Complications In Coronavirus Disease 2019 Patients Research Articles

Neurological Complications in COVID-19 Patients With ECMO Support: A Systematic Review and Meta-Analysis

BackgroundPatients with Coronavirus disease 2019 (COVID-19)-related acute respiratory disease (ARDS) increasingly receive extracorporeal membrane oxygenation (ECMO) support. While ECMO has been shown to increase risk of stroke, few studies have examined this association in COVID-19 patients.ObjectiveWe conducted a systematic review to characterise neurological events during ECMO support in COVID-19 patients.DesignSystematic review of cohort and large case series of COVID-19 patients who received ECMO support.Data SourcesStudies retrieved from PubMed, EMBASE, Cochrane, Cochrane COVID-19 Study Register, Web of Science, Scopus, Clinicaltrials.gov, and medRχiv from inception to November 11, 2020.Eligibility CriteriaInclusion criteria were a) Adult population (>18 year old); b) Positive PCR test for SARS-CoV-2 with active COVID-19 disease; c) ECMO therapy due to COVID-19 ARDS; and d) Neurological events and outcome described while on ECMO support. We excluded articles when no details of neurologic events were available.Results1,322 patients from 12 case series and retrospective cohort studies were included in our study. The median age was 49.2, and 75% (n=985) of the patients were male. Diabetes mellitus and dyslipidaemia were the most common comorbidities (24% and 20%, respectively). Most (95%, n=1,241) patients were on venovenous ECMO with a median P:F ratio at the time of ECMO cannulation of 69.1. The prevalence of intracranial haemorrhage (ICH), ischaemic stroke, and hypoxic ischaemic brain injury (HIBI) was 5.9% (n=78), 1.1% (n=15), and 0.3% (n=4), respectively. The overall mortality of the 1,296 ECMO patients in the 10 studies that reported death was 36% (n=477), and the mortality of the subset of patients who had a neurological event was 92%.ConclusionsNeurological injury is a concern for COVID-19 patients who receive ECMO. Further research is required to explore how neuromonitoring protocols can inform tailored anticoagulation management and improve survival in COVID-19 patients with ECMO support.

Surgical complications in COVID-19 patients in the setting of moderate to severe disease.

The coronavirus disease 2019 (COVID-19) pandemic has had a considerable impact on the work of physicians and surgeons. The connection between the patient and the surgeon cannot be replaced by telemedicine. For example, the surgical staff faces more serious difficulties compared to non-surgical specialists during the COVID-19 pandemic. The primary concerns include the safest solutions for protecting healthcare staff and patients and the ability to provide adequate surgical care. Additionally, the adverse effects of any surgery delays and the financial consequences complicate the picture. Therefore, patients' admission during the COVID-19 pandemic should be taken into consideration, as well as preoperative measures. The COVID-19 situation brings particular risk to patients during surgery, where preoperative morbidity and mortality rise in either asymptomatic or symptomatic COVID-19 patients. This review discusses the recent factors associated with surgical complications, mortality rates, outcomes, and experience in COVID-19 surgical patients.

Clinical and thoracic radiography features determine patient outcome in young and middle age adults with COVID-19

Background: The new coronavirus disease 2019 (COVID-19) emerged in Wuhan, China, in December 2019. Researchers described COVID-19 mortality risk factors as being elderly, male, having comorbidities, and in some ethnicities. Some authors validated the use of first chest x-ray (CXR) severity scores (CSE) as an independent indicator of poor outcomes with COVID-19. Our objective was to evaluate the clinical and CXR findings as predictors of poor outcomes (death, needing intubation, Intensive Care Unit (ICU) admission) in patients with COVID-19. Methods: We performed a retrospective study of case-controls using a sample size of 60 patients admitted with the diagnosis of COVID-19 during the period of July-August 2020 to the Cuban Hospital in Qatar, as determined with the free online OpenEpi software (https://www.openepi.com/SampleSize/SSCC.htm). We defined cases as patients with a complication like death, needing intubation, ICU admission, or organ failure, and controls as patients who did not demonstrate the described complications. The dependent variables used were patient evolution divided into poor outcome or good outcome. The independent variables used were age, history of diabetes mellitus type II, and high blood pressure (HBP), CSE, and white blood count (WBC). The bivariate analysis was performed using the Chi-Square test or Fisher exact test. Multivariate analysis was done using binary logistic regression (IBM SPSS software 25). The results are expressed in Odds Ratio with p-value < 0.05 defined as statistically significant. Results: The bivariate analysis showed being older, having a history of HBP, diabetes, abnormal WBC, and high CSE were linked to poor outcome (p < 0.05) . The multivariate analysis defined WBC and CSE with independent influence over the patient evolution . Conclusion: We demonstrated that the value of WBC and CSE are predictors of poor outcome in patients with COVID-19. WBC increases the possibility of the described complications in COVID-19 patients 68,634 times and CSE 12,201 times.

