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.

COVID-19 Booster Vaccine: is it an absolute need?

Booster vaccine doses are meant to revive the fading immunity created by prior exposure to an immunizing antigen. They stabilize the antibody response ultimately leading to longer and higher protection against pathogens. Immunological studies done for COVID-19 vaccines have documented a steady decrease in antibody levels among vaccinated individuals and evidence of breakthrough infections over a course of time. With an emerging science behind the need for COVID-19 vaccine booster shots, there equally is a contrasting idea regarding its absolute necessity. Copyright © 2021, Kathmandu University. All rights reserved.

Novel recombinant measles virus vaccine prevents measles virus disease in rhesus macaques

Background: Measles-Mumps-Rubella (MMR) is an effective live-virus vaccine against measles virus (MeV). However, use of MMR is limited by its inability to boost MeV immunity, lack of immunogenicity in infants, and contraindication in pregnant and immunocompromised persons. Methods: We evaluated a novel recombinant dimeric MeV hemagglutinin protein vaccine (rMeV) in a rhesus macaque model. Sixteen macaques were primed at day 0 and boosted at day 42 by experimental group: 1) MMR x2;2) rMeV x2;3) MMR prime/rMeV boost;4) control;n=4. Macaques were challenged intratracheally with Bilthoven strain wild type MeV 8 months later. Blood, bone marrow (BM), and lymph node (LN) samples were collected over 3–28 days after challenge. Replication-competent MeV was measured in peripheral blood mononuclear cells (PBMC), BM cells, and LN cells by infectious assay;MeV RNA in PBMC and BM cells was determined by quantitative reverse transcriptase polymerase chain reaction. Plasma was evaluated for MeV-specific IgG and plaque reduction neutralization titer (PRNT). Results: Six months after vaccination, mean PRNT was 2,432 in rMeV x2 (standard deviation (SD) 3,840), 3,584 in MMR-prime/rMeV boost (SD 3,072) and 5,120 in MMR x2 groups (SD 3,547). Upon infectious challenge, macaques who received any MeV-containing vaccine developed no clinical signs of measles and had no detectable infectious virus in PBMC, BM cells, or LN cells. All unvaccinated macaques had virus in PBMC that peaked at day 7 (mean 3,162 TCID50/mL, SD 4.1) and resolved by day 14 post challenge, and one macaque developed an extensive rash. Macaques who received any MeV-containing vaccine had no detectable MeV RNA in PBMC or BM cells, whereas all unvaccinated macaques had detectable MeV RNA that peaked at day 7 (1.6e5 copies, SD 10.5) in PBMC. In all experimental groups, MeV-specific IgG titers increased after MeV challenge. Conclusion: Macaques who received rMeV and/or MMR were protected from rash, viremia, and detection of MeV RNA in PBMC and BM cells, unlike unvaccinated macaques. These data suggest that rMeV vaccine generates protective immune responses against measles and may be a novel candidate for future measles vaccine strategies. Study of cellular responses after rMeV vaccination and MeV challenge is warranted. Disclosures: Jessica Rubens, MD, Mevox: Grant/Research Support Guillaume Stewart-Jones, PhD, Moderna: Inventor of SARS-CoV-2 vaccine sequences;Moderna: Stocks/Bonds Michael Watson, MD, MEVOX Ltd: Board Member;MEVOX Ltd: Ownership Interest;MEVOX Ltd: Stocks/Bonds Barney S. Graham, MD, PhD, BSG: BSG is an inventor on patents for the stabilization of the RSV F protein (WO2014160463A1, Prefusion RSV F proteins and their use).;National Institutes of Health: Inventor on patents for RSV vaccines;National Institutes of Health: inventor on patents for measles and other paramyxovirus vaccines Diane Griffin, MD PhD, Gilead: Grant/Research Support;GlaxoSmithKline: Advisor/Consultant;GreenLight Biosciences: Advisor/Consultant;Merck: Advisor/Consultant;MeVox: Grant/Research Support;Takeda Pharmaceuticals: Advisor/Consultant.

COVID-19 Booster Vaccine: is it an absolute need?

Booster vaccine doses are meant to revive the fading immunity created by prior exposure to an immunizing antigen. They stabilize the antibody response ultimately leading to longer and higher protection against pathogens. Immunological studies done for COVID-19 vaccines have documented a steady decrease in antibody levels among vaccinated individuals and evidence of breakthrough infections over a course of time. With an emerging science behind the need for COVID-19 vaccine booster shots, there equally is a contrasting idea regarding its absolute necessity. Copyright © 2021, Kathmandu University. All rights reserved.

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.

The psychological impact of COVID-19 pandemic in health care workers: a cross-sectional study in Nepal

BACKGROUND: COVID-19 pandemic has affected the healthcare workers (HCWs) worldwide. We plan to assess the psychological impact of this pandemic in different groups of HCWs including female community health volunteers (FCHVs) at various types of health facilities in Nepal, factors associated with it and the degree of satisfaction with the ongoing mental health support system. METHODS: A cross-sectional web-based survey with an option of telephone interview was conducted from June 20 to July 7, 2020. The questionnaire included socio-demographic characteristics, work related characteristics, substance use history, and degree of satisfaction with family, society and institutional support. Depression, anxiety, and stress scales (DASS-21) and the impact of events scale-revised (IES-R) tool were used to access the level of psychological impact. Linear regression was used to analyze factors associated with psychological outcome. RESULTS: Out of 608 respondents, the overall prevalence of depression, anxiety, stress, and post-traumatic stress disorder (PTSD) was 20.89%. 24.18%, 13.82%, and 15.46% respectively. Nurses had higher depression, anxiety, stress, and PTSD scores while FCHVs had high depression and PTSD compared to doctors. For various types of health facilities, HCWs working in provincial-level hospitals had high-stress level. Similarly, "have to go into quarantine" and increased level of substance abuse were directly associated with poor psychological impact. Finally, 62% of HCWs did not have any institutional mental health support system. Among those who had institutional mental health support, 39.4% were not satisfied. CONCLUSIONS: We found mild to extremely severe level of depression, anxiety, stress, and PTSD among HCWs in Nepal. Urgent plans are required to mitigate the mental health risk caused by this current pandemic.

