Coronavirus Severe Acute Respiratory Syndrome Research Articles

Neuroimaging Correlates of Post-COVID-19 Symptoms: A Functional MRI Approach

Backgrounds and Purpose: Post-COVID syndrome is characterized by persistent symptoms, including fatigue and cognitive impairment. These symptoms may be experienced by up to 80% of patients. We aimed to identify possible patterns of brain activation underlying post-COVID fatigue. Methods: The study used functional MRI (Siemens MAGNETOM Prisma 3T scanner with a specially created protocol) of the brain in 30 patients with post-COVID fatigue syndrome and 20 healthy volunteers. Task functional MRI (fMRI) was performed using a cognitive paradigm (modified Stroop test). Eligible patients included adults aged 18–50 years with a >12 weeks before enrolment (less than 12 months) prior history of documented COVID-19 with symptoms of fatigue not attributable to any other cause, and with MFI-20 score > 30 and MoCA at first visit. Healthy control participants had no prior history of COVID-19 and negative tests for severe acute coronavirus respiratory syndrome with MFI-20 score < 30 and MoCA at first visit. Task fMRI data were processed using the SPM12 software package based on MATLAB R2022a. Results: Cognitive task fMRI analysis showed significantly higher activation in the post-COVID group versus healthy volunteers’ group. Between-group analysis showed significant activation differences. Using a threshold of T > 3 we identified eight clusters of statistically significant activation: supramarginal gyri, posterior cingulate cortex, opercular parts of precentral gyri and cerebellum posterior lobe bilaterally. Conclusions: Post-COVID fatigue syndrome associated with subjective cognitive impairment could show changes in brain functional activity in the areas connected with information processing speed and quality.

Improving COVID-19 contact tracing and testing of exposed individuals in Cameroon using digital health technology: a cluster randomised trial

Contact tracing was described as a key strategy to contribute to controlling the spread of severe acute respiratory syndrome of Coronavirus 2 (SARS-CoV-2) but implementing it can be a challenge. Digitalisation of contact tracing is among the proposed solutions being explored in sub-Saharan African settings. We assessed the effectiveness of a digital tool to expand SARS-CoV-2 testing in exposed individuals in Cameroon. We conducted a cluster-randomised (1:1) trial in eight health districts, including 22 facilities and SARS-CoV-2 testing units, randomly assigned to a digital (intervention) or standard (control) contact tracing approach. The intervention consisted of a contact tracing module added to the digital platform "Mamal PRO" used for monitoring and coordination of Coronavirus Disease 2019 pandemic response in Cameroon. The primary outcome was the proportion of contacts declared by SAR-CoV-2 index patients who were successfully traced and tested for SARS-CoV-2 evaluated with a Poisson regression model with cluster adjustment. This study is registered with ClinicalTrials.gov (NCT05684887). Between October 18, 2022, and March 31, 2023, we enrolled 164 index patients in the intervention arm and 149 in the control arm, who identified 854 and 849 contacts, respectively. In the intervention arm, 93.8% (801/854) of identified contacts were successfully reached by the tracing unit versus 54.5% (463/849) in the control arm. The intervention significantly increased the likelihood of successfully tracing contacts (adjusted relative risks (RR) 1.72 [95% CI: 1.00-2.95], p=0.049). The median (interquartile range, IQR) time to successfully tracing contacts was 0 days [IQR: 0, 1] in the intervention and 1 day [IQR: 0, 2] in the control arm. In the intervention arm, 21.3% (182/854) of identified contacts received SARS-CoV-2 testing compared to 14.5% (123/849) in the control arm (adjusted RR 1.47 [95% CI: 0.44-4.90], p=0.530). Digitalising the contact tracing process improved exposure notification and facilitated the tracing of a greater number of contacts of individuals infected with SARS-CoV-2 in resource-limited settings. The study was funded by FIND, United Kingdom (FCDO 40105983), Switzerland (81066910), Netherlands (SDD 4000004160), Canada (DFATD 7429348), The Kingdom of Saudi Arabia (FIND-ACT-A DX PARTNERSHIP 20.08.2020), The Rockefeller Foundation (2020 HTH 059), Germany (BMZ Covid-19 Diagnostic and Surveillance Response 27.07.2021), Australia (DFAT 76442), Kuwait (M239/2020), The Government of Portugal and Partners (ANF, BCP, CGF, APIFARMA) and The BlackRock Foundation (Grant Agreement as of April 20, 2022).