ADME and Pharmacokinetic Properties of Remdesivir: Its Drug Interaction Potential.

On 11 March 2020, the World Health Organization (WHO) classified the Coronavirus Disease 2019 (COVID-19) as a global pandemic, which tested healthcare systems, administrations, and treatment ingenuity across the world. COVID-19 is caused by the novel beta coronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Since the inception of the pandemic, treatment options have been either limited or ineffective. Remdesivir, a drug originally designed to be used for Ebola virus, has antiviral activity against SARS-CoV-2 and has been included in the COVID-19 treatment regimens. Remdesivir is an adenosine nucleotide analog prodrug that is metabolically activated to a nucleoside triphosphate metabolite (GS-443902). The active nucleoside triphosphate metabolite is incorporated into the SARS-CoV-2 RNA viral chains, preventing its replication. The lack of reported drug development and characterization studies with remdesivir in public domain has created a void where information on the absorption, distribution, metabolism, elimination (ADME) properties, pharmacokinetics (PK), or drug-drug interaction (DDI) is limited. By understanding these properties, clinicians can prevent subtherapeutic and supratherapeutic levels of remdesivir and thus avoid further complications in COVID-19 patients. Remdesivir is metabolized by both cytochrome P450 (CYP) and non-CYP enzymes such as carboxylesterases. In this narrative review, we have evaluated the currently available ADME, PK, and DDI information about remdesivir and have discussed the potential of DDIs between remdesivir and different COVID-19 drug regimens and agents used for comorbidities. Considering the nascent status of remdesivir in the therapeutic domain, extensive future work is needed to formulate safer COVID-19 treatment guidelines involving this medication.

Predictors of mortality, ICU hospitalization, and extrapulmonary complications in COVID-19 patients

ObjectiveA major coronavirus disease 2019 (COVID-19) outbreak occurred in Northeastern France in spring 2020. This single-center retrospective observational cohort study aimed to compare patients with severe COVID-19 and those with non-severe COVID-19 (survivors vs. non-survivors, ICU patients vs. non-ICU patients) and to describe extrapulmonary complications. Patients and methodsWe included all patients with a confirmed diagnosis of COVID-19 admitted to Colmar Hospital in March 2020. ResultsWe examined 600 patients (median age 71.09 years; median body mass index: 26.9 kg/m2); 57.7% were males, 86.3% had at least one comorbidity, 153 (25.5%) required ICU hospitalization, and 115 (19.1%) died. Baseline independent factors associated with death were older age (>75 vs. ≤75 years), male sex, oxygen supply, chronic neurological, renal, and pulmonary diseases, diabetes, cancer, low platelet and hemoglobin counts, and high levels of C-reactive protein (CRP) and serum creatinine. Factors associated with ICU hospitalization were age <75 years, oxygen supply, chronic pulmonary disease, absence of dementia, and high levels of CRP, hemoglobin, and serum creatinine. Among the 600 patients, 80 (13.3%) had an acute renal injury, 33 (5.5%) had a cardiovascular event, 27 (4.5%) had an acute liver injury, 24 (4%) had venous thromboembolism, eight (1.3%) had a neurological event, five (0.8%) had rhabdomyolysis, and one had acute pancreatitis. Most extrapulmonary complications occurred in ICU patients. ConclusionThis study highlighted the main risk factors for ICU hospitalization and death caused by severe COVID-19 and the frequency of numerous extrapulmonary complications in France.

Emerging COVID-19 Neurological Manifestations: Present Outlook and Potential Neurological Challenges in COVID-19 Pandemic.

