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1.
Viruses ; 14(5):949, 2022.
Article in English | MDPI | ID: covidwho-1820416

ABSTRACT

Background and Objectives: Cerebral complications related to the COVID-19 were documented by brain MRIs during the acute phase. The purpose of the present study was to describe the evolution of these neuroimaging findings (MRI and FDG-PET/CT) and describe the neurocognitive outcomes of these patients. Methods: During the first wave of the COVID-19 outbreak between March 1 and May 31, 2020, 112 consecutive COVID-19 patients with neurologic manifestations underwent a brain MRI at Strasbourg University hospitals. After recovery, during follow-up, of these 112 patients, 31 (initially hospitalized in intensive care units) underwent additional imaging studies (at least one brain MRI). Results: Twenty-three men (74%) and eight women (26%) with a mean age of 61 years (range: 18–79) were included. Leptomeningeal enhancement, diffuse brain microhemorrhages, acute ischemic strokes, suspicion of cerebral vasculitis, and acute inflammatory demyelinating lesions were described on the initial brain MRIs. During follow-up, the evolution of the leptomeningeal enhancement was discordant, and the cerebral microhemorrhages were stable. We observed normalization of the vessel walls in all patients suspected of cerebral vasculitis. Four patients (13%) demonstrated new complications during follow-up (ischemic strokes, hypoglossal neuritis, marked increase in the white matter FLAIR hyperintensities with presumed vascular origin, and one suspected case of cerebral vasculitis). Concerning the grey matter volumetry, we observed a loss of volume of 3.2% during an average period of approximately five months. During follow-up, the more frequent FDG-PET/CT findings were hypometabolism in temporal and insular regions. Conclusion: A minority of initially severe COVID-19 patients demonstrated new complications on their brain MRIs during follow-up after recovery.

2.
Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology ; 2022.
Article in English | EuropePMC | ID: covidwho-1695327

ABSTRACT

Rationale/Objectives SARS-CoV-2 is the cause of worldwide COVID-19, which severity has been linked to the immune and inflammatory response. Here, we investigate Torquetenovirus (TTV) DNA load - a marker reflecting the intensity of the overall immune response - as well as SARS-CoV-2 RNAemia and IgM/IgG antibodies in COVID-19-positive patients. Methods Two hundred and fifteen COVID-19-positive patients were enrolled, including 87 severe cases and 128 mild-moderate cases. SARS-CoV-2 RNAemia and IgM/IgG antibodies, as well as TTV DNA loads, were measured on longitudinal plasma samples. Results The rate of severe cases was higher in patients with low TTV DNA load in plasma considering a threshold of 700 copies/mL. In severe patients, SARS-CoV-2 RNAemia positivity rates were higher than those in mild-moderate cases at any timepoint. When combined, TTV DNA load and SARS-CoV-2 RNAemia allowed to predict the outcome of COVID-19 infection, with a higher risk (HR=12.4) of ICU admission in patients with low TTV DNA load and positive SARS-CoV-2 RNAemia. Conclusions TTV DNA load and SARS-CoV-2 RNAemia may be effective, non-invasive markers reflecting disease severity and poor outcome that could be conveniently measured in a clinical laboratory setting, as soon as COVID-19 diagnosis is made.

3.
Transfusion Clinique et Biologique ; 28(4):S93-S93, 2021.
Article in French | Academic Search Complete | ID: covidwho-1492695

ABSTRACT

L'émergence de SARS-CoV-2 a entraîné un afflux massif de patients à l'hôpital et particulièrement en réanimation créant de nombreux problèmes. L'un d'entre eux est la transfusion, tant du côté de l'EFS (sécurité, collecte et stocks) que du transfuseur (soins habituels et demande spécifique inconnue liée au COVID-19). Un des risques était la pénurie avec nécessité de planifier des restrictions transfusionnelles. Nous avons analysé en parallèle l'activité transfusionnelle dans un CHU ainsi que la collecte et la délivrance au niveau de l'EFS entre le 24/02 et le 31/05/2020 et les avons comparées aux données de 2019. L'activité globale a baissé de 33 % sur la période (arrêt des soins réglés hors urgence ou soins ne pouvant être différés et admissions de 2291 patients COVID-19) alors que la transfusion n'a été réduite que de 17 %. Un total de 237 patients COVID-19 (10,3 %) ont nécessité une transfusion, dont 45 pour hémorragie. Parallèlement, la baisse des dons a été contenue à 11 % avec une discrète augmentation des stocks. La diminution de l'activité ne se traduit que par une baisse modérée de l'activité transfusionnelle, celle-ci dépendant principalement de la chirurgie urgente, des syndromes hémorragiques et de la prise en charge des patients en aplasie chimio-induite ou ayant des pathologies hématologiques. Le confinement a entraîné une diminution des dons par suppression des collectes mobiles mais avec un impact limité sur une courte période par mobilisation des donneurs réguliers. Il n'a pas été observé d'inadéquation entre demande et suppléance et il n'a donc pas été nécessaire de mettre en place des restrictions. (French) [ABSTRACT FROM AUTHOR] Copyright of Transfusion Clinique et Biologique is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

