Evidence-Based Considerations Exploring Relations between SARS-CoV-2 Pandemic and Air Pollution: Involvement of PM2.5-Mediated Up-Regulation of the Viral Receptor ACE-2.
ABSTRACT: The COVID-19/SARS-CoV-2 pandemic struck health, social and economic systems worldwide, and represents an open challenge for scientists -coping with the high inter-individual variability of COVID-19, and for policy makers -coping with the responsibility to understand environmental factors affecting its severity across different geographical areas. Air pollution has been warned of as a modifiable factor contributing to differential SARS-CoV-2 spread but the biological mechanisms underlying the phenomenon are still unknown. Air quality and COVID-19 epidemiological data from 110 Italian provinces were studied by correlation analysis, to evaluate the association between particulate matter (PM)2.5 concentrations and incidence, mortality rate and case fatality risk of COVID-19 in the period 20 February-31 March 2020. Bioinformatic analysis of the DNA sequence encoding the SARS-CoV-2 cell receptor angiotensin-converting enzyme 2 (ACE-2) was performed to identify consensus motifs for transcription factors mediating cellular response to pollutant insult. Positive correlations between PM2.5 levels and the incidence (r = 0.67, p < 0.0001), the mortality rate (r = 0.65, p < 0.0001) and the case fatality rate (r = 0.7, p < 0.0001) of COVID-19 were found. The bioinformatic analysis of the ACE-2 gene identified nine putative consensus motifs for the aryl hydrocarbon receptor (AHR). Our results confirm the supposed link between air pollution and the rate and outcome of SARS-CoV-2 infection and support the hypothesis that pollution-induced over-expression of ACE-2 on human airways may favor SARS-CoV-2 infectivity.
Project description:Many major cities that witnessed heavy air pollution by nitrogen dioxide (NO2) and particulate matter (PM) have experienced a high rate of infection and severity of the coronavirus disease pandemic (COVID-19). This phenomenon could be explained by the overexpression of the angiotensin converting enzyme 2 (ACE-2) on epithelial cell surfaces of the respiratory tract. Indeed, ACE-2 is a receptor for coronaviruses including the severe acute respiratory syndrome coronavirus 1 and 2 (SARS-CoV), and ACE-2 is overexpressed under chronic exposure to air pollution such as NO2 and PM2.5. In this review, we explain that ACE-2 acts as the sole receptor for the attachment of the SARS-CoV-2 via its spike protein. The fact that respiratory and vascular epithelial cells express ACE-2 has been previously observed during the 2003 epidemic of the SARS-CoV-1 in China, and during the 2012 Middle East respiratory syndrome in Saudi Arabia. High ACE-2 expression in respiratory epithelial cells under air pollution explains the positive correlation between the severity in COVID-19 patients and elevated air pollution, notably high NO2 and PM2.5 levels. Specific areas in India, China, Italy, Russia, Chile and Qatar that experience heavy air pollution also show high rates of COVID-19 infection and severity. Overall, we demonstrate a link between NO2 emissions, PM2.5 levels, ACE-2 expression and COVID-19 infection severity. Therefore, air pollution should be reduced in places where confirmed cases of COVID-19 are unexpectedly high.
Project description:The effects of obesity and smoking in the coronavirus disease 2019 (COVID-19) pandemic remain controversial. Angiotensin converting enzyme 2 (ACE2), a component of the renin-angiotensin system (RAS), is the human cell receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19. ACE2 expression increases on lung alveolar epithelial cells and adipose tissue due to obesity, smoking and air pollution. A significant relationship exists between air pollution and SARS-CoV-2 infection, as more severe COVID-19 symptoms occur in smokers; comorbid conditions due to obesity or excess ectopic fat accumulation as underlying risk factors for severe COVID-19 strongly encourage the virus/ACE2 receptor-ligand interaction concept. Indeed, obesity, air pollution and smoking associated risk factors share underlying pathophysiologies that are related to the Renin-Angiotensin-System in SARS-CoV-2 infection. The aim of this review is to emphasize the mechanism of receptor-ligand interaction and its impact on the enhanced risk of death due to SARS-CoV-2 infection.