Interleukin-1 Receptor Antagonist Gene (IL1RN) Variants Modulate the Cytokine Release Syndrome and Mortality of COVID-19.

We examined effects of single-nucleotide variants (SNVs) of IL1RN, the gene encoding the anti-inflammatory interleukin 1 receptor antagonist (IL-1Ra), on the cytokine release syndrome (CRS) and mortality in patients with acute severe respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. IL1RN CTA haplotypes formed from 3 SNVs (rs419598, rs315952, rs9005) and the individual SNVs were assessed for association with laboratory markers of inflammation and mortality. We studied 2589 patients hospitalized with SARS-CoV-2 between March 2020 and March 2021. Mortality was 15.3% and lower in women than men (13.1% vs 17.3%, P = .0003). Carriers of the CTA-1/2 IL1RN haplotypes exhibited decreased inflammatory markers and increased plasma IL-1Ra. Evaluation of the individual SNVs of the IL1RN, carriers of the rs419598 C/C SNV exhibited significantly reduced inflammatory biomarker levels and numerically lower mortality compared to the C/T-T/T genotype (10.0% vs 17.8%, P = .052) in men, with the most pronounced association observed in male patients ≤74 years old, whose mortality was reduced by 80% (3.1% vs 14.0%, P = .030). The IL1RN haplotype CTA and C/C variant of rs419598 are associated with attenuation of the CRS and decreased mortality in men with acute SARS-CoV-2 infection. The data suggest that the IL1RN pathway modulates the severity of coronavirus disease 2019 (COVID-19) via endogenous anti-inflammatory mechanisms.

A non-invasive AI-based system for precise grading of anosmia in COVID-19 using neuroimaging

COVID-19 (Coronavirus), an acute respiratory disorder, is caused by SARS-CoV-2 (coronavirus severe acute respiratory syndrome). The high prevalence of COVID-19 infection has drawn attention to a frequent illness symptom: olfactory and gustatory dysfunction. The primary purpose of this manuscript is to create a Computer-Assisted Diagnostic (CAD) system to determine whether a COVID-19 patient has normal, mild, or severe anosmia. To achieve this goal, we used fluid-attenuated inversion recovery (FLAIR) Magnetic Resonance Imaging (FLAIR-MRI) and Diffusion Tensor Imaging (DTI) to extract the appearance, morphological, and diffusivity markers from the olfactory nerve. The proposed system begins with the identification of the olfactory nerve, which is performed by a skilled expert or radiologist. It then proceeds to carry out the subsequent primary steps: (i) extract appearance markers (i.e., 1st and 2nd order markers), morphology/shape markers (i.e., spherical harmonics), and diffusivity markers (i.e., Fractional Anisotropy (FA) & Mean Diffusivity (MD)), (ii) apply markers fusion based on the integrated markers, and (iii) determine the decision and corresponding performance metrics based on the most-promising classifier. The current study is unusual in that it ensemble bags the learned and fine-tuned ML classifiers and diagnoses olfactory bulb (OB) anosmia using majority voting. In the 5-fold approach, it achieved an accuracy of 94.1%, a balanced accuracy (BAC) of 92.18%, precision of 91.6%, recall of 90.61%, specificity of 93.75%, F1 score of 89.82%, and Intersection over Union (IoU) of 82.62%. In the 10-fold approach, stacking continued to demonstrate impressive results with an accuracy of 94.43%, BAC of 93.0%, precision of 92.03%, recall of 91.39%, specificity of 94.61%, F1 score of 91.23%, and IoU of 84.56%. In the leave-one-subject-out (LOSO) approach, the model continues to exhibit notable outcomes, achieving an accuracy of 91.6%, BAC of 90.27%, precision of 88.55%, recall of 87.96%, specificity of 92.59%, F1 score of 87.94%, and IoU of 78.69%. These results indicate that stacking and majority voting are crucial components of the CAD system, contributing significantly to the overall performance improvements. The proposed technology can help doctors assess which patients need more intensive clinical care.

