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Metformin and SARS-CoV-2: mechanistic lessons on air pollution to weather the cytokine/thrombotic storm in COVID-19.

ABSTRACT: 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.

SUBMITTER: Menendez JA

PROVIDER: S-EPMC7288975 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Metformin and SARS-CoV-2: mechanistic lessons on air pollution to weather the cytokine/thrombotic storm in COVID-19.

Menendez Javier A JA

Aging 20200527 10

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/Ca<sup>2+</sup> release-activated Ca<sup>2+</sup> channels (CRAC)/IL-6 cascade. Given the linkage between mitoch ...[more]

PMID: 32463794

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Project description:BackgroundUnderstanding how environmental factors affect SARS-CoV-2 transmission could inform global containment efforts. Despite high scientific and public interest and multiple research reports, there is currently no consensus on the association of environmental factors and SARS-CoV-2 transmission. To address this research gap, we aimed to assess the relative risk of transmission associated with weather conditions and ambient air pollution.MethodsIn this global analysis, we adjusted for the delay between infection and detection, estimated the daily reproduction number at 3739 global locations during the COVID-19 pandemic up until late April, 2020, and investigated its associations with daily local weather conditions (ie, temperature, humidity, precipitation, snowfall, moon illumination, sunlight hours, ultraviolet index, cloud cover, wind speed and direction, and pressure data) and ambient air pollution (ie, PM2·5, nitrogen dioxide, ozone, and sulphur dioxide). To account for other confounding factors, we included both location-specific fixed effects and trends, controlling for between-location differences and heterogeneities in locations' responses over time. We built confidence in our estimations through synthetic data, robustness, and sensitivity analyses, and provided year-round global projections for weather-related risk of global SARS-CoV-2 transmission.FindingsOur dataset included data collected between Dec 12, 2019, and April 22, 2020. Several weather variables and ambient air pollution were associated with the spread of SARS-CoV-2 across 3739 global locations. We found a moderate, negative relationship between the estimated reproduction number and temperatures warmer than 25°C (a decrease of 3·7% [95% CI 1·9-5·4] per additional degree), a U-shaped relationship with outdoor ultraviolet exposure, and weaker positive associations with air pressure, wind speed, precipitation, diurnal temperature, sulphur dioxide, and ozone. Results were robust to multiple assumptions. Independent research building on our estimates provides strong support for the resulting projections across nations.InterpretationWarmer temperature and moderate outdoor ultraviolet exposure result in a slight reduction in the transmission of SARS-CoV-2; however, changes in weather or air pollution alone are not enough to contain the spread of SARS-CoV-2 with other factors having greater effects.FundingNone.

Project description:ObjectiveMigraine is a common recurrent headache disorder affecting 14% American adults. Although weather and air pollution are often reported by patients with migraine as precipitating factors, previous studies have had mixed results.MethodsWe prospectively collected migraine headache onset data using electronic questionnaires from 98 adults with episodic migraine in the Greater Boston area (2016-2017). Each participant was followed for an average of 45 days for a total of 4406 days of observation. Temperature, relative humidity, and barometric pressure data were obtained from local weather station. Daily average fine particulate matter, daily maximum 1-hour sulfur dioxide, daily maximum 1-hour nitrogen dioxide, daily maximum 8-hour ozone, and daily maximum 8-hour carbon monoxide from local air pollution monitors. We conducted a repeated measures analysis using fixed effects logistic regression models. In the models we adjusted for day of week, a natural cubic spline term of day of the year with 4 degrees of freedom, and a participant identifier. We additionally adjusted for linear terms of temperature and relative humidity in the air pollution analyses. We also applied logistic regression models with generalized estimating equation (GEE) and autoregressive correlation structure in the sensitivity analysis.ResultsThe mean age was 35 years and 88% were women. Mean temperature was 56.9 °F, relative humidity 67.3%, and fine particulate matter 7.3 μg/m3. Higher relative humidity was associated with higher odds of migraine headache, but the association was only observed in warm season (April-September). Higher levels of daily maximum 8-hour ozone and daily maximum 8-hour carbon monoxide appeared to be associated with higher odds of migraine headache onset in cold season (October-March). Although the associations for ozone and relative humidity were attenuated and no longer statistically significant in the overall GEE analysis, the differing associations by season remained.ConclusionsWe found that higher relative humidity was associated with higher odds of migraine headache onset in warm season, and traffic-related gaseous pollutants may be associated with higher odds of migraine headache onset in cold season.

Project description:As a pandemic hotspot in Japan, between March 1, 2020-October 1, 2022, Tokyo metropolis experienced seven COVID-19 waves. Motivated by the high rate of COVID-19 incidence and mortality during the seventh wave, and environmental/health challenges we conducted a time-series analysis to investigate the long-term interaction of air quality and climate variability with viral pandemic in Tokyo. Through daily time series geospatial and observational air pollution/climate data, and COVID-19 incidence and death cases, this study compared the environmental conditions during COVID-19 multiwaves. In spite of five State of Emergency (SOEs) restrictions associated with COVID-19 pandemic, during (2020-2022) period air quality recorded low improvements relative to (2015-2019) average annual values, namely: Aerosol Optical Depth increased by 9.13% in 2020 year, and declined by 6.64% in 2021, and 12.03% in 2022; particulate matter PM2.5 and PM10 decreased during 2020, 2021, and 2022 years by 10.22%, 62.26%, 0.39%, and respectively by 4.42%, 3.95%, 5.76%. For (2021-2022) period the average ratio of PM2.5/PM10 was (0.319 ± 0.1640), showing a higher contribution to aerosol loading of traffic-related coarse particles in comparison with fine particles. The highest rates of the daily recorded COVID-19 incidence and death cases in Tokyo during the seventh COVID-19 wave (1 July 2022-1 October 2022) may be attributed to accumulation near the ground of high levels of air pollutants and viral pathogens due to: 1) peculiar persistent atmospheric anticyclonic circulation with strong positive anomalies of geopotential height at 500 hPa; 2) lower levels of Planetary Boundary Layer (PBL) heights; 3) high daily maximum air temperature and land surface temperature due to the prolonged heat waves (HWs) in summer 2022; 4) no imposed restrictions. Such findings can guide public decision-makers to design proper strategies to curb pandemics under persistent stable anticyclonic weather conditions and summer HWs in large metropolitan areas.

Dataset Information

Metformin and SARS-CoV-2: mechanistic lessons on air pollution to weather the cytokine/thrombotic storm in COVID-19.

Publications

Metformin and SARS-CoV-2: mechanistic lessons on air pollution to weather the cytokine/thrombotic storm in COVID-19.

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