Project description:In December 2019, a novel disease, coronavirus disease 19 (COVID-19), emerged in Wuhan, People's Republic of China. COVID-19 is caused by a novel coronavirus (SARS-CoV-2) presumed to have jumped species from another mammal to humans. This virus has caused a rapidly spreading global pandemic. To date, over 300,000 cases of COVID-19 have been reported in England and over 40,000 patients have died. While progress has been achieved in managing this disease, the factors in addition to age that affect the severity and mortality of COVID-19 have not been clearly identified. Recent studies of COVID-19 in several countries identified links between air pollution and death rates. Here, we explored potential links between major fossil fuel-related air pollutants and SARS-CoV-2 mortality in England. We compared current SARS-CoV-2 cases and deaths from public databases to both regional and subregional air pollution data monitored at multiple sites across England. After controlling for population density, age and median income, we show positive relationships between air pollutant concentrations, particularly nitrogen oxides, and COVID-19 mortality and infectivity. Using detailed UK Biobank data, we further show that PM2.5 was a major contributor to COVID-19 cases in England, as an increase of 1 m3 in the long-term average of PM2.5 was associated with a 12% increase in COVID-19 cases. The relationship between air pollution and COVID-19 withstands variations in the temporal scale of assessments (single-year vs 5-year average) and remains significant after adjusting for socioeconomic, demographic and health-related variables. We conclude that a small increase in air pollution leads to a large increase in the COVID-19 infectivity and mortality rate in England. This study provides a framework to guide both health and emissions policies in countries affected by this pandemic.
Project description:After the appearance of COVID-19 in China last December 2019, Italy was the first European country to be severely affected by the outbreak. The first diagnosis in Italy was on February 20, 2020, followed by the establishment of a light and a tight lockdown on February 23 and on March 8, 2020, respectively. The virus spread rapidly, particularly in the North of the country in the 'Padan Plain' area, known as one of the most polluted regions in Europe. Air pollution has been recently hypothesized to enhance the clinical severity of SARS-CoV-2 infection, acting through adverse effects on immunity, induction of respiratory and other chronic disease, upregulation of viral receptor ACE-2, and possible pathogen transportation as a virus carrier. We investigated the association between air pollution and subsequent COVID-19 mortality rates within two Italian regions (Veneto and Emilia-Romagna). We estimated ground-level nitrogen dioxide through its tropospheric levels using data available from the Sentinel-5P satellites of the European Space Agency Copernicus Earth Observation Programme before the lockdown. We then examined COVID-19 mortality rates in relation to the nitrogen dioxide levels at three 14-day lag points after the lockdown, namely March 8, 22 and April 5, 2020. Using a multivariable negative binomial regression model, we found an association between nitrogen dioxide and COVID-19 mortality. Although ecological data provide only weak evidence, these findings indicate an association between air pollution levels and COVID-19 severity.
Project description:Pathological signaling in the lung induced by particulate matter (PM) air pollution partially overlaps with that provoked by COVID-19, the pandemic disease caused by infection with the novel coronavirus SARS-CoV-2. Metformin is capable of suppressing one of the molecular triggers of the proinflammatory and prothrombotic processes of urban PM air pollution, namely the mitochondrial ROS/Ca2+ release-activated Ca2+ channels (CRAC)/IL-6 cascade. Given the linkage between mitochondrial functionality, ion channels, and inflamm-aging, the ability of metformin to target mitochondrial electron transport and prevent ROS/CRAC-mediated IL-6 release might illuminate new therapeutic avenues to quell the raging of the cytokine and thrombotic-like storms that are the leading causes of COVID-19 morbidity and mortality in older people. The incorporation of infection rates, severity and lethality of SARS-CoV-2 infections as new outcomes of metformin usage in elderly populations at risk of developing severe COVID-19, together with the assessment of bronchial/serological titers of inflammatory cytokines and D-dimers, could provide a novel mechanistic basis for the consideration of metformin as a therapeutic strategy against the inflammatory and thrombotic states underlying the gerolavic traits of SARS-CoV-2 infection.
Project description:In the previous publication "Can atmospheric pollution be considered a co-factor in extremely high level of SARS-CoV-2 lethality in Northern Italy?" Conticini et al. hypothesized that the surplus of lethality of the novel SARS-CoV-2 in Northern Italy may be at least in part explained by the evidence of highest pollution reported in this area, as both severe COVID-19 and smog exposure are correlated to an innate immune system hyper-activation with subsequent lung inflammation and injury. Since this hypothesis alone does not fully explain why specific subgroups of patients are at major risk, we hypothesized that obesity may be one of the links between COVID-19 severity and high level of air pollution. First, obesity is a predisposing factor for SARS-Cov-2 infection and worse COVID-19 outcomes, and unequivocal evidence demonstrated that fat mass excess is independently associated with several pulmonary diseases and lung inflammation. Moreover, it has been shown that obesity may intensify the detrimental effects of air pollution on the lungs, and this is not surprising if we consider that these conditions share an excessive activation of the immune system and a lung inflammatory infiltrate. Finally, fat mass excess has also been speculated to be itself a consequence of air pollutants exposure, which has been proved to induce metabolic disruption and weight gain in murine models. In conclusion, although many variables must be taken into account in the analysis of the pandemic, our observations suggest that obesity may act as effect modifier of smog-induced lung-injury, and the concomitant presence of these two factors could better explain the higher virulence, faster spread and greater mortality of SARS-CoV-2 in Northern Italy compared to the rest of the country.