Identification of a membrane-associated element (MAE) in the C-terminal region of SARS-CoV-2 nsp6 that is essential for viral replication.

The coronavirus disease 2019 (COVID-19) pandemic, caused by the novel coronavirus severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), has rapidly spread worldwide since its emergence in late 2019. Its ongoing evolution poses challenges for antiviral drug development. Coronavirus nsp6, a multiple-spanning transmembrane protein, participates in the biogenesis of the viral replication complex, which accommodates the viral replication-transcription complex. The roles of its structural domains in viral replication are not well studied. Herein, we predicted the structure of the SARS-CoV-2 nsp6 protein using AlphaFold2 and identified a highly folded C-terminal region (nsp6C) downstream of the transmembrane helices. The enhanced green fluorescent protein (EGFP)-fused nsp6C was found to cluster in the cytoplasm and associate with membranes. Functional mapping identified a minimal membrane-associated element (MAE) as the region from amino acids 237 to 276 (LGV-KLL), which is mainly composed of the α-helix H1 and the α-helix H2; the latter exhibits characteristics of an amphipathic helix (AH). Mutagenesis studies and membrane flotation experiments demonstrate that AH-like H2 is required for MAE-mediated membrane association. This MAE was functionally conserved across MERS-CoV, HCoV-OC43, HCoV-229E, HCoV-HKU1, and HCoV-NL63, all capable of mediating membrane association. In a SARS-CoV-2 replicon system, mutagenesis studies of H2 and replacements of H1 and H2 with their homologous counterparts demonstrated requirements of residues on both sides of the H2 and properly paired H1-H2 for MAE-mediated membrane association and viral replication. Notably, mutations I266A and K274A significantly attenuated viral replication without dramatically affecting membrane association, suggesting a dual role of the MAE in viral replication: mediating membrane association as well as participating in protein-protein interactions.IMPORTANCESevere acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) assembles a double-membrane vesicle (DMV) by the viral non-structural proteins for viral replication. Understanding the mechanisms of the DMV assembly is of paramount importance for antiviral development. Nsp6, a multiple-spanning transmembrane protein, plays an important role in the DMV biogenesis. Herein, we predicted the nsp6 structure of SARS-CoV-2 and other human coronaviruses using AlphaFold2 and identified a putative membrane-associated element (MAE) in the highly conserved C-terminal regions of nsp6. Experimentally, we verified a functionally conserved minimal MAE composed of two α-helices, the H1, and the amphipathic helix-like H2. Mutagenesis studies confirmed the requirement of H2 for MAE-mediated membrane association and viral replication and demonstrated a dual role of the MAE in viral replication, by mediating membrane association and participating in residue-specific interactions. This functionally conserved MAE may serve as a novel anti-viral target.

The Impact of the Novel Coronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Pandemic on Case Fatality Rates and Cost of Surgical Care in Brazil.

