Current Coronavirus Disease 2019 Patients Research Articles

Proteomic profiling of single extracellular vesicles reveals colocalization of SARS-CoV-2 with a CD81/integrin-rich EV subpopulation in sputum from COVID-19 severe patients.

The global outbreak of COVID-19, and the limited availability of clinical treatments, forced researchers around the world to search for the pathogenesis and potential treatments. Understanding the pathogenesis of SARS-CoV-2 is crucial to respond better to the current coronavirus disease 2019 (COVID-19) pandemic. We collected sputum samples from 20 COVID-19 patients and healthy controls. Transmission electron microscopy was used to observe the morphology of SARS-CoV-2. Extracellular vesicles (EVs) were isolated from sputum and the supernatant of VeroE6 cells, and were characterized by transmission electron microscopy, nanoparticle tracking analysis and Western-Blotting. Furthermore, a proximity barcoding assay was used to investigate immune-related proteins in single EV, and the relationship between EVs and SARS-CoV-2. Transmission electron microscopy images of SARS-COV-2 virus reveal EV-like vesicles around the virion, and western blot analysis of EVs extracted from the supernatant of SARS-COV-2-infected VeroE6 cells showed that they expressed SARS-COV-2 protein. These EVs have the infectivity of SARS-COV-2, and the addition can cause the infection and damage of normal VeroE6 cells. In addition, EVs derived from the sputum of patients infected with SARS-COV-2 expressed high levels of IL6 and TGF-β, which correlated strongly with expression of the SARS-CoV-2 N protein. Among 40 EV subpopulations identified, 18 differed significantly between patients and controls. The EV subpopulation regulated by CD81 was the most likely to correlate with changes in the pulmonary microenvironment after SARS-CoV-2 infection. Single extracellular vesicles in the sputum of COVID-19 patients harbor infection-mediated alterations in host and virus-derived proteins. These results demonstrate that EVs derived from the sputum of patients participate in virus infection and immune responses. This study provides evidence of an association between EVs and SARS-CoV-2, providing insight into the possible pathogenesis of SARS-CoV-2 infection and the possibility of developing nanoparticle-based antiviral drugs.

Manipulation of innate immune signaling pathways by SARS-CoV-2 non-structural proteins.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the current coronavirus disease 2019 (COVID-19) pandemic, induces an unbalanced immune response in the host. For instance, the production of type I interferon (IFN) and the response to it, which act as a front-line defense against virus invasion, are inhibited during SARS-CoV-2 infection. In addition, tumor necrosis factor alpha (TNF-α), a proinflammatory cytokine, is upregulated in COVID-19 patients with severe symptoms. Studies on the closely related betacoronavirus, SARS-CoV, showed that viral proteins such as Nsp1, Orf6 and nucleocapsid protein inhibit IFN-β production and responses at multiple steps. Given the conservation of these proteins between SARS-CoV and SARS-CoV-2, it is not surprising that SARS-CoV-2 deploys similar immune evasion strategies. Here, we carried out a screen to examine the role of individual SARS-CoV-2 proteins in regulating innate immune signaling, such as the activation of transcription factors IRF3 and NF-κB and the response to type I and type II IFN. In addition to established roles of SARS-CoV-2 proteins, we report that SARS-CoV-2 proteins Nsp6 and Orf8 inhibit the type I IFN response but at different stages. Orf6 blocks the translocation of STAT1 and STAT2 into the nucleus, whereas ORF8 inhibits the pathway in the nucleus after STAT1/2 translocation. SARS-CoV-2 Orf6 also suppresses IRF3 activation and TNF-α-induced NF-κB activation.

HIV infection does not affect the risk of death of COVID-19 patients: A systematic review and meta-analysis of epidemiological studies.

