First-Generation SARS-CoV-2 Vaccines: A Comparative Analysis between Vaccinated and Unvaccinated Hospitalized Patients Infected with SARS-CoV-2.

Background Severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) variants, which have emerged due to several mutations in spike protein, have a potential to escape immune protection provided by the first-generation vaccines, thereby resulting in breakthrough infections. Objective To identify the socio-demographic factors, clinical features, and outcomes in both vaccinated and unvaccinated hospitalized patients infected with SARS-CoV-2. Method Socio-demographic details, clinical features, and the outcomes among fully vaccinated (double for Covishield/AstraZeneca and BBIBP-CorV and single for Janssen), partially vaccinated, and unvaccinated hospitalized patients with coronavirus disease of 2019 (COVID-19) were collected and analyzed using SPSS version 17. Result Among the hospitalized COVID-19 patients (n=299), 175 (58.5%) patients received a single-dose, 82 (27.4%) double-dose, and 124 (41.5%) did not receive any dose of the COVID-19 vaccines. The risk of SARS-CoV-2 infection when compared between vaccinated and unvaccinated patients was found to be associated among professional degree holders (23.4% versus 9.7%) (p<0.05), professional workers (43.4% vs. 25.0%) (p<0.05), hospitalization to general ward (76.6% vs. 72.6%) (p<0.05), and presence of multiple symptoms (> or equel 3) (86.8% vs. 75.0%) (p>0.05) and comorbidities (> or equal 2) (15.5% vs. 13.7%) (p>0.05). Despite such approximate incidences, the risk of in-hospital mortality among the vaccinated patients was reduced (0.6% vs. 3.2%) (p>0.05), when compared to the unvaccinated patients. The risk of in-hospital mortality was associated with the older age and the presence of multiple comorbidities including bronchial asthma, diabetes, and hypertension. Conclusion Full or partial vaccination against the SARS-CoV-2 variants of concerns might be effective in preventing in-hospital mortality among COVID-19 patients.

Safety and Efficacy of Convalescent Plasma Therapy for the Management of COVID-19: A Systematic Review

Introduction: Till date, no proven therapy exists for coronavirus disease (COVID-19), though different types of treatment modalities are being practiced around the world. Different studies regarding Convalescent Plasma (CP) therapy from COVID-19 recovered donors have shown favorable results with fewer adverse consequences. In this systematic review, we aimed to determine the safety and efficacy of CP as a therapy for COVID-19. Material(s) and Method(s): The English language databases of PubMed, Google Scholar, and Sci-enceDirect were searched up to 22 May 2020. Eligibility for inclusion, risk of bias assessment, and data extraction from the included studies were determined and a narrative synthesis was conducted. Result(s): A total of 12 studies were selected for review. The overall risks of bias were moderate to high. The results revealed significance in the initiation of CP therapy during the early stages of viremia from a safety and efficacy viewpoint. The patients also received concomitant drugs and other supportive therapies in most cases. Some cases of mortality were reported in 3 studies. Viral loads were documented to decrease and become negative in 8 studies within 3-26 days post-transfu-sion. The improvement in clinical symptoms following CP therapy was demonstrated in 9 studies. Most of the patients experienced very few adverse effects. Conclusion(s): The rational practice of CP therapy based on a risk-benefit judgment can prove to be an efficacious therapeutic option as a last resort until the approval of any therapeutic and/or prophy-lactic agent(s). The substantial randomized controlled trials (RCTs) are necessary to validate the effectiveness of such therapy.Copyright © 2021 Bentham Science Publishers.

