key: cord-0331227-z34od208
authors: Muscat Baron, Y.
title: Airborne PM2.5 and the Emergence of 10 SARS-CoV-2 Variants: The Multifaceted Influence of an Airborne Pollutant on Viral Natural Selection determining SARS-CoV-2 Evolution - An Environmental Wake-up Call or an Ecological Fallacy?
date: 2021-07-02
journal: nan
DOI: 10.1101/2021.06.27.21259602
sha: e07375aac3760f87c84cf2044c765b6335d9698c
doc_id: 331227
cord_uid: z34od208

Background: Airborne particulate matter has been suggested as a co-factor for SARS-CoV-2 infection. Besides the deleterious effect this pollutant has on pulmonary immunity and the propagation of respiratory ACE-2 receptors (angiotensin converting enzyme II), the SARS-CoV-2 point of entry, particulate matter has also been proposed as a vector for this virus transmission. Particulate matter may also be a marker for anthropogenic activity acting as a surrogate for increased human to human contact, increasing both transmission and the mutagenic viral load. Genes coding for SARS-CoV-2 have been detected on airborne particulate matter and its proximity to the virus, may have caused this pollutant to act as a mutagen causing the inception of SARS-CoV-2 variants and simultaneously being genotoxic to the progenitor viruses, differentially favouring variant emergence. Since the initial phases of the pandemic, a multitude of SARS-CoV-2 variants have been detected, but the few that survive to promulgate human infection have increased transmissibility. It also appears that there is a limited set of persistent mutations SARS-CoV-2 can produce. This set of mutations has been found in widely disparate and distant regions. This may suggest that besides intra-host mutation in an inflammatory ambience, an ubiquitous factor such as an environmental mutagen, may have resulted in convergent evolution leading to the emergence of similar variants. This paper examines a possible association in a multi-modal manner between the airborne pollutant PM2.5 and the emergence of ten of the most clinically and epidemiologically relevant SARS-CoV-2 variants. Methods: The daily average levels of PM2.5 of a number of cities, where variants were detected, were obtained from the World Air Quality Index (WAQI), a real-time assessment of atmospheric pollution. PM2.5 levels were correlated with SARS-CoV-2 variants including Variants of Concern (VOC) or Variants of Interest (VOI). These variants included the G614 variant in Beijing, the 20A.EU1 variant in Valencia, the B.1.351 variant in South Africa, the B.1.1.7 variant in the UK, the USA variants B.1.429 in Los Angeles, B.1.2 in Louisiana and New Mexico, the B.1.526 variant found in New York, the variant B.1.1.248 in Brazil. During mid-March 2021, the B.1.617 variant first detected in October 2020, surged in Nagpur, India and the R.1 variant was detected in Kentucky U.S.A. The average daily PM2.5 levels were assessed, the evaluation initiating just before the occurrence of the first spike/s in this pollutant s atmospheric concentration, till after the emergence of the variants. Where available the daily number of new cases of COVID-19 diagnosed was matched to the PM2.5 levels. Results: There appears a common pattern of PM2.5 in most of the regions prior and during the emergence of the SARS-CoV-2 variants. An initial spike/s of PM2.5 were noted on average 50 days prior to the emergence of the variants and another smaller spike/s in PM2.5 were noted just before or contemporaneous with the emergence of the variant. Prior to the emergence of to the G614 variant in Beijing, the average PM2.5 level during its peaks was 153.4mug/m3 (SD+/-63.9) to settle to a baseline of 94.4mug/m3 (SD+/-47.8)(p<0.001). Before the appearance of the 20A.EU1 variant in Valencia, the PM2.5 spikes averaged at 61.3mug/m3 (SD+/-21.8) to decrease to a mean of 41.2mug/m3 (SD+/-15.5) (p<0.04). In Kent, U.K. a solitary PM2.5 spike averaged 82mug/m3 (SD+/-29) before the detection of the B.1.1.7 and following the PM2.5 spike the baseline level of this pollutant was 27.8mug/m3 (SD+/-18.0) (p<0.03). In Nelson Mandela Bay South Africa, where B.1.351 was first detected, the PM2.5 mean baseline level was reported as 40.4mug/m3 (SD+/-14.0), while prior to this variant s emergence, the PM2.5 spike averaged 85.1mug/m3 (SD +/-17.3)(p<0.0001). In Brazil the average PM2.5 during its spike was 107.4mug/m3 (SD+/-34.2) before B.1.1.248 variant emerged and after the spike the baseline PM2.5 was 48.3mug/m3 (SD+/-18) (p<0.0001). In the USA the average PM2.5 peak levels prior to the emergence of the SARS-CoV-2 variants were 118mug/m3 (SD+/-28.8) in Los Angeles (baseline 66.1mug/m3 (SD+/-25.1), 75+/-27.8mug/m3 (baseline 43.3(SD+/-14.4)mug/m3 in Louisiana, 71.4+/-11.3mug/m3 (baseline 43.6(SD+/-12.4)mug/m3 New Mexico, 54.3+/-13.8mug/m3 (baseline 34.4(SD+/-11.6)mug/m3 in New York and 37.7+/-7mug/m3 (baseline 28.5 SD+/-6.8)mug/m3 in Eastern Kentucky. All the spike patterns of PM2.5 levels noted in the USA were significantly higher when compared to their respective baselines (p<0.0001). Prior to the surge of the variant in India, the PM2.5 spike in Nagpur averaged 166.8+/-10.8mug/m3 (baseline 123.2SD+/-16.9mug/m3) (p<0.0001). In the regions where the quantity of daily new cases was available, a number of significant correlations were obtained between PM2.5 levels and the number of new cases of SARS-CoV-2 in most of the regions reviewed. Conclusion: There appears to be an association between the levels of atmospheric PM2.5 and the emergence of SARS-CoV-2 variants. In most regions two groups of spike/s of PM2.5 were noted prior to the emergence of these variants. The first PM2.5 spike/s approximately 50 days before the variant emergence may suggest that anthropogenic activity was increased possibly reflecting augmented human to human contact, consequently increasing the viral burden of the progenitor virus. The first PM2.5 spike may also have made populations more susceptible to SARS-CoV-2 through the propagation of the respiratory ACE receptor. There is the potential that coronavirus-laden, PM2.5 induced mutagenesis in the SARS-CoV-2 genome resulted in establishing persistent variants and contemporaneously was genotoxic to the progenitor virus, expediting the latter s disappearance. PM2.5 may have further diminished the pulmonary immunity inviting further viral invasion. The second spike/s prior to the emergence of variants, may suggest another anthropogenic spike in human activity. With the second spike/s in PM2.5, this airborne pollutant may have acted as a viral vector encouraging variant emergence. This may have not only led to increasing viral transmission, catalysed by the preceding risk factors, but resulted in an overwhelming viral load, providing fertile ground for variant emergence. The above findings suggest that antecedent spikes in PM2.5 prior to variant emergence not only contributed to transmission, but also impacted the immediate viral environs which resulted in its natural selection, effecting SARS-CoV-2 evolution. Keywords: PM2.5;SARS-CoV-2; COVID-19;Mutations;Variant emergence; Evolution.