Background The coronavirus disease 2019 (COVID-19) pandemic provoked disruptions in healthcare delivery. Following the recommendations of major surgical societies and surgical departments globally, most surgeries were widely canceled or postponed, causing significant disruptions to healthcare delivery worldwide, including in Brazil. Brazil's public healthcare system - Sistema Único de Saúde (SUS) was particularly affected, with a substantial decline in elective procedures, especially during the pandemic's early stages. The impact of the pandemic on surgical services in Brazil has not been adequately studied since most studies only cover the early phases of the pandemic. Thus, this study aims to analyze the case fatality rates and costs, associated with the different surgical procedure subgroups performed during the pre-pandemic, pandemic, recovery, and post-pandemic periods in all five regions of Brazil. Methods A retrospective cross-sectional design was used to examine surgical cases from 2019 to 2022. Data was divided into four time periods, named as the pre-pandemic (March-December 2019), pandemic (March-December 2020), recovery (March-December 2021), and post-pandemic (March-December 2022), and was analyzed for the cost of surgical procedures in the aforementioned four periods. In addition, the case fatality rates and rate ratios in the four periods stratified according to region were calculated. Results The cost of surgical procedures decreased during the pandemic and recovery period compared with pre-pandemic for all procedures except thoracic surgery where it was higher in the recovery period than pre-pandemic. No statistically significant change in cost was observed in surgeries of the central and peripheral nervous system, circulatory system, obstetric, and oncology. Case fatality rates increased among all five regions of Brazil in pandemic and recovery periods compared to pre-pandemic and post-pandemic periods. Case fatality rates increased during the pandemic and/or recovery as compared to pre-pandemic in all procedures except visual apparatus and obstetric surgeries were not affected by the pandemic in terms of case fatality rates. Conclusion The COVID-19 pandemic had a significant impact on surgical care costs and case fatality rates for surgery in Brazil. There was a decreasing trend in the costs of procedures during the pandemic, followed by a gradual recovery to baseline values, except for thoracic surgery. Case fatality rates rose initially and then declined, ultimately reaching baseline levels. The pandemic posed significant challenges to the healthcare system, affecting medical services, including surgical care.

Evaluation of SARS Cov-2 disease epidemiology, clinical and diagnostic profile-a regional study from tertiary care center of North India

Background: A novel coronavirus severe acute respiratory syndrome coronavirus-2 (SARSCoV-2) that emerged in China in December 2019 has spread rapidly globally to many countries including India and World Health Organization declared it as a pandemic on March 11th, 2020. Aims and Objectives: The current study endeavors to determine the SARS-CoV-2 positivity rate as well as epidemiological, clinical, and diagnostic profiles from the second wave. Materials and Methods: We performed a retrospective analysis of all suspected COVID-19 cases from January 2021 to October 2021 presenting at a large testing center for SARS-CoV-2 infection by real-time polymerase chain reaction (RT-PCR). Descriptive analysis has been performed for profiling of clinical-epidemiological aspects of suspected cases. Results: A total of 694427 participants were enrolled during the study from January 2021 to October 2021. Overall RT-PCR positivity rate was found to be 1.7% in the year 2021 and the positivity was maximum in April 2021 which represents the second wave of COVID-19 infection in India. In the study population, more than half (57.07%) of the persons screened for COVID-19 infection were between 21 and 40 years of age, and about two-thirds (65.20%) of the persons screened were male followed by 34.79% were female. Conclusions: SARS-CoV-2 poses a high burden of infections in the community. Males had a higher RT-PCR detection rate as compared to females. The younger age group (<20 years) expressed the least RT-PCR positivity rate and the elderly population (>80 years) expressed the highest positivity rate.

SARS-CoV-2 NSP12 utilizes various host splicing factors for replication and splicing regulation.

The RNA-dependent RNA polymerase (RdRp) is a crucial element in the replication and transcription of RNA viruses. Although the RdRps of lethal human coronaviruses severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV) have been extensively studied, the molecular mechanism of the catalytic subunit NSP12, which is involved in pathogenesis, remains unclear. In this study, the biochemical and cell biological results demonstrate the interactions between SARS-CoV-2 NSP12 and seven host proteins, including three splicing factors (SLU7, PPIL3, and AKAP8). The entry efficacy of SARS-CoV-2 considerably decreased when SLU7 or PPIL3 was knocked out, indicating that abnormal splicing of the host genome was responsible for this occurrence. Furthermore, the polymerase activity and stability of SARS-CoV-2 RdRp were affected by the three splicing factors to varying degrees. In addition, NSP12 and its homologues from SARS-CoV and MERS-CoV suppressed the alternative splicing of cellular genes, which were influenced by the three splicing factors. Overall, our research illustrates that SARS-CoV-2 NSP12 can engage with various splicing factors, thereby impacting virus entry, replication, and gene splicing. This not only improves our understanding of how viruses cause diseases but also lays the foundation for the development of antiviral therapies.