BackgroundEven during the current Coronavirus Disease 2019 (COVID-19) pandemic, the infection with the Human Immunodeficiency Virus (HIV) continues to pose a major threat, worldwide. In fact, the World Health Organization (WHO) defined the HIV infection as a risk factor for both severe COVID-19, at hospital admission, and in-hospital mortality. Despite this evidence, however, there remains the need for investigating whether SARS-CoV-2 infection could increase the risk of death among people living with HIV (PLHIV). Thus, we conducted a systematic review and meta-analysis to assess the impact of the SARS-CoV-2 infection on the risk of death among PLHIV and HIV- seronegative people.MethodsThe literature search was carried out on PubMed, Embase and Web of Science databases, from the inception to February 2022. Epidemiological studies on patients tested positive for SARS-CoV-2 infection, which compared the proportion of deaths between PLHIV and HIV-seronegative people, were considered eligible for the inclusion. The pooled odds ratio (OR) was obtained through meta-analysis of the comparison between PLHIV and HIV-seronegative people. Study quality was assessed by using the Newcastle-Ottawa Quality Assessment.ResultsOn a total of 1001 records obtained from the literature search, the present systematic review and meta-analysis included 28 studies on 168 531 PLHIV and 66 712 091 HIV-seronegative patients with SARS-CoV-2 infection. The meta-analysis showed no difference in the risk of death between PLHIV and HIV-seronegative patients (OR = 1.09; 95% confidence interval (CI) = 0.93-1.26; P > 0.001). However, a significant heterogeneity was found for this comparison (I2 = 88.8%, P < 0.001).ConclusionsAlthough our meta-analysis suggests no difference in the risk of death of PLHIV with SARS-CoV-2 infection, if compared with HIV-seronegative patients, further research should be encouraged to improve the current knowledge about the impact of SARS-CoV-2 and HIV co-infection.

Robust antiviral activity of commonly prescribed antidepressants against emerging coronaviruses: in vitro and in silico drug repurposing studies

During the current coronavirus disease 2019 (COVID-19) pandemic, symptoms of depression are commonly documented among both symptomatic and asymptomatic quarantined COVID-19 patients. Despite that many of the FDA-approved drugs have been showed anti-SARS-CoV-2 activity in vitro and remarkable efficacy against COVID-19 in clinical trials, no pharmaceutical products have yet been declared to be fully effective for treating COVID-19. Antidepressants comprise five major drug classes for the treatment of depression, neuralgia, migraine prophylaxis, and eating disorders which are frequently reported symptoms in COVID-19 patients. Herein, the efficacy of eight frequently prescribed FDA-approved antidepressants on the inhibition of both SARS-CoV-2 and MERS-CoV was assessed. Additionally, the in vitro anti-SARS-CoV-2 and anti-MERS-CoV activities were evaluated. Furthermore, molecular docking studies have been performed for these drugs against the spike (S) and main protease (Mpro) pockets of both SARS-CoV-2 and MERS-CoV. Results showed that Amitriptyline, Imipramine, Paroxetine, and Sertraline had potential anti-viral activities. Our findings suggested that the aforementioned drugs deserve more in vitro and in vivo studies targeting COVID-19 especially for those patients suffering from depression.

Neutrophil Extracellular Traps, Sepsis and COVID-19 - A Tripod Stand.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current coronavirus disease 2019 (COVID-19) pandemic. Majority of COVID-19 patients have mild disease but about 20% of COVID-19 patients progress to severe disease. These patients end up in the intensive care unit (ICU) with clinical manifestations of acute respiratory distress syndrome (ARDS) and sepsis. The formation of neutrophil extracellular traps (NETs) has also been associated with severe COVID-19. Understanding of the immunopathology of COVID-19 is critical for the development of effective therapeutics. In this article, we discuss evidence indicating that severe COVID-19 has clinical presentations consistent with the definitions of viral sepsis. We highlight the role of neutrophils and NETs formation in the pathogenesis of severe COVID-19. Finally, we highlight the potential of therapies inhibiting NETs formation for the treatment of COVID-19.

A systematic review on neutrophil extracellular traps and its prognostication role in COVID-19 patients.

