Antiviral activity of the human endogenous retrovirus-R envelope protein against SARS-CoV-2

Coronavirus-induced disease-19 (COVID-19), caused by SARS-CoV-2, is still a major global health challenge. Human endogenous retroviruses (HERVs) represent retroviral elements that were integrated into the ancestral human genome. HERVs are important in embryonic development as well as in the manifestation of diseases, including cancer, inflammation, and viral infections. Here, we analyze the expression of several HERVs in SARS-CoV-2-infected cells and observe increased activity of HERV-E, HERV-V, HERV-FRD, HERV-MER34, HERV-W, and HERV-K-HML2. In contrast, the HERV-R envelope is downregulated in cell-based models and PBMCs of COVID-19 patients. Overexpression of HERV-R inhibits SARS-CoV-2 replication, suggesting its antiviral activity. Further analyses demonstrate the role of the extracellular signal-regulated kinase (ERK) in regulating HERV-R antiviral activity. Lastly, our data indicate that the crosstalk between ERK and p38 MAPK controls the synthesis of the HERV-R envelope protein, which in turn modulates SARS-CoV-2 replication. These findings suggest the role of the HERV-R envelope as a prosurvival host factor against SARS-CoV-2 and illustrate a possible advantage of integration and evolutionary maintenance of retroviral elements in the human genome.Copyright © 2023 The Authors.

Response assessment and clinical efficacy of 188Re-NDEDC/ Lipiodol trans-arterial Radionuclide therapy (TART) in patients with Hepatocellular carcinoma: A prospective single center study

Aim/Introduction: Inoperable HCC patients with multifocal lesions and malignant portal vein thrombosis (PVT) have poorer prognosis with limited treatment options. 188Re-N-DEDC lipiodol is an emerging agent for such cases due to its simple and on-site labelling procedure, cost-effectiveness and least radiation induced side effects. We aimed to explore the response assessment, safety and efficacy of 188Re-N-DEDC-lipiodol in multifocal HCC with/without PVT. Material(s) and Method(s): Radiologically and biochemically confirmed HCC patients with/without PVT having ECOG performance status <=2 and Child Pugh score A /B were recruited. Baseline serum alpha-fetoprotein (AFP) was obtained for biochemical correlation and follow-up. After lipiodol labelling & QC checks, therapeutic activity of 188Re-N-DEDC/lipiodol were injected under fluoroscopic guidance through femoral branch in super-selective artery of tumor. Post-therapy planar and SPECT/CT imaging were performed at 2, 6, 12, 24, 48 and 72hrs to see tumoral retension. Response was assessed at 2 months post-therapy by mRECIST criteria and S. AFP level. Clinical & biochemical toxicities were graded by CTCAE v5.0. Result(s): Thirty-One (31) patients (27 male;4 female) with mean age 55.9 +/- 9.78 years have been recruited for therapy. Overall mean injected activity of 188Re-N-DEDC lipiodol was 2.9+/-0.9GBq (78.4+/-24.2mCi). The median follow-up period was of 6 months. One patient was lost to follow-up due to prevailing COVID situations and 3 patient died before follow-up due to internal variceal bleeding, so radiological and biochemical response were assessed only in 27/31 patients by mRECIST criteria and serum AFP tumor marker level respectively. Radiologically, objective response rate was seen in 12/27 patients (~45%) and disease control rate was seen in 20/27 patients (~74%). 6/27 patients had non-AFP producing tumor i.e. serum AFP were normal at baseline and follow-ups while in remaining 21 patients, biochemical objective response rate was seen in 11/21 patients (~52%) and disease control rate was 14/21 patients (~67%). Post-therapy clinical toxicities (Nausea, Vomiting, Fever, abdominal pain) were observed in most of the patients for 2-3 days and were treated symptomatically. One patient showed grade 3 liver toxicity & progressive worsening of LFT, 20 patients showed grade 1 derangements in liver enzymes & 6 patients showed grade 2 derangements in liver enzymes. Hematological toxicities were seen in 4 patients (<=Grade 2 in 2 patients & grade 3 in two patients). Conclusion(s): In patients of HCC with/without PVT, trans-arterial Re188-N-DEDC/lipiodol therapy proved to be safe and effective with good disease control.

