key: cord-0952310-vwf44gtg
authors: Curtis, Luke
title: PM(2.5), NO(2), wildfires, and other environmental exposures are linked to higher Covid 19 incidence, severity, and death rates
date: 2021-08-19
journal: Environ Sci Pollut Res Int
DOI: 10.1007/s11356-021-15556-0
sha: 57b0d91da9190d04958bbf80414d52f7f6fbad69
doc_id: 952310
cord_uid: vwf44gtg

Numerous studies have linked outdoor levels of PM(2.5), PM(10), NO(2), O(3), SO(2), and other air pollutants to significantly higher rates of Covid 19 morbidity and mortality, although the rate in which specific concentrations of pollutants increase Covid 19 morbidity and mortality varies widely by specific country and study. As little as a 1-μg/m(3) increase in outdoor PM(2.5) is estimated to increase rates of Covid 19 by as much as 0.22 to 8%. Two California studies have strongly linked heavy wildfire burning periods with significantly higher outdoor levels of PM(2.5) and CO as well as significantly higher rates of Covid 19 cases and deaths. Active smoking has also been strongly linked significantly increased risk of Covid 19 severity and death. Other exposures possibly related to greater risk of Covid 19 morbidity and mortality include incense, pesticides, heavy metals, dust/sand, toxic waste sites, and volcanic emissions. The exact mechanisms in which air pollutants increase Covid 19 infections are not fully understood, but are probably related to pollutant-related oxidation and inflammation of the lungs and other tissues and to the pollutant-driven alternation of the angiotensin-converting enzyme 2 in respiratory and other cells.

Covid 19 (CoronaVIrus Disease 2019) is caused by SARS2 Cov 2 (severe acute respiratory syndrome coronavirus 2), which is a RNA respiratory virus which is believed to be transmitted mostly by droplet nuclei in the air (Brandt and Mersha 2021) . Covid 19 is especially dangerous to older humans as death rates for those over 70 years of age is more than 10%, while less than 0.1% for children and young adults (Signorelli and Odone 2020) . Covid 19 infection rates in the USA are also significantly higher in African Americans as compared to the population as a whole (Brandt et al. 2020; Phillips et al. 2020) .

Many papers and reviews have reported that exposure to air pollutants such as PM 2.5 , NO 2 , and O 3 are associated with higher rates of Covid 19 incidence, severity, or mortality (Brandt and Mersha 2021; Copat et al. 2020 ). In addition, other pollutant sources such as wildfires and smoking have also been associated with greater risks of Covid 19 infection and mortality (Meo et al. 2020; Salah et al. 2020) . This review will attempt to review the published data on environmental factors and Covid 19 on papers published up to March 21, 2021 . This review will also briefly discuss possible mechanisms in which environmental factors may affect Covid 19 morbidity and mortality. papers which measured O 3 , 5 papers which measured SO 2 , 5 papers which measured CO, and 1 paper each for NH 3 , methane, lead, total volatile organics, and non-methane volatile organics. Table 1 is sorted first by various pollutants (PM 2.5 , PM 10 , NO 2 , etc.), then it is arranged with the papers which reported quantitative relationships between pollutant levels and rates of Covid 19 morbidity and mortality first, studies which calculated R o (the basic reproduction ratio for Covid 19 values) are listed last, and other papers in the middle sections. Because many papers do not report social distancing measures, it was decided not to include social distancing measures in Table 1 . Forest plots were also presented in Figs. 1, 2, and 3 to summarize the estimated relationships (in 4 or more studies cited-for the other pollutants, there were less than 4 studies and were presented in the text but not in the forest plots) between a 1 μg/m 3 increases in ambient PM 2.5 , PM 10 , and NO 2 and % increases in Covid 19 cases.

In "Material and methods"section, a brief review was conducted of selected papers which measured changes in outdoor air quality as a result of the Covid 19 crises and lockdown. To save space, not all papers which measured changes in ambient air pollutants during the Covid 19 era were reported. Two papers measured the effects of wildfires on Covid 19 were reported (both from California, USA) ("Results" section). Four meta-analysis examining the effects of smoking on Covid 19 are reported in "Results" section, as well as some studies reporting the effects of smoking on other respiratory infections. To save space, not all individual smoking studies were reported. In "Results" section, some papers examining possible links with Covid 19 and environmental exposures such as pesticides, heavy metals, dust storms, incense, sewage, forested areas, and volcanoes. Section 6 examines possible links between airborne dust and respiratory infections. Section 7 summarizes possible physiological and biochemical mechanisms in which air pollutants may increase Covid 19 morbidity and mortality, including lung inflammation, oxidation, and altered expression of the ACE2 receptors. & Other studies have reported that higher levels of air pollutants are associated with significantly higher infection rates for influenza and other respiratory viruses.

