Pseudotyped virus infection of multiplexed ACE2 libraries reveals SARS-CoV-2 variant shifts in receptor usage (preprint)

Pairwise compatibility between virus and host proteins can dictate the outcome of infection. During transmission, both inter- and intraspecies variabilities in receptor protein sequences can impact cell susceptibility. Many viruses possess mutable viral entry proteins and the patterns of host compatibility can shift as the viral protein sequence changes. This combinatorial sequence space between virus and host is poorly understood, as traditional experimental approaches lack the throughput to simultaneously test all possible combinations of protein sequences. Here, we created a pseudotyped virus infection assay where a multiplexed target-cell library of host receptor variants can be assayed simultaneously using a DNA barcode sequencing readout. We applied this assay to test a panel of 30 ACE2 orthologs or human sequence mutants for infectability by the original SARS-CoV-2 spike protein or the Alpha, Beta, Gamma, Delta, and Omicron BA1 variant spikes. We compared these results to an analysis of the structural shifts that occurred for each variant spikes interface with human ACE2. Mutated residues were directly involved in the largest shifts, although there were also widespread indirect effects altering interface structure. The N501Y substitution in spike conferred a large structural shift for interaction with ACE2, which was partially recreated by indirect distal substitutions in Delta, which does not harbor N501Y. The structural shifts from N501Y greatly influenced the set of animal orthologs the variant spike was capable of interacting with. Out of the thirteen non-human orthologs, ten exhibited unique patterns of variant-specific compatibility, demonstrating that spike sequence changes during human transmission can toggle ACE2 compatibility and potential susceptibility of other animal species, and cumulatively increase overall compatibilities as new variants emerge. These experiments provide a blueprint for similar large-scale assessments of protein compatibility during entry by diverse viruses. This dataset demonstrates the complex compatibility relationships that occur between variable interacting host and virus proteins.

COVID-19 South African Vaccine Hesitancy Models Show Boost in Performance Upon Fine-Tuning on M-pox Tweets (preprint)

Very large numbers of M-pox cases have, since the start of May 2022, been reported in non-endemic countries leading many to fear that the M-pox Outbreak would rapidly transition into another pandemic, while the COVID-19 pandemic ravages on. Given the similarities of M-pox with COVID-19, we chose to test the performance of COVID-19 models trained on South African twitter data on a hand-labelled M-pox dataset before and after fine-tuning. More than 20k M-pox-related tweets from South Africa were hand-labelled as being either positive, negative or neutral. After fine-tuning these COVID-19 models on the M-pox dataset, the F1-scores increased by more than 8% falling just short of 70%, but still outperforming state-of-the-art models and well-known classification algorithms. An LDA-based topic modelling procedure was used to compare the miss-classified M-pox tweets of the original COVID-19 RoBERTa model with its fine-tuned version, and from this analysis, we were able to draw conclusions on how to build more sophisticated models.

Prevalence and pattern of Post Covid-19 symptoms in recovered patients of Delhi: A Population-Based study (preprint)

Background: Post-coronavirus disease (COVID) is widely reported but the data of Post COVID-19 after infection with the Omicron variant is limited. This prospective study was conducted to determine the prevalence, pattern, and duration of symptoms related to Covid-19 recovered patients. Methods: Adults (>18 years old) in 11 districts of Delhi who had recovered from Covid-19 were followed up at 3 months and 6 months post-recovery. Results: The study found that the participants had a mean age of 42.07 years, with a standard deviation of 14.89. Additionally, a significant proportion of the participants (79.7%) experienced post-Covid symptoms. The participants elicited a history of Joint Pain (36%), Persistent dry cough (35.7%), anxiousness (28.4%) and shortness of breath (27.1%). The other symptoms reported were persistent fatigue (21.6%), persistent headache (20%), forgetfulness (19.7%) and weakness in limbs (18.6%). The longest duration of symptom was observed in participants reporting anxiousness (138.75 +54.14) followed by fatigue (137.57+48.33), shortness of breath (131.89+60.21) and joint pain/swelling (131.59+58.76). During the first follow-up, 2.2% of participants had an abnormal ECG reading, while no abnormalities were reported during the second follow-up. Additionally, 4.06% of participants had abnormal chest X-ray findings during the first follow-up, with this number decreasing to 2.16% during the second follow-up. Conclusion: Our study concluded that the clinical symptoms persist in participants until 6 months and a multi-system involvement is seen in the post-COVID period. Thus, the findings necessitate long-term, regular follow-ups.

