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1.
Exp Physiol ; 2021 May 31.
Article in English | MEDLINE | ID: covidwho-1807292

ABSTRACT

NEW FINDINGS: What is the topic of this review? Lactate is considered an important substrate for mitochondria in the muscles, heart and brain during exercise and is the main gluconeogenetic precursor in the liver and kidneys. In this light, we review the (patho)physiology of lactate metabolism in sepsis and coronavirus disease 2019 (COVID-19). What advances does it highlight? Elevated blood lactate is strongly associated with mortality in septic patients. Lactate seems unrelated to tissue hypoxia but is likely to reflect mitochondrial dysfunction and high adrenergic stimulation. Patients with severe COVID-19 exhibit near-normal blood lactate, indicating preserved mitochondrial function, despite a systemic hyperinflammatory state similar to sepsis. ABSTRACT: In critically ill patients, elevated plasma lactate is often interpreted as a sign of organ hypoperfusion and/or tissue hypoxia. This view on lactate is likely to have been influenced by the pioneering exercise physiologists around 1920. August Krogh identified an oxygen deficit at the onset of exercise that was later related to an oxygen 'debt' and lactate accumulation by A. V. Hill. Lactate is considered to be the main gluconeogenetic precursor in the liver and kidneys during submaximal exercise, but hepatic elimination is attenuated by splanchnic vasoconstriction during high-intensity exercise, causing an exponential increase in blood lactate. With the development of stable isotope tracers, lactate has become established as an important energy source for muscle, brain and heart tissue, where it is used for mitochondrial respiration. Plasma lactate > 4 mM is strongly associated with mortality in septic shock, with no direct link between lactate release and tissue hypoxia. Herein, we provide evidence for mitochondrial dysfunction and adrenergic stimulation as explanations for the sepsis-induced hyperlactataemia. Despite profound hypoxaemia and intense work of breathing, patients with severe coronavirus disease 2019 (COVID-19) rarely exhibit hyperlactataemia (> 2.5 mM), while presenting a systemic hyperinflammatory state much like sepsis. However, lactate dehydrogenase, which controls the formation of lactate, is markedly elevated in plasma and strongly associated with mortality in severe COVID-19. We briefly review the potential mechanisms of the lactate dehydrogenase elevation in COVID-19 and its relationship to lactate metabolism based on mechanisms established in contracting skeletal muscle and the acute respiratory distress syndrome.

2.
Crit Care Explor ; 2(10): e0266, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-1795045

ABSTRACT

OBJECTIVES: There is accumulating evidence of a distinct coagulopathy in severe acute respiratory syndrome coronavirus 2 infection which is associated with poor prognosis in coronavirus disease 2019. Coagulation abnormalities in blood samples resemble systemic coagulopathies in other severe infections but demonstrate specific features such as a very high d-dimer. These clinical observations are consistent with histopathologic findings of locally disturbed pulmonary microvascular thrombosis and angiopathy in end-stage coronavirus disease 2019. However, exact underlying processes and the sequence of events are not fully understood. DATA SOURCES: CT perfusion may provide insight in the dynamic aspect of the vascularity in pulmonary lesions in coronavirus disease 2019 infection as, in contrast to dual energy CT, a multiphase perfusion pattern is displayed. STUDY SELECTION: In six patients with coronavirus disease 2019 pneumonia, findings on additional CT perfusion series were correlated with known histopathologic vascular patterns upon pulmonary autopsy of patients who had died of coronavirus disease 2019. DATA EXTRACTION: In this case series, we were able to show perfusion changes on CT scans in typical pulmonary lesions illustrating diverse patterns. DATA SYNTHESIS: We demonstrated hyperperfusion in areas with ground glass and a severely decreased perfusion pattern in more consolidated areas often seen later in the course of disease. A combination was also observed, illustrating temporal heterogeneity. CONCLUSIONS: These findings provide new insights into the pathophysiology of coronavirus disease 2019 pneumonia and further understanding of the mechanisms that lead to respiratory failure in these patients.

3.
Klin Lab Diagn ; 65(11): 688-692, 2020 Dec 04.
Article in English | MEDLINE | ID: covidwho-1780383

ABSTRACT

The study presents the results of the creation and evaluation of the diagnostic characteristics of the rapid immunochromatographic test for the qualitative detection and differentiation of IgM/IgG antibodies to SARS-CoV-2 in human serum, plasma, and whole blood "ИХА-COVID-19-IgM / IgG". Have been tested some samples without antibodies to SARS-CoV-2 and a samples with two and one type of specific antibodies. The coincidence of the results of immunochromatographic analysis with the results of the immunochemiluminescent method was 87.2%. Test kit can be use as the rapid diagnostic test in the context of the COVID-19 pandemic and to assess the immune status of convalescents.