The SARS-CoV-2 pandemic has reappeared in subsequent waves in the form of more transmissible and potentially more virulent variants. This increase in COVID-19 incidence has been attributed to the reversal of regional lockdowns and measures, endorsing physical distancing which were legally enforced in most countries. Following lockdown, a contemporaneous reduction in COVID-19 rates and atmospheric pollution including particulate matter (PM 2.5 ) were noted only to be partially reversed once lockdown was ceased. This reversal of lockdown also involved a recrudescence of elevated levels of the pollutant particulate matter PM 2.5 .

The first study suggesting an association between PM 2.5 and SARS-CoV-2 was noted in the United States, whereby a link between long-term exposure to particulate matter PM 2.5 and COVID-19 related mortality was demonstrated . A recent preprint has confirmed that PM 2.5 was a robust variable in connection with increasing SARS-CoV-2 rates (Milicevic et al 2021) . Morphological evidence also confirmed that genes coding for SARS-CoV-2 were found attached to particulate matter (Setti et al 2020a) . In a large number of Chinese cities, a 2% increase in COVID-19 new cases was demonstrated with every 10μg/m3 increment in airborne PM 2.5 (Zhu et al 2020) . The deleterious effects of particulate matter on pulmonary microbial defences may encourage SARS-CoV-2 colonization of the respiratory epithelium (Domingo and Rovira, 2020) , (Paital and Agrawal, 2020) . Particulate matter increases the number of ACE-2 receptors, the point of host cell entry of SARS-CoV-2 (Paital and Agrawal, 2020), Sagawa et al., 2021) . Particulate matter may actually act as a vector for transmission of COVID-19 infection by increasing its airborne reach surrounding the human habitat (Comunian et al. 2020 ) (Contini and Costabile, 2020) and also aiding deeper penetration into the respiratory tract (Qu et al., 2020) .

It has been suggested that particulate matter PM 2.5 was not only responsible for SARS-CoV-2 transmission, but may also have been involved in this virus' evolution (Muscat Baron 2020a), (Muscat Baron 2021a). Acting as a SARS-CoV-2 vector, PM 2.5 may have been responsible for exerting selective pressure determining the emergence of the first variant called the G614 variant (Muscat Baron 2020a), (Muscat Baron 2021a).

A recurring set of mutations, mainly E484K, N501Y and K417N suggests SARS-CoV-2 may be undergoing convergent evolution (Gupta 2021 ). This convergent evolution may be catalyzed by the presence of a common environmental mutagen such as the ubiquitous pollutant PM 2.5 which has repeatedly been shown to be a robust co-factor in the SAR-CoV-2 Pandemic (Milicevic et This paper examines the possibility that pollution with PM 2.5 changes augmented COVID-19 infection and had a hand in SARS-CoV-2's natural selection, strongly suggesting that particulate matter may have acted co-factor in a multi-modal manner catalyzing the SARS-CoV-2 Pandemic through the emergence of its variants.

The average levels of particulate matter PM 2.5 of a number of cities were obtained from the World Air Quality Index (WAQI). This Air Quality Index is a real-time measurement of atmospheric pollutants, including PM 2.5 (EPA Environmental Protection Agency 2020-2021). The daily average PM 2.5 levels were assessed prior to a prominent spike in PM 2.5 till beyond the emergence of the SARS-CoV-2 variants in each region. During 2020, the regions noted to have COVID-19 variants included Beijing, Valencia, Nelson Mandela Bay in South Africa, Bexely (U.K.), Los Angeles, New York, Louisiana, and New Mexico in the USA and Sao Paolo in Brazil. Recently in mid-March 2021, two variants emerged in Nagpur, in the Maharashtra region of India and in Eastern Kentucky U.S.A respectively. In Beijing, the period between January 20 th and mid-February 2020 was chosen when the G614 variant (Chart 1. and 2.) with the G614 clade appears to have been detected (Korber et al 2020) . In Valencia the first peak of PM 2.5 (Chart 3. and 4.) was noted around the 11 th of April and the 20A.EU1 variant appears to have been detected at the end of May 2020 (Hodcroft et al 2020) . The PM 2.5 in Bexely, U.K. peaked on the 12 th August 2020, 40 days before the B.1.17 variant was detected on the 20 th of September (Chart 5. and 6.). In Nelson Mandela Bay the origins of the B.1.351 variant in South Africa were noted in early October, 60 days after the PM 2.5 peak on the 19 th July 2020 (Chart 7.). In Los Angeles the first case of the B.1.429 variant was noted during a solitary PM 2.5 spike on the 6th of July which was followed by another two wider spikes in mid-September and the beginning of October after which a surge in COVID-19 cases was noted in November (Chart 8. and 9.). The B.1.526 variant was detected in the in New York at the end November, 15 days after a spike in PM 2.5 . The surge in the B.1.526 variant followed in mid-December contemporaneous with a PM 2.5 spike (Chart 10. and 11.). In Louisiana and New Mexico, the B.1.2 variant followed a similar pattern with three spikes in PM 2.5 , the first and most prominent 45 days before the variant was detected in September, the second spike at detection in November and the third smaller spike in early December when COVID-19 cases surged (Chart 12, 13, 14 and 15). In Sao Paolo Brazil two peaks of PM 2.5 were noted during September to be followed by the emergence of the B.1.1.248 variant in early December (Chart 17).