Detecting the Presence of COVID-19 Vaccination Hesitancy from South African Twitter Data Using Machine Learning (preprint)

Very few social media studies have been done on South African user-generated content during the COVID-19 pandemic and even fewer using hand-labelling over automated methods. Vaccination is a major tool in the fight against the pandemic, but vaccine hesitancy jeopardizes any public health effort. In this study, sentiment analysis on South African tweets related to vaccine hesitancy was performed, with the aim of training AI-mediated classification models and assessing their reliability in categorizing UGC. A dataset of 30000 tweets from South Africa were extracted and hand-labelled into one of three sentiment classes: positive, negative, neutral. The machine learning models used were LSTM, bi-LSTM, SVM, BERT-base-cased and the RoBERTa-base models, whereby their hyperparameters were carefully chosen and tuned using the WandB platform. We used two different approaches when we pre-processed our data for comparison: one was semantics-based, while the other was corpus-based. The pre-processing of the tweets in our dataset was performed using both methods, respectively. All models were found to have low F1-scores within a range of 45$\%$-55$\%$, except for BERT and RoBERTa which both achieved significantly better measures with overall F1-scores of 60$\%$ and 61$\%$, respectively. Topic modelling using an LDA was performed on the miss-classified tweets of the RoBERTa model to gain insight on how to further improve model accuracy.

Evaluation of Mental Health and Quality of Life among Indian Professionals Embarked as COVID-19 Survivors.

Background: Government guidelines for lockdown and quarantine measures impacted the daily lives and health of individuals amid the coronavirus disease 2019 (COVID-19) pandemic. The pandemic caused significant changes in the daily routine and lifestyles of individuals worldwide with the simultaneous emergence of mental health disorders. Stress caused by COVID-19 pandemic outbreaks and consequent social isolation significantly influenced the mental health and quality of life of professionals among Indian population. This study aimed to evaluate the mental health and quality of life among Indian professionals embarked as COVID-19 survivors. Methods: A 20-item self-administered questionnaire was developed and circulated among the participants with the following domains: helplessness, apprehension, mood swing, physical activity, restlessness, insomnia, irritation, mental stress, and emotional instability to assess their mental health and quality of life. Results: Of the total 322 participants, 73.6% of individuals experienced helplessness, 56.2% felt the need for counseling, 65.5% reported feeling irritated even over minor issues, 62.1% experienced negative thoughts during isolation, 76.5% experienced difficulty in falling asleep, and 71.9% felt restless during their course of illness. Conclusion: The study concludes that mental health and quality of life among COVID-19 survivors was affected by sleep, physical activities, emotional instability, and job profile, as well as support from others, mood swings, and the need for counseling.

Quality assessment of global health care system in the shadow of COVID-19: - a systematic review.

INTRODUCTION: The healthcare system is critical to the country's overall growth, which involves the healthy development of individuals, families, and society everywhere. This systematic review focuses on providing an overall assessment of the quality of healthcare delivery during COVID-19. METHODOLOGY: The literature search was conducted from March 2020 till April 2023 utilising the databases "PubMed," "Google Scholar," and "Embase." A total of nine articles were included. Descriptive statistics was performed using Microsoft Excel. PROSPERO registration ID- CRD42022356285. RESULTS: According to the geographic location of the studies included, four studies were conducted in Asia [Malaysia(n = 1); India (Madhya Pradesh) (n = 1); Saudi Arabia(n = 1); Indonesia (Surabaya) (n = 1)], three in Europe [U.K. (n = 1); Poland (n = 1); Albania (n = 1)] and two in Africa [Ethiopia(n = 1); Tunisia (n = 1)]. Overall patient satisfaction was found highest among studies conducted in Saudi Arabia (98.1%) followed by India (Madhya Pradesh) (90.6%) and the U.K. (90%). CONCLUSION: This review concluded five different aspects of patients satisfaction level i.e. reliability, responsiveness, assurance, empathy, and tangibility. It was found that the empathy aspect had the greatest value of the five factors, i.e., 3.52 followed by Assurance with a value of 3.51.