Subject(s)
Antibodies, Viral/analysis , COVID-19 Serological Testing , COVID-19/diagnosis , Immunoassay , Immunoglobulin G/analysis , Immunoglobulin M/analysis , Humans
4.
Regen Eng Transl Med ; : 1-11, 2021 Mar 25.
Article in English | MEDLINE | ID: covidwho-1756993

ABSTRACT

ABSTRACT: Poly(ethylene glycol) (PEG) is a nontoxic, hydrophilic polymer that is often covalently attached to proteins, drugs, tissues, or materials; a procedure commonly referred to as PEGylation. PEGylation improves solubility, circulation time, and reduces immunogenicity of therapeutic molecules. Currently, there are 21 PEGylated drugs approved by the Food and Drug Administration (FDA), and more in the developmental stage. In addition to the polymer's applications in the clinic, PEG is widely used as a solvent and emulsifying agent in the formulation of cosmetics, cleaning, and personal care products. Due to the ubiquitous presence of the polymer in everyday products, patients can develop antibodies against PEG (αPEG Abs) that can be problematic when a PEGylated drug is administered. These αPEG Abs can provoke hypersensitivity reactions, accelerated drug clearance, and decreased therapeutic efficacy. Herein, we review how the prevalence of PEG in everyday products has induced αPEG Abs within the general public as well as the effect of these Abs on the performance of PEGylated therapeutics. We will focus on clinical manifestations following the administration of PEGylated drugs. LAY SUMMARY: Poly(ethylene glycol) (PEG) is a polymer found in products including cosmetics, personal care products, cleaning agents, medicine, and food. Due to the prevalence of PEG, people can develop antibodies (αPEG Abs) against the polymer, which recognize PEG as foreign. Of note, PEG is frequently incorporated into drug formulations to improve therapeutic efficacy. Complications can arise when a patient receiving a PEGylated drug has previously developed αPEG Abs from interactions with PEG in everyday products. The presence of high concentrations of αPEG Abs in blood can result in decreased treatment efficacy and allergic reactions to a wide range of therapeutics.

5.
Pharmaceuticals (Basel) ; 13(3)2020 Mar 21.
Article in English | MEDLINE | ID: covidwho-1725914

ABSTRACT

The COVID-19 coronavirus is currently spreading around the globe with limited treatment options available. This article presents the rationale for potentially using old drugs (emetine, other ipecac alkaloids or analogues) that have been used to treat amoebiasis in the treatment of COVID-19. Emetine had amongst the lowest reported half-maximal effective concentration (EC50) from over 290 agents screened for the Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) coronaviruses. While EC50 concentrations of emetine are achievable in the blood, studies show that concentrations of emetine can be almost 300 times higher in the lungs. Furthermore, based on the relative EC50s of emetine towards the coronaviruses compared with Entamoeba histolytica, emetine could be much more effective as an anti-coronavirus agent than it is against amoebiasis. This paper also discusses the known side effects of emetine and related compounds, how those side effects can be managed, and the optimal method of administration for the potential treatment of COVID-19. Given the serious and immediate threat that the COVID-19 coronavirus poses, our long history with emetine and the likely ability of emetine to reach therapeutic concentrations within the lungs, ipecac, emetine, and other analogues should be considered as potential treatment options, especially if in vitro studies confirm viral sensitivity.

