Severe Acute Respiratory Syndrome Novel Coronavirus 2 Research Articles

Angiotensin Converting Enzyme 2 (ACE2) - A macromolecule and its impact on human reproduction during COVID-19 pandemic

Coronavirus disease 2019 (COVID 19) is caused by severe acute respiratory syndrome novel coronavirus 2 (SARS-nCoV-2). It has been declared a pandemic by the World Health Organization (WHO) on March 11, 2020. Since then, several researchers have worked/ are working on this virus by a multifactorial approach to finding out the mechanism of entry, transmission route, post-infection replication process, survival, and post-recovery utilities. As we know, SARS, MERS, and Zika viruses have affected human reproductive potentials, consequently, COVID 19 also can affect both men's and women's reproductive potential through ACE2 macromolecule. This study aimed to summarize the role of ACE2- macromolecule in COVID 19 entry and further processes in the reproductive path of both men and women. Research articles were searched in NCBI-NLM, Google Scholar, and Scopus databases. We searched based on the phrase “COVID 19”, “ACE2”, “ACE2 in testes”, “ACE2 in the female reproductive tract”, “ACE2 during pregnancy”, “ACE2 during early embryo”, “COVID 19 and impact in human reproduction” and selected the articles for summarizing this article. Most recent articles and the mechanism of COVID 19 were selected for our understanding. The results of the study revealed that COVID 19 impacts the reproductive potential of both men and women. Testes are the most vulnerable organ prone to infection in men, and vaginal fluid and the uterus could be the choice of infection in the female. Till now, COVID 19 has not been directly detected in semen samples and vaginal fluid. Results of the study can be concluded that ACE2 plays a major role in COVID 19 infection, ACE2 expression could be more in the testes, ovary, uterus, and vagina. COVID 19 could impact more on human reproduction and lead to a loss of fertility status for a while. All antiviral treatments could pose a negative impact on human reproduction. Further research should be carried out on the already existing theoretical hypothesis of SARS-Co-V-2 on human reproduction.

Mechanism of Blood‐Heart‐Barrier Leakage: Implications for COVID‐19 induced Cardiovascular Injury

Although blood‐heart‐barrier (BHB) leakage is the hallmark of congestive (cardio‐pulmonary) heart failure (CHF), the primary cause of death in elderly, and during viral myocarditis resulting from the novel coronavirus such as the severe acute respiratory syndrome novel corona virus 2 (SARS‐CoV‐2) known as COVI‐19, the mechanism is unclear. The goal of this project is to determine the mechanism BHB in CHF. Endocardial endothelium (EE) is the BHB against leakage of blood from endocardium to the interstitium; however, this BHB is broken during CHF. Previous studies from our laboratory, and others have shown a robust activation of matrix metalloproteinase‐9 (MMP‐9) during CHF. MMP‐9 degrades connexins leading to EE dysfunction. We demonstrated juxtacrine coupling of EE with myocyte, and mitochondria (Mito) but how it works still remains at large. To test whether activation of MMP‐9 causes EE barrier dysfunction, we hypothesized that if that were the case then treatment with hydroxychloroquine (HCQ) could, in fact, inhibit MMP‐9, and thus preserve the EE barrier/juxtacrine signaling, and synchronous endothelial‐myocyte coupling. To determine this, CHF was created by aorta‐vena cava fistula (AVF) employing the mouse as a model system. The sham, and AVF mice were treated with HCQ. Cardiac hypertrophy, tissue remodeling‐induced mitochondrial‐myocyte, and endothelial‐myocyte contractions were measured. Microvascular leakage was measured using FITC‐albumin conjugate. The cardiac function was measured by echocardiography (Echo). Results suggest that MMP‐9 activation, endocardial endothelial leakage, endothelial‐myocyte (E‐M) uncoupling, dyssynchronous mitochondrial fusion‐fission (Mfn2/Drp1 ratio) and mito‐myocyte uncoupling in AVF heart failure were found to be rampant however, treatment with HCQ successfully mitigated some of the deleterious cardiac alterations during CHF. The findings have direct relevance to the gamut of cardiac manifestations, and the resultant phenotypes arising from the ongoing complications of COVID‐19 in human subjects.