Mindfulness and Subjective Well-Being of Indian University Students: Role of Resilience during COVID-19 Pandemic.

The coronavirus (COVID-19) pandemic is presently a global health issue that negatively affects the mental health and well-being of students globally. The latest investigations have recognized the role of mindfulness in individual subjective well-being. This study explores the mediating role of resilience in the overall relationship between mindfulness and subjective well-being among Indian university students during the COVID-19 pandemic. The data was collected between 10 August 2020 to 24 October 2020 via a self-administered questionnaire from 589 university students in India. Results revealed that resilience has a partial mediating role between mindfulness and subjective well-being. The results substantiate that resilience has an important role in mindfulness, exercising its advantageous effects on mental health of the students in higher education institutions. This research adds to the knowledge base of mindfulness and subjective well-being of university students, especially in contingent times. Lastly, the study contributes to the existing mindfulness theory.

Study of Characteristics of COVID-19 Patients with Fatal Outcome during Wave-2 from a Tertiary Care Center in Western India.

BACKGROUND: A large surge of intensive care unit (ICU) admissions leading to mortal outcome was observed in wave-2 of coronavirus disease 2019 (COVID-19) due to the higher virulence of the Delta variant of the COVID-19 virus, which led to the scarcity of resources in hospitals. This study was done to observe the clinical characteristics of COVID-19 patients with fatal outcomeMaterials and methods: We conducted a retrospective cross-sectional study in adults with COVID-19 pneumonia having fatal outcome during wave-2 of COVID-19, and their clinical characteristics were studiedResults: Out of 136 patients included in the study, the most common risk factors leading to adverse outcome were in the male gender, age (middle and elderly), with hypertension and diabetes mellitus (DM) as predominant comorbidities, early onset dyspnea, high C-reactive protein (CRP), high neutrophil to lymphocyte ratio (NLR), high D-dimer, bilateral lower zone involvement of lungs in chest X-ray (CXR), and development of acute kidney injury (AKI)Conclusion: The characteristics of the severely ill COVID-19 patients highlighted in the study could help clinicians in the early identification and management of high-risk patients. This study would help with resource planning and preparation for further COVID-19 waves and future pandemics.

Overview of the adoption of online food ordering services in spain and india. An analytical approach based on the stimulus-organism-response model

COVID-19 pandemic, the foodservice industry has had to modify the way it offers its services. The aim of this paper is to examine the drivers of intention to use and recommendation of online food delivery (OFD) using the SOR model, to analyze the perceived risk of COVID-19 and its relationship with the perceived risk for online purchase of OFD as well as to analyze the cultural effect between Spain and India. For this purpose, an online questionnaire was developed by obtaining a sample of 422 users and structural equation modeling (PLS-SEM) was used to determine which variables had a significant influence on the adoption of the OFD. The results confirm that attitude is the main antecedent of intention to use and recommendation, in contrast to the subjective norm relationships, where it was only confirmed by recommendation. This finding demonstrates how individuals' attitude toward intention and recommendation is more favorable than influence of third parties on decisions. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

Alcohol Consumption during the Covid-19 Pandemic in India

The study examines the impact of Covid-19-induced economic stressors (such as incomes and job losses) on household alcohol consumption in India. Our analysis, based on eight waves of the Centre for Monitoring Indian Economy–Consumer Pyramids Household Survey (CMIE-CPHS) for the period January 2019–August 2021, confirms an increased consumption of alcohol during the pandemic despite supply restrictions imposed by the state. A spurt was witnessed across socioeconomic groups with varying intensities. This confirms the self-medication hypothesis and stress-response-dampening theory that households responded to the pandemic-related economic and psychological shocks by increasing the consumption of alcohol and is more significant for the poor and the marginalised.JEL Codes: D12, C23 [ FROM AUTHOR] Copyright of Journal of Asian & African Studies (Sage Publications, Ltd.) is the property of Sage Publications, Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Blood filtering system for COVID-19 management: novel modality of the cytokine storm therapeutics.