6.
Clin Infect Dis ; 74(5): 871-881, 2022 03 09.
Article in English | MEDLINE | ID: covidwho-1700735

ABSTRACT

BACKGROUND: The Recipient Epidemiology and Donor Evaluation Study-IV-Pediatric (REDS-IV-P) Epidemiology, Surveillance and Preparedness of the Novel SARS-CoV-2 Epidemic (RESPONSE) seroprevalence study conducted monthly cross-sectional testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in blood donors in 6 US metropolitan regions to estimate the extent of SARS-CoV-2 infections over time. METHODS: During March-August 2020, approximately ≥1000 serum specimens were collected monthly from each region and tested for SARS-CoV-2 antibodies using a well-validated algorithm. Regional seroprevalence estimates were weighted based on demographic differences compared with the general population. Seroprevalence was compared with reported coronavirus disease 2019 (COVID-19) case rates over time. RESULTS: For all regions, seroprevalence was <1.0% in March 2020. New York, New York, experienced the biggest increase (peak seroprevalence, 15.8% in May). All other regions experienced modest increases in seroprevalence (1%-2% in May-June to 2%-4% in July-August). Seroprevalence was higher in younger, non-Hispanic black, and Hispanic donors. Temporal increases in donor seroprevalence correlated with reported case rates in each region. In August, 1.3-5.6 estimated cumulative infections (based on seroprevalence data) per COVID-19 case were reported to the Centers for Disease Control and Prevention. CONCLUSIONS: Increases in seroprevalence were found in all regions, with the largest increase in New York. Seroprevalence was higher in non-Hispanic black and Hispanic than in non-Hispanic white blood donors. SARS-CoV-2 antibody testing of blood donor samples can be used to estimate the seroprevalence in the general population by region and demographic group. The methods derived from the RESPONSE seroprevalence study served as the basis for expanding SARS-CoV-2 seroprevalence surveillance to all 50 states and Puerto Rico.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , Blood Donors , COVID-19/epidemiology , Child , Cross-Sectional Studies , Humans , Seroepidemiologic Studies
7.
Alzheimers Dement (Amst) ; 13(1): e12145, 2021.
Article in English | MEDLINE | ID: covidwho-1680307

ABSTRACT

INTRODUCTION: This study investigated alternative pre-analytical handling of blood for neurofilament light (NfL) analysis where resources are limited. METHOD: Plasma NfL was measured with single molecule array after alternative blood processing procedures: dried plasma spots (DPS), dried blood spots (DBS), and delayed 48-hour centrifugation. These were compared to standardized plasma processing (reference standard [RS]). In a discovery cohort (n = 10) and a confirmatory cohort (n = 21), whole blood was obtained from individuals with unknown clinical etiology. In the confirmatory cohort, delayed centrifugation protocol was paired with either 37°C incubation or sample shaking to test the effect of these parameters. RESULTS: Delayed centrifugation (R2 = 0.991) and DPS (discovery cohort, R2 = 0.954; confirmatory cohort, DPS: R2 = 0.961) methods were strongly associated with the RS. Delayed centrifugation with higher temperatures (R2 = 0.995) and shaking (R2 = 0.975) did not affect this association. DPS (P < 0.001) returned concentrations considerably lower than the RS. DISCUSSION: DPS or delayed centrifugation are viable pre-analytical procedures for the accurate quantification of plasma NfL.

8.
Allergy ; 77(1): 118-129, 2022 01.
Article in English | MEDLINE | ID: covidwho-1597019

ABSTRACT

BACKGROUND: COVID-19 can present with lymphopenia and extraordinary complex multiorgan pathologies that can trigger long-term sequela. AIMS: Given that inflammasome products, like caspase-1, play a role in the pathophysiology of a number of co-morbid conditions, we investigated caspases across the spectrum of COVID-19 disease. MATERIALS & METHODS: We assessed transcriptional states of multiple caspases and using flow cytometry, the expression of active caspase-1 in blood cells from COVID-19 patients in acute and convalescent stages of disease. Non-COVID-19 subject presenting with various comorbid conditions served as controls. RESULTS: Single-cell RNA-seq data of immune cells from COVID-19 patients showed a distinct caspase expression pattern in T cells, neutrophils, dendritic cells, and eosinophils compared with controls. Caspase-1 was upregulated in CD4+ T-cells from hospitalized COVID-19 patients compared with unexposed controls. Post-COVID-19 patients with lingering symptoms (long-haulers) also showed upregulated caspase-1activity in CD4+ T-cells that ex vivo was attenuated with a select pan-caspase inhibitor. We observed elevated caspase-3/7levels in red blood cells from COVID-19 patients compared with controls that was reduced following caspase inhibition. DISCUSSION: Our preliminary results suggest an exuberant caspase response in COVID-19 that may facilitate immune-related pathological processes leading to severe outcomes. Further clinical correlations of caspase expression in different stages of COVID-19 will be needed. CONCLUSION: Pan-caspase inhibition could emerge as a therapeutic strategy to ameliorate or prevent severe COVID-19.


