# In silico analysis of the impact of toxic metals on COVID-19 complications: molecular insights

**Authors:** Jovana Živanović, Katarina Baralić, Katarina Živančević, Dragica Božić, Đurđica Marić, Evica Antonijević Miljaković, Aleksandra Buha Đorđević, Marijana Ćurčić, Zorica Bulat, Biljana Antonijević, Danijela Đukić-Ćosić

PMC · DOI: 10.2478/aiht-2024-75-3819 · Archives of Industrial Hygiene and Toxicology · 2024-06-29

## TL;DR

This study explores how exposure to toxic metals may worsen COVID-19 complications by affecting genes related to inflammation.

## Contribution

The study identifies common genes affected by toxic metals and SARS-CoV-2, revealing potential molecular links to severe disease.

## Key findings

- Five common genes (IL1B, CXCL8, IL6, IL10, TNF) are shared between toxic metals and COVID-19, all related to cytokine activity.
- Physical interactions are most common among genes affected by multiple metals, while co-expression dominates for individual metals.
- The identified genes are involved in biological processes and pathways linked to cytokine storms, which are associated with severe COVID-19.

## Abstract

COVID-19 can cause a range of complications, including cardiovascular, renal, and/or respiratory insufficiencies, yet little is known of its potential effects in persons exposed to toxic metals. The aim of this study was to answer this question with in silico toxicogenomic methods that can provide molecular insights into COVID-19 complications owed to exposure to arsenic, cadmium, lead, mercury, nickel, and chromium. For this purpose we relied on the Comparative Toxicogenomic Database (CTD), GeneMANIA, and ToppGene Suite portal and identified a set of five common genes (IL1B, CXCL8, IL6, IL10, TNF) for the six metals and COVID-19, all of which code for pro-inflammatory and anti-inflammatory cytokines. The list was expanded with additional 20 related genes. Physical interactions are the most common between the genes affected by the six metals (77.64 %), while the dominant interaction between the genes affected by each metal separately is co-expression (As 56.35 %, Cd 64.07 %, Pb 71.5 %, Hg 81.91 %, Ni 64.28 %, Cr 88.51 %). Biological processes, molecular functions, and pathways in which these 25 genes participate are closely related to cytokines and cytokine storm implicated in the development of COVID-19 complications. In other words, our findings confirm that exposure to toxic metals, alone or in combinations, might escalate COVID-19 severity.

## Linked entities

- **Genes:** IL1B (interleukin 1 beta) [NCBI Gene 3553], CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576], IL6 (interleukin 6) [NCBI Gene 3569], IL10 (interleukin 10) [NCBI Gene 3586], TNF (tumor necrosis factor) [NCBI Gene 7124]
- **Chemicals:** arsenic (PubChem CID 5359596), cadmium (PubChem CID 23973), lead (PubChem CID 5352425), mercury (PubChem CID 23931), nickel (PubChem CID 935), chromium (PubChem CID 23976)
- **Diseases:** COVID-19 (MONDO:0100096)

## Full-text entities

- **Genes:** IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}
- **Diseases:** inflammatory (MESH:D007249), cardiovascular, renal, and/or respiratory insufficiencies (MESH:D012131), COVID-19 (MESH:D000086382)
- **Chemicals:** Hg (MESH:D008628), Cr (MESH:D002857), Ni (MESH:D009532), As (MESH:D001151), Pb (MESH:D007854), Cd (MESH:D002104)

## Full text

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## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11223505/full.md

## References

41 references — full list in the complete paper: https://tomesphere.com/paper/PMC11223505/full.md

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Source: https://tomesphere.com/paper/PMC11223505