. Measurements: Lung biopsies and histopathological analyses were performed in deceased patients with COVID-19 related ARDS. Clinical data and patient course were evaluated. Results: The median patient age was 66 [63 - 74] years; 73% were males. The median duration of mechanical ventilation was 17 [8 - 24] days. COVID-19 induced pulmonary injury was characterized by an exudative phase in the first week of the disease, followed by a proliferative/organizing phase in the second and third weeks, and finally an end-stage fibrosis phase after the third week. Viral RNA and proteins were detected in pneumocytes and macrophages in a very early stage of the disease, and were no longer detected after the second week. Limitation: Limited sample size. Conclusions: The chronological evolution of COVID-19 lung histopathological lesions seems to be similar to that seen in other forms of ARDS. In particular, lung lesions consistent with potentially corticosteroid-sensitive lesions are seen.