The newly emerged coronavirus (SARS-CoV-2) is virulent, contagious, and has rapidly gained many mutations, which makes it highly infectious and swiftly transmissible around the world. SARS-CoV-2 infects people of all ages and targets all body organs and their cellular compartments, starting from the respiratory system, where it shows many deleterious effects, to other tissues and organs. Systemic infection can lead to severe cases that require intensive intervention. Multiple approaches were elaborated, approved, and successfully used in the intervention of the SARS-CoV-2 infection. These approaches range from the utilization of single and/or mixed medications to specialized supportive devices. For critically ill COVID-19 patients with acute respiratory distress syndrome, both extracorporeal membrane oxygenation (ECMO) and hemadsorption are utilized in combination or individually to support and release the etiological factors responsible for the "cytokine storm" underlying this condition. The current report discusses hemadsorption devices that can be used as part of supportive treatment for the COVID-19-associated cytokine storm.

Emergency Medicine Residents' Perceptions of Working and Training in a Pandemic Epicenter: A Qualitative Analysis.

INTRODUCTION: We sought to describe the range of emergency medicine (EM) resident physicians' perceptions and experiences of working and training during the initial coronavirus 2019 (COVID-19) pandemic surge at two, large-volume, urban training hospitals in Brooklyn, New York. METHODS: A total of 25 EM resident physicians who worked at either of two large emergency departments (ED) from March 15-April 11, 2020 participated in semi-structured interviews conducted in July and August 2020. Interviews were conducted by the authors who were also emergency medicine resident physicians working in the ED during this time. We asked open-ended questions to residents about their experiences and emotions at work and outside of work, including their relationship with co-workers, patients, and their community. The interviews were audio-recorded and transcribed. We then conducted a thematic analysis to identify, classify, and define themes from interview transcripts. Iterative commonalities and differences between interview response themes were grouped to create a broadly applicable narrative of the residents' perceptions and experiences of working and training during this initial wave of a novel pandemic. Interviewees also responded to a demographics survey. RESULTS: Study participants described four major aspects of their perceptions and experiences of working and training during the stated time, including emotional challenges such as anxiety and feeling underappreciated; protective thoughts, including camaraderie, and sense of duty; workplace challenges such as limited knowledge surrounding COVID-19 and a higher volume of acute patients; and adaptive strategies including increased communication with ED administrators. CONCLUSION: Emergency medicine residents have a unique perspective and were key frontline hospital responders during a prolonged disaster and mass triage event within a local health system. Considering the chronic case and mortality fluctuations and new variants of COVID-19, as well as the anticipation of future infectious disease pandemics, we believe it is important for key decision-makers in resident education, hospital administration, and all levels of public health management to inform themselves about residents' emotional and workplace challenges when establishing hospital and residency program disaster protocols.

Evaluation of Rapid Antigen Test as a Marker of SARS-CoV-2 Infectivity.

Background Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that emerged in late 2019 continues to spread globally. Reverse transcriptase polymerase chain reaction (RT-PCR), which is considered the gold standard for diagnosis, does not always indicate contagiousness. This study was planned to evaluate the performance of the rapid antigen test (RAT) with the duration of symptoms and the usefulness of these tests in determining the infectivity of patients by performing sub-genomic RT-PCR. Methodology This prospective, observational study was designed to compare the diagnostic value of the COVID-19 RAT (SD Biosensor, Korea) with COVID-19 RT-PCR (Thermo Fisher, USA) by serial testing of patients. To evaluate the infectivity of the virus, sub-genomic RT-PCR was performed on previous RAT and RT-PCR-positive samples. Results Of 200 patients, 102 were positive on both RT-PCR and RAT, with 87 patients serially followed and tested. The sensitivity and specificity of RAT were 92.73% and 93.33%, respectively, in symptomatic patients. The mean duration of RAT positivity was 9.1 days, and the mean duration of RT-PCR positivity was 12.6 days. Sub-genomic RT-PCR test was performed on samples that were reported to be positive by RAT, and 73/87 (83.9%) patients were found to be positive. RAT was positive in symptomatic patients whose duration of illness was less than 10 days or those with a cycle threshold value below 32. Conclusions Thus, RAT can be used as the marker of infectivity of SARS-CoV-2 in symptomatic patients, especially in healthcare workers.