The unremitting coronavirus disease 2019 (COVID-19) pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) marked a year-long phase of public health adversaries and has severely compromised healthcare globally. Early evidence of COVID-19 noted its impact on the pulmonary and cardiovascular functions, while multiple studies in recent time shed light on its substantial neurological complications, though a comprehensive understanding of the cause(s), the mechanism(s), and their neuropathological outcomes is scarce. In the present review, we conferred evidence of neurological complications in COVID-19 patients and shed light on the SARS-CoV-2 infection routes including the hematogenous, direct/neuronal, lymphatic tissue or cerebrospinal fluid, or infiltration through infected immune cells, while the underlying mechanism of SARS-CoV-2 invasion to the central nervous system (CNS) was also discussed. In an up-to-date manner, we further reviewed the impact of COVID-19 in developing diverse neurologic manifestations associated with CNS, peripheral nervous system (PNS), skeletal muscle, and also pre-existing neurological diseases, including Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, epilepsy, and myasthenia gravis. Furthermore, we discussed the involvement of key factors including age, sex, comorbidity, and disease severity in exacerbating the neurologic manifestations in COVID-19 patients. An outlook of present therapeutic strategies and state of existing challenges in COVID-19 management was also accessed. Conclusively, the present report provides a comprehensive review of COVID-19-related neurological complications and emphasizes the need for their early clinical management in the ongoing COVID-19 pandemic.Graphical abstract

Review: Obesity and COVID-19: A Detrimental Intersection.

Obesity has been recognized as an independent risk factor for critical illness and major severity in subjects with coronavirus disease 2019 (COVID-19). The role of fat distribution, particularly visceral fat (often linked to metabolic abnormalities), is still unclear. The adipose tissue represents a direct source of cytokines responsible for the pathological modifications occurring within adipose tissue in obese subjects. Adipokines are a crucial connection between metabolism and immune system: their dysregulation in obesity contributes to chronic low-grade systemic inflammation and metabolic comorbidities. Therefore the increased amount of visceral fat can lead to a proinflammatory phenotypic shift. This review analyzes the interrelation between obesity and COVID-19 severity, as well as the cellular key players and molecular mechanisms implicated in adipose inflammation, investigating if adipose tissue can constitute a reservoir for viral spread, and contribute to immune activation and cytokines storm. Targeting the underlying molecular mechanisms might have therapeutic potential in the management of obesity-related complications in COVID-19 patients.

Radiological findings of COVID-19-related thromboembolic complications

BackgroundThe ongoing global pandemic of coronavirus disease 2019 (COVID-19) may cause, in addition to lung disease, a wide spectrum of non-respiratory complications. Among these are thromboembolic complications. The theories that explain the mechanism of thromboembolic complications of COVID-19 are accumulating rapidly, and in addition to the role of imaging for assessment of COVID-19 pneumonia, CT may be useful for identification of these complications, such as pulmonary embolism, ischaemic stroke, mesenteric ischaemia, and acro-ischaemia.ResultsThromboembolic manifestations were diagnosed in 10% of our patients (124 patients out of the total 1245 COVID-19 patients); 56 patients (45.2%) presented with pulmonary embolism, 32 patients (25.8%) presented with cerebrovascular manifestations, 17 patients (13.7%) presented with limb affection, and 19 patients (15.3%) presented with gastrointestinal thromboembolic complications.Most of our patients had significant comorbidities; diabetes was found in 72 patients (58%), dyslipidemia in 72 patients (58%), smoking in 71 patients (57.3%), hypertension in 63 patients (50.8%), and morbid obesity in 40 patients (32.2%).Thromboembolic events were diagnosed on admission in 41 patients (33.1%), during the first week in 61 patients (49.2%), and after the first week in 22 patients (17.7%).ConclusionsThe incidence of thromboembolic complications in COVID-19 patients is relatively high resulting in a multisystem thrombotic disease. In addition to the crucial role of imaging for assessment of COVID-19 pneumonia, CT is important for assessment of the thromboembolic complications, such as pulmonary embolism, ischaemic stroke, mesenteric ischaemia, and peripheral ischaemia, especially in patients with elevated d-dimer levels and those with sudden clinical deterioration.