Subject(s)
COVID-19 , Caspase Inhibitors , CD4-Positive T-Lymphocytes , COVID-19/complications , COVID-19/drug therapy , Caspase 1 , Caspase 3 , Caspase 7 , Caspase Inhibitors/therapeutic use , Caspases/genetics , Humans
9.
J Leukoc Biol ; 111(1): 269-281, 2022 01.
Article in English | MEDLINE | ID: covidwho-1591653

ABSTRACT

The immune system plays a crucial role in the response against severe acute respiratory syndrome coronavirus 2 with significant differences among patients. The study investigated the relationships between lymphocyte subsets, cytokines, and disease outcomes in patients with coronavirus disease 2019 (COVID-19). The measurements of peripheral blood lymphocytes subsets and cytokine levels were performed by flow cytometry for 57 COVID-19 patients. Patients were categorized into two groups according to the severity of the disease (nonsevere vs. severe). Total lymphocytes, T cells, CD4+ T cells, CD8+ T cells, B cells, and natural killer cells were decreased in COVID-19 patients and statistical differences were found among different severity of illness and survival states (P ˂ 0.01). The levels of IL-6 and IL-10 were significantly higher in severe and death groups and negatively correlated with lymphocyte subsets counts. The percentages of Th17 in the peripheral blood of patients were higher than those of healthy controls whereas the percentages of Th2 were lower. For the severe cases, the area under receiver operating characteristic (ROC) curve of IL-6 was the largest among all the immune parameters (0.964; 95% confidence interval: 0.927-1.000, P < 0.0001). In addition, the preoperative IL-6 concentration of 77.38 pg/ml was the optimal cutoff value (sensitivity: 84.6%, specificity: 100%). Using multivariate logistic regression analysis and ROC curves, IL-6 > 106.44 pg/ml and CD8+ T cell counts <150 cells/µl were found to be associated with mortality. Measuring the immune parameters and defining a risk threshold can segregate patients who develop a severe disease from those with a mild pathology. The identification of these parameters may help clinicians to predict the outcome of the patients with high risk of unfavorable progress of the disease.


Subject(s)
COVID-19/blood , COVID-19/mortality , Interleukin-6/blood , Severity of Illness Index , Africa, Northern , Aged , Biomarkers/blood , CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Cytokines/metabolism , Female , Humans , Kaplan-Meier Estimate , Lymphocyte Count , Lymphocyte Subsets/immunology , Male , Middle Aged , Multivariate Analysis , Prognosis , Treatment Outcome
10.
Curr Med Imaging ; 17(11): 1316-1323, 2021.
Article in English | MEDLINE | ID: covidwho-1574962

ABSTRACT

BACKGROUND: Though imaging manifestations of COVID-19 and other types of viral pneumonia are similar, their clinical treatment methods differ. Accurate, non-invasive diagnostic methods using CT imaging can help develop an optimal therapeutic regimen for both conditions. OBJECTIVE: To compare the initial CT imaging features in COVID-19 with those in other types of viral pneumonia. METHODS: Clinical and imaging data of 51 patients with COVID-19 and 69 with other types of viral pneumonia were retrospectively studied. All significant imaging features (Youden index >0.3) were included for constituting the combined criteria for COVID-19 diagnosis, composed of two or more imaging features with a parallel model. McNemar's chi-square test or Fisher's exact test was used to compare the validity indices (sensitivity and specificity) among various criteria. RESULTS: Ground glass opacities (GGO) dominated density, peripheral distribution, unilateral lung, clear margin of lesion, rounded morphology, long axis parallel to the pleura, vascular thickening, and crazy-paving pattern were more common in COVID-19 (p <0.05). Consolidation-dominated density, both central and peripheral distributions, bilateral lung, indistinct margin of lesion, tree-inbud pattern, mediastinal or hilar lymphadenectasis, pleural effusion, and pleural thickening were more common in other types of viral pneumonia (p < 0.05). GGO-dominated density or long axis parallel to the pleura (with the highest sensitivity), and GGO-dominated density or long axis parallel to the pleura or vascular thickening (with the highest specificity) are well combined criteria of COVID-19. CONCLUSION: The initial CT imaging features are helpful for the differential diagnosis of COVID-19 and other types of viral pneumonia.