Project description:The COVID-19 epidemic, caused by the SARS-CoV-2 virus, has resulted in 3352 deaths in China as of April 12, 2020. This study aimed to investigate the associations between particulate matter (PM) concentrations and the case fatality rate (CFR) of COVID-19 in 49 Chinese cities, including the epicenter of Wuhan. We used the Global Moran's I to analyze spatial distribution and autocorrelation of CFRs, and then we used multivariate linear regression to analyze the associations between PM2.5 and PM10 concentrations and COVID-19 CFR. We found positive associations between PM pollution and COVID-19 CFR in cities both inside and outside Hubei Province. For every 10 ?g/m3 increase in PM2.5 and PM10 concentrations, the COVID-19 CFR increased by 0.24% (0.01%-0.48%) and 0.26% (0.00%-0.51%), respectively. PM pollution distribution and its association with COVID-19 CFR suggests that exposure to such may affect COVID-19 prognosis.
Project description:Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The initial interaction between Transmembrane Serine Protease 2 (TMPRSS2) primed SARS-CoV-2 spike (S) protein and host cell receptor angiotensin-converting enzyme 2 (ACE-2) is a pre-requisite step for this novel coronavirus pathogenesis. Here, we expressed a GFP-tagged SARS-CoV-2 S-Ectodomain in Tni insect cells. That contained sialic acid-enriched N- and O-glycans. Surface resonance plasmon (SPR) and Luminex assay showed that the purified S-Ectodomain binding to human ACE-2 and immunoreactivity with COVID-19 positive samples. We demonstrate that bromelain (isolated from pineapple stem and used as a dietary supplement) treatment diminishes the expression of ACE-2 and TMPRSS2 in VeroE6 cells and dramatically lowers the expression of S-Ectodomain. Importantly, bromelain treatment reduced the interaction between S-Ectodomain and VeroE6 cells. Most importantly, bromelain treatment significantly diminished the SARS-CoV-2 infection in VeroE6 cells. Altogether, our results suggest that bromelain or bromelain rich pineapple stem may be used as an antiviral against COVID-19. Highlights:Bromelain inhibits / cleaves the expression of ACE-2 and TMPRSS2Bromelain cleaves / degrades SARS-CoV-2 spike proteinBromelain inhibits S-Ectodomain binding and SARS-CoV-2 infection.
Project description:The pandemic of coronavirus disease 2019 (COVID-19) is generating a high number of total infected individuals and deaths. One of the current questions is how climatological factors and environmental pollution can affect the diffusion of COVID-19 in human society. This study endeavours to explain the relation between wind speed, air pollution and the diffusion of COVID-19 to provide insights to constrain and prevent future pandemics and epidemics. The statistical analysis here focuses on case study of Italy and reveals two main findings: 1) cities with high wind speed have lower numbers of COVID-19 related infected individuals; 2) cities located in hinterland zones (mostly those bordering large urban conurbations) with little wind speed and frequently high levels of air pollution had higher numbers of COVID-19 related infected individuals. Results here suggest that high concentrations of air pollutants, associated with low wind speeds, may promote a longer permanence of the viral particles in the air, thus favouring an indirect means of diffusion of viral infectivity of the novel coronavirus (SARS-CoV-2), in addition to the direct diffusion with human-to-human transmission dynamics.
Project description:To elucidate the T cell epitopes of SARS-CoV-2, we stimulated human PBMCs from healthy donors and convalescent COVID-19 patients with various SARS-CoV-2 antigens, sorted the activated T cells and performed sc-RNA and -TCR sequencing. We obtained thousands of T cell clonotypes that responded to SARS-CoV-2 antigens, and identified the epitopes and restricting HLAs of several clonotypes that were significantly expanded in the COVID-19 patients. Overall design: Determination of the TCR and mRNA expression of human T cells stimulated with SARS-CoV-2 antigens.