Multivariate time series analysis of COVID-19 Pandemic and gold price by using Error Corrections Model

Coronavirus (COVID-19) severe acute respiratory syndrome is an infectious disease that has a direct influence on the world’s population, as is obvious from the prevalence of COVID-19. However, as the COVID-19 virus continues to proliferate, its impact is becoming more and more significant and extensive. Accordingly, the study’s goal is to use the Error Corrections Model (ECM) to examine the relationships between the COVID-19 pandemic and gold prices. An Error Corrections Model was used by the researchers in this investigation. Error Correction Models and long-term equilibrium can be found for non-stationary time series that have been cointegrated together. Two-step estimation can be used to estimate the ECM since a proportion of the imbalance from one period is adjusted in the succeeding period, the system returns to equilibrium. The calculated cointegrating relations are used to create the error correction terms, and the estimation of VAR is done by a first differencing process, and then appears in the model as an explanatory variable, with the term of error correction. The COVID-19 pandemic and gold price data were made available to the general public in a sample data. For the year 2020, it includes data on daily observations for the relevant variables. R-language results show that the COVID-19 pandemic and gold prices have been demonstrated to have a long-term causal relationship. During the most recent period of variance decomposition, 99.76 percent of the variance in covid-19 explains only 0.24 percent of the variance in gold price. This explains that there is no short-term causal relationship between covid-19 and gold price, as indicated by the Wald test results, the granger causality results have shown that the gold price is influenced not only by itself but also by the Covid-19 pandemic. Finally, there is a positive relationship between the Covid-19 pandemic and the price of gold, and this has a negative impact on human life during 2020.

Influence of Vitamin D Level on Inflammatory and Prognostic Markers in COVID-19 - A Retrospective Study.

The ongoing pandemic of severe acute respiratory syndrome coronavirus 2019 (SARS-CoV-2) has caused an immense public health crisis worldwide. Emerging evidence has suggested that inflammatory response plays a critical role in the pathogenesis and prognosis of the disease. As vitamin D can modulate the immune system, this study has been designed to correlate vitamin D with inflammatory and prognostic markers in COVID-19 patients. The present study is a retrospective study examining the relationship between vitamin D levels and inflammatory markers in the COVID-19 disease. COVID-19 patients who were investigated for vitamin D, ferritin, D-dimer, C-reactive protein (CRP), and procalcitonin (PCT) level were only included. The patients were divided into hypovitaminosis D, and normal vitamin D. Correlation and logistic regression analyses were carried out to identify the strength and association of hypovitaminosis D with inflammatory markers in COVID-19 disease. The hypovitaminosis D group had significantly higher inflammatory markers compared to the normal vitamin D group. The correlation between hypovitaminosis D and procalcitonin was negative (r = -0.433), with a strong and significant association (p = 0.002). The correlation between hypovitaminosis D, CRP, and ferritin was weak and insignificant. The logistic regression between hypovitaminosis D and procalcitonin established a significant regression equation, leading to a significant linear model. This study concludes that patients with hypovitaminosis D should be treated with vitamin D therapy to reduce the severity of COVID-19 disease.

Molecular Docking and ADME-TOX Profiling of Moringa oleifera Constituents against SARS-CoV-2.

The SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2019) etiological agent, which has a high contagiousness and is to blame for the outbreak of acute viral pneumonia, is the cause of the respiratory disease COVID-19. The use of natural products grew as an alternative treatment for various diseases due to the abundance of organic molecules with pharmacological properties. Many pharmaceutical studies have focused on investigating compounds with therapeutic potential. Therefore, this study aimed to identify potential antiviral compounds from a popular medicinal plant called Moringa oleifera Lam. against the spike, Mpro, ACE2, and RBD targets of SARS-CoV-2. For this, we use molecular docking to identify the molecules with the greatest affinity for the targets through the orientation of the ligand with the receptor in complex. For the best results, ADME-TOX predictions were performed to evaluate the pharmacokinetic properties of the compounds using the online tool pkCSM. The results demonstrate that among the 61 molecules of M. oleifera, 22 molecules showed promising inhibition results, where the compound ellagic acid showed significant molecular affinity (-9.3 kcal.mol-1) in interaction with the spike protein. These results highlight the relevance of investigating natural compounds from M. oleifera as potential antivirals against SARS-CoV-2; however, additional studies are needed to confirm the antiviral activity of the compounds.