A number of studies have reported that exposure to PM 2.5 , PM 10 , ozone, SO 2 , and NO 2 are associated with higher rates of Covid 19 cases and mortality. Please see the following paragraphs and Table 1 for a summary of these studies. Some of these studies have estimated relationships between increased air pollution levels and increased (or decreased) rates of Covid 19 cases and mortality. For forest plots of the relationships between PM 2.5 , PM 10 , and NO 2 and increases in Covid 19 cases,-please see Figs 1, 2, and 3 (data expressed as mean and 95% confidence intervals). Nine studies estimated that a 1-μg/m 3 increase in outdoor PM 2.5 increased case rates or death rates of Covid 19 by as much as 0.22 to 8%, with an unweighted average of a 2.74% increase per 1 μg/m 3 PM 2.5 (de Angelis et al. 2021 , López-Feldman et al. 2021 , Meo et al. 2021a , b, Sahoo 2021 , Solimini et al. 2021 , Stieb et al. 2020 , Zheng et al. 2021 . Four published studies reported that a 10-μg/m 3 increase in ambient NO 2 was associated with a 4.56 to 37.8% increase in Covid 19 cases (Sahoo 2021; Zheng et al. 2021; Zhu et al. 2020) or a 7% decrease in Covid 19 cases (de Angelis et al. 2021) . The average unweighted increase in Covid 19 cases per 10 μg/m 3 NO 2 was 10.57%.

Sharma's study in 10 nations reported that temperature and pressure are negatively associated with Covid 19 cases, while ambient PM 2.5 are significantly associated with more Covid 19 cases and deaths ). Solomini's large study of 237,749 Covid-19 cases from 63 countries and 5 continents reported that a 10-μg/m 3 increase in PM 2.5 was associated with an 8.1% (95% CI 5.4 to 10.5%) increase in Covid 19 cases in a 14-day window (Solimini et al. 2021) . Barnett reported that both ambient PM 2.5 and nitrogen oxides were associated with significantly increased rates of both Covid 19 morbidity and mortality in 32 OECD countries (Barnett-Itzhaki and Levi 2021). De Angelis reported that a 10-μg/m 3 increase in ambient PM 2.5 was associated with a 58% increased risk of Covid 19 incidence in 1439 Lombardy Italian municipalities (95% CI 1.31-1.90, p < 0.01) (de Angelis et al. 2021) .

A large US study of 3000 US counties (comprising 98% of the population) up to April 22, 2020 reported that only a 1-μg/ m 3 increase in PM 2.5 was associated with an 8% increase in Covid 19 deaths (95% CI 2-15%) .

A study of 120 Chinese cities reported that an 10-μg/m 3 increase in PM 2.5 was associated with a 2.24% increase in Covid 19 mortality (95% CI 1.012 to 3.46) . A 2021 study reported that an increase of 1 μg/m 3 of PM 2.5 was associated with a 7.4% increased risk of Covid 19 death in Mexico City (López-Feldman et al. 2021) . Several Italian studies have also reported a significant association between ambient PM 2.5 and significantly increased rates of Covid 19 cases, hospitalizations, and deaths (Bianconi et al. 2020; Cascetta et al. 2021; Fiasca et al. 2020) . A study in all 107 Italian provinces reported that Covid 19 incidence and mortality were significantly higher in areas closest to Lodi, Lombardy and these effects were amplified by higher ozone levels (Tripepi et al. 2020) . A study in Queens, New York, reported that increased ambient ozone were associated with increased Covid 19 cases (p < 0.001) but fewer Covid 19 deaths (p = 0.38), while increased PM 2.5 were actually associated with lower risk of Covid 19 cases (p < 0.001) and mortality (p = 0.044) (Adhikari and Yin 2020).

A study of 49 Chinese cities reported that for every 10 μg/ m 3 increase in PM 2.5 , the case fatality rate (CFR) of Covid 19 increased by 0.24% (95% CI of 0.01-0.48%) (Yao et al. 2020) . A nitrogen dioxide mapping study in Italy, Spain, France, and Germany reported that nitrogen dioxide levels above 100 μm/m 3 were associated with 83% of the Covid 19 deaths (Ogen 2020) . A study in Lima, Peru, reported that higher PM 2.5 levels were associated with significantly higher Covid 19 incidence and case mortality rates (Vasquez-Apestegui et al. 2020) . A study of 111 regions in all Canadian provinces reported that each 1 μg/m 3 increase in PM 2.5 was associated with a 7% increased incidence of Covid 19 (OR 1.07, 95% CI 0.97-1.18) (Stieb et al. 2020) .

A large study in 9 nations (China, Japan, Korea, Canada, the USA, Russia, England, Germany, and France) reported that higher levels of PM 2.5 , PM 10 , SO 2 , NO 2 , and O 3 generally were associated with significantly higher rates of Covid 19 infection ). This study also concluded that the effects of PM 2.5 and PM 10 on Covid 19 incidence are more sensitive in Russia, England, Germany, and France, while O 3 and PM 2.5 effects are more sensitive to Covid 19 incidence in the USA and Canada .