Neutrophil extracellular traps (NETs) are extracellular webs composed of neutrophil granular and nuclear elements. Because of the potentially dangerous amplification circuit between inflammation and tissue damage, NETs are becoming one of the investigated components in the current Coronavirus Disease 2019 (COVID-19) pandemic. The purpose of this systematic review is to summarize studies on the role of NETs in determining the prognosis of COVID-19 patients. The study used six databases: PubMed, Science Direct, EBSCOHost, Europe PMC, ProQuest, and Scopus. This literature search was implemented until October 31, 2021. The search terms were determined specifically for each databases, generally included the Neutrophil Extracellular Traps, COVID-19, and prognosis. The Newcastle Ottawa Scale (NOS) was then used to assess the risk of bias. Ten studies with a total of 810 participants were chosen based on the attainment of the prerequisite. Two were of high quality, seven were of moderate quality, and the rest were of low quality. The majority of studies compared COVID-19 to healthy control. Thrombosis was observed in three studies, while four studies recorded the need for mechanical ventilation. In COVID-19 patients, the early NETs concentration or the evolving NETs degradations can predict patient mortality. Based on their interactions with inflammatory and organ dysfunction markers, it is concluded that NETs play a significant role in navigating the severity of COVID-19 patients and thus impacting their prognosis.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12026-022-09293-w.

Study protocol for the St James's Hospital, Tallaght University Hospital, Trinity College Dublin Allied Researchers' (STTAR) Bioresource for COVID-19

Background: The current coronavirus disease 2019 (COVID-19) pandemic began in Ireland with the first confirmed positive case in March 2020. In the early stages of the pandemic clinicians and researchers in two affiliated Dublin hospitals identified the need for a COVID-19 biobanking initiative to support and enhance research into the disease. Through large scale analysis of clinical, regional, and genetic characteristics of COVID-19 patients, biobanks have helped identify, and so protect, at risk patient groups The STTAR Bioresource has been created to collect and store data and linked biological samples from patients with SARS-CoV-2 infection and healthy and disease controls. Aim: The primary objective of this study is to build a biobank, to understand the clinical characteristics and natural history of COVID-19 infection with the long-term goal of research into improved disease understanding, diagnostic tests and treatments. Methods: This is a prospective dual-site cohort study across two tertiary acute university teaching hospitals. Patients are recruited from inpatient wards or outpatient clinics. Patients with confirmed COVID-19 infection as well as healthy and specific disease control groups are recruited. Biological samples are collected and a case report form detailing demographic and medical background is entered into the bespoke secure online Dendrite database. Impact: The results of this study will be used to inform national and international strategy on health service provision and disease management related to COVID-19. In common with other biobanks, study end points evolve over time as new research questions emerge. They currently include patient survival, occurrence of severe complications of the disease or its therapy, occurrence of persistent symptoms following recovery from the acute illness and vaccine responses.

Study protocol for theSt James's Hospital, Tallaght University Hospital, Trinity College Dublin Allied Researchers' (STTAR) Bioresource for COVID-19.

Background: The current coronavirus disease 2019 (COVID-19) pandemic began in Ireland with the first confirmed positive case in March 2020. In the early stages of the pandemic clinicians and researchers in two affiliated Dublin hospitals identified the need for a COVID-19 biobanking initiative to support and enhance research into the disease. Through large scale analysis of clinical, regional, and genetic characteristics of COVID-19 patients, biobanks have helped identify, and so protect, at risk patient groups The STTAR Bioresource has been created to collect and store data and linked biological samples from patients with SARS-CoV-2 infection and healthy and disease controls. Aim: The primary objective of this study is to build a biobank, to understand the clinical characteristics and natural history of COVID-19 infection with the long-term goal of research into improved disease understanding, diagnostic tests and treatments. Methods: This is a prospective dual-site cohort study across two tertiary acute university teaching hospitals. Patients are recruited from inpatient wards or outpatient clinics. Patients with confirmed COVID-19 infection as well as healthy and specific disease control groups are recruited. Biological samples are collected and a case report form detailing demographic and medical background is entered into the bespoke secure online Dendrite database. Impact: The results of this study will be used to inform national and international strategy on health service provision and disease management related to COVID-19. In common with other biobanks, study end points evolve over time as new research questions emerge. They currently include patient survival, occurrence of severe complications of the disease or its therapy, occurrence of persistent symptoms following recovery from the acute illness and vaccine responses.

Three Specific Potential Epitopes That Could Be Recognized by T Cells of Convalescent COVID-19 Patients Were Identified From Spike Protein.