The Role of Primary Care in Bridging Adolescents Awaiting Eating Disorder Treatment.

The striking rise in adolescent eating disorders since the severe acute respiratory coronavirus syndrome 2 pandemic has amplified demands for specialty eating disorders services and contributed to protracted delays in care. In the context of these delays, patients are at risk for increased weight loss, medical instability, escalating disease progression and poor prognosis. Primary care providers (PCPs) are frequently the first point of contact for young patients with eating disorders and are often left to bridge the gap while families struggle to establish specialty care. Yet, beyond case detection and medical comanagement, there are no evidence-based guidelines that can assist PCPs to prepare families for treatment, halt disease progression, and begin the lengthy process of weight and nutritional restoration in efforts to reduce medical complications and support a favorable prognosis. We present the case of a 13-year-old girl with a restrictive eating disorder to illustrate how PCPs can use intervention principles and strategies derived from evidence-based eating disorder treatment to successfully manage adolescent patients until they can access specialty treatment. We offer concrete guidelines for decision-making, as well as suggested behavioral and medical interventions for the PCP. With evidence-based tools, PCPs are well-positioned to support young patients with restrictive eating disorders and their family members as they begin the process of recovery from an eating disorder.

Depression, anxiety and stress among healthcare workers in the context of the COVID-19 pandemic: a cross-sectional study in a tertiary hospital in Northern Vietnam.

The outbreak of coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) had significant effects on the mental well-being in general, particularly for healthcare professionals. This study examined the prevalence of depression, anxiety, and stress, and identified the associated risk factors amongst healthcare workers during the COVID-19 outbreak in a tertiary hospital located in Vietnam. We conducted a cross-sectional study at a tertiary-level hospital, where the Depression Anxiety and Stress Scale 21 (DASS-21) web-based questionnaire was employed. We analyzed the determinant factors by employing multivariate logistic models. The prevalence of depression, anxiety, and stress symptoms were 19.2%, 24.7%, and 13.9%, respectively. Factors such as engaging in shift work during the pandemic, taking care of patients with COVID-19, and staff's health status were associated with mental health issues among health professionals. In addition, having alternate rest periods was likely to reduce the risk of stress. The prevalence of mental health problems in healthcare workers during the COVID-19 pandemic was relatively high. Having resting periods could potentially mitigate the development of stress among health professionals. Our findings could be taken into account for improving mental health of the health professional population.

Comprehensive Review of the Initial 11 WHO Emergency Use Listed COVID-19 Vaccine Candidates: Mechanisms, Efficacy, and Comparative Attributes for Safety and Well-Being

Since December 2019, the world has witnessed a massive outbreak of a novel coronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which prompted cross-national collaboration to establish essential diagnostics, effective treatment protocols, and most importantly the design and development of suitable COVID-19 vaccine candidates. This effort has been fueled by collaborations among academic researchers, funding agencies, companies, and regulatory authorities. As a result, more than 242 vaccine candidates are currently under clinical trial, and nearly 50 vaccines have been approved in different countries. In this study, we conduct a comprehensive review of 11 vaccine candidates that have been granted Emergency Use Listing (EUL) by the World Health Organization (WHO). Our review summarizes the mode of synthesis, mechanism of action, approval authority, target age group, efficacy, merits, and gaps of these vaccine candidates. Additionally, we provide comparative attributes of these vaccine candidates to enhance understanding of safety and well-being.

Impact of ACE2 on the susceptibility and vulnerability to COVID-19.