A study of about 1.48 million Covid 19 cases in 33 European Nations from 2/11/20 to 5/17/20 reported that increasing outdoor concentrations of PM 2.5 , NO 2 , NH 3 , methane, and non-methane volatile organic compounds were all independently associated with significantly increased risk of both Covid 19 incidence and deaths (Landoni et al. 2021 Fig. 3 Relationships between 1 μg/m 3 increase ambient NO 2 and Covid Increasing SO 2 was not associated with significantly greater Covid 19 cases and mortality (Landoni et al. 2021) . A large study of more than 58,000 Covid 19 cases in 120 Chinese cities reported that 10 μg/m 3 increases (lag 0-14) in the following pollutants were associated with the following increases in Covid 19 cases: PM 2.5 2.24% (95% CI 1.02 to 3.46), PM 10 1.76%(95% CI 0.89 to 2.63), NO 2 6.94% (2.38 to 11.51), O 3 4.76% increase (95% CI 1.99 to 7.52), and CO 15.11% increase (0.44 to 29.77%) . A 10-μg/ m 3 increase in SO 2 was associated with a 7.79% decrease in Covid 19 cases (95% CI − 14.57 to − 1.01) . A German study involving 123,248 Covid 19 cases reported that higher levels of NO 2 and O 3 were all associated with significantly higher rates of Covid 19 cases and deaths, while higher levels of PM 2.5 were associated with significantly lower levels of Covid 19 cases and deaths . A geographically weighted regression model in China reported that both higher outdoor levels of PM 2.5 and higher AQI (Air Quality Index) (consisting of PM 2.5 , PM 10 , SO 2 , NO 2 , CO, and ozone) were associated with significantly higher Covid 19 incidences (Pei et al. 2021 ).

Hou reported that long-term (1, 3, or 5 years), worse (higher) AQI in 14 Chinese cities was associated significantly higher Covid 19 case fatality rate (Hou et al. 2021) . A study in 12 Lombardy, Italy, provinces reported that ambient PM 2.5 exposure was associated with significantly greater rates of Covid 19 infection with lag rates as high as 10 days (Dragone et al. 2021 ). An Indian study reported that 10 μg/ m 3 increase during (Lag 0-14 days) of the following outdoor air pollutants were associated with significantly increased risk of Covid 19 infections PM 2.5 2.21% increase (95% CI 1.13 to 3.29%), PM 10 2.67% increase (95% CI 0.33 to 5.01%), and NO 2 4.56% increase (95% CI 2.22 to 6.90%) (Sahoo 2021) . A study in 5 Indian megacities (Bangalore, Chennai, Delhi, Kolkata, and Mumbai) reported that higher outdoor levels of PM 2.5 , PM 10 , CO, and O 3 were associated with significantly higher levels of both Covid 19 cases and deaths (Kolluru et al. 2021) .

A study in 324 Chinese cities reported that each increase of 10 μg/m 3 of the following pollutants was associated with a significant increase in Covid 19 rates: NO 2 37.8% increase (95% CI 23.8-53.0%), PM 2.5 32.3% increase (95% CI 22.5-42.4%), and PM 10 14.2% increase (7.9-20.5%) (Zheng et al. 2021) . A study of more than 11 million Covid 19 cases in 6 South Asian nations (Afghanistan, Bangladesh, India, Nepal, Pakistan, and Sri Lanka) reported that higher outdoor PM 2.5 was associated with significantly higher rates of both Covid 19 infection and death .

A study in London, England, reported that the following increases in outdoor air pollutants were associated with the following increases in Covid 19 cases and Covid 19 deaths respectively: for each 1 μg/m 3 increase in PM 2.5 1.1 and 2.3% increases in cases and mortality, for each 1 ppm increase in CO 21.3 and 21.8% increases in cases and mortality, and for each 10 ppb 03 0.8 and 4.4% increases in cases and mortality (Meo et al. 2021b ).

An English study of over 300,000 Covid 19 cases reported that each 1 μg/m 3 increase in outdoor PM 2.5 was associated with a 12% increase in Covid 19 cases (Travaglio et al. 2021 ). An Italian study reported that relatively high levels of longterm exposure to outdoor pollutants (NO 2 , O 3 , PM 2.5 , PM 10 ) during the period 2016-2020 were associated with significantly higher levels of Covid 19 cases (Fattorini and Regoli 2020 (Chakrabarty et al. 2021) . Each increment in ambient 1 μg/m 3 PM 2.5 was associated with a significant 0.25 increase in R o (95% CI 0.048-0.447) (Chakrabarty et al. 2021) . During this time, R o was the highest in New Jersey at 3.41 and New York at 3.30 and lowest in Alaska at 1.60 and Wyoming at 1.76 (Chakrabarty et al. 2021) . During this time period, R o values generally dropped from early March to late April 2020 with the institution of social distancing and school/workplace closures (Chakrabarty et al. 2021) .

A study of 63 Chinese cities also reported that higher outdoor NO 2 levels were associated with significantly higher R o basic reproduction rate (Yao et al. 2021) . Each 10 μg/m 3 increase in NO 2 was associated with a R o increase of 0.12 outside Hubei Province and 0.52 inside Hubei Province (Yao et al. 2021) .

Other studies have reported that higher air pollution levels can significantly increase risk of respiratory infections in general. A study of 6814 multi-ethnic adults aged 44 to 84 years in 6 US cities reported that an increase of estimated PM 2.5 and NO x from 25 to 75% percentile increased the risk of respiratory infections by 1.04 (OR 1.04, 95% CI 1.00 to 1.09) and 1.15 (OR 1.15, 95% CI 1.10 to 1.20), respectively (Kirwa et al. 2021) . A Chinese study reported that increased outdoor levels of PM 2.5 , PM 10 , CO, and SO 2 were associated with significantly higher levels of influenza-like illness in both children and adults (Su et al. 2019) . A Utah study involving 112,467 subjects with lower respiratory infection (77% of which were 2 years or less) reported that higher PM 2.5 levels were associated with significantly higher rates of lower respiratory illness (Horne et al. 2018) .