High rate of bleeding and arterial thrombosis in COVID-19: Saudi multicenter study

BackgroundSeveral observational studies have reported the rate of venous and arterial thrombotic events in patients infected with COVID-19, with conflicting results. The aim of this study was to estimate the rate of thrombotic and bleeding events in hospitalized patients diagnosed with Coronavirus disease 2019 (COVID-19).MethodsThis was a multicenter study of 636 patients admitted between 20 March 2020 and 31 May 2020 with confirmed COVID-19 in four hospitals.ResultsOver a median length of stay in the non-ICU group of 7 days and of 19 days in the ICU group, twelve patients were diagnosed with Venous thromboembolism (VTE) (1.8 %) (95 % CI, 1.1–3). The rate in the non-ICU group was 0.19 % (95 % CI, 0.04–0.84), and that in the ICU group was 10.3 % (95 % CI, 6.4–16.2). The overall rate of arterial event is 2.2 % (95 % CI, 1.4–3.3). The rates in the non-ICU and ICU groups were 0.94 % (95 % CI, 0.46–0.1.9) and 8.4 % (95 % CI, 5.0–14.0). The overall composite event rate was 2.9 % (95 % CI, 2.0–4.3). The composite event rates in the non-ICU and ICU groups were 0.94 % (95 % CI, 0.46–0.1.9) and 13.2 % (95 % CI, 8.7–19.5). The overall rate of bleeding is 1.7 % (95 % CI, 1.0–2.8). The bleeding rate in the non-ICU group was 0.19 % (95 % CI, 0.04–0.84), and that in the ICU group was 9.4 % (95 % CI, 5.7–15.1). The baseline D-dimer level was a significant risk factor for developing VTE (OR 1.31, 95 % CI, 1.08–1.57, p = 0.005) and composite events (OR 1.32, 95 % CI, 1.12–1.55, p = 0.0007).ConclusionsIn this study, we found that the VTE rates in hospitalized patients with COVID-19 might not be higher than expected. In contrast to the risk of VTE, we found a high rate of arterial and bleeding complications in patients admitted to the ICU. An elevated D-dimer level at baseline could predict thrombotic complications in COVID-19 patients and may assist in the identification of these patients. Given the high rate of bleeding, the current study suggests that the intensification of anticoagulation therapy in COVID-19 patients beyond the standard of care be pursued with caution and would best be evaluated in a randomized controlled study.

Revealing Tissue-Specific SARS-CoV-2 Infection and Host Responses using Human Stem Cell-Derived Lung and Cerebral Organoids.

SummaryCOVID-19 is a transmissible respiratory disease caused by a novel coronavirus, SARS-CoV-2, and has become a global health emergency. There is an urgent need for robust and practical in vitro model systems to investigate viral pathogenesis. Here, we generated human induced pluripotent stem cell (iPSC)-derived lung organoids (LORGs), cerebral organoids (CORGs), neural progenitor cells (NPCs), neurons, and astrocytes. LORGs containing epithelial cells, alveolar types 1 and 2, highly express ACE2 and TMPRSS2 and are permissive to SARS-CoV-2 infection. SARS-CoV-2 infection induces interferons, cytokines, and chemokines and activates critical inflammasome pathway genes. Spike protein inhibitor, EK1 peptide, and TMPRSS2 inhibitors (camostat/nafamostat) block viral entry in LORGs. Conversely, CORGs, NPCs, astrocytes, and neurons express low levels of ACE2 and TMPRSS2 and correspondingly are not highly permissive to SARS-CoV-2 infection. Infection in neuronal cells activates TLR3/7, OAS2, complement system, and apoptotic genes. These findings will aid in understanding COVID-19 pathogenesis and facilitate drug discovery.

Hyperglycemia at admission is a strong predictor of mortality and severe/critical complications in COVID-19 patients: a meta-analysis.