Multi-pathogen based chimeric vaccine to fight against COVID-19 and concomitant coinfections.

BACKGROUND: COVID-19 has proved to be a fatal disease of the year 2020, due to which thousands of people globally have lost their lives, and still, the infection cases are at a high rate. Experimental studies suggested that SARS-CoV-2 interacts with various microorganisms, and this coinfection is accountable for the augmentation of infection severity. METHODS AND RESULTS: In this study, we have designed a multi-pathogen vaccine by involving the immunogenic proteins from S. pneumonia, H. influenza, and M. tuberculosis, as they are dominantly associated with SARS-CoV-2. A total of 8 antigenic protein sequences were selected to predict B-cell, HTL, and CTL epitopes restricted to the most prevalent HLA alleles. The selected epitopes were antigenic, non-allergenic, and non-toxic and were linked with adjuvant and linkers to make the vaccine protein more immunogenic, stable, and flexible. The tertiary structure, Ramachandran plot, and discontinuous B-cell epitopes were predicted. Docking and MD simulation study has shown efficient binding of the chimeric vaccine with the TLR4 receptor. CONCLUSION: The in silico immune simulation analysis has shown a high level of cytokines and IgG after a three-dose injection. Hence, this strategy could be a better way to decrease the disease's severity and could be used as a weapon to prevent this pandemic.

Electrocardiographic abnormalities in patients with COVID-19 pneumonia and raised interleukin-6.

Background: Cardiac injury is associated with high mortality in patients with COVID-19 infection. Electrocardiographic changes can give clues to the underlying cardiovascular abnormalities. Raised inflammatory markers like raised interleukin-6 (IL-6) are associated with arrhythmia, heart failure, and coronary artery disease. However, past studies have not highlighted the electrocardiographic abnormalities in patients with COVID-19 infection with raised IL- 6 levels. This study compared the electrocardiogram (ECG) changes in COVID-19 patients with high and normal IL-6 levels. Methods: A retrospective analysis of ECG of 306 patients with COVID-19 infection was done, out of which 250 patients had normal IL- 6 levels, whereas 56 patients had raised IL-6 levels. IL-6 levels were measured in all the patients. Detailed clinicodemographic profile of all the serial COVID-19 patients admitted with moderate to severe COVID-19 pneumonia was noted from the hospital record section. Electrocardiographic findings and biochemical parameters of all the patients were noted. Results: Out of 56 patients with raised IL-6 levels, 41 (73.2%) patients had ECG abnormalities compared to 177 (70.8%) patients with normal IL-6 levels. This difference was not statistically significant. However, ECG abnormality such as sinus tachycardia was significantly more common in patients with raised IL-6 levels than those with normal levels. Among patients with raised IL-6 levels who were discharged, 5 (16.6%) had sinus tachycardia, 2 (6.6%) had ST/T wave changes as compared to 15 (57.6%), and 10 (38.4%) who had tachycardia and ST/T wave change respectably succumbed to death. This difference was statistically significant. Conclusions: Sinus tachycardia followed by atrial fibrillation and right bundle branch block are common ECG changes in patients with COVID-19 infection with raised IL-6. The possible association of cardiac injury in patients with COVID-19 infection with coexisting raised IL-6 levels should be explored further.

Kinetic analysis of RNA cleavage by coronavirus Nsp15 endonuclease: Evidence for acid-base catalysis and substrate-dependent metal ion activation.