Thromboelastography Determined Fibrinolysis Shutdown and Its Correlation with Complications and Outcomes in Patients with Coronavirus Disease 2019

Introduction: Coronavirus disease 2019 (COVID-19) causes abnormalities in the hemostatic system, which are referred to as COVID-associated coagulopathy. Whole blood viscoelastic studies, such as thromboelastography (TEG), are the best way to determine the dynamics of clot formation. The hypercoagulable state seen in COVID-19 patients is aggravated by a severe state of fibrinolysis shutdown, which is caused by overexpression of plasminogen activator inhibitor 1 and thrombin activated fibrinolysis inhibitor. Method(s): An automated thromboelastogram was used to perform TEG on 28 COVID-19 patients. Based on TEG parameters such as R-time, K-time, alpha angle, maximum amplitude (MA), and clotting index (CI), the hemostatic state was classified as hypercoagulable in 17 (63 percent), hypocoagulable in 2 (7 percent), or normal in 8 (30 percent) patients. Result(s): Twenty-seven patients were included, with a median age of 50 years (IQR 40-60 years) and a male to female ratio of 0.9:1. COVID-19 was mild in 6 (22.2%), moderate in 2 (7.4%), and severe in 19 (70.4%) patients. Fibrinolytic shutdown was detected in 4 (15%) patients. TEG analysis revealed that they were hypercoagulable. All four patients showed high D-dimer levels and a LY-30 of 0%, as well as decreased K-time and increased alpha angle or MA. Conclusion(s): Despite thromboprophylaxis, hypercoagulable states and severe inflammatory states are prevalent in COVID-19 patients. Patients with hypocoagulable and hypercoagulable conditions had greater 28-day mortality than those with normal coagulation. (Log-rank test, P=0.002). Only two of the four patients who had their fibrinolytic systems turned down survived. These patients had no clinically evident thrombosis.

Thromboelastography Determined Fibrinolysis Shutdown And Its Correlation With Complications And Outcomes In Patients With Coronavirus Disease 2019

Introduction: Coronavirus disease 2019 (COVID-19) causes abnormalities in the hemostatic system, which are referred to as COVIDassociated coagulopathy. Whole blood viscoelastic studies, such as thromboelastography (TEG), are the best way to determine the dynamics of clot formation. The hypercoagulable state seen in COVID-19 patients is aggravated by a severe state of ''fibrinolysis shutdown,'' which is caused by overexpression of plasminogen activator inhibitor 1 and thrombin activated fibrinolysis inhibitor. Aims & Objectives: We aimed to study the coagulation pattern in COVID-19 patients on TEG and explored the predictors of outcomes in our patients. Material(s) and Method(s): An automated thromboelastogram was used to perform TEG on 28 COVID-19 patients. Based on TEG parameters such as R-time, K-time, alpha angle, maximum amplitude (MA), and clotting index (CI), the hemostatic state was classified as hypercoagulable in 17 (63 percent), hypocoagulable in 2 (7 percent), or normal in 8 (30 percent) patients. Result(s): Twenty-seven patients were included, with a median age of 50 years (IQR 40-60 years) and a male to female ratio of 0.9:1. COVID-19 was mild in 6 (22.2%), moderate in 2 (7.4%), and severe in 19 (70.4%) patients. Fibrinolytic shutdown was detected in 4 (15%) patients. TEG analysis revealed that they were hypercoagulable. All four patients showed high D-dimer levels and a LY-30 of 0%, as well as decreased K-time and increased alpha angle or MA. Conclusion(s): Despite thromboprophylaxis, hypercoagulable states and severe inflammatory states are prevalent in COVID-19 patients. Patients with hypocoagulable and hypercoagulable conditions had greater 28-day mortality than those with normal coagulation. (Logrank test, P = 0.002). Only two of the four patients who had their fibrinolytic systems turned down survived. These patients had no clinically evident thrombosis.