Background: Hyperglycemia at admission has been demonstrated to exacerbate the outcomes of coronavirus disease 2019 (COVID-19) but a meta-analysis is lacking to further confirm this hypothesis. The purpose of this meta-analysis was to summarize the evidence on the association between hyperglycemia at admission and the development of COVID-19. Method: Four databases namely, PubMed, Web of Science, Embase and Cochrane Library, were screened for eligible studies. STATA software was utilized to pool data for this meta-analysis. The primary outcomes included mortality and severity. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated with random-effects models, and the quality of evidence was appraised by the Newcastle–Ottawa Scale (NOS). This meta-analysis was prospectively registered online on PROSPERO, CRD42020191763. Results: Sixteen observational studies with 6386 COVID-19 patients relating hyperglycemia at admission to COVID-19 outcomes were included. The overall data demonstrated that, compared with the control, the hyperglycemia at admission group was more likely to have increased mortality (OR = 3.45, 95% CI, 2.26–5.26) and severe/critical complications (OR = 2.08, 95% CI, 1.45–2.99) of COVID-19. Conclusion: Hyperglycemia at admission in COVID-19 patients may be a strong predictor of mortality and complications.

Targeting Endolysosomal Two-Pore Channels to Treat Cardiovascular Disorders in the Novel COronaVIrus Disease 2019.

Emerging evidence hints in favor of a life-threatening link between severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and the cardiovascular system. SARS-CoV-2 may result in dramatic cardiovascular complications, whereas the severity of COronaVIrus Disease 2019 (COVID-19) and the incidence of fatalities tend to increase in patients with pre-existing cardiovascular complications. SARS-CoV-2 is internalized into the host cells by endocytosis and may then escape the endolysosomal system via endosomes. Two-pore channels drive endolysosomal trafficking through the release of endolysosomal Ca2+. Recent evidence suggested that the pharmacological inhibition of TPCs prevents Ebola virus and Middle East Respiratory Syndrome COronaVirus (MERS-CoV) entry into host cells. In this perspective, we briefly summarize the biophysical and pharmacological features of TPCs, illustrate their emerging role in the cardiovascular system, and finally present them as a reliable target to treat cardiovascular complications in COVID-19 patients.

Testicular Atrophy and Hypothalamic Pathology in COVID-19: Possibility of the Incidence of Male Infertility and HPG Axis Abnormalities.

Coronavirus disease 2019 (COVID-19), which resulted from the pandemic outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causes a massive inflammatory cytokine storm leading to multi-organ damage including that of the brain and testes. While the lungs, heart, and brain are identified as the main targets of SARS-CoV-2-mediated pathogenesis, reports on its testicular infections have been a subject of debate. The brain and testes are physiologically synchronized by the action of gonadotropins and sex steroid hormones. Though the evidence for the presence of the viral particles in the testicular biopsies and semen samples from COVID-19 patients are highly limited, the occurrence of testicular pathology due to abrupt inflammatory responses and hyperthermia has incresingly been evident. The reduced level of testosterone production in COVID-19 is associated with altered secretion of gonadotropins. Moreover, hypothalamic pathology which results from SARS-CoV-2 infection of the brain is also evident in COVID-19 cases. This article revisits and supports the key reports on testicular abnormalities and pathological signatures in the hypothalamus of COVID-19 patients and emphasizes that testicular pathology resulting from inflammation and oxidative stress might lead to infertility in a significant portion of COVID-19 survivors. Further investigations are required to monitor the reproductive health parameters and HPG axis abnormalities related to secondary pathological complications in COVID-19 patients and survivors.

Cardiovascular complications of SARS-CoV-2 infection (COVID-19): a systematic review and meta-analysis

Coronavirus Disease 2019 (COVID-19) originated in Wuhan, China in December 2019 and rapidly spread worldwide. Herein, we conducted a systematic review and meta-analysis to find the association between COVID-19 and cardiovascular complications. We conducted a systematic literature search of the PubMed and Embase databases from 01 December 2019 to 30 November 2020. We then statistically analyzed the incidence of cardiovascular complications in COVID-19 patients. We included 3044 confirmed COVID-19 cases from 12 studies. The most common cardiovascular complications in COVID-19 patients were myocardial injury (21.2%, 95% CI 12.3-30.0%) and arrhythmia (15.3%, 95% CI 8.4-22.3%), followed by heart failure (14.4%, 95% CI 5.7-23.1%) and acute coronary syndrome (1.0%, 95% CI 0.5-1.5%). The pooled incidence of heart failure, arrhythmia and myocardial injury in non-survivors were 47.8% (95% CI 41.4-54.2%), 40.3% (95% CI 1.6-78.9%) and 61.7% (95% CI 46.8-76.6%), respectively. Also, the data separately showed significantly higher incidence of heart failure and cardiac injury in non-survivors (relative risks = 5.13, 95% CI 2.46-10.7, Z = 4.36, P = 0.017) and (relative risks = 6.91, 95% CI 3.19-14.95, Z = 4.91, P = 0.009). Myocardial injury and arrhythmia were the most common complications in COVID-19 patients. Myocardial injury and heart failure were more common in patients who died, regardless of a history of cardiovascular disease. The incidence of heart failure and myocardial injury were higher in non-survivors compared to the survivors. Accordingly, in addition to basic support, cardiac reactions of patients with confirmed COVID-19 with or without underlying cardiovascular diseases should be closely monitored.

