Potential Therapeutic Role of Mesenchymal-Derived Stem Cells as an Alternative Therapy to Combat COVID-19 through Cytokines Storm.

Medical health systems continue to be challenged due to newly emerging COVID-19, and there is an urgent need for alternative approaches for treatment. An increasing number of clinical observations indicate cytokine storms to be associated with COVID-19 severity and also to be a significant cause of death among COVID-19 patients. Cytokine storm involves the extensive proliferative and hyperactive activity of T and macrophage cells and the overproduction of pro-inflammatory cytokines. Stem cells are the type of cell having self-renewal properties and giving rise to differentiated cells. Currently, stem cell therapy is an exciting and promising therapeutic approach that can treat several diseases that were considered incurable in the past. It may be possible to develop novel methods to treat various diseases by identifying stem cells' growth and differentiation factors. Treatment with mesenchymal stem cells (MSCs) in medicine is anticipated to be highly effective. The present review article is organized to put forward the positive arguments and implications in support of mesenchymal stem cell therapy as an alternative therapy to cytokine storms, to combat COVID-19. Using the immunomodulatory potential of the MSCs, it is possible to fight against COVID-19 and counterbalance the cytokine storm.

Premorbid echocardiography and risk of hospitalization in COVID-19

BackgroundCOVID-19 has caused a global pandemic unprecedented in a century. Though primarily a respiratory illness, cardiovascular risk factors predict adverse outcomes. We aimed to investigate the role of baseline echocardiographic abnormalities in further refining risk in addition to clinical risk factors.MethodsAdults with COVID-19 positive RT-PCR test across St Luke’s University Health Network between March 1st 2020-October 31st 2020 were identified. Those with trans-thoracic echocardiography (TTE) within 15–180 days preceding COVID-19 positivity were selected, excluding severe valvular disease, acute cardiac event between TTE and COVID-19, or asymptomatic patients positive on screening. Demographic, clinical, and echocardiographic variables were manually extracted from patients’ EHR and compared between groups stratified by disease severity. Logistic regression was used to identify independent predictors of hospitalization.Results192 patients met inclusion criteria. 87 (45.3%) required hospitalization, 34 (17.7%) suffered severe disease (need for ICU care/mechanical ventilation/in-hospital death). Age, co-morbidities, and several echocardiographic abnormalities were more prevalent in those with moderate-severe disease than in mild disease, with notable exceptions of systolic/diastolic dysfunction. On multivariate analysis, age (OR 1.039, 95% CI 1.011–1.067), coronary artery disease (OR 4.184, 95% CI 1.451–12.063), COPD (OR 6.886, 95% CI 1.396–33.959) and left atrial diameter ≥ 4.0 cm (OR 2.379, 95% CI 1.031–5.493) predicted need for hospitalization. Model showed excellent discrimination (ROC AUC 0.809, 95% CI 0.746–0.873).ConclusionsBaseline left atrial enlargement is an independent risk factor for risk of hospitalization among patients with COVID-19. When available, baseline LA enlargement may identify patients for (1) closer outpatient follow up, and (2) counseling vaccine-hesitancy.

Premorbid echocardiography and risk of hospitalization in COVID-19

Background COVID-19 has caused a global pandemic unprecedented in a century. Though primarily a respiratory illness, cardiovascular risk factors predict adverse outcomes. We aimed to investigate the role of baseline echocardiographic abnormalities in further refining risk in addition to clinical risk factors. Methods Adults with COVID-19 positive RT-PCR test across St Luke’s University Health Network between March 1st 2020-October 31st 2020 were identified. Those with trans-thoracic echocardiography (TTE) within 15–180 days preceding COVID-19 positivity were selected, excluding severe valvular disease, acute cardiac event between TTE and COVID-19, or asymptomatic patients positive on screening. Demographic, clinical, and echocardiographic variables were manually extracted from patients’ EHR and compared between groups stratified by disease severity. Logistic regression was used to identify independent predictors of hospitalization. Results 192 patients met inclusion criteria. 87 (45.3%) required hospitalization, 34 (17.7%) suffered severe disease (need for ICU care/mechanical ventilation/in-hospital death). Age, co-morbidities, and several echocardiographic abnormalities were more prevalent in those with moderate-severe disease than in mild disease, with notable exceptions of systolic/diastolic dysfunction. On multivariate analysis, age (OR 1.039, 95% CI 1.011–1.067), coronary artery disease (OR 4.184, 95% CI 1.451–12.063), COPD (OR 6.886, 95% CI 1.396–33.959) and left atrial diameter ≥ 4.0 cm (OR 2.379, 95% CI 1.031–5.493) predicted need for hospitalization. Model showed excellent discrimination (ROC AUC 0.809, 95% CI 0.746–0.873). Conclusions Baseline left atrial enlargement is an independent risk factor for risk of hospitalization among patients with COVID-19. When available, baseline LA enlargement may identify patients for (1) closer outpatient follow up, and (2) counseling vaccine-hesitancy. Supplementary Information The online version contains supplementary material available at 10.1007/s10554-022-02565-4.