Role of IL-13-induced Th2 inflammation in host responses to SARSCoV-2

Background: Chronic lung inflammation affects the response to respiratory viruses such as SARS-CoV-2 in airway epithelia. Based on the pattern associated with disease endotype, airway inflammation can be simplified into type 2 and type 17. Half of asthmatics have type 2 high endotype driven by IL-13/IL-4 cytokine signaling that induces goblet cell metaplasia. Other inflammatory diseases such as cystic fibrosis, chronic bronchitis, and sarcoidosis are associated with the type 17 cytokines IL-17 and TNF-α. Recent case-control studies have suggested that asthma may protect against or at least not worsen SARS-CoV-2 infection. However, the effect of inflammation on COVID-19 outcomes is unclear. Although interferons and cytokine-driven inflammation may modulate antiviral response, epithelial remodeling might also affect susceptibility to viruses.We applied a singlecell RNA-seq approach to investigate responses to SARS-CoV-2 in primary human airway epithelia treated with inflammatory cytokines. We hypothesized that IL-13-induced type 2 inflammation and IL-17-induced type 17 inflammation would respond differently to SARS-CoV-2-infected human airway epithelia and that IL-13 would protect the epithelia from SARS-CoV-2 infection through goblet cell-secreted factors Methods: We infected primary human airway epithelia (n = 3 donors) grown at the air–liquid interface with 0.1 multiplicity of infection of SARSCoV- 2 and obtained viral titers and single-cell suspensions at 6 and 72 hours after infection. The epitheliawere pretreated with IL-13 or IL-17 plus TNF-α for a short (4 days) or long (56 days) course to differentiate the early effects of cytokine response from late goblet cell metaplasia that develops over weeks. We then performed single-cell RNA-seq to analyze viral transcripts Results: We found that IL-13, but not IL17 plus TNF-α, protected epithelia from SARS-CoV-2 at 72 hours after infection. Moreover, the protection seemed to be independent of interferons because interferon-stimulated genes, induced by short IL-13 exposure, failed to protect the epithelia from viral infection. Our analysis shows that the genes with the largest expression change in long-course IL-13-treated epithelia were mediated by the appearance of goblet cells andwere goblet-specific genes. Using our single-cell RNA-seq data, we analyzed how cytokines change response in each cell type after viral infection. We found that, when cells become infected, their response is not abnormal. Conclusion: IL-13 protects human airway epithelia from SARS-CoV-2 infection in vitro;the protective mechanism may involve secreted products from goblet cells. IL-13-treated airway epithelial cells have an otherwise normal response to SARS-CoV-2. Our findings suggest that products secreted by goblet cells may have potential therapeutic applications for respiratory viral diseases.

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

COVID-19 and youth: Uncertainty, stress, anxiety

Purpose: The purpose of this study is to examine how Nepali youths’ experience uncertainty, stress, and anxiety during the pandemic and how they response to these factors. Design/methodology/approach: To obtain the information, semi-structured qualitative interviews were conducted with twenty youth living within the one square kilometre area of the central part of the capital city of Nepal. Findings: The study revealed that uncertainty has created scattered future and unemployment in youths. Similarly, stress has caused by the life pattern change and unmanaged and unorganized expectation whereas anxiety has developed pessimism, grief and loss, and loneliness among the Nepali youth. Value: This is a highly relevant topic regarding the impact of COVID-19 faced by the youths globally. © 2021 RESTORATIVE JUSTICE FOR ALL.

Epidemiological and clinical profile of covid-19 in nepali children: An initial experience

Introduction: COVID-19 has spread all around the world with huge toll of human lives and suffering since it evolved in China. Nepal had slow rise in morbidity due to COVID 19 in early days but has been gripped by the pandemic's exponential growth lately. This study was conducted with the aim to describe the clinical and epidemiological features of Nepali children in early phase of the pandemic. Methods: This was an observational study conducted at 11 COVID care centres designated by the Government of Nepal with availability of supervision by paediatricians between January and August 2020 in children under 18 years of age diagnosed with COVID 19. Data was collected based on definitions outlined in data collection resources available at WHO-ISARIC Global COVID-19 clinical resources platform and analysed. Results: One hundred and twenty one children diagnosed with COVID 19 who presented to the designated centres were enrolled. Majority of children (83.4%) were identified as a part of contact tracing, 28.1% had an identified contact to a person with COVID 19 prior to their diagnosis and 20.7% had another household member diagnosed with COVID 19. The mean age of admitted children was 8.8 years (SD 5.6 years) with the largest proportion being adolescents (40.5%). Male (58.7%) children were more commonly affected. There were 15 (12.4%) infants and 8 (6%) of them were under two months of age. Most children (87, 71.9%) were asymptomatic, 21 (22.3%) had mild symptoms and six (4.9%) had moderately severe symptoms. Fever (18.2%) was the most commonly reported symptom. All children were discharged after a median of 14 days of hospitalisation. Conclusions: Nepali children of all ages are affected by COVID 19 and present with asymptomatic or mildly symptomatic infection. Fever and respiratory symptoms are the most commonly reported symptoms. Most children do not develop complications. Continued surveillance in larger population of children as the pandemic unfolds will generate more stringent observations.