Local Complement Contributes to Pathogenic Activation of Lung Endothelial Cells in SARS-CoV-2 Infection.

Endothelial dysfunction and inflammation contribute to the vascular pathology of Coronavirus Disease 2019 (COVID-19). However, emerging evidence does not support direct infection of endothelial or other vascular wall cells and thus inflammation may be better explained as secondary responses to epithelial cell infection. In this study, we sought to determine whether lung endothelial or other resident vascular cells are susceptible to productive SARS-CoV-2 infection and how local complement activation contributes to endothelial dysfunction and inflammation in response to hypoxia and SARS-CoV-2 infected lung alveolar epithelial cells. We found that ACE2 and TMPRSS2 mRNA expression in lung vascular cells including primary human lung microvascular endothelial cells (HLMVEC), pericytes, smooth muscle cells and fibroblasts was 20-90-fold lower compared to primary human alveolar epithelial type II (AT2) cells. Consistently, we found that HLMVEC and other resident vascular cells were not susceptible to productive SARS-CoV-2 infection under either normoxic or hypoxic conditions. However, viral uptake without replication (abortive infection) was observed in HLMVEC when exposed to conditioned medium from SARS-CoV-2 infected human ACE2 stably transfected A549 epithelial cells (hACE2-A549). Furthermore, we demonstrated that exposure of HLMVEC to conditioned medium from SARS-CoV-2 infected hACE2-A549 cells and hypoxia resulted in upregulation of inflammatory factors such as ICAM1, VCAM1, IL-6 as well as complement components such as C3, C3AR1, C1QA and CFB. Taken together, our data support a model in which lung endothelial/vascular dysfunction during COVID-19 involves the activation of complement and inflammatory signaling and does not involve productive viral infection of endothelial cells. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).

Ethnopharmacological Potential of Phytochemicals and Phytogenic Products against Human RNA Viral Diseases as Preventive Therapeutics

RNA viruses have been the most destructive due to their transmissibility and lack of control measures. Developments of vaccines for RNA viruses are very tough or almost impossible as viruses are highly mutable. For the last few decades, most of the epidemic and pandemic viral diseases have wreaked huge devastation with innumerable fatalities. To combat this threat to mankind, plant-derived novel antiviral products may contribute as reliable alternatives. They are assumed to be nontoxic, less hazardous, and safe compounds that have been in uses in the beginning of human civilization. In this growing COVID-19 pandemic, the present review amalgamates and depicts the role of various plant products in curing viral diseases in humans.

Circulating SARS-CoV-2+ Megakaryocytes Associate with Severe Viral Infection in COVID-19.

Several independent lines of evidence suggest that megakaryocytes are dysfunctional in severe COVID-19. Herein, we characterized peripheral circulating megakaryocytes in a large cohort of COVID-19 inpatients and correlated subpopulation frequencies with clinical outcomes. Using peripheral blood, we show that megakaryocytes are increased in the systemic circulation in COVID-19, and we identify and validate S100A8/A9 as a defining marker of megakaryocyte dysfunction. We further reveal a subpopulation of S100A8/A9+ megakaryocytes that contain SARS-CoV-2 protein and RNA. Using flow cytometry of peripheral blood and in vitro studies on SARS-CoV-2 infected primary human megakaryocytes, we demonstrate that megakaryocytes can transfer viral antigens to emerging platelets. Mechanistically, we show that SARS-CoV-2 containing megakaryocytes are NFκB-activated, via p65 and p52, express NFκB-mediated cytokines, IL-6 and IL-1ß, and display high surface expression of TLR2 and TLR4, canonical drivers of NFκB. In a cohort of 218 COVID-19 inpatients, we correlate frequencies of megakaryocyte subpopulations with clinical outcomes and show that SARS-CoV-2 containing megakaryocytes are a strong risk factor for mortality and multi-organ injury, including respiratory failure, mechanical ventilation, acute kidney injury, thrombotic events, and ICU admission. Further, we show that SARS-CoV-2+ megakaryocytes are present in lung and brain autopsy tissues from deceased COVID-19 donors. This study offers the first evidence implicating SARS-CoV-2+ peripheral megakaryocytes in severe disease and suggests that circulating megakaryocytes warrant investigation in inflammatory disorders beyond COVID-19.

Ethnopharmacological Potential of Phytochemicals and Phytogenic Products against Human RNA Viral Diseases as Preventive Therapeutics.

