Background and aim As a result of its rapid spread in various countries around the world, on March 11, 2020, WHO issued an announcement of the change in coronavirus disease 2019 status from epidemic to pandemic disease. The virus that causes this disease is indicated originating from animals traded in a live animal market in Wuhan, China. Severe Acute Respiratory Syndrome Coronavirus 2 can attack lung cells because there are many conserved receptor entries, namely Angiotensin Converting Enzyme-2. The presence of this virus in host cells will initiate various protective responses leading to pneumonia and Acute Respiratory Distress Syndrome. This review aimed to provide an overview related to this virus and examine the body’s responses and possible therapies. Method We searched PubMed databases for Severe Acute Respiratory Syndrome Coronavirus-2, Middle East respiratory syndrome-related coronavirus and Severe Acute Respiratory Syndrome Coronavirus. Full texts were retrieved, analyzed and developed into an easy-to-understand review. Results We provide a complete review related to structure, origin, and how the body responds to this virus infection and explain the possibility of an immune system over-reaction or cytokine storm. We also include an explanation of how this virus creates modes of avoidance to evade immune system attacks. We further explain the therapeutic approaches that can be taken in the treatment and prevention of this viral infection. Conclusion In summary, based on the structural and immune-evasion system of coronavirus, we suggest several approaches to treat the disease.

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Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): An overview of viral structure and host response.

Summary Background There are few primary care studies of the COVID-19 pandemic. We aimed to identify demographic and clinical risk factors for testing positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within the Oxford Royal College of General Practitioners (RCGP) Research and Surveillance Centre primary care network. Methods We analysed routinely collected, pseudonymised data for patients in the RCGP Research and Surveillance Centre primary care sentinel network who were tested for SARS-CoV-2 between Jan 28 and April 4, 2020. We used multivariable logistic regression models with multiple imputation to identify risk factors for positive SARS-CoV-2 tests within this surveillance network. Findings We identified 3802 SARS-CoV-2 test results, of which 587 were positive. In multivariable analysis, male sex was independently associated with testing positive for SARS-CoV-2 (296 [18·4%] of 1612 men vs 291 [13·3%] of 2190 women; adjusted odds ratio [OR] 1·55, 95% CI 1·27–1·89). Adults were at increased risk of testing positive for SARS-CoV-2 compared with children, and people aged 40–64 years were at greatest risk in the multivariable model (243 [18·5%] of 1316 adults aged 40–64 years vs 23 [4·6%] of 499 children; adjusted OR 5·36, 95% CI 3·28–8·76). Compared with white people, the adjusted odds of a positive test were greater in black people (388 [15·5%] of 2497 white people vs 36 [62·1%] of 58 black people; adjusted OR 4·75, 95% CI 2·65–8·51). People living in urban areas versus rural areas (476 [26·2%] of 1816 in urban areas vs 111 [5·6%] of 1986 in rural areas; adjusted OR 4·59, 95% CI 3·57–5·90) and in more deprived areas (197 [29·5%] of 668 in most deprived vs 143 [7·7%] of 1855 in least deprived; adjusted OR 2·03, 95% CI 1·51–2·71) were more likely to test positive. People with chronic kidney disease were more likely to test positive in the adjusted analysis (68 [32·9%] of 207 with chronic kidney disease vs 519 [14·4%] of 3595 without; adjusted OR 1·91, 95% CI 1·31–2·78), but there was no significant association with other chronic conditions in that analysis. We found increased odds of a positive test among people who are obese (142 [20·9%] of 680 people with obesity vs 171 [13·2%] of 1296 normal-weight people; adjusted OR 1·41, 95% CI 1·04–1·91). Notably, active smoking was linked with decreased odds of a positive test result (47 [11·4%] of 413 active smokers vs 201 [17·9%] of 1125 non-smokers; adjusted OR 0·49, 95% CI 0·34–0·71). Interpretation A positive SARS-CoV-2 test result in this primary care cohort was associated with similar risk factors as observed for severe outcomes of COVID-19 in hospital settings, except for smoking. We provide evidence of potential sociodemographic factors associated with a positive test, including deprivation, population density, ethnicity, and chronic kidney disease. Funding Wellcome Trust.

Risk factors for SARS-CoV-2 among patients in the Oxford Royal College of General Practitioners Research and Surveillance Centre primary care network: a cross-sectional study.

COVID-19: Immunology and treatment options.

Bone marrow‐derived mesenchymal stem cells (MSCs) hold great promise for treating immune disorders because of their immunoregulatory capacity, but the mechanism remains controversial. As we show here, the mechanism of MSC‐mediated immunosuppression varies among different species. Immunosuppression by human‐ or monkey‐derived MSCs is mediated by indoleamine 2,3‐dioxygenase (IDO), whereas mouse MSCs utilize nitric oxide, under the same culture conditions. When the expression of IDO and inducible nitric oxide synthase (iNOS) were examined in human and mouse MSCs after stimulation with their respective inflammatory cytokines, we found that human MSCs expressed extremely high levels of IDO, and very low levels of iNOS, whereas mouse MSCs expressed abundant iNOS and very little IDO. Immunosuppression by human MSCs was not intrinsic, but was induced by inflammatory cytokines and was chemokine‐dependent, as it is in mouse. These findings provide critical information about the immunosuppression of MSCs and for better application of MSCs in treating immune disorders. STEM CELLS 2009;27:1954–1962

Species Variation in the Mechanisms of Mesenchymal Stem Cell-Mediated Immunosuppression

The hypercoagulable state in COVID-19: Incidence, pathophysiology, and management.