Human endogenous retrovirus-R envelope is a host restriction factor against severe acute respiratory syndrome-coronavirus-2 (preprint)

Coronavirus induced disease-19 (COVID-19), caused by the SARS-CoV-2 remains a major global health challenge. Human endogenous retroviruses (HERVs) represent retroviral elements that got integrated into the ancestral human genome. HERVs are important in development and diseases, including cancer, inflammation and viral infections. Here, we analyzed the expression of several HERVs in SARS-CoV-2 infected cells and observed increased activity of HERV-E, HERV-V, HERV-FRD, HERV-MER34, HERV-W and HERV-K-HML2. In contrast, HERV-R-envelope was downregulated in cell-based models and COVID-19 patient PBMCs. HERV-R overexpression inhibited SARS-CoV-2 replication, suggesting its antiviral action. Further studies demonstrated the role of extracellular signal-regulated kinase (ERK) in regulating HERV-R antiviral activity. Cross-talk between the ERK and p38 MAPK controls HERV-R envelope synthesis, which in turn modulates the replication of SARS-CoV-2. These findings establish the importance of HERV-R envelope as a host restriction factor against SARS-CoV-2 and illustrate the advantage of integration and evolutionary maintenance of retroviral-elements in the human genome.

Analisis penelusuran masker sebagai protokol kesehatan saat pandemi COVID-19 di Indonesia: Studi Google trends

Medical masks are also used by people at risk who are indicated to need them. The supply of medical masks is limited the general public is encouraged to use non-medical masks or cloth masks. This article will discuss the comparison of search results for sensi masks cloth masks and N-95 masks using google trend analysis. This research method is a qualitative and quantitative study using time series data with quantitative analysis time-lag correlation is used to assess whether an increase in GT data is correlated with an increase in COVID-19 cases. Data from google trends regarding keywords related to one of the preventive measures for COVID-19 namely masks such as sensi masks cloth masks and N-95 masks. Each search interest usually reaches a peak depending on the situation and conditions that occur at that time. The keyword search for N-95 masks experienced a peak when 2 Indonesians were confirmed positive for COVID-19 namely on March 2 2020 and the day after that the keyword sensi mask also experienced the highest peak of searches. The keyword search for cloth masks peaked on March 6 2020 when the price of sensi masks began to rise. The results of the keyword correlation test for sensi mask cloth mask and N-95 mask show that the keyword search results on Google trended a decline in line with the increase in COVID-19 cases in Indonesia. Public interest in tracing increased at the beginning of COVID-19 entering Indonesia. However, the interest in this search continues to decline and is inversely proportional to the increase in the incidence of COVID-19 cases in Indonesia. Keywords:  COVID-19 sensi masks medical masks cloth masks N-95 masks Google trends

Psychological distress, fear and coping among Malaysians during the COVID-19 pandemic.

INTRODUCTION: The COVID-19 pandemic has enormously affected the psychological well-being, social and working life of millions of people across the world. This study aimed to investigate the psychological distress, fear and coping strategies as a result of the COVID-19 pandemic and its associated factors among Malaysian residents. METHODS: Participants were invited to an online cross-sectional survey from Aug-Sep 2020. The study assessed psychological distress using the Kessler Psychological Distress Scale, level of fear using the Fear of COVID-19 Scale, and coping strategies using the Brief Resilient Coping Scale. Univariate and multivariate logistic regression analyses were conducted to adjust for potential confounders. RESULTS: The mean age (±SD) of the participants (N = 720) was 31.7 (±11.5) years, and most of them were females (67.1%). Half of the participants had an income source, while 216 (30%) identified themselves as frontline health or essential service workers. People whose financial situation was impacted due to COVID-19 (AOR 2.16, 95% CIs 1.54-3.03), people who drank alcohol in the last four weeks (3.43, 1.45-8.10), people who were a patient (2.02, 1.39-2.93), and had higher levels of fear of COVID-19 (2.55, 1.70-3.80) were more likely to have higher levels of psychological distress. Participants who self-isolated due to exposure to COVID-19 (3.12, 1.04-9.32) and who had moderate to very high levels of psychological distress (2.56, 1.71-3.83) had higher levels of fear. Participants who provided care to a family member/patient with a suspected case of COVID-19 were more likely to be moderately to highly resilient compared to those who did not. CONCLUSION: Vulnerable groups of individuals such as patients and those impacted financially during COVID-19 should be supported for their mental wellbeing. Behavioural interventions should be targeted to reduce the impact of alcohol drinking during such crisis period.