A 2002-2003 Chinese study reported that higher levels of API (air pollution index consisting of airborne outdoor levels of particulate matter, sulfur and nitrogen dioxides, carbon monoxide, and ground level ozone) were associated with significantly higher mortality rates due to SARS (severe acute respiratory syndrome) (Cui et al. 2003) . A 2019 Korean study linked higher ambient levels of PM 10 with significantly higher rates of adenovirus (HAdV), metapneumovirus (HMPV), human coronavirus (HCoV), human bocavirus (HBov), human parainfluenza virus (HPIV), and influenza virus (IV) (Cheon et al. 2019 On the positive side, a number of studies have noted that Covid 19 lockdowns and reduced industrial/traffic activity have been associated with drops in ambient levels of PM 2.5 and other pollutants (Srivastava 2021 ).

An analysis of 10,000+ sampling sites in 380 World Cities reported that during the 2020 lockdown periods PM 2.5 and NO 2 fell by an average of 16.1 and 45.8%, while ozone levels rose by an average of 5.4% . A study of 50 more polluted capital cities reported a mean drop in PM 2.5 of 11% (Rodríguez-Urrego and Rodríguez-Urrego 2020) . A study of more than 1500 air monitoring sites in 377 Chinese cities reported a mean 16 and 20% reduction of PM 2.5 and PM 10 when comparing January 20 to April 8, 2020, with the same period in 2019 (Fan et al. 2020) . A study in Baghdad, Iran, reported mean pollution drops of 6% for NO 2 , and 8% for PM 2.5 during the March 1 to July 24, 2020, as compared to 2019 (Hashim et al. 2021) . Another study noted significant drops in outdoor PM 2.5 during the Covid 19 crisis in 9 world cities including New York City, Los Angeles, Zaragoza, Rome, Dubai, Delhi, Mumbai, Beijing, and Shanghai (Chauhan and Singh 2020) . Studies in 4 large Pakistani cities (Lahore, Islamabad, Karachi, and Pewshawar) reported that during the Covid 19 period, average PM 2.5 levels fell 13 to 33% in satellite observations and 23 to 58% in ground based observations (Ali et al. 2021) . A Chinese study reported that comparing outdoor pollutant levels from January 21 to March 23 during the both 2020 and 2019, reported that average PM 2.5 levels fell by an average of 35%, 29%, and 19% respectively in Wuhan, Hubei (Wuhan excluded), and China (Hubei excluded) and NO 2 levels fell by an average of 53%, 50%, and 30% respectively in Wuhan, Hubei, and China respectively (Chu et al. 2021) . During the lockdown period between March 1 to May 31, 2020, mean outdoor levels of PM 10 , PM 2.5 , NO, NO 2 , and CO levels fell by an average of 58%, 47%, 76%, 68 and 58% respectively in Delhi, India, as compared to the 2019 values . A study in 7 Korean cities reported that mean PM 2.5 levels fell by an average of 7.5 to 24.9% during the 2020 lockdown as compared to 2019 (Kwak et al. 2021 ). An Italian study reported reductions in outdoor PM 2.5 as high as 53% and reductions in NO 2 as high as 67% (Donzelli et al. 2021) .

At least two studies have reported significant declines in average ambient volatile organic compounds (VOCs) during the lockdown period-including a 37-57% reduction of total VOCs in China ) and a 48-68% reduction in benzene in Italy (Collivignarelli et al. 2020) .

& Two California studies have reported significant increases in both ambient PM 2.5 and Covid 19 cases and/or deaths during heavy wildfire burning periods.

Wildfires and extensive wood burning both produce large quantities of carbon monoxide, fine particulates, and other toxic chemicals (such as carcinogenic polycyclic aromatic hydrocarbons or PAHs) which have been documented to be associated with significantly higher rates of respiratory and cardiovascular problems (Larson and Koenig 1994; Naeher et al. 2007; Reid et al. 2016; Youssouf et al. 2014) . A study of 10 California counties affected by the severe 2020 wildfires reported that during the heavy burning period between August 15, 2020, and September 22, 2020, mean PM 2.5 levels increased by 221% (92.91 vs 28.97 μg/m 3 , p < 0.001), mean carbon monoxide levels increased by 151% (4.77 vs 1.90 ppm, p < 0.001), and during this same wildfire period, Covid 19 cases jumped by 57% (p < 0.001), and the number of Covid 19-related deaths rose by 148% (p < 0.001) (Meo et al. 2021a) . A study conducted by same authors reported significantly higher rates of Covid 19 cases and significantly higher PM 2.5 outdoor levels in San Francisco during this same 2020 wildfire period (Meo et al. 2020) .

Other studies and reviews have reported that exposure to wildfire smoke in firefighters are associated with significantly greater risk of respiratory infections such as pneumonia and acute bronchitis (Navarro et al. 2021 ).

& Most studies have reported that Covid 19 morbidity and mortality rates are significantly higher in smokers.