Pivoting to online: The benefits, challenges and possibilities for international programme evaluations

Global South non-government organizations rely on international funding and aid for continued service delivery. Service evaluation plays a significant role in ensuring compliance and ongoing service funding. Traditional service evaluation approaches could not take place during 2021 due to COVID-19, alternate mechanisms needed to be embraced. This article reports on the benefits and challenges of undertaking service evaluations online during the pandemic and the learnings and possibilities for a post-pandemic world. It emphasizes the importance of translating a relational approach to service evaluation to the online environment. Key learnings include that while some of the benefits of context and in-person connection are lost, taking a relational approach involving careful planning and reflexivity means the online evaluation process can be successful. Undertaking service evaluations online offers possibilities in a post-pandemic world as cost-effective alternatives to the expensive and time-consuming reality of in-person service evaluation across international borders and within development contexts. © The Author(s) 2022.

First-Generation SARS-CoV-2 Vaccines: A Comparative Analysis between Vaccinated and Unvaccinated Hospitalized Patients Infected with SARS-CoV-2

Background Severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) variants, which have emerged due to several mutations in spike protein, have a potential to escape immune protection provided by the first-generation vaccines, thereby resulting in breakthrough infections. Objective To identify the socio-demographic factors, clinical features, and outcomes in both vaccinated and unvaccinated hospitalized patients infected with SARS-CoV-2. Method Socio-demographic details, clinical features, and the outcomes among fully vaccinated (double for Covishield/AstraZeneca and BBIBP-CorV and single for Janssen), partially vaccinated, and unvaccinated hospitalized patients with coronavirus disease of 2019 (COVID-19) were collected and analyzed using SPSS version 17. Result Among the hospitalized COVID-19 patients (n=299), 175 (58.5%) patients received a single-dose, 82 (27.4%) double-dose, and 124 (41.5%) did not receive any dose of the COVID-19 vaccines. The risk of SARS-CoV-2 infection when compared between vaccinated and unvaccinated patients was found to be associated among professional degree holders (23.4% versus 9.7%) (p<0.05), professional workers (43.4% vs. 25.0%) (p<0.05), hospitalization to general ward (76.6% vs. 72.6%) (p<0.05), and presence of multiple symptoms (>=3) (86.8% vs. 75.0%) (p>0.05) and comorbidities (>=2) (15.5% vs. 13.7%) (p>0.05). Despite such approximate incidences, the risk of in-hospital mortality among the vaccinated patients was reduced (0.6% vs. 3.2%) (p>0.05), when compared to the unvaccinated patients. The risk of in-hospital mortality was associated with the older age and the presence of multiple comorbidities including bronchial asthma, diabetes, and hypertension. Conclusion Full or partial vaccination against the SARS-CoV-2 variants of concerns might be effective in preventing in-hospital mortality among COVID-19 patients. Copyright © 2022, Kathmandu University. All rights reserved.

Overview of Drug Therapy of COVID-19 with Safety and the Potential Clinical Benefits

The discovery and development of the drug/vaccine for Coronavirus Disease 2019 (COVID-19) is the process of developing a preventive vaccine or treatment drug to reduce the severity of COVID-19. Internationally, hundreds of pharmaceutical companies, biotechnology companies, university research groups, and the World Health Organization (WHO) have developed vaccines for the past few centuries. Currently, they are continuously putting effort into developing possible therapies for COVID-19 disease, which are now at various stages of the preclinical or clinical research stage. In addition, researchers are trying to accelerate the development of vaccines, antiviral drugs, and postinfection treatments. Many previously approved drug candidates are already studied to alleviate discomfort during the disease complication. In this paper, we reviewed the research progress of COVID19 therapeutic drugs. Copyright © 2022 Bentham Science Publishers.

