Across Borders, Worse COVID Outcomes Seen in Polluted Areas

During the pandemic, people exposed to more air pollution were at greater risk of COVID-19 infection, hospitalization, and death, a nationwide study from Denmark showed.

Based on the country's COVID-19 surveillance system covering over 3.7 million residents, there were significant associations between local levels of inhalable particulate matter (PM_2.5) and nitrogen dioxide (NO₂) and incident COVID-19 from March 2020 to April 2021:

• PM_2.5 and COVID infection (HR 1.10 per 0.53 µg/m³, 95% CI 1.05-1.14)
• PM_2.5 and COVID hospitalization (HR 1.09, 95% CI 1.01-1.17)
• PM_2.5 and COVID death (HR 1.23, 95% CI 1.04-1.44)
• NO₂ and COVID infection (HR 1.18 per 3.6 µg/m³, 95% CI 1.14-1.23)
• NO₂ and COVID hospitalization (HR 1.19, 95% CI 1.12-1.27)
• NO₂ and COVID death (HR 1.18, 95% CI 1.03-1.34)

Associations were particularly strong among the lowest socioeconomic groups and among patients with chronic respiratory, cardiometabolic, and neurodegenerative disease, Zorana Jovanovic Andersen, PhD, an environmental epidemiologist at the University of Copenhagen in Denmark, and coauthors reported in the European Respiratory Journal.

Another study, published in the same journal, saw similar results in two Belgian hospitals among patients hospitalized with COVID-19. Increased exposure of both PM_2.5 and NO₂ by one interquartile range (IQR) in the week prior to hospitalization was associated with a longer length of stay by 4.22 (95% CI 0.74-7.69) and 4.33 days (95% CI 1.30-7.37), respectively.

Investigator Tim Nawrot, PhD, of Hasselt University in Belgium, and coauthors also reported that an IQR increase of black carbon (BC) accumulated in the blood was significantly associated with an increase in intensive care hospitalization from COVID-19 (OR 1.36, 95% CI 1.11-1.70).

Overall, Nawrot's group noted that the observed effects of air pollution exposure was "roughly equivalent to the effect on hospitalization of a 10-year increase in age."

These results build on other findings in studies from across the globe, including England, the U.S., Korea, and China, indicating that the relationship between pollution and COVID-19 outcomes stretches across continents.

"The moment we see the same trend repeating in several locations in the world it kind of suggests that there's a fairly significant link, a statistically significant link. It could be a small impact or a big impact, and that needs to be researched further," according to Yizhou Yu, BSc, of the MRC Toxicology Unit at the University of Cambridge, England, a PhD candidate and coauthor on a prior paper linking regional NO₂, nitrogen oxide (NO) and O₃ and incident COVID-19 in England.

Yu told MedPage Today that the present findings, and the previous research they build on, strengthen the possible association between pollution and worse health outcomes, indicating that reducing air pollution is a crucial part of public health and must be further studied.

In light of these findings, the role that stricter environmental policies might play was highlighted by Jordi Sunyer, MD, PhD, and Payam Dadvand, MD, PhD, of the Universitat Pompeu Fabra in Barcelona, Spain, who emphasized the need to focus on reducing air pollution.

In a linked editorial, they noted that air quality standards worldwide are still above the values that scientists have shown to be harmful, citing as an example the EU's legal standard for particulates being five times higher than recommended by the World Health Organization. "And, even with these rather laxed standards, most cities in the world, including many European cities, still do not meet them," the pair lamented.

Both Danish and Belgian groups both acknowledged their reliance on aggregate air pollution data over broad areas in their attempts to estimate pollution exposure to the individual level.

Danish investigators relied on national model estimates of annual air pollution exposure in 1 km × 1 km neighborhood blocks. Exposure was determined by 2019 estimates and supported by 3-year and 10-year averages.

As for the Belgian study of COVID-positive patients, daily residential exposure to particulate matter was modeled using data spanning 2016 to 2019.

In the Danish study, a negative association between O₃ and COVID-19 was seen for incidence (HR 0.86, 95% CI 0.84-0.89), hospitalization (HR 0.86, 95% CI 0.82-0.91), and death (HR 0.87, 95% CI 0.78-0.96). This may reflect NO₂ and O₃ being traffic pollutants that are negatively correlated: when O₃ is close to major roads and other combustion sources, it reacts with nitric oxide to form oxygen and NO₂, according to Jovanovic Andersen and colleagues.

These researchers noted that there is still more to understand about how pollution might affect viral infection and pathogenesis of COVID-19.

"Exposure to air pollution may promote upregulation of the [ACE2] receptor relevant for viral entry, replication, and assembly, and activate proinflammatory transcription factors, producing local inflammation," wrote Jovanovic Andersen and coauthors. "Furthermore, pollutant exposure reduces mucociliary clearance, promotes epithelial permeability, prevents macrophage uptake, and disrupts natural killer cell function, all of which can increase viral spread and inflammation."