A number of studies have reported that tobacco smoking is related to increased Covid 19 risk. Salah's meta-analysis reported smoking about doubled Covid 19 mortality risk (OR 2.07, 95% CI 1.59-2.69, 10 studies of 11,189 patients) (Salah et al. 2020) . A July 2020 meta-analysis of 47 studies of 32,849 hospitalized Covid 19 patients reported that current smokers had much greater risks of severe Covid 19 disease versus former smokers/non-smokers, including greater risk of severe Covid 19 (OR 1.31, 1,12-1.54) and Covid 19 mortality (OR 1.26, 95% CI 1.20-1.32) (Reddy et al. 2021) . A meta-analysis of 22 published studies on 5689 Covid 19 patients reported that severe disease risk was significantly greater in smokers (OR 1.34, 95% CI 1.07-1.67) (Karanasos et al. 2020) . A 2021 meta-analysis of 19 studies reported that smoking was associated with an almost doubled risk of worse Covid 19 progression (OR 1.96, 95% CI 1.36-2.82) (Jiménez-Ruiz et al. 2021) . A 2021 analysis of 109 articles involving 517,020 Covid 19 patients reported that a smoking history was associated with a significantly increased risk of ICU admission (OR 1.73, 95% CI 1.36-2.19) and significantly increased risk of death (OR 1.58, 95% CI 1.38-1.81) . A 2021 review reported that there have not been any studies so far on the associations between secondhand tobacco smoke and Covid 19 (Brandt and Mersha 2021) .

Smoking can also increase the risk of other respiratory infections such as influenza and tuberculosis. A 2019 meta-analysis of 9 studies with 40,685 participants reported that current smokers are more than 5 times more likely to develop laboratory confirmed influenza than never smokers (OR 5.69, 95% CI 2.79-11.60, 3 studies). Meta-analyses of the relationships between smoking and tuberculosis (TB) have reported that active smoking is associated with a 2.284-fold increased risk of developing pulmonary TB (OR 2284, 95% CI 1765-2.954, 14 studies) and a 2.236-fold increased risk of dying from TB (OR 2.236, 95% CI 1.340-3.732, 6 studies) (Slama et al. 2007 ). Secondhand tobacco exposure as compared to no first-or secondhand exposure was associated with a 3.353fold increased risk of TB (OR 3.353, 95% CI 2.028-5.543, 3 studies) (Slama et al. 2007 ).

Other possible environmental risk factors for Covid 19 transmission-incense, pesticides, metals, desert dust/sand, toxic waste sites, volcanic emissions Key points & Other possible risk factors for Covid 19 incidence and/or mortality include incense, pesticides, metals, sand, toxic waste sites, and volcanic emissions.

Some researchers have postulated that exposure to incense sticks (Amoatey et al. 2020) , pesticides (Rajak et al. 2021) , and heavy metals (Skalny et al. 2020 ) may increase risk of Covid 19 morbidity and mortality. It has been hypothesized that pesticides exposure may increase risk of Covid 19 by damaging the respiratory, immune, cardiovascular, hepatic, and nervous systems (Rajak et al. 2021) . Many toxic heavy metals can damage the immune system, and human and animal studies have reported that toxic heavy metal exposure can increase risk of respiratory infections like respiratory syncytial virus (RSV) and influenza (Skalny et al. 2020) . Some researchers have suggested that indoor incense exposure may increase Covid 19 risks (Amoatey et al. 2020) . A US study of 3143 counties up to May 31, 2020, reported that diesel particulate concentrations and proximity to Risk Management Plan (RMP) and toxic waste sites were associated with significantly higher Covid 19 mortality rates (Hendryx and Luo 2020) .

Some have postulated that dust storms may also be associated with greater Covid 19 risk (Middelton 2020) . Every year, about half a billion tons of desert dust become airborne and can travel for thousands of miles (Middelton 2020). Dust storms may also spread influenza (both Covid 19/SARS Cov2 and influenza are RNA respiratory viruses). A Taiwan study reported that mean outdoor airborne influenza concentrations were 21 to 31 times higher during 24 days of dust storms as compared to 10 control days (mean concentrations of influenza per cubic meter of outdoor air at Wan-Li station 268 vs. 13, p = 0.02, at Shin-Jhaung station 276 vs. 9, p = 0.01) (Chen et al. 2010) .

Other researchers have noted that viable Covid 19 is found in human sewage, which may potentially be a major source of Covid 19 infection (Rooney et al. 2021; Senatore et al. 2021 ).

An Italian study reported significantly lower Covid 19 mortality rates in heavily forested areas (more than 1 hectare forest per person) (Roviello and Roviello 2020) . The authors hypothesized that the lower Covid 19 death rates in the forested Italian regions could be due to the PM 2.5 filtering ability of forests and/or the production of anti-viral volatile organics (which are both volatilized in the atmosphere and present in foodstuffs like Bay leaves) by common Italian trees/shrubs such as Laurus nobilis or bay laurel (Roviello and Roviello 2020) .

Italian researchers reported relatively high Covid 19 infection rates on Sicily east of volcanic Mt. Etna (which have been active for much of 2020 and early 2021) and hypothesized that toxic gases and trace metals may play some role in promoting Covid 19 (Raciti and Calabrò 2020 & Viability of SARS Cov 2 has been estimated to be perhaps about 1.2 h in air and from several hours to several days on living and inanimate surfaces.