Coverage of a Firecracker Blast Injury of the Right Hand With a Chest Wall Flap Under Wide Awake Local Anaesthesia no Tourniquet Technique.

A flap is done to cover expose structures such as bone, tendon and ligament. Chest wall flaps are usually performed under general anaesthesia due to a fairly large area of surgery and at two different sites which are the chest and the hand. This is the first known reported case of a chest wall flap for coverage of the hand under Wide awake local anaesthesia no tourniquet technique (WALANT). We here report the case of a 32-year-old man who had a firecracker injury over his right hand with bone exposed in his right index and middle finger and distal amputation of the thumb with first carpometacarpal joint dislocation. Chest wall flap reconstruction for coverage of a severe blast injury in the hand is possible and safe under WALANT. The proper technique and administration will lead to a successful surgery without general anesthesia complications and risks. This alternative option may be useful in districts or smaller hospitals where resources are limited.

Efficacy of Famotidine for COVID-19: A Systematic Review and Meta-analysis (preprint)

Background: Coronavirus Disease 2019 (COVID-19) pandemic continues unabated in many parts of the world. In the absence of any definite antiviral therapy except some benefit of remdesivir, there is an ongoing search for effective therapy. Famotidine has been shown to reduce mortality in hospitalized patients in a few studies. We conducted a systematic review on the use of famotidine in COVID-19. Methods: We searched the databases Medline, Embase, Cochrane CENTRAL and Medrxiv. Title/abstract screening, full text screening and data abstraction were carried out in by two reviewers. Case series, cohort studies and randomized trials were included. Results: Five studies were eligible for inclusion: all were retrospective cohort or case series. Low quality evidence suggests a likely clinical benefit for the use of famotidine in decreasing mortality in hospitalized patients with moderate to severe COVID-19. A meta-analysis of two cohort studies showed a statistically significant decrease in the composite outcome for death and intubation with famotidine (HR 0.44, 95% CI 0.27 to 0.73). Conclusion: Further evidence from RCTs is required for famotidine to treat COVID 19.

Outcome of Conservative Therapy in COVID-19 Patients Presenting with Gastrointestinal Bleeding (preprint)

Background/ObjectiveThere is a paucity of data on the management of gastrointestinal (GI) bleeding in patients with COVID-19 amid concerns about the risk of transmission during endoscopic procedures. We aimed to study the outcomes of conservative treatment for GI bleeding in patients with COVID-19. MethodsIn this retrospective analysis, 24 of 1342 (1.8%) patients with COVID-19, presenting with GI bleeding from 22 April to 22 July 2020, were included. ResultsThe mean age of patients was 45.8{+/-}12.7 years; 17 (70.8%) were males; upper GI (UGI) bleeding: lower GI (LGI) 23:1. Twenty-two (91.6%) patients had evidence of cirrhosis-21 presented with UGI bleeding while one had bleeding from hemorrhoids. Two patients without cirrhosis were presumed to have non-variceal bleeding. The medical therapy for UGI bleeding included vasoconstrictors-somatostatin in 17 (73.9%) and terlipressin in 4 (17.4%) patients. All patients with UGI bleeding received proton pump inhibitors and antibiotics. Packed red blood cells (PRBCs), fresh frozen plasma and platelets were transfused in 14 (60.9%), 3 (13.0%) and 3 (13.0%), respectively. The median PRBCs transfused was 1 (0-3) unit(s). The initial control of UGI bleeding was achieved in all 23 patients and none required an emergency endoscopy. At 5-day follow-up, none rebled or died. Two patients later rebled, one had intermittent bleed due to gastric antral vascular ectasia, while another had rebleed 19 days after discharge. Three (12.5%) cirrhosis patients succumbed to acute hypoxemic respiratory failure during hospital stay. ConclusionConservative management strategies including pharmacotherapy, restrictive transfusion strategy, and close hemodynamic monitoring can successfully manage GI bleeding in COVID-19 patients and reduce need for urgent endoscopy. The decision for proceeding with endoscopy should be taken by a multidisciplinary team after consideration of the patients condition, response to treatment, resources and the risks involved, on a case to case basis.