RNA viruses have been the most destructive due to their transmissibility and lack of control measures. Developments of vaccines for RNA viruses are very tough or almost impossible as viruses are highly mutable. For the last few decades, most of the epidemic and pandemic viral diseases have wreaked huge devastation with innumerable fatalities. To combat this threat to mankind, plant-derived novel antiviral products may contribute as reliable alternatives. They are assumed to be nontoxic, less hazardous, and safe compounds that have been in uses in the beginning of human civilization. In this growing COVID-19 pandemic, the present review amalgamates and depicts the role of various plant products in curing viral diseases in humans.

Plasma Microbiome in COVID-19 Subjects: An Indicator of Gut Barrier Defects and Dysbiosis.

The gut is a well-established route of infection and target for viral damage by SARS-CoV-2. This is supported by the clinical observation that about half of COVID-19 patients exhibit gastrointestinal (GI) complications. We aimed to investigate whether the analysis of plasma could provide insight into gut barrier dysfunction in patients with COVID-19 infection. Plasma samples of COVID-19 patients (n = 146) and healthy individuals (n = 47) were collected during hospitalization and routine visits. Plasma microbiome was analyzed using 16S rRNA sequencing and gut permeability markers including fatty acid binding protein 2 (FABP2), peptidoglycan (PGN), and lipopolysaccharide (LPS) in both patient cohorts. Plasma samples of both cohorts contained predominately Proteobacteria, Firmicutes, Bacteroides, and Actinobacteria. COVID-19 subjects exhibit significant dysbiosis (p = 0.001) of the plasma microbiome with increased abundance of Actinobacteria spp. (p = 0.0332), decreased abundance of Bacteroides spp. (p = 0.0003), and an increased Firmicutes:Bacteroidetes ratio (p = 0.0003) compared to healthy subjects. The concentration of the plasma gut permeability marker FABP2 (p = 0.0013) and the gut microbial antigens PGN (p < 0.0001) and LPS (p = 0.0049) were significantly elevated in COVID-19 patients compared to healthy subjects. These findings support the notion that the intestine may represent a source for bacteremia and contribute to worsening COVID-19 outcomes. Therapies targeting the gut and prevention of gut barrier defects may represent a strategy to improve outcomes in COVID-19 patients.

Chapter 8 - Primary health-care goal and principles

Primary health care (PHC) is targeted to ensure the highest possible level of health and well-being and their equitable distribution by concentrating on the public needs for a sustainable healthy life without any financial burden on patients. It is also explained how to give special preference to women, families, and rural communities on a priority basis. The most impressive part of this chapter is the role of PHC in handling the COVID-19 pandemic, which is still beyond perfect control. In this connection, the role of WHO to bring preventive measures at the state and country level is also well explained.

Chapter 6 - Emergency disaster risk management for health

This chapter narrates how biological disasters cause the outbreak of conterminous diseases leading to pandemics, if timely care is not taken. In this connection, the authors explain the difference between outbreak, epidemic and pandemic nature of the contagious disease and how it can be controlled and what type of safety measure to be taken to stop its further spread. WHO advises mitigating disaster risks such as infection outbreaks, unsafe food, and water;chemical and radiation contamination, natural and technological hazards, wars and their societal conflicts, and other challenges are explained to challenge the emergency of a biological disaster. It is also explained how WHO participates in a number of forums that influence the policy and practice of emergency risk management for health. How WHO works informed by international frameworks such as Sedan framework for disaster risk reduction 2015–2030 and other UN system policies and plans.

Chapter 5 - Global rural health-care outlooks

This chapter is exclusively dedicated to explaining how rural health infrastructure is comparable with the health-care facilities provided in an urbanized area with examples. In this connection, in South Asia, infant mortality rates (IMR) in the rural area are 1.6 times higher than the urban area. Even in developing countries like India mortality rate is 1.5 times higher than in urbanized areas. In this connection, the authors explain about determinants that are responsible. It has also been discussed in detail how various organizations like multilateral organizations, bilateral agenesis, and nongovernment organization jointly try to resolve the issue related to health risk, especially caused by pandemic diseases like COVID-19. In addition, it has emphasized the primary health-care VS Universal health Coverage with some self-explained fundamental models. In this connection, the role of WHO also incorporates while covering different aspects of health coverage at the global level.