PM 2.5 may possibly serve as a direct vector for transmission of Covid 19/SARS Cov2 and other viruses. SARS Cov 2 has been found to bind to particulate matter surrounded by water (Borisova and Komisarenko 2020) . In addition, PM 2.5 and SARS Cov 2 can enter the nose to brain olfactory nerve delivery system and cause neurological symptoms (Borisova and Komisarenko 2020) . Several studies have reported viable SARS Cov2 can be detected in PM 2.5 or PM 10 fractions of air (Tung et al. 2021) . Viable SARS Cov 2 has been detected on PM 10 fractions on 2020 outdoor air in Italy (Chirizzi et al. 2021; Setti et al. 2020 ) and on PM 2.5 and smaller airborne fractions from 2 Chinese hospitals . A Malaysian study reported that RNA from SARS Cov 2 was collected from the PM 2.5 from the air of hospital wards housing SARS Cov 2 patients (Nor et al. 2021 ). On the other hand, a study in Leipzig, Germany, found no evidence of SARS Cov 2 RNA in either 8 weekly outdoor air particulate samples collected during the pandemic or in purified extracts from 9 species of pollen (Dunker et al. 2021) .

To spread Covid 19, the virus would have to survive its travel on droplets or air particulates. Information on SARS Cov2 virus survival time in air droplets or particulates is sparse. Von Dormelan reported that SARS Cov2 has a median half-life of about 1.1-1.2 h on airborne aerosols (van Doremalen et al. 2020) . SARS Cov 2/Covid 19 survival on inanimate surfaces vary considerable from study to studythey had been reported as long as 3 to 9 days on plastic surfaces, 2 days on stainless steel, 1 day on cardboard, and 4 h on copper (Marquès and Domingo 2020) . SARS Cov2 viability is generally longer under conditions of lower temperature and humidity (Marquès and Domingo 2020) . Viability/survival of SARS Cov2/Covid 19 has been estimated at 9 h for hands as compared to influenza (another RNA respiratory virus) of 1.8 h (Hirose et al. 2020) . Some studies have suggested that particulate pollution may increase airborne survival of many types of viruses times by binding to bacteria and providing protection from UV light and by reducing dehydration (Navarro et al. 2021; Reche et al. 2018 Besides direct transmission on particulates, air pollutants may also help spread Covid 19 infection by other mechanisms including promoting lung damage, or binding to and overexpression of angiotensin-converting enzyme 2 (Comunian et al. 2020) . Various human, animal, and cell studies have reported that exposure to particulate pollution can increase lung inflammation and oxidation (Comunian et al. 2020) .

Exposure to PM 2.5 and NO 2 may increase incidence and severity of Covid 19 by altering expression of angiotensinconverting enzyme 2 (ACE2) in respiratory cells (Alifano et al. 2020; Paital and Agrawal 2020; Samavati and Uhal 2020) . ACE2 is a membrane enzyme found in the lungs, nasal epithelium, arteries, kidney, heart, and intestines and regulates blood pressure by modifying angiotensin 2 into angiotensin 1-7, which is a vasodilator and anti-inflammatory agent (Comunian et al. 2020) . ACE2 receptors are a receptor for coronavirus binding including SARS Cov 2/Covid 19 (Alifano et al. 2020; Paital and Agrawal 2020) . SARS Cov2 binding to these ACE2 receptors can alter expression causing increased inflammation and cardiac damage (Comunian et al. 2020; Samavati and Uhal 2020) . Exposure to airborne PM 2.5 has been shown to increase ACE2 receptors in mice (Lin et al. 2018) . ACE2 receptors tend to both more common in older humans, and the greater number of ACE2 receptors in elders may partially explain the significantly higher Covid 19 morbidity and mortality seen in older patients (Comunian et al. 2020; Wong et al. 2020) . The significantly higher rates of Covid 19 cases and death seen in African Americans in the USA may be due to a number of factors including ACE2 genetic polymorphisms, higher average exposures to PM 2.5 and other pollutants, more crowded housing, and socioeconomic factors (Brandt et al. 2020; Phillips et al. 2020) .

Italian researchers have proposed a "double-hit" hypothesis in which combined exposure to PM 2.5 and NO 2 can increase susceptibility to Covid 19 (Frontera et al. 2020 ). In the first step, chronic exposure to PM 2.5 causes lung damage, inflammation, increased susceptibility to viral infection, and alveolar ACE-2 overexpression (Frontera et al. 2020 ). This may increase viral load by depleting ACE-2 receptors and impairing host defenses. Exposure to NO 2 can then cause additional lung damage including inflammation and edema, and increased susceptibility to infections including Covid 19 (Frontera et al. 2020) . After the lungs have experienced a PM 2.5 and NO 2 "double hit," they are much more susceptible to SARS Cov 2 binding the ACE-2 sites and causing serious infection (Frontera et al. 2020) .