COVID-19 Overview, Natural Immune-Boosting Medication, and The Economic Implication

Abstract An outbreak of severe acute respiratory syndrome (SARS) novel coronavirus-2 (SARS-nCoV-2) caused unprecedented ongoing health and socioeconomic crises. So far, millions have got infected, living with life-threatening challenges. The corporate world is striving to survive. The scientific community explores various strategies to invent vaccines and/or therapeutic options to control this viral pandemic. This SARS-nCoV-2 is highly contagious and can be exponentially transmitted from human to human. Most of the patients have similar pneumonia symptoms, and at a later stage, it causes lung damage, breathing difficulties, and reduced gas exchange. More specifically, this infection exacerbates the problem in the case of secondary illness or disease. There is a striving need for a novel strategy to control the virus spread and treat related pathogens with all these challenges. Researchers have suggested some natural compounds (curcumin, quercetin, cinnamaldehyde, and lactoferrin), nutraceuticals, probiotics, and vitamin therapy for immune-boosting because they have high anti-inflammatory effects. Here, in this review, we compiled the updated information on the current status, clinical symptoms, pathogenesis, possible new green targets (herbal medicine), and challenges associated with developing potential vaccines.

Mechanism of Blood-Heart-Barrier Leakage: Implications for COVID-19 Induced Cardiovascular Injury.

Although blood–heart-barrier (BHB) leakage is the hallmark of congestive (cardio-pulmonary) heart failure (CHF), the primary cause of death in elderly, and during viral myocarditis resulting from the novel coronavirus variants such as the severe acute respiratory syndrome novel corona virus 2 (SARS-CoV-2) known as COVID-19, the mechanism is unclear. The goal of this project is to determine the mechanism of the BHB in CHF. Endocardial endothelium (EE) is the BHB against leakage of blood from endocardium to the interstitium; however, this BHB is broken during CHF. Previous studies from our laboratory, and others have shown a robust activation of matrix metalloproteinase-9 (MMP-9) during CHF. MMP-9 degrades the connexins leading to EE dysfunction. We demonstrated juxtacrine coupling of EE with myocyte and mitochondria (Mito) but how it works still remains at large. To test whether activation of MMP-9 causes EE barrier dysfunction, we hypothesized that if that were the case then treatment with hydroxychloroquine (HCQ) could, in fact, inhibit MMP-9, and thus preserve the EE barrier/juxtacrine signaling, and synchronous endothelial-myocyte coupling. To determine this, CHF was created by aorta-vena cava fistula (AVF) employing the mouse as a model system. The sham, and AVF mice were treated with HCQ. Cardiac hypertrophy, tissue remodeling-induced mitochondrial-myocyte, and endothelial-myocyte contractions were measured. Microvascular leakage was measured using FITC-albumin conjugate. The cardiac function was measured by echocardiography (Echo). Results suggest that MMP-9 activation, endocardial endothelial leakage, endothelial-myocyte (E-M) uncoupling, dyssynchronous mitochondrial fusion-fission (Mfn2/Drp1 ratio), and mito-myocyte uncoupling in the AVF heart failure were found to be rampant; however, treatment with HCQ successfully mitigated some of the deleterious cardiac alterations during CHF. The findings have direct relevance to the gamut of cardiac manifestations, and the resultant phenotypes arising from the ongoing complications of COVID-19 in human subjects.

