The Secretive Liaison of Particulate Matter and SARS-CoV-2. A Hypothesis and Theory Investigation

Abstract

As the novel coronavirus disease sweeps across the world, there is growing speculation on the role that atmospheric factors may have played on the different distribution of SARS-CoV-2, and on the epidemiological characteristics of COVID-19. Knowing the role that environmental factors play in influenza virus outbreaks, environmental pollution and, in particular, atmospheric airborne (particulate matter, PM) has been considered as a potential key factor in the spread and mortality of COVID-19. A possible role of the PM as the virus carrier has also been debated. The role of PM in exacerbating respiratory and cardiovascular disease has been well recognized. Accumulating evidence support the hypothesis that PM can trigger inflammatory response at molecular, cellular and organ levels. On this basis, we developed the hypothesis that PM may play a role as a booster of COVID-19 rather than as a carrier of SARS-CoV-2. To support our hypothesis, we analyzed the molecular signatures detected in cells exposed to PM samples collected in one of the most affected areas by the COVID-19 outbreak, in Italy. T47D human breast adenocarcinoma cells were chosen to explore the global gene expression changes induced by the treatment with organic extracts of PM 2.5. The analysis of the KEGG's pathways showed modulation of several gene networks related to the leucocyte transendothelial migration, cytoskeleton and adhesion system. Three major biological process were identified, including coagulation, growth control and immune response. The analysis of the modulated genes gave evidence for the involvement of PM in the endothelial disease, coagulation disorders, diabetes and reproductive toxicity, supporting the hypothesis that PM, directly or through molecular interplay, affects the same molecular targets as so far known for SARS-COV-2, contributing to the cytokines storm and to the aggravation of the symptoms triggered by COVID-19. We provide evidence for a plausible cooperation of receptors and transmembrane proteins, targeted by PM and involved in COVID-19, together with new insights into the molecular interplay of chemicals and pathogens that could be of importance for sustaining public health policies and developing new therapeutic approaches.

Keywords: COVID-19; SARS-CoV-2; cytokine storm; environmental pollution; molecular mechanisms; molecular signatures; particulate matter; receptors cross-talk.

FIGURE 1

Experimental design. (A) The experimental design. T47D Cytotoxicity assay, Microarray experiments (whole human genome, 4 × 44k): winter and summer PM_2.5 extracts 8 m³ 4 h treatment, Data analysis: winter and/or summer PM_2.5 extracts, Biological interpretation: winter PM_2.5 extracts. (B) GeneSpring (GeneSpring GX, Agilent Technologies) Data analysis. Data normalization and filtration for intensity and quality signal, One-Way ANOVA Analysis (winter and summer PM_2.5 extracts, P < 0.01 Bonferroni, 11,483 differentially expressed genes) to select differentially expressed genes among the treatments and the control, Principal Component Analysis (PCA), Analysis of markers of environmental exposure (CYP1A1, CYP1B1, HMOX1), t-test analysis on winter PM_2.5 samples: MXW vs. GMA, CTW vs. GMA, MXW vs. CTW (P < 0.01 Benjamini–Hockberg). (C) Biological interpretation on winter PM_2.5 extracts. Microarray analysis: Pathway express (PE), Gene Set Enrichment Analysis (GSEA). Real time PCR: AGT, CRH, TAC3, PLAT, TFPI.

FIGURE 2

Leukocyte transendothelial migration KEGG, as obtained from Pathway Express (PE) analysis, MXW vs. GMA, CTW vs. GMA. Red: up-regulation. Blue: down-regulation.

FIGURE 3

GSEA leading edge analysis of the significantly enriched KEGG pathway (A,B) and GO Biological Processes (C,D). The results are shown as a similarity matrix where the intensity of the green color directly correlates with the extent of the intersection between the leading edge core genes of each gene set combination. (A,C) = MXW vs. GMA; (B,D) = CTW vs. GMA.

FIGURE 4

Role of PM-mediated inflammation in COVID-19. Created with Biorender.com.