Much more study on the relationships on the ACE2 receptors, SARS Cov 2/Covid-19, and air pollutants are needed (Samavati and Uhal 2020) . For a good 2020 discussion on ACE2 receptors, please see Samavati and Uhal (2020) 

Particulate pollution may also increase the risk of many other infections. A mouse study reported that long-term exposure to PM 2.5 enhanced survival of the influenza virus by downregulating pulmonary macrophage Kdm6a and altering histone modification in IL-6 and IFNβ promoter regions (Ma et al. 2017) . Another murine study reported that intratracheal PM 2.5 exposure reduces influenza immunity by inhibiting activation of NLRP3 inflammasome and expression of interferon-β (Tao et al. 2020 ).

Many environmental exposures have been strongly linked to higher Covid 19 morbidity and mortality including PM 2.5 , PM 10 , NO 2 , O 3 , wildfires, and smoking. Other exposures which may possibly be related to higher Covid 19 morbidity and mortality include sulfur oxides, carbon monoxide, volatile organic chemicals, incense, pesticides, heavy metals, dust/sandstorms, toxic waste sites, and volcanic emissions.

Outdoor exposure to PM 2.5 and other particulate fractions have been consistently associated with higher levels of Covid 19 incidence, severity, and mortality, although the degree in which a given amount of PM 2.5 increases Covid 19 factors varies considerable from study to study (Table 1) . Table 1 notes that significantly higher rates of Covid 19 morbidity and/or mortality were associated with higher outdoor levels of the following pollutants: PM 2.5 in 27 out of 29 studies, PM 10 in 12 out of 14 studies, NO 2 in 11 out of 13 cases, O 3 in 7 out of 8 cases, SO 2 in 2 out of 5 cases, and CO in 4 out of 5 cases.

One limitation of this review is that most of these studies published to date have involved air pollution and Covid 19 morbidity and mortality only during the early pandemic period up until sometime between January and October 2021 (please see Table 1 ). Additional studies examining the effects of air pollutants on Covid 19 cases/deaths during the late pandemic period in late 2020 or 2021 might yield interesting information.

Most of the studies to date have compared Covid 19 rates while measuring only one outdoor air pollutant and have not considered multiple outdoor air pollutants at the same time. Of course, interactions and correlations between pollutants could have played a major role in influencing Covid 19 morbidity and mortality rates. In the future, large epidemiological studies with good statistical power of Covid 19 and multiple air pollutants might be able to yield useful data on the interactions between pollutants. In addition to epidemiological studies, more studies are needed to study the effects on air pollution and infection at the molecular and cellular levels.

A complication with comparing outdoor pollution levels with Covid 19 morbidity and mortality is that many other factors can also play a role in determining Covid 19 morbidity and mortality: including weather, social distancing measures, Covid 19 vaccines, population density, age structure, socioeconomic factors, the quality and affordability of health care systems, mask wearing, handwashing, nasal disinfection, surface cleaning, HEPA air filters, quarantine, and nutrition (Aggarwal et al. 2020; Ayenigbara et al. 2020; Calzetta et al. 2021; Chiesa et al. 2021; Chu et al. 2020; Curtis 2021; Ferrer and Sanchez-Gonzalez 2021; Fouladi Dehaghi et al. 2020; Hradsky and Komarek 2021; Matrajt and Leung 2020; Mechanick et al. 2021; Nussbaumer-Streit et al. 2020; Pradhan et al. 2020; Rodríguez et al. 2021; Romano Spica et al. 2020; Thu et al. 2020) . A meta-analysis of 29 unadjusted and 9 adjusted studies has reported that social distancing measures can play a major role in reducing Covid 19 spread (Chu et al. 2020 ). On the other hand, lack of social distancing, mask wearing, and other protective behaviors can increase risk of Covid 19 spread. For example, the Sturgis, South Dakota, USA Motorcycle Rally which was held from August 7 to 16, 2020, had about 500,000 attendees from all over the USA, had relatively little social distancing and mask usage, and was estimated to cause an additional 115,208 to 266,790 cases of Covid 19 throughout the USA (Dave and Sabia 2020). Social distancing may play a major role in modifying the effects of air pollution on Covid 19 morbidity and mortality. However, a limitation of this review is the fact that many of the studies cited in Table 1 did not describe social distancing methods in detail. Therefore, social distancing methods was not reported in Table 1 , although they might have been very interesting. Further study is needed to determine how various factors like air pollution, social distancing, mask usage, handwashing, surface cleaning, HEPA, quarantine, medical care, Covid 9 vaccinations, social-economic factors, and nutrition interact with each other.

Another limitation of this review is that it reviewed papers published only up to March 21, 2021. Certainly, more useful papers and insights on air pollution effects on Covid 19 will be produced after 3/21/21. Hopefully, this review will encourage other clinicians, researchers, and public health experts to further examine the complex relationships between air pollution and infection with Covid 19 and other pathogens.

These studies linking higher Covid 19 morbidity and mortality offer additional arguments for reducing air pollution levels in both the developed and developing worlds. In 2015, it was estimated that outdoor PM 2.5 pollution alone caused 4.2 million annual deaths (95% CI 3.7 to 4.8 million) and 103.1 million (95% CI 90.8 to 115.1 million) disabilityadjusted life-years (Cohen et al. 2017) . Cutting back on air pollution by using cleaner transportation, heating, and industrial methods and by reducing biomass (wood/leaves/straw/ forest/wildfire) burning can reduce risk of many health problems including Covid 19 and other respiratory infections. Use of face masks can also reduce risk from both PM 2.5 and Covid 19 exposure ).

