PMC:7264098 / 1882-7139 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7264098","sourcedb":"PMC","sourceid":"7264098","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7264098","text":"Understanding Coronaviruses and Their Impact on Health\nA new strain of coronavirus, SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2, as named by the International Committee on Taxonomy of Viruses) discovered in Wuhan, China, in December 2019, has caused a global disruption and COVID-19 pandemic. SARS-CoV-2 is classified as Betacoronavirus. In general, coronavirus is the name of viruses that belong to the family Coronaviridae. These are classified into four categories: Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus. Alpha- and betacoronaviruses infect mammals, gammacoronaviruses infect avian species, and deltacoronaviruses infect both mammalian and avian species (Li, 2016). Coronaviruses are typically spherical, fatty enveloped viruses, which encapsulate large single-stranded RNA genomes, notably, the largest genome among all RNA viruses, typically ranging from 27 to 32 kb. The genome is packed inside a helical capsid formed by the nucleocapsid protein (N) and further surrounded by the envelope.\nGraphical Abstract Mesenchymal stem cells and their secreted extracellular vesicles are capable of abrogating inflammation and inducing lung regeneration, which can improve recovery of the patients hospitalized with COVID-19. Coronaviruses have characteristic clove-shape spikes (“corona”) protruding from the surface. The spikes are protein complexes that virus uses to bind to a receptor (receptor-binding subunit S1) and mediate entry into host cells (a membrane-fusion subunit S2). Upon binding virus fuses with the human cell membrane, allowing the genome of the virus to enter the cell and begin replication. The receptor-binding domain of SARS-CoV-2 spikes are closely related to those of SARS-CoVs (73.8–74.9% amino acid identity) and SARS-like CoVs (75.9–76.9% amino acid identity) (Wu et al., 2020). SARS-CoV-2 uses the human angiotensin I converting enzyme 2 (ACE2) receptor for cell entry (Lu et al., 2020), which could potentially facilitate human-to-human transmission. In addition to mediating virus entry, the spike feature is a critical determinant of viral host range and tissue tropism and a cause of host immune responses.\nSince the ACE2 receptor is widely distributed on the human alveolar type II cells and capillary endothelium (Hamming et al., 2004), lungs are particularly susceptible to the SARV-CoV-2 infections. Indeed, recent studies demonstrated that the disease could affect a large portion of the lungs causing widespread damage (Figure 1), which subsequently may lead to permanent changes to the lung function. Recent MRI study of a 59-year old male patient diagnosed with COVID-19 showed that the disease is not confined to any particular area, but that it can spread across the entire lungs (Figure 1; Mortman, 2020). However, this is not caused directly by the virus, but rather the host immune response leading to overwhelming cytokine storm in the lungs. The overexpression of cytokines such as IL-2, IL-6, IL-7, GSCF, IP10, MCP1, MIP1A, and TNFα is followed by edema, which impairs oxygen exchange, and may lead to acute respiratory distress syndrome (ARDS) causing potential acute cardiac injury, secondary infection (Huang et al., 2020), and death.\nFigure 1 Widespread distribution of the areas affected by COVID-19 and the effects of stem cells and extracellular vesicles on the recovery of lung function. Most recent observations suggest that the devastating complication of COVID-19 may not be a typical pneumonia or ARDS, but rather a dysfunction in blood oxygenation. This statement is supported by the fact that over 80% of COVID-19 patients placed on ventilators in New York City have died (Baker, 2020). According to Dr. Cameron Kyle-Sidell (Maimonides Medical Center, New York, March 31, 2020), COVID-19 patients show symptoms associated with high altitude without adaptation response (Gattinoni et al., 2020a,b). Clinically these cases resemble more closely high-altitude sickness characterized by decompression pulmonary sickness or high-altitude pulmonary edema (HAPE) with distinctive features of severe hypoxemia often associated with near normal respiratory system compliance.\nSince cytokines and inflammation play dominant role in the development of COVID-19-induced lung damage, immunological therapies capable of attenuating cytokine storm may be the key treatment options. However, traditional immunomodulatory capacity of common immunotherapeutics are targeted at one or two factors, which may not induce a strong enough response.\nMesenchymal stem/stromal cells (MSCs) have demonstrated potent and broad immunomodulatory and anti-inflammatory capacity (Abdi et al., 2008; Wada et al., 2013). Therefore, MSC-based therapy could potentially be an effective treatment for COVID-19. Notably, due to their regenerative properties (Mahla, 2016), MSCs can promote the repair of damaged tissue, in order to prevent long-term lung damage inflicted by COVID-19. Importantly, MSCs have been shown to stabilize endothelial fluid leakage and maintain alveolar-capillary barrier function, which is vital to sustain or decrease lung permeability due to inflammation, thus attenuating the development of interstitial lung edema (Bhattacharya and Matthay, 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