Suppression of the hypothalamic-pituitary-thyroid axis is associated with the severity of prognosis in hospitalized patients with COVID-19

BackgroundThe outbreak of severe acute respiratory syndrome novel coronavirus 2 (SARS-CoV-2) has spread rapidly worldwide. SARS-CoV-2 has been found to cause multiple organ damage; however, little attention has been paid to the damage to the endocrine system caused by this virus, and the subsequent impact on prognosis. This may be the first research on the hypothalamic-pituitary-thyroid (HPT) axis and prognosis in coronavirus disease 2019 (COVID-19).MethodsIn this retrospective observational study, 235 patients were admitted to the hospital with laboratory-confirmed SARS-CoV-2 infection from 22 January to 17 March 2020. Clinical characteristics, laboratory findings, and treatments were obtained from electronic medical records with standard data collection forms and compared among patients with different thyroid function status.ResultsAmong 235 patients, 17 (7.23%) had subclinical hypothyroidism, 11 (4.68%) severe non-thyroidal illness syndrome (NTIS), and 23 (9.79%) mild to moderate NTIS. Composite endpoint events of each group, including mortality, admission to the ICU, and using IMV were observed. Compared with normal thyroid function, the hazard ratios (HRs) of composite endpoint events for mild to moderate NTIS, severe NTIS, subclinical hypothyroidism were 27.3 (95% confidence interval [CI] 7.07–105.7), 23.1 (95% CI 5.75–92.8), and 4.04 (95% CI 0.69–23.8) respectively. The multivariate-adjusted HRs for acute cardiac injury among patients with NTF, subclinical hypothyroidism, severe NTIS, and mild to moderate NTIS were 1.00, 1.68 (95% CI 0.56–5.05), 4.68 (95% CI 1.76–12.4), and 2.63 (95% CI 1.09–6.36) respectively.ConclusionsOur study shows that the suppression of the HPT axis could be a common complication in COVID-19 patients and an indicator of the severity of prognosis. Among the three different types of thyroid dysfunction with COVID-19, mild to moderate NTIS and severe NTIS have a higher risk of severe outcomes compared with subclinical hypothyroidism.

A Study on the Safety of Percutaneous Tracheostomy in Patients with Severe Acute Respiratory Syndrome Novel Corona Virus 2 (SARS-nCoV2) Infection: A Single-Center Observational Cohort Study in a CoVID Intensive Care Unit.

BackgroundWe studied the safety of percutaneous dilatational tracheostomy (PCDT) in severe acute respiratory syndrome novel coronavirus 2 (SARS-nCoV2).Patients and MethodsFrom 01 March 20 to 30 November 2020, 1635 required hospital admission of which 145 (9%) required intensive (ICU) care. The primary outcomes are mortality and secondary outcomes were duration of invasive mechanical ventilation (IMV), length of stay (LOS) in ICU and hospital, and days required for decannulation.ResultsOut of the 145 (9%), 107 (73.7%) were males (mean 61.4 years, median body mass index (BMI) of 28.2 kg/m2), and 38 (26.2%) were females (mean 58.10 years, median BMI of 31.2 kg/m2). In the cohort of 80 (55.17%) requiring IMV, 19 (23.7%) died within 72 hours and were not included in the study, 37 (group “NT”) and 24 (group “T”) had a median duration of ventilation of 9 d (IQR, 6-11) and 12 d (IQR, 11-17.25) respectively. Patients in group “T” underwent PCDT based on clinical criteria (fraction of inspired oxygen (FiO2) of ≤ 50% with positive end-expiratory pressure (PEEP) of ≤ 10 cms of H2O with stable hemodynamics), and 16 (66.7%) had survived. The reverse transcription-polymerase chain reaction (RT-PCR) does not need to be negative, and none of the health care workers (HCW’s) were infected. The Cox-hazard ratio [HR] is 0.19, 95% confidence interval [CI] (0.09, 0.41) with a P-value of <0.001, 83 (57.2%) were discharged with a mortality of 42.8%.ConclusionsPCDT is safe and effective in patients anticipated in need of prolonged mechanical ventilation.