Two variants emerged in mid-March 2021, one occurring in Nagpur India (Chart 18. and 19.) and the second in Eastern Kentucky, USA( Chart 16). Prior to the B.1.617 variant in India a wide peak of PM 2.5 was noted during the first three weeks of January and 50 days later, during another smaller peak, the B. 1 pollution in Brazil appears to perennially occur in October due to anthropogenic and natural factors. The B.1.617 variant appears to have been first detected in India in November 2020, but its emergence as a VOC was noted in Nagpur in Mid-March 2021. As may be noted in the absence of solid evidence, in some cities certain assumptions had to be taken to decide the site from which PM 2.5 levels had to be assessed.

The data was analysed for normality and all the data were found to be nonparametric. The Mann Whitney U test was applied for comparing nonparametric variables of both groups of cities and the Spearman Rank test was applied for nonparametric correlations.

There appears a common pattern of PM 2.5 in most of the regions assessed prior and during the emergence of the COVID-19 variants. An initial spike/s of PM 2.5 was noted on average 50 days prior to the surge of the variants and another smaller spike/s in PM 2.5 was noted just before or contemporaneous with the emergence of the variant (Charts 1-18 

This paper indicates that a common pattern appears to occur in relation to PM 2.5 levels in most of the locations where SARS-CoV-2 variants emerged. Approximately 50 days prior to the emergence of the ten most persistent SARS-CoV-2 variants, a spike/s in the atmospheric levels of the airborne pollutant PM 2.5 was noted for most of the variants that appear to have continued to promulgate human infection. Just before or contemporaneous with the variant surge, another smaller spike/s in PM 2.5 was also noted for most of the SARS-CoV-2 variants. Similar to this study, a lag phase in the emergence of influenza infection has been noted following exposure to particulate matter PM 2.5 . A study in Montana showed that the rate of influenza in winter increased following wildfires in summer. Elevated daily mean PM 2.5 concentrations during the summer wildfire season positively correlated with increased rates of influenza in the following winter. With every 1 μ g/m3 increase in average daily summer PM2.5, two analyses indicated a 16% and 22% increase in influenza rates respectively (Langruth et al 2020).

The sources of PM 2.5 very much depend on the characteristics of the regions' activities. In the industrial regions the carbonaceous sources of PM 2.5 are coal combustion, vehicles' gasoline and diesel exhaust (Zhang et al 2014) . A prime example is the elevated levels of PM 2.5 in China due to the daily combustion of 80,000 tonnes of coal (Ghosh 2020). Wuhan, the site thought to be SARS-CoV-2's . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted July 2, 2021. ;  origin, is considered the Chinese hub of transportation earning the moniker as the "Chicago of China". Residential and commercial areas have similar sources of PM 2.5 in the form of gasoline and diesel exhausts and biomass combustion due to cooking and heating.

In a trans-seasonal study done in Amsterdam and Helsinki, the sources of indoor and outdoor PM 2.5 were very similar. In a sizable proportion (41%), the major sources of PM 2.5 were secondary pollution, whereby primary pollutants interacted with atmospheric molecules. The remaining 59% of PM 2.5 sources were motor vehicles' exhaust, calcium-rich particles, biomass burning, soil and road dust, and marine aerosols. A similar pattern was noted for median personal, indoor, and outdoor PM 2.5 concentrations, whereby in Amsterdam the levels of this pollutant were 13.6µg/m3, 13.6µg/m3, and 16.5µg/m3 respectively, while in Helsinki the PM 2.5 concentrations were 9.2µg/m3, 9.2µg/m3, and 11.1µg/m3. In both Amsterdam and Helsinki, the personal and indoor PM 2.5 concentrations highly correlated with outdoor concentrations (median R= 0.7-0.8) (Brunekreef et al 2005) .

Specific habitats have their own species of PM 2.5 depending on the activities carried out in these areas. In a study of schools in Barcelona, on average 47% of indoor PM 2.5 was due to soil particles (13%) and organic sources (34%) and calcium-rich particles from chalk and building deterioration. The remaining 53% of PM 2.5 in schools was derived from emissions from outdoor sources including week-day traffic (Amato et al 2014). Significant pollution with particulate matter may also occur emanating from natural causes such as wildfires (Meo et al. 2020) . Of particular relevance especially in the U.S.A, in regions where there are perennially very low levels of PM 2.5, this pollutant suddenly shoots up are due wildfires. This aspect is of significance because, whereas most by-products of wildfires are rapidly transformed while suspended in the atmosphere, PM 2.5 remains unchanged for several days (Rodgers et al 2020).

The relevance of particulate matter PM 2.5 and PM 10 during the pandemic became evident when epidemiological studies demonstrated that a large proportion of sporadic cases of COVID-19 could not be explained through direct human to human contact. Epidemiological studies indicated that aerosol and droplet contact could not explain these sporadic cases and the regional differences in the transmission of SARS-CoV-2 (Cai et al. 2020 ).

Long-term exposure to PM 2.5 was associated with increased the SARS-CoV-2 related infection and mortality rates. A study in the USA showed that an increment of just 1 μ g/m3 in PM 2.5 exposure, correlated with an 8% augmentation in the COVID-19 mortality rate . Another study in the USA demonstrated an increase of only 1μg/m3 in PM 2.5 exposure was associated with a 13% increase in COVID-19 related mortality rate (Correa-Agudelo et al 2020).

In a large Chinese study of 120 cities, an increase of 10μg/m3 in PM 2.5 was linked to with a 2.24% (95% CI: 1.02 -3.46) rise in the daily new cases of COVID-19 respectively (Zhu et al 2020). Another study in China showed that a 10μg/m3 increment in atmospheric PM 2.5 increased the SARS-CoV-2 case-fatality ratio by 0.24% (0.01%-0.48%) (Yao et al. 2020 ).

In the Lombardy region of Italy, PM 2.5 levels as high as 38.31μg/m3 have been recorded (WHO acceptable upper limit 25μg/m3) (Comunian et al 2020) . Atmospheric concentrations of PM 2.5 in Northern Italy correlated with SARS-CoV-2 infection incidence (R = 0.67, p < 0.0001), the COVID-19 related death rate (R = 0.65, p < 0.0001) and the case-fatality rate (R = 0.7, p < 0.0001) (Comunian et al. 2020 ).

An international study from 63 countries over five continents similarly demonstrated a connection between PM 2.5 and COVID-19 cases. This study showed that a 10 μ g/m3 increase of PM 2.5 pollution level was associated with 8.1% (95% CI 5.4% -10.5%) increase in the number of COVID-19 cases during the 14 day period of assessment (Solimini et al 2021).