Subject(s)
COVID-19 , COVID-19 Testing , Humans , Retrospective Studies , SARS-CoV-2 , Tomography, X-Ray Computed
11.
Clin Transl Immunology ; 10(4): e1271, 2021.
Article in English | MEDLINE | ID: covidwho-1525427

ABSTRACT

OBJECTIVES: Emerging evidence of dysregulation of the myeloid cell compartment urges investigations on neutrophil characteristics in coronavirus disease 2019 (COVID-19). We isolated neutrophils from the blood of COVID-19 patients receiving general ward care and from patients hospitalised at intensive care units (ICUs) to explore the kinetics of circulating neutrophils and factors important for neutrophil migration and activation. METHODS: Multicolour flow cytometry was exploited for the analysis of neutrophil differentiation and activation markers. Multiplex and ELISA technologies were used for the quantification of protease, protease inhibitor, chemokine and cytokine concentrations in plasma. Neutrophil polarisation responses were evaluated microscopically. Gelatinolytic and metalloproteinase activity in plasma was determined using a fluorogenic substrate. Co-culturing healthy donor neutrophils with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) allowed us to investigate viral replication in neutrophils. RESULTS: Upon ICU admission, patients displayed high plasma concentrations of granulocyte-colony-stimulating factor (G-CSF) and the chemokine CXCL8, accompanied by emergency myelopoiesis as illustrated by high levels of circulating CD10-, immature neutrophils with reduced CXCR2 and C5aR expression. Neutrophil elastase and non-metalloproteinase-derived gelatinolytic activity were increased in plasma from ICU patients. Significantly higher levels of circulating tissue inhibitor of metalloproteinase 1 (TIMP-1) in patients at ICU admission yielded decreased total MMP proteolytic activity in blood. COVID-19 neutrophils were hyper-responsive to CXCL8 and CXCL12 in shape change assays. Finally, SARS-CoV-2 failed to replicate inside human neutrophils. CONCLUSION: Our study provides detailed insights into the kinetics of neutrophil phenotype and function in severe COVID-19 patients, and supports the concept of an increased neutrophil activation state in the circulation.

12.
Clin Infect Dis ; 73(10): 1909-1912, 2021 11 16.
Article in English | MEDLINE | ID: covidwho-1522148

ABSTRACT

Maternal and cord blood sera were collected from 20 parturients who received the BNT162b2 vaccine. All women and infants were positive for anti S- and anti-receptor binding domain antibody-specific immunoglobulin G. Cord blood antibody concentrations were correlated to maternal levels and to time since vaccination. Antenatal severe acute respiratory syndrome coronavirus 2 vaccination may provide maternal and neonatal protection.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , COVID-19 Vaccines , Female , Humans , Infant, Newborn , Pregnancy , RNA, Messenger , Vaccination
13.
Toxicol Rep ; 8: 646-656, 2021.
Article in English | MEDLINE | ID: covidwho-1525967

ABSTRACT

Humans are frequently exposed to Quaternary Ammonium Compounds (QACs). QACs are ubiquitously used in medical settings, restaurants, and homes as cleaners and disinfectants. Despite their prevalence, nothing is known about the health effects associated with chronic low-level exposure. Chronic QAC toxicity, only recently identified in mice, resulted in developmental, reproductive, and immune dysfunction. Cell based studies indicate increased inflammation, decreased mitochondrial function, and disruption of cholesterol synthesis. If these findings translate to human toxicity, multiple physiological processes could be affected. This study tested whether QAC concentrations could be detected in the blood of 43 human volunteers, and whether QAC concentrations influenced markers of inflammation, mitochondrial function, and cholesterol synthesis. QAC concentrations were detected in 80 % of study participants. Blood QACs were associated with increase in inflammatory cytokines, decreased mitochondrial function, and disruption of cholesterol homeostasis in a dose dependent manner. This is the first study to measure QACs in human blood, and also the first to demonstrate statistically significant relationships between blood QAC and meaningful health related biomarkers. Additionally, the results are timely in light of the increased QAC disinfectant exposure occurring due to the SARS-CoV-2 pandemic. MAIN FINDINGS: This study found that 80 % of study participants contained QACs in their blood; and that markers of inflammation, mitochondrial function, and sterol homeostasis varied with blood QAC concentration.