Poor Outcomes in Patients with Cirrhosis and COVID-19 (preprint)

Background and AimThere is a paucity of data on the clinical presentations and outcomes of Coronavirus disease 2019(COVID-19) in patients with underlying liver disease. We aimed to summarize the presentations and outcomes of COVID-19 positive patients and compare with historical controls.MethodsPatients with known chronic liver disease who presented with superimposed COVID- 19(n=28) between 22nd April and 22nd June 2020 were studied. Seventy-eight cirrhotic patients from historical controls were taken as comparison group.ResultsA total of 28 COVID patients- two without cirrhosis, one with compensated cirrhosis, sixteen with acute decompensation (AD), and nine with acute-on-chronic liver failure(ACLF) were included. The etiology of cirrhosis was alcohol(n=9), non-alcoholic fatty liver disease(n=2), viral(n=5), autoimmune hepatitis(n=4), and cryptogenic cirrhosis(n=6). The clinical presentations included complications of cirrhosis in 12(46.2%), respiratory symptoms in 3(11.5%) and combined complications of cirrhosis and respiratory symptoms in 11(42.3%) patients. The median hospital stay was 8(7-12) days. The mortality rate in COVID-19 patients was 42.3%(11/26), as compared to 23.1%(18/78) in the historical controls(p=0.077). All COVID-19 patients with ACLF(9/9) died compared to 53.3%(16/30) in ACLF of historical controls(p=0.015). Mortality rate was higher in COVID patients with compensated cirrhosis and AD as compared to historical controls 2/17(11.8%) vs 2/48(4.2%), though not statistically significant (p=0.278). Requirement of mechanical ventilation independently predicted mortality (hazard ratio, 13.68). Both non-cirrhotic patients presented with respiratory symptoms and recovered uneventfully.ConclusionCOVID-19 is associated with poor outcomes in patients with cirrhosis, with worst survival rates in ACLF. Mechanical ventilation is associated with a poor outcome.

Chloroquine and Hydroxychloroquine for the treatment of COVID-19: A Systematic Review and Meta-analysis (preprint)

Background: There is no effective therapy for COVID-19. Hydroxychloroquine (HCQ) and chloroquine (CQ) have been used for its treatment but their safety and efficacy remain uncertain. Objective: We performed a systematic review to synthesize the available data on the efficacy and safety of CQ and HCQ for the treatment of COVID-19. Methods: Two reviewers searched for published and pre-published relevant articles between December 2019 to 8th June 2020. The data from the selected studies were abstracted and analyzed for efficacy and safety outcomes. Critical appraisal of the evidence was done by Cochrane risk of bias tool and Newcastle Ottawa scale. The quality of evidence was graded as per the GRADE approach. Results: We reviewed 12 observational and 3 randomized trials which included 10659 patients of whom 5713 received CQ/HCQ and 4966 received only standard of care. The efficacy of CQ/HCQ for COVID-19 was inconsistent across the studies. Meta-analysis of included studies revealed no significant reduction in mortality with HCQ use [RR 0.98 95% CI 0.66-1.46] , time to fever resolution [mean difference -0.54 days (-1.19-011)] or clinical deterioration/development of ARDS with HCQ [RR 0.90 95% CI 0.47-1.71]. There was a higher risk of ECG abnormalities/arrhythmia with HCQ/CQ [RR 1.46 95% CI 1.04 to 2.06]. The quality of evidence was graded as very low for these outcomes. Conclusions: The available evidence suggests that CQ or HCQ does not improve clinical outcomes in COVID-19. Well-designed randomized trials are required for assessing the efficacy and safety of HCQ and CQ for COVID-19.