The G614 variant was the first prominent variant that appears to have originated in China early in 2020. Prior to the emergence of the G614 variant in Beijing, the average PM 2.5 level during its peak was 153.4µg/m3 (SD+/-63.9) and later settled to 94.4µg/m3 (SD+/-47.8)(p<0.001) when the G614 variant surge occurred ( Chart 1.). In Beijing the downward trend of the number of daily new cases mirrored that of the PM 2.5 levels, however it must be mentioned that the number of new cases available were at latter part of the bell-shaped curve.

Interestingly the PM 2.5 levels in Wuhan preceded those of Beijing by a month (Muscat Baron 2020b). This may suggest that the G614 mutation may have occurred in Wuhan with the elevated PM 2.5 levels having "primed" the population as an ideal reservoir. The population in Wuhan may have acted as the ideal reservoir due the presence of a high viral load of the progenitor Wuhan 1, with a PM 2.5 weakened pulmonary immunity, a PM 2.5 -induced increase in the respiratory viral point of entry (ACE receptor) in the presence of a multitude of people crammed together in constrained PM 2.5 -replete places such as train platforms or restricted spaces indoors during the Chunyun Spring Festival (Muscat Baron 2020d).

The G614 variant may have replaced the original Wuhan 1 during the mass movements of the Chinese population attending the Chunyun Spring festival which is held 15 days before the New Year and lasts a total of 40 days. The Chunyun festival is the largest mass movement occurring on the globe, involving nearly 400,000,000 individuals and over 2.9 billion journeys are made during the internal migration. A study between January 6th and February 6th, 2020 indicated that the diagnosis of COVID-19 was more likely within 11-12 days after people moved from Wuhan to 16 nearby cities in the Hubei Province. Following the spike in COVID-19 diagnoses, the number of cases declined after the implementation of cities' lockdown (Jiang and Luo 2020). This mass movement of the Chinese population during Chunyun Spring festival overlapped with the PM 2.5 peaks in Beijing noted in this study. Thereafter the incidence of COVID-19 in China dropped dramatically possibly due to strict social . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted July 2, 2021. ; distancing, face protection and a possible innate immunity of the Chinese populations towards the G614 variant (Muscat Baron 2021b).

The G614 variant which dominated and persisted throughout the SARS-CoV-2 genomic variant landscape involved a mutation whereby an amino acid alteration in the viral spike protein gene occurred at D614G position. This mutation involved a single genomic modification with the replacement of aspartic acid by glycine at the amino acid G614 position of the spike protein. In vitro, the G614 mutation has demonstrated increased cellular infectivity, however this does not seem to be consistently the case in vivo (Korber et al 2020) .

Genomic alteration at the G614 position appears to have led to a modification in the phenotypic configuration and functionality of the spike protein peptide. The original Wuhan 1 coronavirus had its spike protein's three peptides aligned in a "closed" configuration whereas the G614 variant's spike protein peptides are consistently found in an "open" orientation (Wrapp et al 2020).

SARS-CoV-2 adherence to the respiratory angiotensin II receptors (ACE) receptors on the pneumocyte II and goblet cells depends on spike protein's trimeric peptide configuration. The spike protein adheres to respiratory cells' ACE receptors if at least two of its three peptides are positioned in an "open orientation" (Yurkovetskiy et al 2020) . This may also be the case impacting SARS-CoV-2 adherence to particulate matter if the latter acts as its vector. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted July 2, 2021.

Similar to humans, where population density is a risk factor for high COVID-19 infection rates, the mass confinement of minks led to widespread infection of the caged animals. This undoubtedly led to a high R o factor in the confined animal population due to the exponential infection rate presenting fertile ground for the inception of variants (Muscat Baron 2021c). High reproduction rates are a prerequisite for the occurrence of mutations which eventually may flourish adapting to natural selective pressures (Domingo et al. 2016 ).

Spain following Italy, was one of the first European countries to have succumbed to the COVID-19 pandemic. The first Italian residents noted to have contracted SARS-CoV-2 infection were in a small town near to Milan on the 21 st of February (Sanfelici et al 2020). The suggestion is that a superspreader event occurred when a well attended (50,000) football match between the Spanish team of Valencia and the Italian team of Atalanta was played in the stadium of Bergamo on the 19 th February 2020. Unknowingly early in February, Bergamo was already the focus for seeding COVID-19 throughout the Lombardy region of Northern Italy. Following Italy, not unexpectedly, coronavirus made its appearance in Valencia and soon after the rest of Spain was plunged into lockdown as the pandemic engulfed the whole nation leading to high mortality rates in the elderly and vulnerable individuals (Mas Romero et al 2020). The East Cape of South Africa has been hit by a 6 year drought. In July 2020 the water reservoir in Nelson Mandela Bay was down to 18% of its capacity due to the paucity of rainfall. Severe drought has a significant impact on atmospheric pollution and acts as one of largest causes of airborne PM 2.5 . PM 2.5 aerosol concentration in the Owens Lake area in California's southwest increases abruptly from less than 5 µg/m3 to 25 µg/m3 during the drought period (Borlina et al 2017).

The B.1.351 is considered a variant of concern as it possesses the E484K mutation.

The E484K mutation appears to confer some resistance to antibodies against the SARS-CoV-2 spike protein. The B.1.351 variant appears not only refractory to neutralization by most N-terminal domain monoclonal antibodies but also by multiple individual monoclonal antibodies to the receptor-binding motif on receptor binding domain due to an E484K mutation (Wang et al 2021). On the 6 th of July the B.1.429 variant was detected in Los Angeles coinciding with a solitary peak in PM 2.5 (Chart 8.). This peak also coincided with the use of a multitude . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted July 2, 2021. ;  of fireworks in the Angeles area. In Los Angeles the average PM 2.5 peak levels prior to the emergence of the SARS-CoV-2 variants was 118(SD+/-28.8)µg/m3 in Los Angeles while its baseline was 66.1(SD+/-25.1)µg/m3. Two peaks of COVID-19 cases in Los Angeles occurred approximately 50 days apart. The first peak in COVID-19 cases occurred following the first spike in PM 2.5 on the 6 th July and the second peak of COVID-19 cases occurred after two spikes in PM 2.5 in September. Simultaneous with this latter peak in PM 2.5 there existed an ongoing wildfire called the "Bobcat fire" which 

In Sao Paolo Brazil, two peaks of PM 2.5 were noted prior to the emergence of the B.1.1.248 variant in early December. The first peak of PM 2.5 started in mid-September and another peak in PM 2.5 occurred in mid-October 2021. The average PM 2.5 during its peak in Sao Paolo was 107.4µg/m3 (SD+/-34.2) before B.1.1.248 variant was detected when the baseline PM 2.5 was 48.3µg/m3 (SD+/-18). The main cause of air pollution in Sao Paolo appears to be vehicular exhaust (Kabuto et al 1990) . This is on the increase due to mass urbanization, increasing the population density which in turn elevates vehicular usage. The elevated population density in itself significantly increases human to human contact encouraging further SARS-CoV-2 transmission. Biomass combustion by the population and wildfires also contribute to the PM 2.5 atmospheric load.

