Severe air pollution links to higher mortality in COVID-19 patients: The "double-hit" hypothesis

J Infect. 2020 Aug;81(2):255-259. doi: 10.1016/j.jinf.2020.05.031. Epub 2020 May 21.


Objectives: In areas of SARS-CoV-2 outbreak worldwide mean air pollutants concentrations vastly exceed the maximum limits. Chronic exposure to air pollutants have been associated with lung ACE-2 over-expression which is known to be the main receptor for SARS-CoV-2. The aim of this study was to analyse the relationship between air pollutants concentration (PM 2.5 and NO2) and COVID-19 outbreak, in terms of transmission, number of patients, severity of presentation and number of deaths.

Methods: COVID-19 cases, ICU admissions and mortality rate were correlated with severity of air pollution in the Italian regions.

Results: The highest number of COVID-19 cases were recorded in the most polluted regions with patients presenting with more severe forms of the disease requiring ICU admission. In these regions, mortality was two-fold higher than the other regions.

Conclusions: From the data available we propose a "double-hit hypothesis": chronic exposure to PM 2.5 causes alveolar ACE-2 receptor overexpression. This may increase viral load in patients exposed to pollutants in turn depleting ACE-2 receptors and impairing host defences. High atmospheric NO2 may provide a second hit causing a severe form of SARS-CoV-2 in ACE-2 depleted lungs resulting in a worse outcome.

MeSH terms

  • Air Pollutants / adverse effects
  • Air Pollution / adverse effects*
  • Air Pollution / statistics & numerical data
  • Betacoronavirus*
  • COVID-19
  • Coronavirus Infections / epidemiology
  • Coronavirus Infections / etiology
  • Coronavirus Infections / mortality*
  • Disease Outbreaks / statistics & numerical data
  • Hospitalization / statistics & numerical data
  • Humans
  • Intensive Care Units / statistics & numerical data
  • Italy / epidemiology
  • Nitrogen Dioxide / adverse effects
  • Pandemics
  • Particulate Matter / adverse effects
  • Pneumonia, Viral / epidemiology
  • Pneumonia, Viral / etiology
  • Pneumonia, Viral / mortality*
  • Risk Factors
  • SARS-CoV-2
  • Severity of Illness Index


  • Air Pollutants
  • Particulate Matter
  • Nitrogen Dioxide