Understanding the functional properties of severe acute respiratory syndrome coronavirus 2 nonstructural proteins is essential for defining their roles in the viral life cycle, developing improved therapeutics and diagnostics, and countering future variants. Coronavirus nonstructural protein Nsp15 is a hexameric U-specific endonuclease whose functions, substrate specificity, mechanism, and dynamics are not fully defined. Previous studies report that Nsp15 requires Mn2+ ions for optimal activity; however, the effects of divalent ions on Nsp15 reaction kinetics have not been investigated in detail. Here, we analyzed the single- and multiple-turnover kinetics for model ssRNA substrates. Our data confirm that divalent ions are dispensable for catalysis and show that Mn2+ activates Nsp15 cleavage of two different ssRNA oligonucleotide substrates but not a dinucleotide. Biphasic kinetics of ssRNA substrates demonstrates that Mn2+ stabilizes alternative enzyme states that have faster substrate cleavage on the enzyme. However, we did not detect Mn2+-induced conformational changes using CD and fluorescence spectroscopy. The pH-rate profiles in the presence and absence of Mn2+ reveal active-site ionizable groups with similar pKas of ca. 4.8 to 5.2. An Rp stereoisomer phosphorothioate modification at the scissile phosphate had minimal effect on catalysis supporting a mechanism involving an anionic transition state. However, the Sp stereoisomer is inactive because of weak binding, consistent with models that position the nonbridging phosphoryl oxygen deep in the active site. Together, these data demonstrate that Nsp15 employs a conventional acid-base catalytic mechanism passing through an anionic transition state, and that divalent ion activation is substrate dependent.

Hospital Resource Management -A Survey

Healthcare is a limited resource that is constantly in high demand because everyone requires it. When demand exceeds supply, resources become relatively scarce, making the overall resource allocation in healthcare even more difficult, as we have seen at the time of COVID-19. Effective resource allocation faces obstacles such as a lack of trained human resources, inefficient resource use, a lack of focus on improvement, and inefficient resource reallocation. This paper will outline a study of the numerous approaches to resource allocation in healthcare, outlining the methods employed, the outcomes, and benefits and drawbacks of each approach. In order to address any kind of emergency situation that may arise in the future, it was our goal to pinpoint the research gap between the work that had already been done and the solution to this problem through the survey analysis. In order to boost hospital resource management, the paper identifies a variety of potential solutions which can be categorized further into subcategories which can be seen through different perspectives and a range of approaches that can be implemented during COVID-19 or in any other emergency condition. © 2023 IEEE.

Higher proinflammatory responses possibly contributing to suppressed cytotoxicity in patients with COVID-19 associated mucormycosis.

INTRODUCTION: COVID-19 Associated Mucormycosis (CAM), an opportunistic fungal infection, surged during the second wave of SARS Cov-2 pandemic. Since immune responses play an important role in controlling this infection in immunocompetent hosts, it is required to understand immune perturbations associated with this condition for devising immunotherapeutic strategies for its control. We conducted a study to determine different immune parameters altered in CAM cases as compared to COVID-19 patients without CAM. METHODOLOGY: Cytokine levels in serum samples of CAM cases (n = 29) and COVID-19 patients without CAM (n = 20) were determined using luminex assay. Flow cytometric assays were carried out in 20 CAM cases and 10 controls for determination of frequency of NK cells, DCs, phagocytes, T cells and their functionalities. The cytokine levels were analyzed for their association with each other as well as with T cell functionality. The immune parameters were also analyzed with respect to the known risk factors such as diabetes mellitus and steroid treatment. RESULTS: Significant reduction in frequencies of total and CD56 + CD16 + NK cells (cytotoxic subset) was noted in CAM cases. Degranulation responses indicative of cytotoxicity of T cell were significantly hampered in CAM cases as compared to the controls. Conversely, phagocytic functions showed no difference in CAM cases versus their controls except for migratory potential which was found to be enhanced in CAM cases. Levels of proinflammatory cytokines such as IFN-γ, IL-2, TNF-α, IL-17, IL-1ß, IL-18 and MCP-1 were significantly elevated in cases as compared to the control with IFN-γ and IL-18 levels correlating negatively with CD4 T cell cytotoxicity. Steroid administration was associated with higher frequency of CD56 + CD16- NK cells (cytokine producing subset) and higher MCP-1 levels. Whereas diabetic participants had higher phagocytic and chemotactic potential and had higher levels of IL-6, IL-17 and MCP-1. CONCLUSION: CAM cases differed from the controls in terms of higher titers of proinflammatory cytokines, reduced frequency of total and cytotoxic CD56 + CD16 + NK cell. They also had reduced T cell cytotoxicity correlating inversely with IFN-γ and IL-18 levels, possibly indicating induction of negative feedback mechanisms while diabetes mellitus or steroid administration did not affect the responses negatively.