Computational investigation reveals that the mutant strains of SARS-CoV2 have differential structural and binding properties.

BACKGROUND AND OBJECTIVES: Remarkable infectivity of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV2) is due to the rapid emergence of various strains which enable the virus to ruling the world. Over the course of SARS-CoV2 pandemic, the scientific communities worldwide are responding to newly emerging genetic variants. However, mechanism behind the persistent infection of these variants is still not known due to the paucity of study of these variants at molecular level. In this scenario, computational methods have immense utility in understanding the molecular and functional properties of different variants. METHODS: The various mutants (MTs) of SpikeS1 receptor binding domain (RBD) of highly infectious SARS-CoV2 strains were manifested and elucidated the protein structure and binding strength using molecular dynamics (MD) simulation and protein-protein docking approaches. RESULTS: MD simulation study showed that all MTs exhibited stable structures with altered functional properties. Furthermore, the binding strength of different MTs along with WT (wildtype) was revealed that MTs showed differential binding affinities to host protein with high binding strength exhibited by V367F and V483A MTs. CONCLUSION: Hence, this study shed light on the molecular basis of infection caused by different variants of SARS-CoV2, which might play an important role in to cease the transmission and pathogenesis of virus and also implicate in rational designing of a specific drug.

Immunological Mechanisms of Vaccine-Induced Protection against SARS-CoV-2 in Humans

The SARS-CoV-2 infection spread rapidly throughout the world and appears to involve in both humoral and cell-mediated immunity. SARS-CoV-2 is attached to host cells via binding to the viral spike (S) proteins and its cellular receptors angiotensin-converting enzyme 2 (ACE2). Consequently, the S protein is primed with serine proteases TMPRSS2 and TMPRSS4, which facilitate the fusion of viral and cellular membranes result in the entry of viral RNA into the host cell. Vaccines are urgently required to combat the coronavirus disease 2019 (COVID-19) outbreak and aid in the recovery to pre-pandemic levels of normality. The long-term protective immunity is provided by the vaccine antigen (or pathogen)-specific immune effectors and the activation of immune memory cells that can be efficiently and rapidly reactivated upon pathogen exposure. Research efforts aimed towards the design and development of vaccines for SARS-CoV-2 are increasing. Numerous coronavirus disease 2019 (COVID-19) vaccines have passed late-stage clinical investigations with promising outcomes. This review focuses on the present state and future prospects of COVID-19 vaccines research and development, with a particular emphasis on immunological mechanisms of various COVID-19vaccines such as adenoviral vector-based vaccines, mRNA vaccines, and DNA vaccines that elicits immunological responses against SARS-CoV-2 infections in humans.

Is it all in the heart? Myocardial injury as major predictor of mortality among hospitalized COVID-19 patients.