Role of Lipid Nanoparticles in COVID-19 in Repurposing Drugs and Vaccines

Background: The spread of new coronavirus 2019, the causative agent of viral pneumonia documented in Wuhan, brought a recent public health crisis globally. The best solution to overcome this pandemic is developing suitable and effective vaccines and therapeutics. However, discovering and creating a new drug is a lengthy process requiring rigorous testing and validation. Objective: Despite many newly discovered and old repurposed COVID-19 drugs under clinical trial, more emphasis should be given to research on COVID-19 NPs-based medicines, which could improve the efficacy of antiviral drugs to reduce their side effects. The use of NPs as carriers can reduce the frequency and duration of drug ingestion, enhance approved antiviral therapeutics' effectiveness, and overcome their limitations, such as low bioavailability. Besides, they can play a crucial role in fighting against the COVID-19 pandemic. In this regard, nanotechnology provides opportunities to develop new strategies for preventing, diagnosing, and treating COVID-19. Conclusion: This review highlighted the importance of NMs-based technical solutions in antiviral drugs for testing against the SARS-CoV-2 virus emergencies in the form of nanotherapeutics.

A CASE REPORT ON EXTENSIVE ARTERIAL THROMBOSIS AS A COMPLICATION OF COVID-19 INFECTION

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: Coronavirus disease (COVID-19) is a global health crisis. It is associated with increased activation of the clotting system leading to thrombotic complications in 5 to 23% of cases[1]. It is known to cause significant venous thromboembolism and few cases with arterial thrombosis with increased risk of life-threatening complications like myocardial infarction, ischemic stroke, splenic infarct, and left ventricular clot have been reported[2]. CASE PRESENTATION: A 70-year-old female with a past medical history of coronary artery disease, Hypertension, COPD, recent COVID-19 (3 weeks ago) not requiring admission to hospital presented to the hospital with bilateral leg and forearm pain. Leg pain was worse with activity. She had feeble peripheral pulses on palpation.She underwent Computed Tomography angiography which showed extensive arterial thrombosis involving the distal abdominal aorta, left common iliac artery, superior mesenteric artery, and also showed an area of wedge-shaped infarction in the spleen. She had a thrombus at the apex of the left ventricle, with incidental 1.3 cm spiculated mass in the left lung. There was no evidence of venous thromboembolism in imaging.She was started on therapeutic anticoagulation with heparin. After multidisciplinary discussion with Hematology, Vascular surgery, and Cardiology, her anticoagulation was changed to Enoxaparin. She was managed medically. Workup including JAK2, beta-2 glycoprotein antibodies, lupus anticoagulant, and anticardiolipin antibodies was negative. DISCUSSION: The exact mechanisms that activate coagulation cascade in SARS-CoV-2 infection are still unknown, but they are found to be associated with increased thrombogenesis. SARS-CoV-2 viral infection can activate the plasmatic clotting system by activating multiple procoagulant pathways. Angiotensin-converting enzymes 2 are normally found on various cells such as lymphocytes, alveolar cells, monocytes/macrophages, and platelets. In SARS-CoV-2 infection, Surface S protein of SARS-CoV-2 binds to its target transmembrane receptor( ACE2 protein) and down-regulates the expression of ACE2 protein. It leads to the accumulation of angiotensin II in the body which interacts with platelets and endothelial cells leading to further promotion of clot formation[3]. This was the likely cause of hypercoagulable state in our patient leading to thrombosis. CONCLUSIONS: An extensive arterial clot can be the initial presentation in COVID-19 patients and can be treated promptly with anticoagulation. Early introduction of prophylactic anticoagulation is necessary to prevent clot formation. REFERENCE #1:.Thromboinflammation and the hypercoagulability of COVID-19. Connors JM, Levy JH J Thromb Haemost.2020 Jul;18(7):1559-1561. REFERENCE #2: Coagulation disorders in coronavirus infected patients: COVID-19, SARS-CoV-1, MERS-CoV, and lessonsfrom the past.Giannis D, Ziogas IA, Gianni P J Clin Virol. 2020 Jun;127():104362. REFERENCE #3: Smith S A, Mutch N J, Baskar D, Rohloff P, Docampo R, Morrissey J H. Polyphosphate modulates bloodcoagulation and fibrinolysis. Proc Natl Acad Sci U S A. 2006;103(04):903–908. DISCLOSURES: No relevant relationships by Sumit Gami, source=Web Response No relevant relationships by Subash Ghimire, source=Web Response No relevant relationships by Sushmita Khadka, source=Web Response No relevant relationships by Shobha Mandal, source=Web Response