Airborne pollutants play an important role in Covid 19 infection and severity. Limiting environmental exposures offer great potential for reducing both morbidity and mortality from Covid 19 and other respiratory infections like influenza. Much more research on the interplay between Covid 19/other infections, air pollutants, and other factors such as handwashing/ vaccination/nutrition are needed.

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Facemasks for prevention of viral respiratory infections in community settings: a systematic review and meta-analysis

Exploring the linkage between PM(2.5) levels and Covid-19 spread and its implications for socio-economic circles

Renin-angiotensin system at the heart of Covid-19 pandemic

Impact of building ventilation systems and habitual indoor incense burning on SARS-CoV-2 virus transmissions in Middle Eastern countries

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The effects of air pollution, sea exposure and altitude on Covid-19 hospitalization rates in Italy

Ambient PM(2.5) exposure and rapid spread of Covid-19 in the United States

Decline in PM(2.5) concentrations over major cities around the world associated with Covid-19

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Influence of fine particulate matter 10 on respiratory virus infection in the Republic of Korea

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Nutrition is associated with Covid 19 incidence, severity, and mortality

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Relations between air quality and Covid-19 lockdown measures in Valencia, Spain

Aerosol and surface stability of SARS-CoV-2 as compared with SARS-CoV-1

Analysis of the chemical and physical environmental aspects that promoted the spread of SARS-CoV-2 in the Lombard area

SARS-CoV-2 detected in air samples (pollen and particulate matter) in Leipzig during the first spread

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PM(2.5) and PM(10) concentrations and assessing air quality changes in Baghdad

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Covid-19 and smoking: a systematic review and meta-analysis of the evidence

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Ambient air pollution and risk of respiratory infection among adults: evidence from the multiethnic study of atherosclerosis (MESA)

Association of air pollution and meteorological variables with Covid-19 incidence: evidence from five megacities in India

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Air pollutants and SARS-CoV-2 in 33 European countries

Wood smoke: emissions and noncancer respiratory effects

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Instillation of particulate matter 2.5 induced acute lung injury and Environ Sci Pollut Res attenuated the injury recovery in ACE2 knockout mice

Aerodynamic analysis of SARS-CoV-2 in two Wuhan hospitals

Association between air pollution and COVID-19 infection: evidence from data at national and municipal levels

Air pollution exposure and Covid-19: a look at mortality in Mexico City using individual-level data

Longterm exposure to PM2.5 lowers influenza virus resistance via downregulating pulmonary macrophage Kdm6a and mediates histones modification in IL-6 and IFN-β promoter regions

Contamination of inert surfaces by SARS-CoV-2: persistence, stability and infectivity. A review

Evaluating the effectiveness of social distancing interventions to delay or flatten the epidemic curve of coronavirus disease

Clinical nutrition research and the Covid-19 Pandemic: a scoping review of the ASPEN COVID-19 Task Force on Nutrition Research

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Effect of environmental pollutants PM-2.5, carbon monoxide, and ozone on the incidence and mortality of SARS-COV-2 infection in ten wildfire affected counties in California

Effect of environmental pollution PM2.5, carbon monoxide, and ozone on the incidence and mortality due to SARS-CoV-2 infection in London, United Kingdom

UN program-impacts of sand and dust stors on oceans: a scientoific environmental assessment for policy makers

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Air pollution by NO2 and PM2.5 explains COVID-19 infection severity by overexpression of angiotensinconverting enzyme 2 in respiratory cells: a review

Do air pollutants as well as meteorological factors impact Corona virus disease 2019 (COVID-19)? Evidence from China based on the geographical perspective

The perfect storm: COVID-19 health disparities in US blacks

A review of current interventions for Covid-19 prevention

Can volcanic trace elements facilitate Covid-19 diffusion? A hypothesis stemming from the Mount Etna area

Immunotoxic role of organophosphates: an unseen risk escalating SARS-CoV-2 pathogenicity

Deposition rates of viruses and bacteria above the atmospheric boundary layer

The effect of smoking on Covid-19 severity: a systematic review and meta-analysis

Critical review of health impacts of wildfire smoke exposure

Are the portable air cleaners (PAC) really effective to terminate airborne SARS-CoV-2?

Air quality during the Covid-19: PM(2.5) analysis in the 50 most polluted capital cities in the world

Swimming pool safety and prevention at the time of Covid-19: a consensus document from GSMS-SItI

Tracking Covid-19 via sewage

Lower COVID-19 mortality in Italian forested areas suggests immunoprotection by Mediterranean plants

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Age-specific Covid-19 case-fatality rate: no evidence of changes over time

Toxic metal exposure as a possible risk factor for Covid-19 and other respiratory infectious diseases

Tobacco and tuberculosis: a qualitative systematic review and meta-analysis

A global association between Covid-19 cases and airborne particulate matter at regional level

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Air-filtering masks for respiratory protection from PM(2.5) and pandemic pathogens

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Association between short-term exposure to air pollution and Covid-19 infection: evidence from China

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