4.
Sci Transl Med ; 14(628): eabj7521, 2022 Jan 19.
Article in English | MEDLINE | ID: covidwho-1483988

ABSTRACT

The drivers of critical coronavirus disease 2019 (COVID-19) remain unknown. Given major confounding factors such as age and comorbidities, true mediators of this condition have remained elusive. We used a multi-omics analysis combined with artificial intelligence in a young patient cohort where major comorbidities were excluded at the onset. The cohort included 47 "critical" (in the intensive care unit under mechanical ventilation) and 25 "non-critical" (in a non-critical care ward) patients with COVID-19 and 22 healthy individuals. The analyses included whole-genome sequencing, whole-blood RNA sequencing, plasma and blood mononuclear cell proteomics, cytokine profiling, and high-throughput immunophenotyping. An ensemble of machine learning, deep learning, quantum annealing, and structural causal modeling were used. Patients with critical COVID-19 were characterized by exacerbated inflammation, perturbed lymphoid and myeloid compartments, increased coagulation, and viral cell biology. Among differentially expressed genes, we observed up-regulation of the metalloprotease ADAM9. This gene signature was validated in a second independent cohort of 81 critical and 73 recovered patients with COVID-19 and was further confirmed at the transcriptional and protein level and by proteolytic activity. Ex vivo ADAM9 inhibition decreased severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uptake and replication in human lung epithelial cells. In conclusion, within a young, otherwise healthy, cohort of individuals with COVID-19, we provide the landscape of biological perturbations in vivo where a unique gene signature differentiated critical from non-critical patients. We further identified ADAM9 as a driver of disease severity and a candidate therapeutic target.


Subject(s)
COVID-19 , ADAM Proteins , Artificial Intelligence , Humans , Intensive Care Units , Membrane Proteins , Respiration, Artificial , SARS-CoV-2
6.
Transfusion ; 61(8): 2327-2335, 2021 08.
Article in English | MEDLINE | ID: covidwho-1307871

ABSTRACT

BACKGROUND: The outbreak of a SARS-CoV-2 resulted in a massive afflux of patients in hospital and intensive care units with many challenges. Blood transfusion was one of them regarding both blood banks (safety, collection, and stocks) and consumption (usual care and unknown specific demand of COVID-19 patients). The risk of mismatch was sufficient to plan blood transfusion restrictions if stocks became limited. STUDY DESIGN AND METHODS: Analyses of blood transfusion in a tertiary hospital and blood collection in the referring blood bank between February 24 and May 31, 2020. RESULTS: Withdrawal of elective surgery and non-urgent care and admission of 2291 COVID-19 patients reduced global activity by 33% but transfusion by 17% only. Only 237 (10.3) % of COVID-19 patients required blood transfusion, including 45 (2.0%) with acute bleeding. Lockdown and cancellation of mobile collection resulted in an 11% reduction in blood donation compared to 2019. The ratio of reduction in blood transfusion to blood donation remained positive and stocks were slightly enhanced. DISCUSSION: Reduction of admissions due to SARS-CoV-2 pandemic results only in a moderate decrease of blood transfusion. Incompressible blood transfusions concern urgent surgery, acute bleeding (including some patients with COVID-19, especially under high anticoagulation), or are supportive for chemotherapy-induced aplasia or chronic anemia. Lockdown results in a decrease of blood donation by cancellation of mobile donation but with little impact on a short period by mobilization of usual donors. No mismatch between demand and donation was evidenced and no planned restriction to blood transfusion was necessary.