Wildfires in south-east Brazil produce smoke that aggravates air pollution in major cities such as Sao Paulo. In a study on asthma in children the average dose of PM 2. In a study by Singh et al 2021, amongst all cities assessed, Delhi was found to have the highest air pollution, followed by Kolkata, Mumbai, Hyderabad, and Chennai. A common pattern was noted in most of these cities except for Chennai, whereby the highest concentrations of PM 2.5 occurred in the winter while the lowest levels of this . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted July 2, 2021. ; https://doi.org/10.1101/2021.06.27.21259602 doi: medRxiv preprint pollutant were noted during the monsoon season. PM 2.5 levels in the cities exceeded WHO safety cut-off levels for 50% and 33% of days annually except for Chennai. In New Delhi for more than 200 days in a year exceeded the WHO safety cut-off levels. Compared to the previous years a decrease has been noted and can be attributed to the recent policies and regulations implemented in Indian cities attenuating air pollution. PM 2.5 levels are however still elevated requiring stricter compliance to the Indian National Clean Air Program to further accelerate the reduction of the pollution levels (Singh et al 2021).

The occurrence of PM 2.5 spikes a few weeks prior to the emergence of SARS-CoV-2 variants may have primed the effected populations to be more susceptible to COVID-19. The point of entry of the SARS-CoV-2 virus is the Angiotensin II Converting Enzyme Receptor (ACE-2) which is commonly found on type-2 pneumocytes responsible for gaseous exchange and mucus producing goblet cells. Specifically the ACE-2 protein acts as the receptor for the attachment of the SARS-CoV-2 spike protein, consequently increasing the risk for infection as well as severity of the disease in humans.

Preclinical studies utilizing the murine model exposed to particulate matter impacted both the ACE-2 protein and TMPRSS-2 (transmembrane protease serine type 2) (Sagawa et al 2021). Both the ACE-2 protein and TMPRSS-2 are required for the entry of SARS-CoV-2 into respiratory host cells. Immunohistochemical assessments indicated that exposure to particulate matter increased the expression of ACE-2 protein and TMPRSS-2. Image cytometry demonstrated increased expression of ACE-2 protein and TMPRSS-2 specifically in the type-2 pneumocytes which are potential targets for SARS-CoV-2. (Sagawa et al 2021) . In another murine model endowed with human ACE-2 receptors, the bronchial instillation of particulate matter significantly increased the expression of ACE-2 and TMPRSS-2 in the lungs ( In humans, during the COVID-19 pandemic in Italy, Borro et al showed that in response to exposure to PM 2.5, bioinformatic analysis demonstrated increased DNA sequences encoding for the ACE-2 receptor. The bioinformatic analysis of the ACE-2 gene identified nine recognized nucleic acid sequences for the aryl hydrocarbon receptor. In the same study correlations were noted between PM 2.5 levels and COVID-19 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) (Borro et al 2020).

Pollution with both nitrous oxide and PM 2.5 has been shown to increase the concentration of ACE receptors in the lung (Paital et al 2021). Both pollutants induce an inflammatory change in the respiratory epithelium. This may occur with both chronic and acute inflammation. In an effort to cleanse the bronchial tree from pollutants, the number of mucus-producing goblet cells increase, with a consequent increase in these cells' ACE-2 receptors (Paital and Agrawal 2021).

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

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The above suggest a close link between exposure to particulate matter and the increase in the viral points of cell entry, the ACE-2. The spikes in PM 2.5 may have acted differentially according to the time before variant emergence. The spike in PM 2.5 approximately 50 days before the variant emergence, may have instigated an inflammatory response with a consequent induction in ACE-2 receptors in the respiratory tract. The PM 2.5 spike immediately prior to the emergence of the variant may have indicated heightened human to human contact increasing viral load, which in the presence of readily available points of entry, increased infection rates. In the presence of high infection rates and a higher viral load the possibility of viral mutation became a greater possibility.

The COVID-19 pandemic appears to have spread during March 2020, from Wuhan in China, then to Qom in Iran and soon later to the Lombardy region in Northern Italy. An environmental variable common to all these three cities is the presence of elevated atmospheric levels of particulate matter (Muscat Baron 2020b) (Muscat Baron 2020c). Atmospheric particulate matter in the Lombardy region showed that out of 34 RNA extractions for the genes E, N and RdRP coding for SARS-CoV-2, twenty detected one of these genes ( In a teaching hospital in Kuala Lumpur Malaysia, a study showed that the highest SARS-CoV-2 RNA on PM 2.5 in the ward correlated with number of patients with COVID-19 and the absence of air purifiers. High levels (74 ± 117.1 copies μ L−1) of SARS-CoV-2 genes on PM 2.5 were noted in the single room ward without an air purifier compared to a general ward with an air purifier (10 ± 7.44 copies μ L−1) ( Nor et al 2021) .

The link between airborne pollution and infectious disease is not a novel one. Measles has the highest R 0 of all infectious diseases with an R 0 of 18 and has been closely associated with airborne pollution. In China, "dust events" in the Gansu region, have been linked with increased incidence of measles (Ma et al 2017) . In the Niger, greater . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted July 2, 2021. ; atmospheric pollution during the dry season is associated with measles-related childhood deaths which subside at the onset of the rainy season (Ferrari et al 2008) . In 1935 during the Dust Bowl period, the state of Kansas experienced the most severe measles epidemic in USA history (Brown et al 1935) . Following World War II, outbreaks of polio in the USA initiated at the beginning of summers and declined with the arrival of September rains (Oshinisky 2014 ).