The current coronavirus disease 2019 (COVID-19) vaccines are used to prevent viral infection by inducing neutralizing antibody in the body, but according to the existing experience of severe acute respiratory syndrome coronavirus (SARS) infection, T-cell immunity could provide a longer durable protection period than antibody. The research on SARS-CoV-2-specific T-cell epitope can provide target antigen for the development and evaluation of COVID-19 vaccines, which is conducive to obtain COVID-19 vaccine that can provide long-term protection. For screening specific T-cell epitopes, a SARS-CoV-2 S protein peptide library with a peptide length of 15 amino acids was synthesized. Through flow cytometry to detect percentage of IFN-γ+ T cells after mixed COVID-19 convalescent patients’ peripheral blood mononuclear cell with peptide library, seven peptides (P77, P14, P24, P38, P48, P74, and P84) that can be recognized by the T cells of COVID-19 convalescent patients were found. After excluding the nonspecific cross-reactions with unexposed population, three SARS-CoV-2-specific T-cell potential epitopes (P38, P48, and P84) were finally screened with the positive reaction rates between 15.4% and 48.0% in COVID-19 convalescent patients. This study also provided the HLA allele information of peptide-positive-response COVID-19 convalescent patients, thus predicting the population coverage of these three potential epitopes. Some HLA alleles showed higher frequency of occurrence in COVID-19 patients than in total Chinese population but no HLA alleles related to the T-cell peptide response and the severity of COVID-19. This research provides three potential T-cell epitopes that are helpful for the design and efficacy evaluation of COVID-19 vaccines. The HLA information provided by this research supplies reference significance for subsequent research such as finding the relation of HLA genotype with disease susceptibility.

Medico-demographic characteristics and outcomes of COVID-19 patients admitted to a Provincial Hospital in Center-West of Morocco

The current Coronavirus Disease 2019 (COVID-19) pandemic that emerged in December 2019 in China continues to claim a thousand lives worldwide. This study aimed to report characteristics and in-hospital outcomes of a Moroccan COVID-19 cohort, and identify factors which predispose patients to hospitalization and mortality from COVID-19. We conducted a cross-sectional study of symptomatic COVID-19 patients referred to COVID-19 ward of the Settat Provincial Hospital, during October 2020. A confirmed COVID-19 case was defined by a positive detection of SARS-CoV-2 genome using real-time RT-PCR assay performed on nasopharyngeal swabs. Patients´ demographic and clinical characteristics were collected and analyzed using SPSS V22.0. Univariate followed by multivariate logistic regression analysis was performed to identify factors associated with mortality due to COVID-19. In total, 269 patients were reported. The median age was 64 years [IQR 54-73], 48.7% were elderly (≥ 65 years), 51.7% were men, and the case-fatality rate (CFR) was 5.58%. Males had a higher CFR (6.5%) than females (4.6%). In deceased people: 60% males, 73.3% were elderly, and oxygen saturation values of 90% or less on admission were more frequent (86.7%) than in recovered ones (10.9%). Most patients (80.3%) had at least one comorbidity: 100% of deaths, 59% older than 60 years, CFR was 6.94% and the most prevalent diseases were diabetes (54.6%), hypertension (41.7%), and cardiac disease (40.7%). The most common symptoms on presentation were dyspnea (67.7%), fever (65.4%) and cough (58.4%). Multivariable logistic regression analysis showed that only older age (AOR: 10.860, 95% CI: 3.382-34.86; p<0.001) and cardiac disease (AOR: 0.244, 95% CI: 0.074-0.799; p=0.02) were associated with higher mortality rates. Categorizing patients at admission according to risk factors identified by multivariate and also univariate analyses (mainly dyspnea) is essential to help in deciding the hospitalization priority and the strategy that will eventually reduce death risk.

Mild COVID-19 and Impaired Blood Cell-Endothelial Crosstalk: Considering Long-Term Use of Antithrombotics?

Current coronavirus disease 2019 (COVID-19) pandemic reveals thrombotic, vascular, and endothelial dysfunctions at peak disease. However, the duration, degree of damage, and appropriate long-term use of antithrombotic strategies are unclear. Most COVID data are yielded from random clinical observations or autopsy of postmortem samples, while precise blood cellular data in survivors are insufficient. We analyzed erythrocytes, circulating endothelial cells, and echinocytes by electron microscopy and flow cytometry in patients with confirmed COVID-19 (n = 31) and matched healthy controls (n = 32) on admission and at hospital discharge. All patients experienced mild disease, none required pulmonary support, and all survived. Admission number of circulating endothelial cells was significantly (40-100 times) higher in COVID-19 patients. Cells were massively damaged by multiple fenestrae in membranes with diameter comparable to the size of supercapsid in SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) virus. COVID-19 also provoked formation of stacked aggregated erythrocytes capable of clogging microvascular bed and of diminishing oxygen supply. In some patients, such abnormalities persisted at hospital discharge revealing remaining intracellular penetration of SARS-CoV-2 where it may be replicated and returned to circulation. These observational and descriptive data suggest that persistent viral cell injury may cause blood vessel damage; their increased permeability resulted in tissue edema, inflammation, platelet activation, and augmented thrombosis. There is a residual blood cell damage following the acute phase in some COVID-19 survivors. Controlled outcome-driven trials are urgently needed for exploring optimal use of long-term antithrombotics and vascular protection strategies even after mild COVID-19.

How SARS-CoV-2 might affect potassium balance via impairing epithelial sodium channels?

Severe acute respiratory syndrome coronaviruses 2 (SARS-CoV-2) is the causative agent of current coronavirus disease 2019 (COVID-19) pandemic. Electrolyte disorders particularly potassium abnormalities have been repeatedly reported as common clinical manifestations of COVID-19. Here, we discuss how SARS-CoV-2 may affect potassium balance by impairing the activity of epithelial sodium channels (ENaC). The first hypothesis could justify the incidence of hypokalemia. SARS-CoV-2 cell entry through angiotensin-converting enzyme 2 (ACE2) may enhance the activity of renin–angiotensin–aldosterone system (RAAS) classical axis and further leading to over production of aldosterone. Aldosterone is capable of enhancing the activity of ENaC and resulting in potassium loss from epithelial cells. However, type II transmembrane serine protease (TMPRSS2) is able to inhibit the ENaC, but it is utilized in the case of SARS-CoV-2 cell entry, therefore the ENaC remains activated. The second hypothesis describe the incidence of hyperkalemia based on the key role of furin. Furin is necessary for cleaving both SARS-CoV-2 spike protein and ENaC subunits. While the furin is hijacked by the virus, the decreased activity of ENaC would be expected, which causes retention of potassium ions and hyperkalemia. Given that the occurrence of hypokalemia is higher than hyperkalemia in COVID-19 patients, the first hypothesis may have greater impact on potassium levels. Further investigations are warranted to determine the exact role of ENaC in SARS-CoV-2 pathogenesis.

Effects of Renin-Angiotensin-Aldosterone Inhibitors on Early Outcomes of Hypertensive COVID-19 Patients: A Randomized Triple-Blind Clinical Trial.

Background The role of angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) has been addressed in some studies related to the current coronavirus disease-2019 (COVID-19) pandemic with possible higher severity and mortality in patients with hypertension. A triple-blind randomized controlled trial was designed to evaluate the effects of these medications on the COVID-19 progression.Methods Patients were enrolled in this trial between April and September 2020. They were randomized in two groups. The former dosage of ACEis/ARBs was continued in one group while in another group, the ACEis/ARBs were replaced by amlodipine ± carvedilol according to the dose equivalents. The primary outcomes were length of stay in hospitals and intensive care units. Other outcomes include mechanical ventilation, non-invasive ventilation, readmission, and COVID-19 symptoms after discharge.Results We randomized 64 patients with COVID-19 into two groups. Most patients were aged 66-80 and 46-65 years-old, 33 (51.6%) and 27 (42.2%), respectively. The study groups were nearly similar in baseline vital signs and characteristics. In addition, there was no significant difference in terms of recorded systolic and diastolic blood pressure measurements between groups. Furthermore, we did not find a significant difference between the days of intensive care unit or ward admission, the discharge rate, or readmission rates between the two groups.Conclusions This randomized triple-blind multi-centric clinical trial did not show any deleterious effects of ACEi/ARB medications in hypertensive COVID-19 patients.