Subject(s)
Blood Banks , Blood Donors , Blood Transfusion , COVID-19/prevention & control , Communicable Disease Control , COVID-19/epidemiology , Humans , Retrospective Studies , SARS-CoV-2/isolation & purification , Tertiary Care Centers
7.
Anaesth Crit Care Pain Med ; 40(4): 100931, 2021 08.
Article in English | MEDLINE | ID: covidwho-1306763

ABSTRACT

AIM: Describing acute respiratory distress syndrome patterns, therapeutics management, and outcomes of ICU COVID-19 patients and indentifying risk factors of 28-day mortality. METHODS: Prospective multicentre, cohort study conducted in 29 French ICUs. Baseline characteristics, comorbidities, adjunctive therapies, ventilatory support at ICU admission and survival data were collected. RESULTS: From March to July 2020, 966 patients were enrolled with a median age of 66 (interquartile range 58-73) years and a median SAPS II of 37 (29-48). During the first 24 h of ICU admission, COVID-19 patients received one of the following respiratory supports: mechanical ventilation for 559 (58%), standard oxygen therapy for 228 (24%) and high-flow nasal cannula (HFNC) for 179 (19%) patients. Overall, 721 (75%) patients were mechanically ventilated during their ICU stay. Prone positioning and neuromuscular blocking agents were used in 494 (51%) and 460 (48%) patients, respectively. Bacterial co-infections and ventilator-associated pneumonia were diagnosed in 79 (3%) and 411 (43%) patients, respectively. The overall 28-day mortality was 18%. Age, pre-existing comorbidities, severity of respiratory failure and the absence of antiviral therapy on admission were identified as independent predictors of 28-day outcome. CONCLUSION: Severity of hypoxaemia on admission, older age (> 70 years), cardiovascular and renal comorbidities were associated with worse outcome in COVID-19 patients. Antiviral treatment on admission was identified as a protective factor for 28-day mortality. Ascertaining the outcomes of critically ill COVID-19 patients is crucial to optimise hospital and ICU resources and provide the appropriate intensity level of care.


Subject(s)
COVID-19 , SARS-CoV-2 , Aged , Cohort Studies , Critical Care , Humans , Intensive Care Units , Middle Aged , Prospective Studies , Respiration, Artificial
8.
J Control Release ; 336: 252-261, 2021 08 10.
Article in English | MEDLINE | ID: covidwho-1281447

ABSTRACT

Current therapeutic treatments improving the impaired transportation of oxygen in acute respiratory distress syndrome (ARDS) have been found to be relevant and beneficial for the therapeutic treatment of COVID-19 patients suffering from severe respiratory complications. Hence, we report the preclinical and the preliminary results of the Phase I/II clinical trial of LEAF-4L6715, a liposomal nanocarrier encapsulating the kosmotropic agent trans-crocetin (TC), which, once injected, enhance the oxygenation of vascular tissue and therefore has the potential to improve the clinical outcomes of ARDS and COVID-19 in severely impacted patients. We demonstrated that the liposomal formulation enabled to increase from 30 min to 48 h the reoxygenation properties of free TCs in vitro in endothelial cells, but also to improve the half-life of TC by 6-fold in healthy mice. Furthermore, we identified 25 mg/kg as the maximum tolerated dose in mice. This determined concentration led to the validation of the therapeutic efficacy of LEAF-4 L6715 in a sepsis mouse model. Finally, we report the preliminary outcomes of an open-label multicenter Phase I/II clinical trial (EudraCT 2020-001393-30; NCT04378920), which was aimed to define the appropriate schedule and dosage of LEAF-4L6715 and to confirm its tolerability profile and preliminary clinical activity in COVID-19 patients treated in intensive care unit.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , Animals , Carotenoids , Endothelial Cells , Humans , Mice , Respiration, Artificial , Respiratory Distress Syndrome/drug therapy , SARS-CoV-2 , Vitamin A/analogs & derivatives
10.
J Clin Med ; 10(6)2021 Mar 23.
Article in English | MEDLINE | ID: covidwho-1154431

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic has spread rapidly worldwide, with more than two million deaths. Evidence indicates the critical role of the vascular endothelium in its pathophysiology but, like potential changes in functional vasodilation, the vascular effect of SARS-CoV-2 at a given distance from the acute infection is largely unknown. We assessed brachial artery flow-mediated dilatation (FMD) in 27 COVID-19 patients needing conventional or intensive care unit hospitalization, three months after SARS-CoV-2 infection diagnosis and in nine age- and sex- matched control subjects. Interestingly, the FMD was lower in COVID-19 patients as compared to controls (8.2 (7.2-8.9) vs. 10.3 (9.1-11.7)); p = 0.002, and half of the hospitalized COVID-19 survivors presented with a reduced FMD < 8% at three months of COVID-19 onset. Impaired FMD was not associated with severe or critical SARS-CoV-2 infection, reflected by ICU hospitalization, total hospitalization duration, or severity of lung damage. In conclusion, reduced FMD is often observed even three months after hospitalization for SARS-CoV-2 infection, but such alteration predominantly appears to not be related to COVID-19 severity. Longer and larger follow-up studies will help to clarify the potential prognosis value of FMD among COVID-19 patients, as well as to further determine the mechanisms involved.

