COVID outcomes worse in polluted cities

More evidence suggests that people exposed to more air pollution during the pandemic are at greater risk for COVID-19 infection, hospitalization, and death, but the exact mechanism behind the link is unknown.

Data from Denmark’s COVID-19 surveillance system, covering 3.7 million residents, showed significant associations between levels of inhalable particulate matter (PM_2.5) and nitrogen dioxide (NO₂) and incident COVID-19. [Eur Respir J 2023;doi:org/10.1183/13993003.00280-2023]

From March 2020 to April 2021, there were 138,742 people infected with SARS-CoV-2 in Denmark, 11,270 of whom were hospitalized, and 2,557 died in a span of 14 months.

“We detected strong associations between long-term exposure to air pollution and contracting SARS-CoV-2 and developing severe COVID-19, resulting in hospitalization and death,” said study author Dr Zorana Jovanovic Andersen, an environmental epidemiologist at the University of Copenhagen, Denmark.

“The association was particularly strong in the lowest socioeconomic groups, which was in part likely explained by indirect impact of lifestyles, such as smoking, obesity, and physical inactivity linked to COVID-19 incidence,” she explained. “Another reason could be the lack of social support, overcrowding, and higher exposure in this population.”

“Enhanced vulnerability to air pollution in large households also likely reflects exposure to higher doses of the virus and higher risk of infection,” Jovanovic Andersen added.

Associations were also strong among patients with chronic respiratory, cardiometabolic, and neurodegenerative diseases.

Longer hospital stays

On average, the length of hospital stays increased by 3–5 days for an interquartile range (IQR) increase of home-outdoor PM_2.5 and PM₁₀ levels during the week before admission, independent of the long-term effects of NO₂ and black carbon (commonly known as soot).

“The magnitude of the increase in the duration of the hospitalization was equivalent to the effect on hospitalization of a 10-year increase in age, and in the order of 40–80 percent of the benefits of the proven novel therapies,” commented Drs Jordi Sunyer and Payam Dadvand in a separate editorial. “This highlights the need for improving air quality in our cities.” [Eur Respir J 2023;doi:org/10.1183/13993003.00818-2023]

“Air pollution abatement through community intervention may protect us from COVID-19 impact, with co-benefits against other respiratory infections,” both experts added.

Testing where data are lacking

Early epidemiological data based on ecological studies (susceptible to confounding) have suggested a link between air pollution and the risk of COVID-19, but evidence from individual-level cohort studies remains scarce. In the study from Denmark, Jovanovic Andersen and her team examined if there’s really a link between the two and which population is most susceptible.

Patients were followed from the day they tested positive for COVID up until hospitalization or death. Cox proportional hazards regression models were used to estimate the link between air pollutants and COVID outcomes, after adjusting for age, sex, socio-economic status, and population density.

PM_2.5, NO_2, and black carbon were all associated with COVID-19 outcomes, but strongest for mortality, with 23 percent and 18 percent higher risks of death for each 0.53 and 3.59 µg/m³ increase in PM_2.5 and NO_2, respectively. No association was found for ozone (O₃).

The results build on findings from another study in Belgium among patients hospitalized for COVID-19. Increased exposure to both PM_2.5 and NO₂ by one IQR in the week prior to hospitalization was associated with increased duration of hospitalization by about 4 days. [Eur J Respir J 2023;doi:org/10.1183/13993003.00309-2023]

An IQR increase of black carbon in the blood was also significantly associated with more intensive care hospitalization from COVID-19 (odds ratio [OR], 1.36).

As in the previous study, “the observed effects of exposure to air pollution on hospitalization duration were roughly equivalent to the effect on hospitalization of a 10-year increase in age,” said the study authors.

More evidence for pollution-COVID link

It appears that the association between air pollution and COVID-19 extends across borders, with a study in China showing positive associations of PM_2.5, PM₁₀, NO₂, and O₃ with COVID-19 confirmed cases. [Sci Total Environ 2020;727:138704]

A 10-μg/m³ increase (lag 0–14) in PM_2.5, PM₁₀, NO₂, and O₃ was associated with a 2.24 percent, 1.76 percent, 6.94 percent, and 4.76 percent increase in the daily counts of confirmed cases, respectively.

Experts said this is likely because highly polluted areas in China are characterized by higher rates of human interaction in the workplace, health and commercial facilities, and a higher volume of international travellers.

Similarly, in a UK study, regional levels of NO₂, nitric oxide (NO), and O₃ correlated with COVID-19 deaths. A small increase in air pollution led to a large increase in COVID-19 infectivity and mortality rate, which could provide a framework guide for both health and emission policies. [Environ Pollut 2021;268(Pt A):115859]

Meanwhile, social distancing measures led to a significant decline in PM_2.5, PM₁₀, NO₂, and carbon monoxide (CO) levels in Korea, which provide a positive effect on air pollution levels in the country through decreased human activities. [Sci Total Environ 2021;750:141521]

More studies needed

The same trend repeating in several sites globally suggests a statistically significant link, said Yizhou Yu, a PhD candidate from the University of Cambridge in Cambridge, UK who was a co-investigator for the UK study. “It could be a small impact or a big impact, but definitely this needs to be studied extensively.”

Although the exact mechanism by which air pollution affects viral infection and COVID pathogenesis remains poorly understood, Jovanovic Andersen said there are several plausible pathways. “Exposure to air pollution may promote upregulation of the angiotensin-converting enzyme 2 receptor relevant for viral entry, replication, and assembly, and activate proinflammatory transcription factors, producing local inflammation.”

She added that 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.