Less COVID-19 deaths in southern and insular Italy explained by forest bathing, Mediterranean environment, and antiviral plant volatile organic compounds

Lay Summary

Mediterranean plants are mostly evergreen that emit volatile compounds (biogenic VOCs) all around the year (including fall and winter) , and these VOCs when inhaled help boost the immune system 


plant VOCs are predicted to bind ACE2-RBD complex potentially preventing SARS-CoV-2 infection


Mediterranean greenest areas experienced lowest COVID-19 impact in Italy


Forest-bathing should be regarded as a therapeutic approach in western countries like in Asia


More attention should be paid to forest (especially evergreen) conservation

Abstract

The coronavirus disease 2019 (COVID-19) is causing major sanitary and socioeconomic issues, yet some locations are less impacted than others. While densely populated areas are likely to favor viral transmission, we hypothesize that other environmental factors could explain lower cases in some areas. We studied COVID-19 impact and population statistics in highly forested Mediterranean Italian regions versus some northern regions where the amount of trees per capita is much lower. We also evaluated the afnity of Mediterranean plant-emitted volatile organic compounds (VOCs) isoprene, α-pinene, linalool and limonene for COVID-19 protein targets by molecular docking modeling. Results show that while mean death number increased about 4 times from 2020 to 2021, the percentage of deaths per population (0.06–0.10%) was lower in the greener Mediterranean regions such as Sardinia, Calabria and Basilica versus northern regions with low forest coverage, such as Lombardy (0.33%) and Emilia Romagna (0.29%). Data also show that the pandemic severity cannot be explained solely by population density. Modeling reveals that plant organic compounds could bind and interfere with the complex formed by the receptor binding domain of the coronavirus spike protein with the human cell receptor. Overall, our fndings are likely explained by sea proximity and mild climate, Mediterranean diet and the abundance of non-deciduous Mediterranean plants which emit immunomodulatory and antiviral compounds. Potential implications include ‘forest bathing’ as a therapeutic practice, designing nasal sprays containing plant volatile organic compounds, and preserving and increasing forest coverage.

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