Superadded Coinfections and Antibiotic Resistance in the Context of COVID-19: Where do We Stand?

Purpose of reviewPoor outcomes in the current coronavirus disease 2019 (COVID-19) pandemic have been attributed to superadded bacterial coinfections. The World Health Organization has reported overzealous usage of broad-spectrum antibiotics during this current pandemic raising concerns of increasing antimicrobial resistance? Therefore, the knowledge of coinfection and the common pathogens during these challenging times is essential for antibiotic stewardship practices.Recent findingsThe incidence of reported superimposed bacterial and viral coinfections in COVID-19 patients is around 0.04 to 17%. However, more than 70% of patients have received broad-spectrum antibiotics. The presence of a simultaneous coinfection can be suspected in patients with neutrophilic lymphocytosis and elevated procalcitonin in the setting of COVID-19. Multiplex polymerase chain reaction (PCR) panels, with its short turnaround time, aid in the definitive diagnosis of possible coinfection. Acinetobacter baumanii, Mycoplasma pneumonia, influenza virus, Aspergillus, Candida, etc., are commonly implicated pathogens.SummaryRapid characterization of coinfection and avoidance of overzealous use of broad-spectrum antibiotics in COVID-19 patients are the key to prevent antibiotic resistance during this pandemic.How to cite this articleKayarat B, Khanna P, Sarkar S. Superadded Coinfections and Antibiotic Resistance in the Context of COVID-19: Where do We Stand? Indian J Crit Care Med 2021;25(6):699–703.

Screening for Sarcopenia (Physical Frailty) in the COVID-19 Era.

Although the numbers of aged populations have risen considerably in the last few decades, the current coronavirus disease 2019 (COVID-19) has revealed an extensive vulnerability among these populations. Sarcopenia is an age-related disorder that increases hospitalization, dependencies, and mortality in older adults. It starts to develop in midlife or even earlier as a result of unbalanced diet/poor nutrition and low levels of physical activity, in addition to chronic disorders such as obesity and diabetes mellitus. Given that social isolation is adopted as the most protective measure against COVID-19, the level of physical activity and the intake of adequate diet have considerably declined, especially among older adults—denoting an increased possibility for developing sarcopenia. Research also shows a higher vulnerability of sarcopenic people to COVID-19 as well as the development of wasting disorders such as sarcopenia and cachexia in a considerable proportion of symptomatic and recovering COVID-19 patients. Muscular wasting in COVID-19 is associated with poor prognosis. Accordingly, early detection and proper management of sarcopenia and wasting conditions in older adults and COVID-19 patients may minimize morbidity and mortality during the current COVID-19 crisis. This review explored different aspects of screening for sarcopenia, stressing their relevance to the detection of altered muscular structure and performance in patients with COVID-19. Current guidelines recommend prior evaluation of muscle strength by simple measures such as grip strength to identify individuals with proven weakness who then would be screened for muscle mass loss. The latter is best measured by MRI and CT. However, due to the high cost and radiation risk entailed by these techniques, other simpler and cheaper techniques such as DXA and ultrasound are given preference. Muscle loss in COVID-19 patients was measured during the acute phase by CT scanning of the pectoralis muscle simultaneously during a routine check for lung fibrosis, which seems to be an efficient evaluation of sarcopenia among those patients with no additional cost. In recovering patients, muscle strength and physical performance have been evaluated by electromyography and traditional tests such as the six-minute walk test. Effective preventive and therapeutic interventions are necessary in order to prevent muscle loss and associated physical decline in COVID-19 patients.