Neurological Manifestations of SARS-CoV-2: A Narrative Review.

Background:Coronavirus disease 2019 (COVID-19) pandemic started as an outbreak in China and soon crossed borders to affect the populations in all countries of the world. During the initial course of the disease, COVID-19 was perceived as a pneumonia-like illness. However, recent findings of COVID-19 patients suggest that the virus has the potential to disseminate to different tissues and organs, and cause significant complications.Summary:Neurological symptoms are of great significance as these usually present in and complicate critical cases. Many case reports and case series have documented the findings of neurological complications in COVID-19 patients. From the existing data, the most frequent symptoms in these patients were broadly classified into the central nervous system (CNS), peripheral nervous system, and skeletal muscular symptoms. CNS symptoms include meningitis, encephalitis, cerebrovascular complications, peripheral nervous system symptoms include anosmia, ageusia, and skeletal muscular symptoms include myalgias. It is postulated that the cause may be direct CNS injury through blood and neuronal pathways or indirectly because of an immune-mediated response, hypoxia caused by decreased oxygen saturation, or by the binding of subacute respiratory syndrome-coronavirus-2 to the host angiotensin-converting enzyme-2 receptors. Striking radiologic findings in COVID-19 patients with neurological symptoms have also emerged.Conclusions:As subacute respiratory syndrome-coronavirus-2 may potentially have lethal implications on the nervous system, it is important that neurologists are better informed about the spectrum of clinical manifestations, radiologic findings, and likely mechanisms of injury. Understanding the symptoms and radiologic imaging allows clinicians to consider brain imaging in any patient with suspected COVID-19 and neurological symptoms.

Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology

Scientists and health professionals are exhaustively trying to contain the coronavirus disease 2019 (COVID-19) pandemic by elucidating viral invasion mechanisms, possible drugs to prevent viral infection/replication, and health cares to minimize individual exposure. Although neurological symptoms are being reported worldwide, neural acute and long-term consequences of SARS-CoV-2 are still unknown. COVID-19 complications are associated with exacerbated immunoinflammatory responses to SARS-CoV-2 invasion. In this scenario, pro-inflammatory factors are intensely released into the bloodstream, causing the so-called “cytokine storm”. Both pro-inflammatory factors and viruses may cross the blood–brain barrier and enter the central nervous system, activating neuroinflammatory responses accompanied by hemorrhagic lesions and neuronal impairment, which are largely described processes in psychiatric disorders and neurodegenerative diseases. Therefore, SARS-CoV-2 infection could trigger and/or worse brain diseases. Moreover, patients with central nervous system disorders associated to neuroimmune activation (e.g. depression, Parkinson’s and Alzheimer’s disease) may present increased susceptibility to SARS-CoV-2 infection and/or achieve severe conditions. Elevated levels of extracellular ATP induced by SARS-CoV-2 infection may trigger hyperactivation of P2X7 receptors leading to NLRP3 inflammasome stimulation as a key mediator of neuroinvasion and consequent neuroinflammatory processes, as observed in psychiatric disorders and neurodegenerative diseases. In this context, P2X7 receptor antagonism could be a promising strategy to prevent or treat neurological complications in COVID-19 patients.