Coronavirus disease 2019 (COVID-19) is an infection caused by the virus SARS-CoV-2, and has caused the most widespread global pandemic in over 100 years. Given the novelty of the disease, risk factors of mortality and adverse outcomes in hospitalized patients remain to be elucidated. We present the results of a retrospective cohort study including patients admitted to a large tertiary-care, academic university hospital with COVID-19. Patients were admitted with confirmed diagnosis of COVID-19 between 1 March and 15 April 2020. Baseline clinical characteristics and admission laboratory variables were retrospectively collected. Patients were grouped based on mortality, need for ICU care, and mechanical ventilation. Prevalence of clinical co-morbidities and laboratory abnormalities were compared between groups using descriptive statistics. Univariate analysis was performed to identify predictors of mortality, ICU care and mechanical ventilation. Predictors significant at P ≤ .10 were included in multivariate analysis. Five hundred and sixty patients were included in the analysis. Age and myocardial injury were only independent predictors of mortality, in patients with/without baseline co-morbidities. Body mass index, elevated ferritin, elevated d-dimer, and elevated procalcitonin predicted need for ICU care, and these along with vascular disease at baseline predicted need for mechanical ventilation. Hence, inflammatory markers (ferritin and d-dimer) predicted severe disease, but not death.

A systematic review of clinical and laboratory parameters of 3,000 COVID-19 cases.

The coronavirus disease 2019 (COVID-19) has spread worldwide. It is still a pandemic and poses major health problem across the globe. In our review, clinical characteristics and laboratory parameters of COVID-19 patients were compiled systematically, with special reference to pregnant women in order to understand the disease course. An extensive literature search on various scientific databases for relevant manuscripts was conducted, which yielded 7 manuscripts for final analysis. The most common symptoms were fever (85%), cough (70.63%), chest tightness (37.36%), expectoration (33.27%), fatigue (32%), dyspnea (31.95%), and shortness of breath (31.19%), while hemoptysis (1.0%) was the least common. The associated comorbidities were hypertension (21.6%) and diabetes (10.0%). In terms of hematological parameters, lower total leukocyte counts were observed in 65% of cases and biochemical parameters, patients demonstrated elevated levels of albumin (53.72%), lactate dehydrogenase (45.71%), and natriuretic peptide (34.84%); however, total bilirubin was elevated in only 8% of cases. In the acute inflammatory cytokine profile, C-reactive protein (59.0%), tumor necrosis factor (58.0%), erythrocyte sedimentation rate (57.0%), interleukin-2 (IL- 2, 54.0%), and IL-6 (52.0%) levels were increased, while prolactin levels (6.5%) were minimally elevated. The recovery rate was approximately 41%, and mortality was about 6.5%. The study also concluded that the clinical symptoms of COVID-19 were similar among pregnant and non-pregnant women. There was no evidence of vertical transmission of COVID-19 infection. This review critically analyzed COVID-19 as a public health hazard in order to help policy makers, health care givers, and primary physicians to promote early diagnosis and prevention.

The liver in COVID-19: prevalence, patterns, predictors, and impact on outcomes of liver test abnormalities.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has caused a global pandemic unprecedented in over a century, with ≈35 million cases, and more than 1 million deaths globally. Though predominantly a lower respiratory illness, other organ injuries are well-recognized. Among these, liver injury is of major interest. OBJECTIVE: To define prevalence, pattern, predictors, and impact of liver injury among patients hospitalized with COVID-19. METHODS: Demographic, clinical, and biochemical data were collected retrospectively among patients admitted to St. Luke's University Hospital with COVID-19 between 1 March and 18 April 2020. Association of liver tests (LTs) with mortality and need for mechanical ventilation, adjusted for demographic, clinical and biochemical predictors, was examined. RESULTS: Data were available on 551 patients. Prevalence of any or ≥3 × upper limit of normal transaminase elevation on was 61.2 and 9.4% on admission, and 72.1 and 22.4% at peak. Bilirubin and alkaline phosphatase elevations were less common on admission (11.4 and 12.6%, respectively), and at peak (17.7 and 22%, respectively). All liver test (LT) elevations were consistently predicted by inflammatory markers. Hyperbilirubinemia predicted mortality on admission and at peak. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) had opposite impact on mortality with AST positively, and ALT negatively associated with mortality. Hence, besides hyperbilirubinemia, AST:ALT ratio emerged as the best marker for mortality among the LTs. CONCLUSION: LT elevations among patients presenting with COVID-19 are very common, though majority are mild. Admission and peak bilirubin ≥1 mg/dl, as well as admission and peak AST:ALT ratio were significant predictors of mortality, along with age, myocardial injury, and chronic medical illness.