11.
J Infect Dis ; 223(4): 600-609, 2021 02 24.
Article in English | MEDLINE | ID: covidwho-1101851

ABSTRACT

BACKGROUND: Neurological manifestations are common in patients with coronavirus disease 2019 (COVID-19), but little is known about pathophysiological mechanisms. In this single-center study, we examined neurological manifestations in 58 patients, including cerebrospinal fluid (CSF) analysis and neuroimaging findings. METHODS: The study included 58 patients with COVID-19 and neurological manifestations in whom severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse-transcription polymerase chain reaction screening and on CSF analysis were performed. Clinical, laboratory, and brain magnetic resonance (MR) imaging data were retrospectively collected and analyzed. RESULTS: Patients were mostly men (66%), with a median age of 62 years. Encephalopathy was frequent (81%), followed by pyramidal dysfunction (16%), seizures (10%), and headaches (5%). CSF protein and albumin levels were increased in 38% and 23%, respectively. A total of 40% of patients displayed an elevated albumin quotient, suggesting impaired blood-brain barrier integrity. CSF-specific immunoglobulin G oligoclonal band was found in 5 patients (11%), suggesting an intrathecal synthesis of immunoglobulin G, and 26 patients (55%) presented identical oligoclonal bands in serum and CSF. Four patients (7%) had a positive CSF SARS-CoV-2 reverse-transcription polymerase chain reaction. Leptomeningeal enhancement was present on brain MR images in 20 patients (38%). CONCLUSIONS: Brain MR imaging abnormalities, especially leptomeningeal enhancement, and increased inflammatory markers in CSF are frequent in patients with neurological manifestations related to COVID-19, whereas SARS-CoV-2 detection in CSF remained scanty.


Subject(s)
Brain Diseases/cerebrospinal fluid , Brain/diagnostic imaging , COVID-19/complications , Aged , Biomarkers/cerebrospinal fluid , Blood-Brain Barrier/diagnostic imaging , Blood-Brain Barrier/pathology , Brain Diseases/diagnostic imaging , Brain Diseases/virology , COVID-19/cerebrospinal fluid , COVID-19/diagnostic imaging , Female , France , Humans , Inflammation/diagnosis , Magnetic Resonance Imaging , Male , Middle Aged , Retrospective Studies
13.
J Neurol ; 268(8): 2676-2684, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-938566

ABSTRACT

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.


Subject(s)
COVID-19 , Extracorporeal Membrane Oxygenation , Cerebral Hemorrhage/complications , Cerebral Hemorrhage/diagnostic imaging , Cerebral Hemorrhage/epidemiology , Critical Illness , Humans , SARS-CoV-2
14.
Diagn Microbiol Infect Dis ; 98(4): 115181, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-725737

ABSTRACT

Rapid and accurate diagnosis is crucial for successful outbreak containment. During the current coronavirus disease 2019 (COVID-19) public health emergency, the gold standard for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection diagnosis is the detection of viral RNA. Additional diagnostic methods õenabling the detection of current or past SARS-CoV-2 infection would be highly beneficial. We assessed 2 immunochromatographic lateral flow assays (LFA-1, LFA-2) and 2 enzyme-linked immunosorbent assay kits (IgA/IgG ELISA-1, IgM/IgG ELISA-2) using 325 samples: serum samples from polymerase chain reaction-confirmed COVID-19 hospitalized patients (n = 55) and healthcare workers (n = 143) and 127 samples from negative controls. Diagnostic performances were assessed according to days after symptom onset (dso) and the antigenic format used by manufacturers. Clinical sensitivities varied greatly among the assays, showing poor mutual agreement. After 15 dso, ELISA-1 (Euroimmun) and LFA-1 (Biosynex) combining IgM and IgG detection showed the best performances. A thorough selection of serological assays for the detection of ongoing or past infections is advisable.