Low Incidence of Severe Gastrointestinal Complications in COVID-19 Patients Admitted to the Intensive Care Unit: A Large, Multicenter Study

Patients hospitalized with Coronavirus Disease 2019 (COVID-19) often have gastrointestinal symptoms, including diarrhea, nausea, vomiting, and abdominal pain.1 However, the rate of gastrointestinal complications in patients with COVID-19 is less well described. Recent reports from a single center have suggested an alarmingly high rate of serious gastrointestinal complications in critically ill patients with COVID-19.2,3 In a retrospective review of 92 patients with severe COVID-19 admitted to the intensive care unit (ICU), 44 patients (48%) had ileus, 4 (4%) had intestinal ischemia, and 2 (2%) had Ogilvie syndrome.

Circulating Biomarkers of COVID-19-Triggered Endotheliopathy: From Conjecture to Certainty

Background: Clinical and analytical data on patients suffering from coronavirus disease-2019 (COVID-19) indicate that endothelial damage plays a key role in the pathophysiology of the disease and is responsible for the pulmonary complications and the thrombotic microangiopathy affecting multiple organs, which contribute directly to mortality (Ackerman et al. N Engl J Med 2020). Detection of biomarkers of endothelial injury in circulating blood may provide critical diagnostic and prognostic information on the disease course (Goshua et al. Lancet Haematology 2020). Endothelial injury is also a cornerstone of pathobiology in other septic and potentially life-threatening inflammatory syndromes.Objectives: To identify circulating markers of endothelial damage in COVID-19 patients, and compare their levels with those observed in other septic syndromes.Methods: Plasma samples from non-critically ill patients with confirmed COVID-19 pneumonia (positive nasopharyngeal swab and confirmatory radiological chest imaging) requiring admission (n=42) were collected during the first 36h of hospitalization. Endothelial damage was evaluated by measuring in plasma: i) markers of endothelial function and activation (sVCAM-1, VWF, ADAMTS-13 activity, Protein C and α2-antiplasmin as a marker of fibrinolysis); ii) heparan sulfate (HS) levels, as indicators of endothelial glycocalyx degradation and loss of endothelial barrier function; and iii) C5b9 deposits on endothelial cells in culture, and soluble C5b9 (sC5b9) levels, to measure complement activation. Circulating dsDNA was analyzed as an indicator of the presence of neutrophil extracellular traps (NETs). ELISA tests were used for sVCAM-1, Protein C, HS, and sC5b9 levels. ADAMTS-13 activity was evaluated by FRETS. VWF, Protein C, and α2-antiplasmin were measured at the Atellica COAG 360 (Siemens Healthineers). C5b9 deposits were assessed by immunofluorescence and dsDNA levels by Quant-iT PicoGreen assay kit. Results were compared with those obtained in healthy donors (controls, n=45), and patients with non-infectious systemic inflammatory response syndrome (NI-SIRS, n=8) and septic shock (SS, n=8).Results: Levels of sVCAM-1 were significantly higher in COVID-19 patients vs. controls, NI-SIRS and SS (159±12 vs. 79±4, 57±8 and 80±10 ng/mL, respectively, p<0.005) (Mean±SDM). VWF was elevated in COVID-19 patients vs. controls (240±26 vs. 96±5%, p<0.001), with similar values in NI-SIRS (271±40%), and significantly reduced vs. SS (476±43%, p<0.001). HS levels in COVID-19 patients were twice those detected in controls (1669±174 vs. 839±36 ng/mL, p=0.001), but they did not differ from those in NI-SIRS (1372±368 ng/mL), and were significantly lower than in SS (3677±880 ng/mL, p<0.001 vs COVID-19). Regarding complement activation, deposits of C5b9 on endothelial cells were significantly increased vs. controls (2-fold, p<0.01), with no notable differences vs. NI-SIRS (3±1-fold) and significantly lower than in SS (8±2-fold, p<0.001). Remarkably, sC5b9 levels were much more elevated in COVID-19 patients (1064±120 vs. 204±11 ng/mL, p<0.001), and no significant differences were observed vs. NI-SIRS (902±160 ng/mL) or SS (958±180 ng/mL). Also of note, presence of NETs was significantly elevated in the plasma of COVID-19 patients vs. controls (16±1.3 vs. 2±0.3 ng/ml, p<0.001), but similar to NI-SIRS (19±5 ng/mL) and clearly inferior to SS (33±6 ng/mL, p<0.001) (Figure). Importantly and in contrast, ADAMTS-13 activity, Protein C, and α2-antiplasmin values were within the normal range in COVID-19 patients.Conclusions: Our data clearly demonstrate the presence of endothelial stress products in the circulating blood of non-critically ill COVID-19 patients. These biomarkers of endothelial injury are suggestive indicators of different aspects of the disease: specifically, release of acute phase reactants, degradation of the endothelial cell glycocalyx, and activation of the complement system. Furthermore, this profile of biomarkers in COVID-19 appears specific, with a differential behavior in comparison with septic shock, in which endothelial damage is also known to be critical. Additional studies are needed to validate these biomarkers as diagnostic and prognostic tools of the endothelial complications in COVID-19 patients, both in early disease and later, as well as supporting specific forms of therapeutic intervention.FigureDisclosuresCarreras:Jazz Pharmaceuticals: Research Funding, Speakers Bureau; German Jose´ Carreras Leukaemia Foundation: Research Funding. Carlo-Stella:Boehringer Ingelheim and Sanofi: Consultancy; ADC Therapeutics and Rhizen Pharmaceuticals: Research Funding; Bristol-Myers Squibb, Merck Sharp & Dohme, Janssen Oncology, AstraZeneca: Honoraria; Servier, Novartis, Genenta Science srl, ADC Therapeutics, F. Hoffmann-La Roche, Karyopharm, Jazz Pharmaceuticals: Membership on an entity’s Board of Directors or advisory committees. Moraleda:Sandoz: Consultancy, Other: Travel Expenses; Novartis: Consultancy, Other: Travel Expenses; Gilead: Consultancy, Other: Travel Expenses; Jazz Pharmaceuticals: Consultancy, Research Funding; Takeda: Consultancy, Other: Travel Expenses. Richardson:Celgene/BMS, Oncopeptides, Takeda, Karyopharm: Research Funding. Diaz-Ricart:German Jose Carreras Leukaemia Foundation: Research Funding; Jazz Pharmaceuticals: Honoraria, Research Funding.