Anxiety and Depression during COVID-19 Pandemic among Medical Students in Nepal

Background Medical students' psychological response to societal lockdown during the COVID-19 pandemic has not been studied much. Objective To assess levels of anxiety and depression among medical students during initial stages of COVID-19 pandemic in Nepal and relate their distress to relevant variables. Method A cross-sectional study with online questionnaire was conducted among medical students at different colleges in Nepal. Hospital Anxiety and Depression Scale (HADS) detected 'anxiety' and 'depression'. The covariates were explored by logistic regression analyses. Result A total 416 medical students [mean age: 22.2 (2.1);males 57.7%, females 42.3%] participated. HADS-anxiety scores [mean: 7.1(4.3)] were significantly and positively correlated with HADS-depression [mean: 5.9 (4.1)] (r=0.695;p < 0.001). Point prevalence of total HADS caseness (HADS-T) was 26.7%. Specific HADS-defined caseness were: anxiety (HADS-A) 11.8%, depression (HADS-D) 5.5%, and comorbid anxiety and depression (HADS-cAD) 9.4%. All four types of caseness were significantly more prevalent among students with a history of mental problems (AOR=4.7, 3.2, 2.6, and 3.2 respectively). HADS-T was higher among those with a concurrent physical illness (AOR=2.4). HADS-T, HADS-A and HADS-D scores were higher among the age group > 22 years (AOR= 2.2, 2.5 and 4.4 respectively). HADS-cAD was almost threetimes higher among those with a possible COVID-19 exposure (AOR=2.8). Conclusion A significant number of medical students in Nepal suffered from high levels of anxiety and depression during the COVID-19 shut-down. The students in the higher (> 22 years) age group, those with past mental disorders, possible COVID-19 exposure, and concurrent physical illness showed elevated levels of anxiety and/or depression.

Repurposing Drugs for COVID-19: An Approach for Treatment in the Pandemic

Context . Drug repurposing is a relevant approach during the COVID-19 pandemic, because development of new drugs is time-consuming and costly, and the safety of new drugs is paramount. Drug repurposing focuses on researching new indications for existing drugs and can reduce the challenges faced in drug development. Objective . The current review intended to examine the current status of drugs being repurposed for COVID-19 treatment. Design . The research team performed a literature review, searching relevant literature databases to find abstracts of relevant articles in journals published from 2010 until May 16, 2020. The sources of data included Google Scholar, PubMed, and ScienceDirect. The search terms used included repositioning of drugs, repurposing of drugs and COVID-19 therapy, and SARS-CoV-2 therapy. Setting . The research team conducted this study at the Department of Pharmacology, Punjab University College of Pharmacy, University of the Punjab, Lahore, Pakistan;Mangalbare Hospital, Morang, Nepal;and Dr Iwamura Memorial Hospital, Bhaktapur, Nepal. Results . Repurposing of drugs from different pharmacological groups including antivirals like remdesivir, lopinavir, ritonavir, arbidol, oseltamivir, penciclovir, favipiravir, ganciclovir, and ribavirin;other antibiotics like azithromycin, ivermectin, eravacycline, valrubicin, streptomycin, nitazoxanide, teicoplanin, caspofungin, and colistin;and other agents like hydroxychloroquine, chloroquine, tocilizumab, camostat, nafamostat, carfilzomib, interferon, aprepitant, and dexamethasone can be considered for COVID-19 therapy. Conclusions . Although current results are promising, limitations to drug repurposing, such as a low success rate and the possibility of adverse events, can't be overlooked. With continuous research and technical advancements, repurposing will no doubt provide a notable scientific contribution to innovation in drug development and pharmacotherapy practice for the treatment of new diseases or existing diseases in a new way.