14.
J Neuroophthalmol ; 41(2): 154-165, 2021 06 01.
Article in English | MEDLINE | ID: covidwho-1517959

ABSTRACT

PURPOSE: To provide a summary of the neuro-ophthalmic manifestations of coronavirus disease 19 (COVID-19) documented in the literature thus far. METHODS: The PubMed and Google Scholar databases were searched using the keywords: Neuro-Ophthalmology, COVID-19, SARS-CoV-2, and coronavirus. A manual search through reference lists of relevant articles was also performed. RESULTS/CONCLUSIONS: The literature on COVID-associated neuro-ophthalmic disease continues to grow. Afferent neuro-ophthalmic complications associated with COVID-19 include optic neuritis, papillophlebitis, papilledema, visual disturbance associated with posterior reversible encephalopathy syndrome, and vision loss caused by stroke. Efferent neuro-ophthalmic complications associated with COVID-19 include cranial neuropathies, Miller Fisher syndrome, Adie's pupils, ocular myasthenia gravis, nystagmus and eye movement disorders. Proposed mechanisms of neurologic disease include immunologic upregulation, vasodilation and vascular permeability, endothelial dysfunction, coagulopathy, and direct viral neurotropism. When patients present to medical centers with new onset neuro-ophthalmic conditions during the pandemic, COVID-19 infection should be kept on the differential.


Subject(s)
COVID-19/complications , Optic Neuritis/etiology , Pandemics , Posterior Leukoencephalopathy Syndrome/etiology , SARS-CoV-2 , COVID-19/epidemiology , Humans
15.
Neurocrit Care ; 35(2): 577-589, 2021 10.
Article in English | MEDLINE | ID: covidwho-1516917

ABSTRACT

BACKGROUND: Multiple studies demonstrate that fever/elevated temperature is associated with poor outcomes in patients with vascular brain injury; however, there are no conclusive studies that demonstrate that fever prevention/controlled normothermia is associated with better outcomes. The primary objective of the INTREPID (Impact of Fever Prevention in Brain-Injured Patients) trial is to test the hypothesis that fever prevention is superior to standard temperature management in patients with acute vascular brain injury. METHODS: INTREPID is a prospective randomized open blinded endpoint study of fever prevention versus usual care in patients with ischemic or hemorrhagic stroke. The fever prevention intervention utilizes the Arctic Sun System and will be compared to standard care patients in whom fever may spontaneously develop. Ischemic stroke, intracerebral hemorrhage or subarachnoid hemorrhage patients will be included within disease-specific time-windows. Both awake and sedated patients will be included, and treatment is initiated immediately upon enrollment. Eligible patients are expected to require intensive care for at least 72 h post-injury, will not be deemed unlikely to survive without severe disability, and will be treated for up to 14 days, or until deemed ready for discharge from the ICU, whichever comes first. Fifty sites in the USA and worldwide will participate, with a target enrollment of 1176 patients (1000 evaluable). The target temperature is 37.0 °C. The primary efficacy outcome is the total fever burden by °C-h, defined as the area under the temperature curve above 37.9 °C. The primary secondary outcome, on which the sample size is based, is the modified Rankin Scale Score at 3 months. All efficacy analyses including the primary and key secondary endpoints will be primarily based on an intention-to-treat population. Analysis of the as-treated and per protocol populations will also be performed on the primary and key secondary endpoints as sensitivity analyses. DISCUSSION: The INTREPID trial will provide the first results of the impact of a pivotal fever prevention intervention in patients with acute stroke ( www.clinicaltrials.gov ; NCT02996266; registered prospectively 05DEC2016).


Subject(s)
COVID-19 , Brain , Critical Care , Humans , Prospective Studies , Randomized Controlled Trials as Topic , SARS-CoV-2
16.
Vox Sang ; 115(3): 146-151, 2020 Apr.
Article in English | MEDLINE | ID: covidwho-1508355

ABSTRACT

BACKGROUND: Emerging viruses like severe acute respiratory syndrome coronavirus (SARS-CoV), Crimean-Congo haemorrhagic fever virus (CCHFV) and Nipah virus (NiV) have been identified to pose a potential threat to transfusion safety. In this study, the ability of the THERAFLEX UV-Platelets and THERAFLEX MB-Plasma pathogen inactivation systems to inactivate these viruses in platelet concentrates and plasma, respectively, was investigated. MATERIALS AND METHODS: Blood products were spiked with SARS-CoV, CCHFV or NiV, and then treated with increasing doses of UVC light (THERAFLEX UV-Platelets) or with methylene blue (MB) plus increasing doses of visible light (MB/light; THERAFLEX MB-Plasma). Samples were taken before and after treatment with each illumination dose and tested for residual infectivity. RESULTS: Treatment with half to three-fourths of the full UVC dose (0·2 J/cm2 ) reduced the infectivity of SARS-CoV (≥3·4 log), CCHFV (≥2·2 log) and NiV (≥4·3 log) to the limit of detection (LOD) in platelet concentrates, and treatment with MB and a fourth of the full light dose (120 J/cm2 ) decreased that of SARS-CoV (≥3·1 log), CCHFV (≥3·2 log) and NiV (≥2·7 log) to the LOD in plasma. CONCLUSION: Our study demonstrates that both THERAFLEX UV-Platelets (UVC) and THERAFLEX MB-Plasma (MB/light) effectively reduce the infectivity of SARS-CoV, CCHFV and NiV in platelet concentrates and plasma, respectively.