The characteristics of laboratory tests at admission and the risk factors for adverse clinical outcomes of severe and critical COVID-19 patients

BackgroundThe current coronavirus disease 2019 (COVID-19) is a public health emergency. In this study, we aimed to evaluate the risk factors for mortality in severe and critical COVID-19 patients.MethodsWe performed a retrospective study of patients diagnosed with severe and critical COVID-19 from four hospitals in Wuhan, China, by evaluating the clinical characteristics and laboratory results, and using Cox proportional hazards model to assess the risk factors involved in disease progression.ResultsIn total, 446 patients with COVID-19 were enrolled. The study indicated a high mortality rate (20.2%) in severe and critical COVID-19 patients. At the time of admission, all patients required oxygen therapy, and 52 (12%) required invasive mechanical ventilation, of which 50 (96%) died. The univariate Cox proportional hazards model showed a white blood cell count of more than 10 × 109/L (HR 3.993,95%CI 2.469 to 6.459) that correlated with an increased mortality rate. The multivariable Cox proportional hazards model demonstrated that older age (HR 1.066, 95% CI 1.043 to 1.089) and higher white blood cell count (HR 1.135, 95% CI 1.080 to 1.192) were independent risk factors for determining COVID-19 associated mortality.ConclusionsCOVID-19 is associated with a significant risk of morbidity and mortality in the population. Older age and higher white blood cell count were found to be independent risk factors for mortality.

COVID-19 and venous thromboembolism: Known and unknown for imaging decisions.

As we continue to fight against the current coronavirus disease-2019 (COVID-19) pandemic, healthcare professionals across the globe are trying to answer questions surrounding how to best help patients with the up-to-date available science while awaiting the development of new therapies and mass vaccination. Since early in the pandemic, studies indicated a heightened risk of venous thromboembolism (VTE) in COVID-19 infected patients. There have been differing expert opinions about how to assess pretest probability of VTE in this patient population. This has been partly due to the high prevalence of respiratory failure in this patient population and the use of D-dimer as a prognostic test which is also frequently elevated in patients with COVID-19 in absence of VTE. Some experts have argued for an approach similar to usual care with testing if clinical suspicion is high enough. Some have argued for more routine screening at different points of care. Others have even suggested empiric therapeutic anti-coagulation in moderate to severely ill COVID-19 patients. In the following article, we review and summarize the most current literature in hopes of assisting clinicians in decision making and guidance for when to be concerned for VTE in COVID-19 patients. We also discuss research gaps and share pathways currently being used within our institution.

A real-life setting evaluation of the effect of remdesivir on viral load in COVID-19 patients admitted to a large tertiary centre in Israel

ObjectivesThe effectiveness of remdesivir, a Food and Drug Administration-approved drug for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has been repeatedly questioned during the current coronavirus disease 2019 (COVID-19) pandemic. Most of the recently reported studies were randomized controlled multicentre clinical trials. Our goal was to test the efficiency of remdesivir in reducing nasopharyngeal viral load and hospitalization length in a real-life setting in patients admitted to a large tertiary centre in Israel. MethodsA total of 142 COVID-19 patients found to have at least three reported SARS-CoV-2 quantitative RT-PCR tests during hospitalization were selected for this study. Of these, 29 patients received remdesivir, while the remaining non-treated 113 patients served as controls. ResultsAmong the tested parameters, the control and remdesivir groups differed significantly only in the intubation rates. Remdesivir treatment did not significantly affect nasopharyngeal viral load, as determined by comparing the differences between the first and last cycle threshold values of the SARS-CoV-2 quantitative RT-PCR tests performed during hospitalization (cycle threshold 7.07 ± 6.85 vs. 7.08 ± 7.27, p 0.977 in the control and treated groups, respectively). Remdesivir treatment shortened hospitalization length by less than a day compared with non-treated controls and by 3.1 days when non-intubated patients from both groups were compared. These differences, however, were not statistically significant, possibly because of the small size of the remdesivir group. DiscussionRemdesivir was not associated with nasopharyngeal viral load changes, but our study had a significant disease severity baseline imbalance and was not powered to detect viral load or clinical differences.

Closed endotracheal suction catheter system related complications in mechanically ventilated COVID-19 patients.