Angiotensin-converting enzyme 2 (ACE2) is not only the viral receptor for the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) but is also classically known as a key carboxypeptidase, which through multiple interacting partners plays vital physiological roles in the heart, kidney, lung, and gastrointestinal tract. An accumulating body of evidence has implicated the dysregulation of ACE2 abundance and activity in the pathophysiology of multiple disease states. ACE2 has recently regained attention due to its evolving role in driving the susceptibility and disease severity of coronavirus disease 2019 (COVID-19). This narrative review outlines the current knowledge of the structure and tissue distribution of ACE2, its role in mediating SARS-CoV-2 cellular entry, its interacting partners, and functions. It also highlights how SARS-CoV-2-mediated dysregulation of membrane-bound and circulating soluble ACE2 during infection plays an important role in the pathogenesis of COVID-19. We explore contemporary evidence for the dysregulation of ACE2 in populations that have emerged as most vulnerable to COVID-19 morbidity and mortality, including the elderly, men, and pregnant women, and draw attention to ACE2 dynamics and discrepancies across the mRNA, protein (membrane-bound and circulating), and activity levels. This review highlights the need for improved understanding of the basic biology of ACE2 in populations vulnerable to COVID-19 to best ensure their clinical management and the appropriate prescription of targeted therapeutics.

Impacts of SARS-CoV-2 on diabetes mellitus: A pre and post pandemic evaluation.

The coronavirus disease 2019 (COVID-19) pandemic caused by the novel beta coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) crippled the whole world and has resulted in large number of morbidity and mortality. The origin of the SARS-CoV-2 is still disputed. The risk of infection with SARS-CoV-2 is dependent on several risk factors as observed in many studies. The severity of the disease depends on many factors including the viral strain, host immunogenetics, environmental factors, host genetics, host nutritional status and presence of comorbidities like hypertension, diabetes, Chronic Obstructive Pulmonary Disease, cardiovascular disease, renal impairment. Diabetes is a metabolic disorder mainly characterized by hyperglycemia. Diabetic individuals are intrinsically prone to infections. SARS-CoV-2 infection in patients with diabetes result in β-cell damage and cytokine storm. Damage to the cells impairs the equilibrium of glucose, leading to hyperglycemia. The ensuing cytokine storm causes insulin resistance, especially in the muscles and liver, which also causes a hyperglycemic state. All of these increase the severity of COVID-19. Genetics also play pivotal role in disease pathogenesis. This review article focuses from the probable sources of coronaviruses and SARS-CoV-2 to its impacts on individuals with diabetes and host genetics in pre- and post-pandemic era.

Assessment and strategy development for SARS-CoV-2 screening in wildlife: A review.

Coronaviruses (members of the Coronaviridae family) are prominent in veterinary medicine, with several known infectious agents commonly reported. In contrast, human medicine has disregarded coronaviruses for an extended period. Within the past two decades, coronaviruses have caused three major outbreaks. One such outbreak was the coronavirus disease 2019 (COVID-19) caused by the coronavirus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Over the 3-year COVID-19 outbreak, several instances of zooanthroponosis have been documented, which pose risks for virus modifications and possible re-emergence of the virus into the human population, causing a new epidemic and possible threats for vaccination or treatment failure. Therefore, widespread screening of animals is an essential technique for mitigating future risks and repercussions. However, mass detection of SARS-CoV-2 in wild animals might be challenging. In silico prediction modeling, experimental studies conducted on various animal species, and natural infection episodes recorded in various species might provide information on the potential threats to wildlife. They may be useful for diagnostic and mass screening purposes. In this review, the possible methods of wildlife screening, based on experimental data and environmental elements that might play a crucial role in its effective implementation, are reviewed.