Subject(s)
Hemorrhagic Fever Virus, Crimean-Congo/radiation effects , Light , Methylene Blue/pharmacology , Nipah Virus/radiation effects , SARS Virus/radiation effects , Ultraviolet Rays , Virus Inactivation , Blood Platelets/virology , Blood Transfusion , Hemorrhagic Fever Virus, Crimean-Congo/drug effects , Humans , Nipah Virus/drug effects , Plasma/virology , SARS Virus/drug effects
17.
J Comput Assist Tomogr ; 44(5): 627-632, 2020.
Article in English | MEDLINE | ID: covidwho-1501243

ABSTRACT

OBJECTIVE: To determine the predictive computed tomography (CT) and clinical features for diagnosis of COVID-19 pneumonia. METHODS: The CT and clinical data including were analyzed using univariate analysis and multinomial logistic regression, followed by receiver operating characteristic curve analysis. RESULTS: The factors including size of ground grass opacity (GGO), GGO with reticular and/or interlobular septal thickening, vascular enlargement, "tree-in-bud" opacity, centrilobular nodules, and stuffy or runny nose were associated with the 2 groups of viral pneumonia, as determined by univariate analysis (P < 0.05). Only GGO with reticular and/or interlobular septal thickening, centrilobular nodules, and stuffy or runny nose remained independent risk factors in multinomial logistic regression analysis. Receiver operating characteristic curve analysis showed that the area under curve of the obtained logistic regression model was 0.893. CONCLUSION: Computed tomography and clinical features including GGO with reticular and/or interlobular septal thickening, absence of centrilobular nodules, and absence of stuffy or runny nose are potential patients with COVID-19 pneumonia.


Subject(s)
Betacoronavirus , Clinical Laboratory Techniques/methods , Coronavirus Infections/diagnosis , Lung/diagnostic imaging , Pneumonia, Viral/diagnosis , Tomography, X-Ray Computed/methods , Adult , COVID-19 , COVID-19 Testing , Diagnosis, Differential , Female , Humans , Male , Middle Aged , Pandemics , Predictive Value of Tests , Reproducibility of Results , Retrospective Studies , SARS-CoV-2
18.
Crit Care Explor ; 2(9): e0194, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-1493997

ABSTRACT

OBJECTIVES: Coronavirus disease 2019 is caused by the novel severe acute respiratory syndrome coronavirus 2 virus. Patients admitted to the ICU suffer from microvascular thrombosis, which may contribute to mortality. Our aim was to profile plasma thrombotic factors and endothelial injury markers in critically ill coronavirus disease 2019 ICU patients to help understand their thrombotic mechanisms. DESIGN: Daily blood coagulation and thrombotic factor profiling with immunoassays and in vitro experiments on human pulmonary microvascular endothelial cells. SETTING: Tertiary care ICU and academic laboratory. SUBJECTS: All patients admitted to the ICU suspected of being infected with severe acute respiratory syndrome coronavirus 2, using standardized hospital screening methodologies, had daily blood samples collected until testing was confirmed coronavirus disease 2019 negative on either ICU day 3 or ICU day 7 if the patient was coronavirus disease 2019 positive. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Age- and sex-matched healthy control subjects and ICU patients that were either coronavirus disease 2019 positive or coronavirus disease 2019 negative were enrolled. Cohorts were well balanced with the exception that coronavirus disease 2019 positive patients were more likely than coronavirus disease 2019 negative patients to suffer bilateral pneumonia. Mortality rate for coronavirus disease 2019 positive ICU patients was 40%. Compared with healthy control subjects, coronavirus disease 2019 positive patients had higher plasma von Willebrand factor (p < 0.001) and glycocalyx-degradation products (chondroitin sulfate and syndecan-1; p < 0.01). When compared with coronavirus disease 2019 negative patients, coronavirus disease 2019 positive patients had persistently higher soluble P-selectin, hyaluronic acid, and syndecan-1 (p < 0.05), particularly on ICU day 3 and thereafter. Thrombosis profiling on ICU days 1-3 predicted coronavirus disease 2019 status with 85% accuracy and patient mortality with 86% accuracy. Surface hyaluronic acid removal from human pulmonary microvascular endothelial cells with hyaluronidase treatment resulted in depressed nitric oxide, an instigating mechanism for platelet adhesion to the microvascular endothelium. CONCLUSIONS: Thrombosis profiling identified endothelial activation and glycocalyx degradation in coronavirus disease 2019 positive patients. Our data suggest that medications to protect and/or restore the endothelial glycocalyx, as well as platelet inhibitors, should be considered for further study.