Paradigm-Shifting Research in Gastroenterology, Hepatology, and Nutrition: A Top 20 List of Articles Published in 2020

Paradigm-Shifting Research in Gastroenterology, Hepatology, and Nutrition: A Top 20 List of Articles Published in 2020

The Nimbleness and Resource Costs of Expedited Review and Concerns of Duplicate Publication: SARS-CoV-2 Manuscripts Submitted to The Journal of Pediatrics

The editorial office at The Journal of Pediatrics received the first manuscript regarding severe acute respiratory syndrome novel coronavirus 2 (SARS-CoV-2) on February 13, 2020. Through November 30, 2020, nearly 550 manuscripts were submitted regarding SARS-CoV-2 in children and adolescents (Figure). We pause to consider the phases of the pandemic as reflected in manuscript submissions and take stock of the benefits, costs, and concerns of journal editors committed to the peer review process as well as to the rapid dissemination of new information.

Characterization of Structural and Energetic Differences between Conformations of the SARS-CoV-2 Spike Protein.

The novel coronavirus disease 2019 (COVID-19) pandemic has disrupted modern societies and their economies. The resurgence in COVID-19 cases as part of the second wave is observed across Europe and the Americas. The scientific response has enabled a complete structural characterization of the Severe Acute Respiratory Syndrome—novel Coronavirus 2 (SARS-CoV-2). Among the most relevant proteins required by the novel coronavirus to facilitate the cell entry mechanism is the spike protein. This protein possesses a receptor-binding domain (RBD) that binds the cellular angiotensin-converting enzyme 2 (ACE2) and then triggers the fusion of viral and host cell membranes. In this regard, a comprehensive characterization of the structural stability of the spike protein is a crucial step to find new therapeutics to interrupt the process of recognition. On the other hand, it has been suggested that the participation of more than one RBD is a possible mechanism to enhance cell entry. Here, we discuss the protein structural stability based on the computational determination of the dynamic contact map and the energetic difference of the spike protein conformations via the mapping of the hydration free energy by the Poisson–Boltzmann method. We expect our result to foster the discussion of the number of RBD involved during recognition and the repurposing of new drugs to disable the recognition by discovering new hotspots for drug targets apart from the flexible loop in the RBD that binds the ACE2.

Clinically Suspected Myocarditis in the Course of Severe Acute Respiratory Syndrome Novel Coronavirus-2 Infection: Fact or Fiction?

Cardiac complications, including clinically suspected myocarditis, have been described in novel coronavirus disease 2019. Here, we review current data on suspected myocarditis in the course of severe acute respiratory syndrome novel coronavirus-2 (SARS-CoV-2) infection. Hypothetical mechanisms to explain the pathogenesis of troponin release in patients with novel coronavirus disease 2019 include direct virus-induced myocardial injury (ie, viral myocarditis), systemic hyperinflammatory response (ie, cytokine storm), hypoxemia, downregulation of angiotensin-converting enzyme 2, systemic virus-induced endothelialitis, and type 1 and type 2 myocardial infarction. To date, despite the fact that millions of SARS-CoV-2 infections have been diagnosed worldwide, there is no definitive proof that SARS-CoV-2 is a novel cardiotropic virus causing direct cardiomyocyte damage. Diagnosis of viral myocarditis should be based on the molecular assessment of endomyocardial biopsy or autopsy by polymerase chain reaction or in-situ hybridization. Blood, sputum, or nasal and throat swab virology testing are insufficient and do not correlate with the myocardial involvement of a given pathogen. Data from endomyocardial biopsies and autopsies in clinically suspected SARS-CoV-2 myocarditis are scarce. Overall, current clinical epidemiologic data do not support the hypothesis that viral myocarditis is caused by SARS-CoV-2, or that it is common. More endomyocardial biopsy and autopsy data are also needed for a better understanding of pathogenesis of clinically suspected myocarditis in the course of SARS-CoV-2 infection, which may include virus-negative immune-mediated or already established subclinical autoimmune forms, triggered or accelerated by the hyperinflammatory state of severe novel coronavirus disease 2019.

