key: cord-0845480-8vrgdktr
authors: Domingo, José L.; Marquès, Montse; Rovira, Joaquim
title: Influence of airborne transmission of SARS-CoV-2 on COVID-19 pandemic. A review
date: 2020-06-23
journal: Environ Res
DOI: 10.1016/j.envres.2020.109861
sha: 9011bd766e9b6e2a011ca50a81b11393efb741a4
doc_id: 845480
cord_uid: 8vrgdktr

In recent years, a number of epidemiological studies have demonstrated that exposure to air pollution is associated with several adverse outcomes, such as acute lower respiratory infections, chronic obstructive pulmonary disease, asthma, cardiovascular diseases, and lung cancer among other serious diseases. Air pollutants such as sulfur oxides, nitrogen oxides, carbon monoxide and dioxide, particulate matter (PM), ozone and volatile organic compounds (VOCs) are commonly found at high levels in big cities and/or in the vicinity of different chemical industries. An association between air concentrations of these pollutants and human respiratory viruses interacting to adversely affect the respiratory system has been also reported. The present review was aimed at assessing the potential relationship between the concentrations of air pollutants on the airborne transmission of SARS-CoV-2 and the severity of COVID-19 in patients infected by this coronavirus. The results of most studies here reviewed suggest that chronic exposure to certain air pollutants leads to more severe and lethal forms of COVID-19 and delays/complicates the recovery of patients of this disease.

Since March 2020, a number of investigations have pointed out that the progression of COVID-19 was more important in cities/areas/regions where certain air pollutants were being detected at comparatively high levels. In the 2000s, a positive association between air pollution and case fatality of SARS-CoV-1 was already observed in the Chinese population during the epidemic caused by that coronavirus (Cui et al., 2003) . Cui and co-workers (2003) were focused on particulate matter (PM), nitrogen dioxide, carbon monoxide, sulfur dioxide and ground-level ozone. These environmental contaminants, as well as volatile organic compounds (VOCs), which derive mainly from vehicular traffic and industrial emissions, have been also suggested to contribute potentially to the severity of COVID-19. They would affect directly the lung ability to clear pathogens, and also indirectly, by exacerbating underlying cardiovascular and/or pulmonary diseases (Brandt et al., 2020) . Thus, for example, the relationship between biomass uses and COVID-19 has even raised a novel concern due to exposure to air pollution of biomass smoke, which would be especially affecting those populations living in the most fragile conditions (Thakur et al., 2020) . Regarding the transmission of SARS-CoV-2, it could be influenced not only by temperature and humidity, but also by food, water, and sewage, among other potential factors (Bashir et al., 2020a; Eslami and Jalili, 2020; Qu et al., 2020) . With respect to COVID-19 vulnerability, in a recent review, Godri Pollitt et al. (2020) have highlighted possible genetic determinants of COVID-19, as well as the contribution of aerosol exposure as a potentially important route of transmission of SARS-CoV-2.

The main routes of person-to-person transmission of respiratory viruses are the following: a) the direct or indirect contact with an infected subject; b) the 4 large droplets emitted by coughing/sneezing that can reach an uninfected subject; and c) the inhalation of small airborne particles remaining in the air (Eissenberg et al., 2020; Qu et al., 2020) . In relation to the latter, Morawska and Cao (2020) have strongly suggested that the SARS-CoV-2 has been spreading through the air. In this same line, Frontera et al. (2020a) have hypothesized that the presence of air pollutants -together with certain climatic conditions -might mean a long permanence of the viral particles in the air, which -in turn -could promote the indirect diffusion of the SARS-CoV-2. Coccia (2020) has suggested that the transmission dynamics of COVID-19 could be due to air pollution-tohuman transmission, rather than the direct human-to-human transmission. This author, using pollution and infected individual data of 55 Italian province capitals, has reported that the quick and vast diffusion of COVID-19 in Northern

Italy showed a high association with the number of days exceeding the PM 10 threshold. Coccia (2020) also highlighted that polluted cities in hinterland with low speed of wind had a high number of infected individuals than coastal cities.

Based on this results, it was suggested that the prevention of future epidemics must be also based on sustainability and environmental sciences. In turn, Riccò and co-workers (2020) have reported that an appropriate way in dealing with, and understanding the potential relationship between air pollution and SARS-CoV-2 infection incidence rates, could be based on comparing geographical areas, which are characterized by similar socio-economic development, but strikingly different environmental status; for example, highly polluted areas vs. zones with low pollution concentrations.

The World Health Organization (WHO, 2014) has defined airborne transmission "as the spread of an infectious agent caused by the dissemination of droplet nuclei, which remain infectious when suspended in air over long distances and time". According to this definition, the rapid spread of the SARS-CoV-2 would suggest that, in addition to the transmission person-to person, other ways -like airborne -can be also involved in the transmission of this coronavirus (Hadei et al., 2020) . Anyhow, despite these clear indications, the determination of the relative weight of air pollution, as well as the identification of the main pollutants potentially responsible of the airborne transmission of SARS-CoV-2, are issues that need still to be widely investigated (Contini and Costabile, 2020; Lewis, 2020) .

We next summarize the scientific information that is currently available in the databases Pubmed (https://pubmed.ncbi.nlm.nih.gov/) and Scopus (https://www.scopus.com/), using "air pollution/pollutants" and "COVID- receptor, which can increase the viral load in patients exposed to air pollutants.

In turn, this would deplete ACE-2 receptors, impairing host defenses. In addition, high atmospheric levels of NO 2 can provide a second hit, causing a severe form of SARS-CoV-2 in ACE-2 depleted lungs, resulting in a worse outcome. According to the above preliminary results, the internationally recommended interpersonal distance of 1.5-2 meters would be considered an effective protection only if individuals are also wearing face masks in their daily life activities (Setti et al., 2020c) .

In contrast to the suggestions/conclusions above summarized, Bontempi (2020a) has reported that direct correlations between high levels of particulate matter and the diffusion of the SARS-CoV-2 are not evident. To reach this conclusion, Bontempi (2020a) analyzed the available data about PM 10 concentrations and infections cases in Lombardy and Piedmont. It was found 7 that the cities of Torino and Alessandria, which were suffering the most severe event of PM 10 pollution in the 20 days before the sanitary crisis, had low infections cases (0.01% and 0.03%, evaluated on total population, respectively, on March 12). However, in Bergamo, where the limit of 50 μg/m 3 for PM 10 concentrations was exceeded only few times, showed the highest number of infectious cases. In order to clarify some potentially confusing information related to airborne diffusion mechanisms of SARS-CoV-2. Bontempi (2020b) have suggested that parameters other than environmental pollution accounting for pollution-to-human transmission mechanisms (e.g., commercial exchanges in human-to-human mechanisms) should be considered to understand the differences in the initial diffusion of the virus in Italy. In a very recent study, Bontempi and co-workers (2020) have suggested that while initial conditions can respond to preexisting economic and environmental factors, the unfolding of contagion is more non-linear and depends on measures, health care system's efficiency, and other factors, which might explain different results (e.g., the different mortality rates in Veneto vs. Lombardy, for example). In summary, Bontempi et al. (2020) have concluded that the current pandemic's diffusion patterns are caused by a multiplicity of environmental, economic and social factors.

The results of studies aimed at establishing the correlation between air pollution and COVID-19 in countries abroad Europe are -in general terms -in the same line than most of the above reviewed investigations. In a study conducted in California (USA), Bashir et al. (2020b) increase of only 1 μg/m 3 in PM 2.5 was associated with an 8% increase in the COVID-19 death rate, being the results statistically significant and robust to secondary and sensitivity analyses. Liang et al. (2020) also in the USA, carried 8 out a cross-sectional nationwide study in order to assess the potential association between long-term county-level exposure to NO 2 , PM 2.5 and O 3 , and county-level COVID-19 case-fatality and mortality rates. A total of 3,122

counties were included in that study. Statistically significant positive associations between long-term exposure to NO 2 and COVID-19 case-fatality rate and mortality rate, were found, independently of the concentrations of PM 2.5 and O 3 . It was concluded that prolonged exposure to NO 2 , an urban trafficrelated air pollutant, may be an important risk factor of severe COVID-19

outcomes.

In England, Travaglio et al. (2020) have investigated the potential links between major air pollutants related to fossil fuels and SARS-CoV-2 mortality in that country. It was found that the levels of multiple markers of poor air quality, including nitrogen oxides and sulfur dioxide, were associated -after adjusting for population density-with an increased number of COVID-19-related deaths across England. In China, Li et al. (2020) investigated whether air quality index (AQI), four ambient air pollutants (PM 2.5 , PM 10 , NO 2 and CO) and five meteorological variables (daily temperature, highest temperature, lowest temperature, temperature difference and sunshine duration) could increase (2020), who raised that only two months of exposure to NO 2 could not be considered as a long-term/chronic exposure. Chudnovsky (2020) also indicated that in countries like Taiwan -with much higher air concentrations of NO 2 -had low fatality cases. The response of Ogen (2020b) was that his results simply showed that the highest number of cases was observed in highly polluted areas of Europe, with very important cultural differences with respect to Taiwan, which would make hard a comparison of the results.

In another vein, recently Tsatsakis et al. (2020) have discussed how long-term exposure to thousand chemicals in mixtures, mostly fossil fuel derivatives, exposure to PM, metals, ultraviolet (UV)-B radiation, ionizing radiation, and lifestyle contribute to immunodeficiency observed in the contemporary pandemics, such as COVID-19. The authors have noticed that environmental-related diseases (e.g., energy-metabolism-immune mediated obesity, type II diabetes, metabolic syndrome and cancers) and infectious diseases (e.g., parasitic, influenza or coronavirus-related epidemic or pandemic) share the same pathogenic mechanisms at the molecular level, particularly the AhR pathway. The immunotoxicity risk of vulnerable groups, taking into account biochemical and biophysical properties of SARS-CoV-2 and its immunopathological implications, were discussed and the common mechanisms by which xenobiotics and SARS-CoV-2 act at the cellular and molecular level was underlined.

The results of most of the studies hereby reviewed suggest/conclude that chronic exposure to certain air pollutants might lead to more severe and lethal forms of COVID-19 and delays/complicates recovery of patients suffering this disease. This suggestion/conclusion, which is obviously new for the SARS-CoV-2, seems to follow a similar pattern as other respiratory viruses. Thus, a notable evidence supports a clear association between concentrations of various air pollutants and human respiratory viruses interacting to adversely affect the respiratory system (Domingo and Rovira, 2020) .

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