19.
Trauma Surg Acute Care Open ; 5(1): e000581, 2020.
Article in English | MEDLINE | ID: covidwho-1476824

ABSTRACT

BACKGROUND: Whole blood viscoelastic testing (VET) devices are routinely used in a variety of clinical settings to assess hemostasis. The Quantra QStat System is a cartridge-based point of care VET device that measures changes in clot stiffness during coagulation and fibrinolysis using ultrasound detection of resonance. The objective of this study was to assess the ability of the Quantra QStat System to detect coagulopathies in trauma patients. METHODS: A multicenter observational study was conducted on adult subjects at two level 1 trauma centers. For each subject, whole blood samples were drawn upon arrival to the emergency department and again, in some cases, after administration of blood products and/or antifibrinolytics. Samples were analyzed on the Quantra in parallel to ROTEM delta. The QStat cartridge provides measures of Clot Time (CT), Clot Stiffness (CS), Fibrinogen and Platelet Contributions to clot stiffness (FCS and PCS), and Clot Stability to Lysis (CSL). Data analyses included linear regression of Quantra and ROTEM parameters and an assessment of the concordance of the two devices for the assessment of hyperfibrinolysis. RESULTS: A total of 56 patients were analyzed. 42% of samples had a low QStat CS value suggestive of an hypocoagulable state. The low stiffness values could be attributed to either low PCS, FCS or combination. Additionally, 13% of samples showed evidence of hyperfibrinolysis based on the QStat CSL parameter. Samples analyzed with ROTEM assays showed a lower prevalence of low CS and hyperfibrinolysis based on EXTEM and FIBTEM results. The correlation of CS, FCS and CT versus equivalent ROTEM parameters was strong with r-values of 0.83, 0.79 and 0.79, respectively. DISCUSSION: This first clinical experience with the Quantra in trauma patients showed that the QStat Cartridge was strongly correlated with ROTEM parameters and that it could detect coagulopathies associated with critical bleeding. LEVEL OF EVIDENCE: Diagnostic test, Level II.

20.
Vox Sang ; 116(9): 983-989, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1462885

ABSTRACT

BACKGROUND: The novel coronavirus disease-2019 (COVID-19) caused a sudden and unexpected increase in the number of hospital admissions and deaths worldwide. The impact of social distancing on blood stocks was significant. Data on the use of blood products by patients with COVID-19 are scarce. MATERIAL AND METHODS: A retrospective observational study was conducted by analysing the medical records of 3014 hospitalized COVID-19 patients in 16 Brazilian hospitals. Individual data related to clinical, laboratory and transfusion characteristics and outcomes of these patients were collected. Patients characteristics association with mortality and transfusion need were tested independently by logistic regression models. RESULTS: Patients mean age was 57·6 years. In 2298 (76·2%) patients, there was an underlying clinical comorbidity. A total of 1657 (55%) patients required admission to intensive care unit (ICU), and 943 (31%) patients required ventilatory support and orotracheal intubation (OTI). There was a total of 471 (15·6%) deaths among all patients. 325 patients (10·7%) required blood transfusion; 3187 blood products were transfused: 1364 red blood cells in 303 patients, 1092 platelet units in 78 patients, 303 fresh frozen plasma in 49 patients and 423 cryoprecipitates in 21 patients. The mortality among patients who received transfusion was substantially higher than that among the total study population. CONCLUSION: Need for transfusion was low in COVID-19 patients, but significantly higher in patients admitted to ICU and in those who needed OTI. Knowledge of the transfusion profile of these patients allows better strategies for maintaining the blood stocks of hospitals during the pandemic.


Subject(s)
COVID-19 , Blood Transfusion , Brazil/epidemiology , Comorbidity , Hospitalization , Humans , Infant, Newborn , Intensive Care Units , Respiration, Artificial , Retrospective Studies , SARS-CoV-2
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