Cancer Screening During the Coronavirus Disease-2019 Pandemic: A Perspective From the National Cancer Institute’s PROSPR Consortium

Cancer Screening During the Coronavirus Disease-2019 Pandemic: A Perspective From the National Cancer Institute’s PROSPR Consortium

Drug repurposing studies targeting SARS-CoV-2: an ensemble docking approach on drug target 3C-like protease (3CLpro)

The COVID-19 pandemic has been responsible for several deaths worldwide. The causative agent behind this disease is the Severe Acute Respiratory Syndrome – novel Coronavirus 2 (SARS-CoV-2). SARS-CoV-2 belongs to the category of RNA viruses. The main protease, responsible for the cleavage of the viral polyprotein is considered as one of the hot targets for treating COVID-19. Earlier reports suggest the use of HIV anti-viral drugs for targeting the main protease of SARS-CoV, which caused SARS in the year 2002–2003. Hence, drug repurposing approach may prove to be useful in targeting the main protease of SARS-CoV-2. The high-resolution crystal structure of the main protease of SARS-CoV-2 (PDB ID: 6LU7) was used as the target. The Food and Drug Administration approved and SWEETLEAD database of drug molecules were screened. The apo form of the main protease was simulated for a cumulative of 150 ns and 10 μs open-source simulation data was used, to obtain conformations for ensemble docking. The representative structures for docking were selected using RMSD-based clustering and Markov State Modeling analysis. This ensemble docking approach for the main protease helped in exploring the conformational variation in the drug-binding site of the main protease leading to the efficient binding of more relevant drug molecules. The drugs obtained as top hits from the ensemble docking possessed anti-bacterial and anti-viral properties. This in silico ensemble docking approach would support the identification of potential candidates for repurposing against COVID-19. Communicated by Ramaswamy H. Sarma

How to Build the Plane While Flying: VTE/PE Thromboprophylaxis Clinical Guidelines for COVID-19 Patients.

Over the years, the practice of medicine has evolved from authority-based to experience-based to evidence-based with the introduction of the scientific process, clinical trials, and outcomes-based data analysis (Tebala GD. Int J Med Sci. 2018;15(12):1397-1405). The time required to perform the necessary randomized controlled trials, a systematic literature review, and meta-analysis of these trials to then create, accept, promulgate, and educate the practicing clinicians to use the evidence-based clinical guidelines is typically measured in years. When the severe acute respiratory syndrome novel coronavirus-2 (SARS-nCoV-2) pandemic commenced in Wuhan, China at the end of 2019, there were few available clinical guidelines to deploy, let alone adapt and adopt to treat the surge of coronavirus disease 2019 (COVID-19) patients. The aim of this study is to first explain how clinical guidelines, on which bedside clinicians have grown accustomed, can be created in the midst of a pandemic, with an evolving scientific understanding of the pathophysiology of the hypercoagulable state. The second is to adapt and adopt current venous thromboembolism diagnostic and treatment guidelines, while relying on the limited available observational reporting of COVID-19 patients to create a comprehensive clinical guideline to treat COVID-19 patients.

How To Maximize Trainee Education During the Coronavirus Disease-2019 Pandemic: Perspectives From Around the World

How To Maximize Trainee Education During the Coronavirus Disease-2019 Pandemic: Perspectives From Around the World

COVID-19 in Newborns and Infants-Low Risk of Severe Disease: Silver Lining or Dark Cloud?

One hundred years after the 1918 influenza pandemic, we now face another pandemic with the severe acute respiratory syndrome–novel coronavirus-2 (SARS-CoV-2). There is considerable variability in the incidence of infection and severe disease following exposure to SARS-CoV-2. Data from China and the United States suggest a low prevalence of neonates, infants, and children, with those affected not suffering from severe disease. In this article, we speculate different theories why this novel agent is sparing neonates, infants, and young children. The low severity of SARS-CoV-2 infection in this population is associated with a high incidence of asymptomatic or mildly symptomatic infection making them efficient carriers. Key Points There is a low prevalence of novel coronavirus disease in neonates, infants, and children.The fetal hemoglobin may play a protective role against coronavirus in neonates.Immature angiotensin converting enzyme (ACE2) interferes with coronavirus entry into the cells.

Current Knowledge and Research Priorities in the Digestive Manifestations of COVID-19

Current Knowledge and Research Priorities in the Digestive Manifestations of COVID-19