In January 2020 the genome of SARS-CoV-2 was sequenced indicating that it consisted of a single strand RNA containing approximately 29,000 nucleotide bases. Following the first sequenced RNA strand, a multitude of SARS-CoV-2 genomes have been sampled confirming that over 13,000 mutations had occurred in 2020 (Callaway 2020) . The vast majority of mutants do not survive, however if the mutation confers an adaptation advantage, then through natural selection it will survive to outpace the incumbent variant.

Mutational potential on SARS-CoV-2 may occur through selective pressure due to an adaptation to the environmental milieu which may possibly be either mutagenic or genotoxic. The environmental factor may also come into play as a vector which may differentially favour mutants increasing their transmission. One such environmental factor may include airborne particulate matter. If this hypothesis is proven, it would be of singular importance as it may suggest that particulate matter may act as both a vector and mutagen for SARS-CoV-2. Moreover particulate matter may furthermore differentially favour variants by not only acting as a mutagen resulting in variant emergence, but actually be genotoxic to the progenitor virus expediting the latter's disappearance.

It has been suggested that particulate matter PM 2.5 acting as a vector, was not only responsible for SARS-CoV-2 transmission but may also have been involved in this virus' evolution (Muscat Baron 2021a). Acting as SARS-CoV-2's vector, the quantity and quality of PM 2.5 may have exerted selective pressure determining the emergence of the first highly transmissible variant G614 in China (Muscat Baron 2021a).

A recurring set of mutations, namely E484K, N501Y, and K417N may suggest that SARS-CoV-2 is undergoing convergent evolution (Gupta 2021) . This convergent evolution of SARS-CoV-2 may be due to the presence of a common mutagenic catalyst and vector in the form of the omnipresent pollutant PM 2.5 which has repeatedly been shown to be a consistent co-factor in the SAR-CoV-2 Pandemic Contrasting effects by PM 2.5 on viral infectivity have been shown possibly due to mutations in viruses and bacteriophages. Viral transmission may be considered a phenotypic reflection of genomic mutation. During the 1968 influenza pandemic and its aftermath, mutations were noted in the influenza virus hemagglutinin serotype H3 molecule and appear to have provided an advantage to the resultant variant to evade antibodies and consequently cause disease in previously immune individuals (Bean et al. 1992 ).

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted July 2, 2021. ;

RNA viruses unlike DNA viruses lack the proofreading function of polymerase enzymes. This may be due to the hypothesized evolutionary precedence of RNA, which appears to have emerged well before the inception of DNA (Becker et al 2018) . As opposed to DNA, RNA may act both as a genetic carrier and as an enzyme. RNA viruses have mutation rates resulting in 10 -3 to 10 -4 errors per incorporated nucleotide, which is significantly higher than DNA viruses' error rate calculated at 10 -8 to 10 -11 errors per incorporated nucleotide (Alberts et al 2002) . SARS-CoV-2 variants' increased transmissible behaviour may therefore be dictated by these relatively frequent (compared to DNA viruses) RNA viral mutations (Fleischmann et al 1996) . Viral mutagenicity due to particulate matter PM 2.5 has been suggested with an experimental study on bacteriophage transmissibility in the presence of this pollutant (Groulx et al 2019) . A study suggested differential effects on the transmissibility of two bacteriophages 

Particulate matter adversely affects pulmonary immunity at all levels of its defences. This is more so with PM 2.5 as its micrometre diameters allow easy passage through the narrowest bronchioles and enter the alveoli. The mucociliary system is impaired by particulate matter disturbing its cleansing function of the respiratory tract. Pulmonary exposure to particulate matter appears to cause mucociliary paresis and promotes goblet cell mucus hypersecretion similar to tobacco smoking ) (Muscat Baron 2020d).

The respiratory epithelium is rendered more permeable at the cell junctions and cell membranes due to particulate matter. Respiratory epithelial permeability to viral invasion is further encouraged by allowing particulate matter-induced proinflammatory mediators which weaken the baso-lateral aspect of respiratory host cells and reducing the concentration of tight junction proteins (Liu, et Particulate matter exposure appears to affect CD4+ and CD8+ T cells leading to the suppression of interleukin IL-2 and interferon 1-γ production (Pierdominici et al. 2014 ). In severe cases of SARS-CoV-2 infection due to resultant significant loss of CD4+ and CD8+ T cells early in the infection, there appears to be . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted July 2, 2021. ; delayed adaptive immune responses, leading to prolonged viral clearance (Channappanavar, et al 2014) .

Evidence is emerging that SARS-CoV- Wang et al suggested that the genetic evolution of the SARS-CoV-2 receptor binding domain may be due to a combination of four factors. These include host cell gene editing, viral proof reading and random genetic drift with natural selection overarching all these three factors (Wang et al. 2021 ). It would be interesting to explore whether the presence of airborne particulate matter in elevated levels, as noted in the spikes of this pollutant preceding the variants' emergence, may actually catalyze these three factors, introducing the environmental element of natural selection. The impact of particulate matter on the propagation of the ACE-2 receptor has already been . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted July 2, 2021. ;  confirmed. This may set a chain reaction to affect both host cell gene editing and viral proof reading and instigate the catalyzed genetic drift.

There is literature that has not confirmed the role of particulate matter in the seeding and spread of COVID-19. A study done by Ong et al. 2020 , demonstrated that SARS-CoV-2 could not be detected in all of the air samples assessed. A caveat to this study indicated that the short sampling time of ¼ hr-4 h might not be representative of the total air volume in the ward and the presence of SARS-CoV-2 might have possibly been diluted during air exchanges in the ward (Ong, S. W. et al. 2020).

Another study in Northern Italy by Collovignarelli et al. put the association between particulate matter and COVID-19 in doubt. Collovignarelli et al. excluded a significant correlation between atmospheric particulate matter and the incidence of COVID-19. This latter study suggested that there may be other factors, including meteorological factors,that may have synergised with particulate matter to spread COVID-19. If one were to look closely at the provinces in Northern Italy as regards seeding and doubling time of COVID-19, the highest rates are to be found in landlocked provinces especially in Lodi, Bergamo, and Aosta. The impact of the vicinity to the sea as a factor determining COVID-19 rates has been alluded to (Muscat Baron 2020b) (Muscat Baron 2020c). By virtue of the absence of particulate matter sources from the sea, the level of this pollutant is likely to be lower and diluted in coastal provinces. Moreover the increased sodium chloride content in particulate matter derived from marine sources may have had a role in deterring the adhesion of the hydrophobic regions in the SARS-CoV-2 spike protein to particulate matter (Muscat Baron 2020c).