Chapter 3 - Public health, food security, and hunger

This chapter explains how world hunger, malnutrition, and extreme poverty act as limiting factors in order to eliminate risk-based health coverage. Hunger has become a chronic challenge for the rural populations living under variable geographic locations and climatic conditions. So, emphasis is given to find out ways and means to resolve the acute shortage of healthy food and nutrition, due to flawed agriculture policies, water security, the effect of climate changes, and violent conflicts. The authors mainly given the emphasis on prevention are primarily responsible for stopping the spread of the epidemic. For example, frequent hand washing, regular bath, and sensitization maintenance are primarily responsible for changing the epidemic into a pandemic form. In this connection, emphasis is given to the rule and protocols for washing hands. Especial instructions are given not to touch, eyes, nose, and mouth without wash hand. In addition, it is explained how touching the surroundings and carpets commonly contaminated by aero drop from contaminated person or patients. It has also been clear how noncommunicable diseases are also responsible for alarming life if timely care is not taken. How inadequate access to health infrastructure, communication gap, deficiency in medicine, and health aides are responsible for health service, timely. This chapter also covers the SDG3 goals responsible for bringing harmony to the health-care system with international collaboration projects.

Chapter 1 - Public health and management

This chapter explains how hospital community health centers and nurseries home provide preventive curative, rehabilitation care for public health management. In this connection, it is explained how security professions, fire, ambulance providers and emergency medical services can be closely coordinated to increase the efficacy of health services. The authors want to develop awareness among doctors to mobilize other health service processions to manage the system under extreme climatic and disaster conditions to save life and social health stability. The last part of the chapter gives insight on systemic management of disease classification and under what circumstance a disease outbreak becomes epidemic and pandemic at the global level if inadequate management is taken. In this connection, the authors try to explain it with the example of the COVID-19 challenge and bring to the attention of the public to either eradicate or bring stability with the passing of time. So, it is necessary to develop a well-organized health-care system either temporarily or upgrade the existing health-care system to meet the demand in an emergency.

SWITCHING BEHAVIOR TOWARD ONLINE SHOPPING: COERCION OR CHOICE DURING COVID-19 PANDEMIC

The pandemic, Covid-19, offered new opportunities for coercive online shopping to Indian consumers. Non techno-savvy and less educated consumers have also switched to online shopping. The present study investigates the customers' switching Behavior during the Covid-19 outbreak due to two attributes, perceived risks of infectious disease and the benefits of online shopping. Purchase and consumption acted as moderators in the model. A systematic empirical study with scientific research design was executed during March to August 2020 when the Covid-19 outbreak peaked, and online shopping became an alternate savior for continuity of life. This was the period when sanitization and mask-wearing, social distancing, avoiding touch was made compulsory. The hierarchical regression determined the catalyst role of Covid-19 in behavior switch and perception modification of online consumers. Findings suggest the change in risk perception during the Covid-19 pandemic lead to a change in marketing policies focused on awareness building. Control variables in the model behaved differently in online shopping, and new behaviors are expected to continue even after the pandemic. This study will contribute to elucidate switching buying behavior and the growth of the online business.

SARS-CoV-2 Infections and ACE2: Clinical Outcomes Linked With Increased Morbidity and Mortality in Individuals With Diabetes.

Individuals with diabetes suffering from coronavirus disease 2019 (COVID-19) exhibit increased morbidity and mortality compared with individuals without diabetes. In this Perspective, we critically evaluate and argue that this is due to a dysregulated renin-angiotensin system (RAS). Previously, we have shown that loss of angiotensin-I converting enzyme 2 (ACE2) promotes the ACE/angiotensin-II (Ang-II)/angiotensin type 1 receptor (AT1R) axis, a deleterious arm of RAS, unleashing its detrimental effects in diabetes. As suggested by the recent reports regarding the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), upon entry into the host, this virus binds to the extracellular domain of ACE2 in nasal, lung, and gut epithelial cells through its spike glycoprotein subunit S1. We put forth the hypothesis that during this process, reduced ACE2 could result in clinical deterioration in COVID-19 patients with diabetes via aggravating Ang-II-dependent pathways and partly driving not only lung but also bone marrow and gastrointestinal pathology. In addition to systemic RAS, the pathophysiological response of the local RAS within the intestinal epithelium involves mechanisms distinct from that of RAS in the lung; however, both lung and gut are impacted by diabetes-induced bone marrow dysfunction. Careful targeting of the systemic and tissue RAS may optimize clinical outcomes in subjects with diabetes infected with SARS-CoV-2.