Subject(s)
Antibodies, Viral/blood , Clinical Laboratory Techniques/methods , Coronavirus Infections/diagnosis , Enzyme-Linked Immunosorbent Assay/methods , Immunoassay/methods , Mass Screening/methods , Pneumonia, Viral/diagnosis , Adult , Aged , Aged, 80 and over , Betacoronavirus/immunology , COVID-19 , COVID-19 Testing , Female , Humans , Immunoglobulin A/blood , Immunoglobulin G/blood , Immunoglobulin M/blood , Male , Middle Aged , Pandemics , Polymerase Chain Reaction , RNA, Viral/analysis , SARS-CoV-2 , Sensitivity and Specificity , Young Adult
15.
Open Forum Infect Dis ; 7(7): ofaa249, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-651101

ABSTRACT

A 56-year-old man presented a particularly severe and multisystemic case of coronavirus disease 2019 (COVID-19). In addition to the common lung and quite common pulmonary embolism and kidney injuries, he presented ocular and intestinal injuries that, to our knowledge, have not been described in COVID-19 patients. Although it is difficult to make pathophysiological hypotheses about a single case, the multiplicity of injured organs argues for a systemic response to pulmonary infection. A better understanding of physiopathology should feed the discussion about therapeutic options in this type of multifocal damage related to severe acute respiratory syndrome coronavirus 2.

16.
Radiology ; 297(2): E242-E251, 2020 11.
Article in English | MEDLINE | ID: covidwho-599380

ABSTRACT

Background Brain MRI parenchymal signal abnormalities have been associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Purpose To describe the neuroimaging findings (excluding ischemic infarcts) in patients with severe coronavirus disease 2019 (COVID-19) infection. Materials and Methods This was a retrospective study of patients evaluated from March 23, 2020, to April 27, 2020, at 16 hospitals. Inclusion criteria were (a) positive nasopharyngeal or lower respiratory tract reverse transcriptase polymerase chain reaction assays, (b) severe COVID-19 infection defined as a requirement for hospitalization and oxygen therapy, (c) neurologic manifestations, and (d) abnormal brain MRI findings. Exclusion criteria were patients with missing or noncontributory data regarding brain MRI or brain MRI showing ischemic infarcts, cerebral venous thrombosis, or chronic lesions unrelated to the current event. Categorical data were compared using the Fisher exact test. Quantitative data were compared using the Student t test or Wilcoxon test. P < .05 represented a significant difference. Results Thirty men (81%) and seven women (19%) met the inclusion criteria, with a mean age of 61 years ± 12 (standard deviation) (age range, 8-78 years). The most common neurologic manifestations were alteration of consciousness (27 of 37, 73%), abnormal wakefulness when sedation was stopped (15 of 37, 41%), confusion (12 of 37, 32%), and agitation (seven of 37, 19%). The most frequent MRI findings were signal abnormalities located in the medial temporal lobe in 16 of 37 patients (43%; 95% confidence interval [CI]: 27%, 59%), nonconfluent multifocal white matter hyperintense lesions seen with fluid-attenuated inversion recovery and diffusion-weighted sequences with variable enhancement, with associated hemorrhagic lesions in 11 of 37 patients (30%; 95% CI: 15%, 45%), and extensive and isolated white matter microhemorrhages in nine of 37 patients (24%; 95% CI: 10%, 38%). A majority of patients (20 of 37, 54%) had intracerebral hemorrhagic lesions with a more severe clinical presentation and a higher admission rate in intensive care units (20 of 20 patients [100%] vs 12 of 17 patients without hemorrhage [71%], P = .01) and development of the acute respiratory distress syndrome (20 of 20 patients [100%] vs 11 of 17 patients [65%], P = .005). Only one patient had SARS-CoV-2 RNA in the cerebrospinal fluid. Conclusion Patients with severe coronavirus disease 2019 and without ischemic infarcts had a wide range of neurologic manifestations that were associated with abnormal brain MRI scans. Eight distinctive neuroradiologic patterns were described. © RSNA, 2020.


Subject(s)
Betacoronavirus , Brain/diagnostic imaging , Brain/pathology , Coronavirus Infections/diagnostic imaging , Coronavirus Infections/pathology , Magnetic Resonance Imaging/methods , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/pathology , Adolescent , Adult , Aged , COVID-19 , Child , Cohort Studies , Female , Humans , Male , Middle Aged , Pandemics , Retrospective Studies , SARS-CoV-2 , Young Adult
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