One may surmise that the occurrence in the spikes of this pollutant in relation to the emergence of variants was just a coincidence. This is unlikely as assessing all the data available on the World Air Quality Index indicates two characteristic patterns of PM 2.5 levels. In some cities such as Beijing and Sao Paolo, PM 2.5 levels demonstrate perennial elevations in December and January as in the case of China or October in Brazil. The other pattern involves unique rises of atmospheric concentrations such as in Kent U.K. and Washington Heights New York.

On the other hand the association between particulate matter and COVID-19 has its support. The increase in pulmonary ACE-2 receptors and its effect on respiratory immunity after exposure to particulate matter has been scientifically confirmed (Paital and Agrawal, 2020) , (Sagawa et al., 2021) . The presence of SARS-CoV-2 genes on particulate matter provides circumstantial evidence of the potential vector effect of this airborne pollutant (Setti et al 2020b) .

It is also biologically plausible that particulate matter's mutagenic and genotoxic effect may also affect SARS-CoV-2 both outside and inside the host, leading to the emergence of variants and the displacement of the progenitor virus. The uncanny . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted July 2, 2021. similarity in the patterns of PM 2.5, prior and during the emergence of the SARS-CoV-2 variant suggests a biological link. Lastly the appearance of similar mutations in the different variants, increasing their transmissibility, in widely disparate and distant regions, lends its itself to suggest that convergent evolution of SARS-CoV-2 is occurring in the presence of an ubiquitous environmental factor.

The average daily PM 2.5 levels are taken in this study and it must be mentioned that there may be wide variations between the maximum and minimum levels of particulate matter throughout the day including when there may be human exposure to this pollutant. Exposure to atmospheric outdoor PM 2.5 was carried out in this review, does not necessarily equate that to humans being similarly exposed to the same levels indoors. A collation of five studies demonstrated that indoor SARS-CoV-2 transmission was very high compared to outdoors (18.7 times; 95% confidence interval, 6.0-57.9) studies compared to outdoor spread (<10%) (Bulfone et al 2021) . Although this study utilized outdoor PM 2.5 , the study by Brunekreef et al. mentioned earlier, demonstrated that indoor PM 2.5 concentrations highly correlated with outdoor concentrations (median R= 0.7-0.8) (Brunekreef et al 2005) . In some countries, such as in China, indoor levels may actually be higher if fossil fuels are used for heating purposes. In Wuhan in 2020, natural gas consumption for heating purposes increased 2.8 times fossil fuel utilization by the traditional stove and water heater, potentially producing another indoor source for particulate matter (Dong et al 2020).

There was a significant difference in new case counts obtained between different states included in this review. This suggests the strong possibility of variation in the frequency and availability of diagnostic testing for SARS-CoV-2. From the Beijing data available only the latter part of the bell-shaped curve for the new case counts could be assessed. These COVID-19 new cases in both Wuhan and Beijing were preceded by spike in PM 2.5 . In this study not all the states assessed had daily COVID-19 new case counts available.

The detection and emergence of variants has its drawbacks especially from the temporal aspect. There is a great variation in the availability and access to RNA sequencing processes. The USA (less than 1% of global COVID-19 sequencing) has the greatest capacity for sequencing but the absence of a single Health System as in the U.K. (9% of global sequencing) hampers the co-ordination of sampling and its availability for sequencing. There is also a significant cost to sequencing procedures (Maxmen 2021). A model has been proposed that within the SARS-CoV-2 perspective, 5% sampling of all positive tests in a population would allow the detection of emerging variants at a prevalence between 0.1% to 1.0%. Attenuating the risk of vaccine escape and the prevention of future coronavirus pandemics very much depends on the availability and easy access to genomic surveillance (Vavrek et  al 2021) .

There appears to be a link between atmospheric PM 2.5 and the emergence of SARS-CoV-2 variants. In most regions assessed, two groups of PM 2.5 spikes were noted prior to the emergence of SARS-CoV-2 variants. These spikes in PM 2.5 spike may suggest that the combination of a number of factors including, a).Anthropogenic activity increasing the viral burden, b). PM 2.5 -induced propagation of the ACE-2 receptor (the viral point of host cell entry), c). Potential PM 2.5 -induced viral mutagenesis resulting in variant emergence and genotoxicity to the progenitor, d). PM 2.5 toxicity diminishing host pulmonary immunity and e). Possible PM 2.5 vector effect, increased the prospect of the emergence SARS-CoV-2 variant. The above findings suggest that significant changes in PM 2.5 levels may not only contribute to transmission, but also to the evolution of SARS-CoV-2. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted July 2, 2021. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted July 2, 2021. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted July 2, 2021. ; https://doi.org/10.1101/2021.06.27.21259602 doi: medRxiv preprint . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

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Exposure to air pollution and COVID-19 mortality in the United States: A nationwide crosssectional study

as a major predictor of COVID-19 basic reproduction number in the USA

SARS-Cov-2RNA found on particulate matter of Bergamo in Northern Italy: First evidence

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

Effects of air pollutants on the transmission and severity of respiratory viral infections

Air pollution by NO(2) and PM(2.5) explains COVID-19 infection severity by overexpression of angiotensin-converting enzyme 2 in respiratory cells: a review

Exposure to particulate matter upregulates ACE2 and COVID-19 Environmental Dependence 21 TMPRSS2 expression in the murine lung

Air Pollution and Covid-19: The Role of Particulate Matter in the Spread and Increase of Covid-19's Morbidity and Mortality

Does Air Pollution Influence COVID-19 Outbreaks? Atmosphere 11

An Imperative Need for Research on the Role of Environmental Factors in Transmission of Novel Coronavirus (COVID-19)

Could changes in the airborne pollutant particulate matter acting as a viral vector have exerted selective pressure to cause COVID-19 evolution?

Atmospheric PM2.5 before and after Lockdown in relation to COVID-19 Evolution and daily Viral Counts: Could Viral Natural Selection have occurred due to changes in the Airborne Pollutant PM2.5 acting as a Vector for SARS-CoV-2?

Will SARS-CoV-2 variants of concern affect the promise of vaccines?

Covid-19 Pandemic in relation to PM2.5, and Ambient Salinity -An Environmental Wake-up Call

Covid-19 and PM2.5 Sodium Chloride Content

Incidence and Case-Fatality Ratio of COVID-19 Infection in Relation to Tobacco Smoking, Population Density and Age Demographics in the USA: could Particulate Matter derived from Tobacco Smoking act as a Vector for COVID-19 Transmission

Elevated levels of PM2.5 in crowded Subways of Cities with High COVID-19 related Mortality

The Pollution Particulate Concentrator (PoPCon): A platform to investigate the effects of particulate air pollutants on viral infectivity

EPA:Environmental Protection Agency. World Air Quality Index. aqicn.orgwaqi

Tracking Changes in SARS-CoV-2 Spike: Evidence that D614G Increases Infectivity of the COVID-19

Emergence and spread of a SARS-CoV-2 variant through Europe in the summer of 2020. medRxiv

Could Mass Confinement of Animals be an Opportunistic Pabulum for the 20A.EU1 Coronavirus Mutation in Europe? From Formosan Pangolin to Mink

Molecular Basis of Genetic Variation of Viruses: Error-Prone Replication

The delayed effect of wildfire season particulate matter on subsequent influenza season in a mountain west region of the USA

These Satellite Photos Show how COVID-19 Lockdowns Have Impacted Global Emissions

Personal, indoor, and outdoor exposures to PM2.5 and its components for groups of cardiovascular patients in Amsterdam and Helsinki. Res Rep Health Eff Inst

Sources of indoor and outdoor PM2.5 concentrations in primary schools

Wildfire and COVID-19 pandemic: effect of environmental pollution PM-2.5 and carbon monoxide on the dynamics of daily cases and deaths due to SARS-COV-2 infection in

Evidence for impacts on surface-level air quality in the northeastern US from long-distance transport of smoke from North American fires during the Long Island Sound Tropospheric Ozone Study (LISTOS) 2018. Atmospheric Chemistry and Physics

Indirect virus transmission in cluster of COVID-19 cases

Identification of Vulnerable Populations and Areas at Higher Risk of COVID-19

Association of particulate matter pollution and case fatality rate of COVID-19 in 49

Evidence-Based Considerations Exploring Relations between SARS-CoV-2 Pandemic and Air Pollution: Involvement of PM 2.5 -Mediated Up-Regulation of the Viral Receptor ACE-2

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

Influence of population mobility on the novel coronavirus disease (COVID-19) epidemic: based on panel data from Hubei

Could the Denisovan Genes have conferred enhanced Immunity against the G614 Mutation of SARS-CoV-2? Human Evolution in press

Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation

Structural and Functional Analysis of the D614G SARS-CoV-2 Spike Protein Variant bioRxiv

Critical Interactions Between the SARS-CoV-2 Spike Glycoprotein and the Human ACE2 Receptor

The Italian Response to the COVID-19 Crisis: Lessons Learned and Future Direction in Social Development

MT COVID-19 outbreak in long-term care facilities from Spain. Many lessons to learn

Evaluation of the lockdowns for the SARS-CoV-2 epidemic in Italy and Spain after one month follow up

Genetic Variants of SARS-CoV-2-What Do They Mean?

Increased Resistance of SARS-CoV-2 Variants B.1.351 and B.1.1.7 to Antibody Neutralization

The Impact of a Severe Drought on Dust Lifting in California's Owens Lake Area

McKeever Inside California's race to contain its devastating National Geographic

Current status of air pollution in Sao Paulo, Brazil: effects and problems associated with the introduction of ethanol-fueled motor vehicles

Risk assessment of PM(2.5) to child residents in Brazilian Amazon region with biofuel production

Surface ozone climatology of South Eastern Brazil and the impact of biomass burning events

An Aspect of Kumbh Mela Massive Gathering and COVID-19

Exceedances and trends of particulate matter (PM2.5) in five Indian megacities

Airborne Transmission Route of COVID-19: Why 2 Meters/6 Feet of Inter-Personal Distance Could Not Be Enough

High Contagiousness and Rapid Spread of Severe Acute Respiratory Syndrome Coronavirus 2

Modeling influenza epidemics and pandemics: insights into the future of swine flu (H1N1)

The reproductive number of COVID-19 is higher compared to SARS coronavirus

Particulate matter (PM 2.5 ) as a potential SARS-CoV-2 carrier

Assessment for the impact of dust events on measles incidence in Western China

The dynamics of measles in sub-Saharan Africa

Dust Storms and their possible effect onhealth: with special reference to the dust Storms in Kansas in 1935

Remembering the Dreaded Summers of Polio Elsevier

The coronavirus is mutating -does it matter? Nature

Assessing the relationship between surface levels of PM2.5 and PM10 particulate matter impact on COVID-19 in

The role of air pollution (PM and NO2) in COVID-19 spread and lethality: A systematic review

Air pollution and COVID-19: Is the connect worth its weight? Indian J Public Health

Evolution of the H3 influenza virus hemagglutinin from human and nonhuman hosts

Wet-dry cycles enable the parallel origin of canonical and noncanonical nucleosides by continuous synthesis

New York: Garland Science; 2002. The RNA World and the Origins of Life

University of Texas Medical Branch at Galveston; 1996. Chapter 43

The role and potential pathogenic mechanism of particulate matter in childhood asthma: a review and perspective

Diesel exhaust particle exposure in vitro impacts T lymphocyte phenotype and function

T cell-mediated immune response to respiratory coronaviruses

Emergence and rapid spread of a new severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) lineage with multiple spike mutations in South Africa medRxiv 2020. 12.21

Higher infectivity of the SARS-CoV-2 new variants is associated with K417N/T, E484K, and N501Y mutants: An insight from structural data

Vaccine-escape and fast-growing mutations in the United Kingdom, the United States

Air, surface environmental, and personal protective equipment contamination by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from a symptomatic patient

Can particulate matter be identified as the primary cause of the rapid spread of CoViD-19 in some areas of Northern Italy?

Particulate matter and SARS-CoV-2: A possible model of COVID-19 transmission

Outdoor Transmission of SARS-CoV-2 and Other Respiratory Viruses: A Systematic Review

Impact of residential building heating on natural gas consumption in the south of China: Taking Wuhan city as example