Sir, In the current coronavirus disease 2019 (COVID-19) pandemic, about 15% of patients may develop severe disease and 5% critical disease requiring admission to an intensive care unit (ICU) and mechanical ventilation.[1] In mechanically ventilated patients, closed endotracheal suctioning system is used to prevent disconnection of circuit and consequent de-recruitment of alveoli and to prevent aerosolisation of droplets and potential contamination of surroundings.[23] However, in times of sudden surge in cases, trained ICU staff may not be always available. Moreover, efficiency is reduced after wearing personal protective equipment (PPE) and visibility may turn poor due to fogging of goggles. Therefore, inadvertent human errors may occur. We report two such cases involving the use of in-line closed suction catheter system (DAR™ closed suction system, Covidien Ireland Limited). In the first case, we noticed that the closed suction catheter was not completely withdrawn outside after suctioning was complete and the rotatory access knob was closed. Presence of part of the suction catheter inside the endotracheal tube led to increase in the peak airway pressures and frequent ventilator alarms that was initially interpreted as bronchospasm [Figure 1a]. However, a very close inspection revealed the actual problem. In another case, although the suction catheter was completely withdrawn, the rotating access knob was not closed, which led to significant leak in the circuit and activation of ventilator alarms [Figure 1b]. Inflated plastic sheath covering of the closed suction system revealed this problem. These kinds of problem may lead to unnecessary troubleshooting warranting treatment/interventions (like treating with bronchodilators in case of misdiagnosed bronchospasm or inflating the pilot balloon further in case of leak), which may even harm the patient (like barotrauma or alveolar de-recruitment). Fortunately, in both our cases, the actual problems were identified and no adverse events were seen. Problems like blocked tip of closed suction catheter leading to inadequate suctioning[4] and migration of piece of closed suction catheter leading to bronchial obstruction have been already reported.[5]Figure 1: (a) Closed suction catheter (black arrow) partially kept inside endotracheal tube and difficult to detect due to transparent colour of distal part of the catheter; (b) rotating access knob was not closed causing leak and overinflated plastic sheathing (white arrow)While the nursing staff were aware of the standard operating procedures for the closed suction system in ICU, impaired visibility due to fogging of goggles was the reason reported behind such inadvertent mistakes in both the cases. The fogging issue has been addressed by regular use of antifogging markers.[6] However, we would like to suggest two design modifications of the closed suction system. First, the colour of the in-line catheter may be made more conspicuous throughout the length of the catheter. The suction catheter of DAR™ closed suction system (Covidien Ireland Limited) is blue in the advancing end while being transparent towards the tail end [Figure 1b] and may evade detection if left inside the ventilator circuit with suboptimal visibility while working with PPEs. Second, an in-line self-sealing valve/diaphragm may be placed at the rotatory access knob to eliminate the risk of circuit leak in case the rotating access knob is inadvertently left open. To conclude, impaired visibility due to fogging of goggles may lead to inadvertent errors while operating equipment like closed suction catheter system in COVID-19 ICUs. Heightened vigilance and appropriate troubleshooting interventions might avoid and resolve such unintentional mistakes. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

AXL is a candidate receptor for SARS-CoV-2 that promotes infection of pulmonary and bronchial epithelial cells

The current coronavirus disease 2019 (COVID-19) pandemic presents a global public health challenge. The viral pathogen responsible, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), binds to the host receptor ACE2 through its spike (S) glycoprotein, which mediates membrane fusion and viral entry. Although the role of ACE2 as a receptor for SARS-CoV-2 is clear, studies have shown that ACE2 expression is extremely low in various human tissues, especially in the respiratory tract. Thus, other host receptors and/or co-receptors that promote the entry of SARS-CoV-2 into cells of the respiratory system may exist. In this study, we found that the tyrosine-protein kinase receptor UFO (AXL) specifically interacts with the N-terminal domain of SARS-CoV-2 S. Using both a SARS-CoV-2 virus pseudotype and authentic SARS-CoV-2, we found that overexpression of AXL in HEK293T cells promotes SARS-CoV-2 entry as efficiently as overexpression of ACE2, while knocking out AXL significantly reduces SARS-CoV-2 infection in H1299 pulmonary cells and in human primary lung epithelial cells. Soluble human recombinant AXL blocks SARS-CoV-2 infection in cells expressing high levels of AXL. The AXL expression level is well correlated with SARS-CoV-2 S level in bronchoalveolar lavage fluid cells from COVID-19 patients. Taken together, our findings suggest that AXL is a novel candidate receptor for SARS-CoV-2 which may play an important role in promoting viral infection of the human respiratory system and indicate that it is a potential target for future clinical intervention strategies.