The outbreak of Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2), has thus far killed over 3,000 people and infected over 80,000 in China and elsewhere in the world, resulting in catastrophe for humans. Similar to its homologous virus, SARS-CoV, which caused SARS in thousands of people in 2003, SARS-CoV-2 might also be transmitted from the bats and causes similar symptoms through a similar mechanism. However, COVID-19 has lower severity and mortality than SARS but is much more transmissive and affects more elderly individuals than youth and more men than women. In response to the rapidly increasing number of publications on the emerging disease, this article attempts to provide a timely and comprehensive review of the swiftly developing research subject. We will cover the basics about the epidemiology, etiology, virology, diagnosis, treatment, prognosis, and prevention of the disease. Although many questions still require answers, we hope that this review helps in the understanding and eradication of the threatening disease.

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COVID-19: what has been learned and to be learned about the novel coronavirus disease.

Despite the long discrepancy over their definition, heterogeneity, and functions, mesenchymal stem cells (MSCs) have proved to be a key player in tissue repair and homeostasis. Generally, somatic tissue-derived MSCs (st-MSCs) are subject to quality variations related to donated samples and biosafety concern for transmission of potential pathogens from the donors. In contrast, human pluripotent stem cells (hPSCs) are unlimited in supply, clear in the biological background, and convenient for quality control, genetic modification, and scale-up production. We, and others, have shown that hPSCs can differentiate in two dimensions or three dimensions to MSCs (ps-MSCs) via embryonic (mesoderm and neural crest) or extraembryonic (trophoblast) cell types under serum-containing or xeno-free and defined conditions. Compared to st-MSCs, ps-MSCs appear less mature, proliferate faster, express lower levels of inflammatory cytokines, and respond less to traditional protocols for st-MSC differentiation to other cell types, especially adipocytes. Nevertheless, ps-MSCs are capable of immune modulation and treatment of an increasing number of animal disease models via mitochondria transfer, paracrine, exosomes, and direct differentiation, and can be potentially used as a universal and endless therapy for clinical application. This review summarizes the progress on ps-MSCs and discusses perspectives and challenges for their potential translation to the clinic. Stem Cells 2019;37:572-581.

https://stemcellsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/stem.2964

Concise Review: Mesenchymal Stem Cells Derived from Human Pluripotent Cells, an Unlimited and Quality-Controllable Source for Therapeutic Applications.

Radiation-induced brain injury (RI) commonly occurs in patients who received head and neck radiotherapy. However, the mechanism of RI remains unclear. We aimed to evaluate whether pyroptosis was involved in RI and the impact of mesenchymal stem cells (MSCs) on it. BALB/c male mice (6–8 weeks) were cranially irradiated (15 Gy), and MSCs were transplanted into the bilateral cortex 2 days later; then mice were sacrificed 1 month later. Meanwhile, irradiated BV-2 microglia cells (10 Gy) were cocultured with MSCs for 24 hours. We observed that irradiated mice brains presented NLRP3 and caspase-1 activation. RT-PCR then indicated that it mainly occurred in microglia cells but not in neurons. Further, irradiated BV-2 cells showed pyroptosis and increased production of IL-18 and IL-1β. RT-PCR also demonstrated an increased expression of several inflammasome genes in irradiated BV-2 cells, including NLRP3 and AIM2. Particularly, NLRP3 was activated. Knockdown of NLRP3 resulted in decreased LDH release. Noteworthily, in vivo, MSCs transplantation alleviated radiation-induced NLRP3 and caspase-1 activation. Moreover, in vitro, MSCs could decrease caspase-1 dependent pyroptosis, NLRP3 inflammasome activation, and ROS production induced by radiation. Thus, our findings proved that microglia pyroptosis occurred in RI. MSCs may act as a potent therapeutic tool in attenuating pyroptosis.

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Mesenchymal Stem Cells Attenuate Radiation-Induced Brain Injury by Inhibiting Microglia Pyroptosis

Spheroidal formation preserves human stem cells for prolonged time under ambient conditions for facile storage and transportation.

Mesenchymal stem/stromal cells (MSCs) have great clinical potential in modulating inflammation and promoting tissue repair. Human embryonic stem cells (hESCs) have recently emerged as a potentially superior cell source for MSCs. However, the generation methods reported so far vary greatly in quality and efficiency. Here, we describe a novel method to rapidly and efficiently produce MSCs from hESCs via a trophoblast-like intermediate stage in approximately 11-16 days. We term these cells "T-MSCs" and show that T-MSCs express a phenotype and differentiation potential minimally required to define MSCs. T-MSCs exhibit potent immunomodulatory activity in vitro as they can remarkably inhibit proliferation of cocultured T and B lymphocytes. Unlike bone marrow MSCs, T-MSCs do not have increased expression of inflammatory mediators in response to IFNγ. Moreover, T-MSCs constitutively express a high level of the immune inhibitory ligand PD-L1 and elicit strong and durable efficacy in two distinct animal models of autoimmune disease, dextran sulfate sodium induced colitis, and experimental autoimmune encephalomyelitis, at doses near those approved for clinical trials. Together, we present a simple and fast derivation method to generate MSCs from hESCs, which possess potent immunomodulatory properties in vitro and in vivo and may serve as a novel and ideal candidate for MSC-based therapies.

Enqin Li

Papers

COVID-19: what has been learned and to be learned about the novel coronavirus disease.

Concise Review: Mesenchymal Stem Cells Derived from Human Pluripotent Cells, an Unlimited and Quality-Controllable Source for Therapeutic Applications.

Mesenchymal Stem Cells Attenuate Radiation-Induced Brain Injury by Inhibiting Microglia Pyroptosis

Spheroidal formation preserves human stem cells for prolonged time under ambient conditions for facile storage and transportation.

Immune modulatory mesenchymal stem cells derived from human embryonic stem cells through a trophoblast-like stage