Licorice-saponin A3 is a broad-spectrum inhibitor for COVID-19 by targeting viral spike and anti-inflammation

Currently, human health due to corona virus disease 2019 (COVID-19) pandemic has been seriously threatened. The coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19. However, the efficacy is compromised by the SARS-CoV-2 evolvement and mutation. Here we report the SARS-CoV-2 S protein receptor-binding domain (RBD) inhibitor licorice-saponin A3 (A3) could widely inhibit RBD of SARS-CoV-2 variants, including Beta, Delta, and Omicron BA.1, XBB and BQ1.1. Furthermore, A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells, with EC50 of 1.016 μM. The mechanism was related to binding with Y453 of RBD determined by hydrogen-deuterium exchange mass spectrometry (HDX-MS) analysis combined with quantum mechanics/molecular mechanics (QM/MM) simulations. Interestingly, phosphoproteomics analysis and multi fluorescent immunohistochemistry (mIHC) respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase (MAPK) pathways and rebalancing the corresponding immune dysregulation. This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.

Association of diabetes with severity and outcome of COVID - 19 positive patients: a retrospective cohort study in King Abdullah Medical Complex, Jeddah, Saudi Arabia

Introduction: The Corona Virus Disease 19 (COVID-19) is a pandemic infectious disease caused by the novel coronavirus Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2). Almost 8 million instances of the illness were confirmed, and there were over 450,000 fatalities. We aim to explore diabetes as a risk factor associated with the severity and outcome of hospital-admitted COVID-19 positive cases. Method: It is a hospital-based retrospective cohort study of hospital admitted RT-PCR COVID positive cases from March to June 2020. Data were outlined using mean and standard deviation (SD) for quantitative variables; categorical sociodemographic data were compared by disease severity and outcome by Pearson’s Chi-square test (X2). Univariate and multivariate logistic regression analyses were used to estimate the risk factor associated with disease severity and outcome of the patients. Result: Of the 224 diagnosed COVID positive patients, 74 (33.04%) have diabetes. Among these 74 COVID-positive cases with diabetes, 52 (43.70%) cases have severe to critical conditions. Both univariate (OR: 2.87, 95% C.I, 1.58 – 5.20; p = 0.00) and multivariate (aOR: 2.76, 95% C.I, 1.34 – 8.42; p = 0.00) analysis show diabetes has a significant association with severity of COVID infection. Regarding the outcome of hospital admitted COVID patients with diabetes, 52 (28.26%) were discharged alive after recovery from COVID infection. In the univariable (OR: 3.16, 95% C.I, 1.57 – 6.38; p = 0.00) and multivariable (aOR: 3.12, 95% C.I, 1.15 – 8.42; p = 0.02) analysis, diabetes has been significantly associated with the outcome of hospital admitted COVID cases. Conclusion: Our study identified diabetes as a risk factor for increased severity of COVID positive cases. Risk factors like older age and obesity also significantly predict COVID-19 disease progression.

Correlation between pulmonary function and six minutes walk test with computed tomography severity score in post COVID patients

Background: The current global pandemic of the coronavirus severe acute respiratory syndrome coronavirus 2 is the world’s most critical ongoing healthcare problem, with 8.2% of critically ill patients developing acute respiratory distress syndrome and requiring Intensive care unit admission. Our study aimed to correlate CT severity score of the patient at the time of diagnosis with spirometry, 6-minute walk test and breath holding time at 12 weeks after discharge, to determine the nature of residual pulmonary dysfunction and if CT severity was a predictor of poor lung function post recovery. Methods: Ambi-directional single center study conducted in Saveetha medical college Hospital, Chennai. Patients over the age of 18 with a positive COVID-19 RTPCR report and a CTSS>1 were enrolled into the study, and a sample size of 50 patients was taken after systematic random sampling. PFT, 6-minute walk test and Breath Holding Time were done at 12 weeks post discharge. Results: Mean CT severity score was: 11.48. 26% of the patients had more than 50% lung involvement on CT. There was significant negative correlation observed between FVC and Severity score (r=-0.366, p=0.009) and Breath holding and Severity score (r=-0.339, p=0.016) while there was no significant correlation between 6-minute walk test and CT Severity. Conclusions: Patients with significant lung involvement during SARS-COV-2 infection showed impaired pulmonary function test parameters in the form of a reduced FVC and breath holding time, 3 months following diagnosis. Long-term follow up and pulmonary rehabilitation is crucial to achieve respiratory recovery.