Humanitas COVID-19 Task Force Venous and Arterial Thromboembolic Complications in COVID-19 Patients Admitted to an Academic Hospital in Milan, Italy

The occurrence of arterial and venous thromboembolic events was unusually high in hospitalized patients with coronavirus disease 2019 (COVID-19) in a Milan hospital from February to April 2020, prompting a revision of the diagnostic strategies and the use of thromboprophylaxis in ambulatory patients with COVID-19.

Asanas in Prone Posture and Slow Pranayamas Can Prevent Respiratory Complications in COVID-19 Patients

Worldwide more than 31 million have been reported till date to suffer from corona virus disease 2019 (COVID-19) and daily about ninety thousand positive cases are reported from India alone. About 10% of all symptomatic COVID-19 patients present with dyspnoea, interstitial pneumonia and few may progress to acute respiratory distress syndrome (ARDS) and multiorgan dysfunction.[1] It has been reported that most common cause of mortality in COVID-19 is the acute respiratory failure. Though antiviral drugs, chloroquine or hydroxychloroquine and respiratory therapies are being used, there are several ongoing clinical trials on traditional medicines for development of new therapies and vaccines, till date there is no evidence of any effective treatment for COVID-19. Prone positioning has been used as an effective therapy in ARDS, particularly when initiated in the early stage of it.[2] Recent reports have suggested improvement in respiratory functions of COVID-19 patients with prone positioning.[3] Based on postures in which asanas are practiced, they are divided into standing asanas, sitting asanas, supine asanas and prone asanas.[4] As prone positioning facilitates pulmonary functions, it is expected that prone asanas will promote respiratory functions. The practice of chandranadi pranayama (left-nostril breathing) and anulom-vilom pranayama (alternatenostril breathing) has been demonstrated to have maximum beneficial effects on autonomic and cardiorespiratory functions.[5,6] Pal’s slow pranayama schedule that comprises of both chandranadi and anulom-vilom pranayama’s has been documented to be effective in preventing ventricular tachycardia by improving vagal tone by modulating the process of respiratory sinus arrythmia.[7] Therefore, we assume that practice of asanas in prone posture and slow pranayama will improve cardio-respiratory functions in COVID-19, especially if practiced in the early phase of the disease.The asana-pranayama schedule could be as given below. Following eight asanas in prone posture as described in yoga book,[4] can be practiced: