Two mechanisms for accelerated diffusion of COVID-19 outbreaks in regions with high intensity of population and polluting industrialization: the air pollution-to-human and human-to-human transmission dynamics

Mario Coccia

is the (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.04.06.20055657 doi: medRxiv preprint 31 | P a g e Coccia M. (2020) Two mechanisms for accelerated diffusion of COVID-19 outbreaks in regions with high intensity of population and polluting industrialization: the air pollution-to-human and human-to-human transmission dynamics different immune cell types, such as particle-clearing macrophages, inflammatory neutrophils, dendritic cells that orchestrate adaptive immune responses and lymphocytes that enact those responses. In general, air pollutants stimulate pro-inflammatory immune responses across multiple classes of immune cell. Air pollution can enhance T helper lymphocyte type 2 and T helper lymphocyte type 17 adaptive immune responses, as seen in allergy and asthma, and dysregulate anti-viral immune responses. In particular, the association between high ambient pollution and exacerbations of asthma and chronic obstructive pulmonary disease (COPD) is consistent with immunological mechanisms. In fact, diseases can result from inadequate responses to infectious microbes allowing fulminant infections, inappropriate/excessive immune responses to microbes leading to more (collateral) damages than the microbe itself, and inappropriate immune responses to self/environment, such as seems to be in the case of COVID-19. Glencross et al. (2020) also discuss evidence that air pollution can cause disease by perturbing multicellular immune responses. Studies confirm associations between elevated ambient particulate matter and worsening of lung function in patients with COPD (Bloemsma et al., 2026) , between COPD exacerbations and both ambient particulate matter and ambient pollutant gasses (Li et al., 2026) and similarly for asthma exacerbations with high concentration of ambient pollutants (Orellano et al., 2017 , Zheng et al., 2015 . In short, the associations between ambient pollution and airways exacerbations are stronger than associations with development of chronic airways diseases. Glencross et al. (2020) also argue that ambient pollutants can directly trigger cellular signaling pathways, and both cell culture studies and animal models have shown profound effects of air pollutants on every type of immune cell studied. In addition to the general pro-inflammatory nature of these effects, many of studies suggest an action of air pollution to augment Th2 immune responses and perturb antimicrobial immune responses. This mechanism also explains the association between high air pollution and increased exacerbations of asthma -a disease characterized by an underlying Th2 immuno-pathology in the airways with severe viral-induced exacerbations. Moreover, as inhaled air pollution deposits primarily on the respiratory mucosa, potential strategies to reduce such effects may be based on vitamin D supplementation. Studies show that plasma levels of vitamin D, activated by ultraviolet B, are significantly . CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity.