covid: air pollution increases risk

 

A Swedish study found that short-term exposure to air pollution was associated with increased Covid incidence (see covid air pollution inc risk JAMA2022 in dropbox, or 10.1001/jamanetworkopen.2022.8109 )

 

Details:

-- the prospective BAMSE birth cohort database in Sweden was linked to their national infectious disease registry to identify PCR-positive SARS-CoV-2 cases from May 2020 to March 2021

    -- BAMSE is a population-based birth cohort including 4089 newborns in 1994-1996, with followup at ages 1,2,4,8,12,16 and 24 (the 2270 participants at the 24-year follow-up were the ones in this study); in August 2020 the study expanded to include Covid-19 follow-up with web questionnaires and a clinical exam.

-- 54% women, median age 25.6 (interquartile range IQR 24.9-26.3), 33% educated to university level, 48% students/45% employed, 23% current smoker, 23% overweight, 31% asthma,

-- covid characteristics: 54% had “any symptoms”: fever 53%, cough 53%, sorethroat 54%, loss of taste or smell 48%, runny nose79%, breathing difficulties 26% [not sure why some of these numbers were greater than the 54% who had “any symptoms”]

-- covid exposures: at home 57%, regularly meeting people during pandemic 74%, use of public transportation 31%

-- air pollution was assessed by the individual's residential address, including an inventory of local emissions from road traffic (exhaust and nonexhaust, the latter including wear particles from studded winter tires, sanding and salting of the road surface, precipitation, etc; for example the contribution from studded tire wear can be 80-90% of the total PM₁₀ levels), residential wood combustion, energy production, industrial processes, off-road machinery and agriculture, etc.

    -- pollutants measured: particulate matter with diameter ≤2.5 µm (PM_2.5), particulate matter with diameter ≤10 µm (PM₁₀), black carbon (BC), and nitrogen oxides (NOx), based on the individuals’ specific residential addresses 

    -- In the regions in Sweden assessed, road traffic was the dominant cause of air pollution 

-- “case day” was defined as the date of the PCR test; this was compared to “control days”which were dates with the same day of the week within the same calendar month and year

-- 425 cases covid were identified

-- the lag time was assessed between the daily air pollution exposure and the subsequent SARS-CoV-2 infection, from 0-7 days

-- demographics in the database included age, sex, educational level, smoking, occupation, BMI, asthma 

-- Main outcomes: confirmed SARS-CoV-2 infection among participants within the BAMSE cohort, assessing the association with particulate matter and black carbon and the lag time from pollutant exposure to SARS-CoV-2 infection

 

Results:

-- median exposure on case days: 

    -- PM_2.5 :  4.4 (IQR 2.6-6.8) 

    -- PM₁₀ : 7.7 (IQR 4.6-11.3) 

    -- BC: 0.3 (IQR 0.2-0.5) 

    -- NOx: 8.2 (IQR 5.6-14.1) 

-- median exposure on control days: 

    -- PM_2.5 : 3.8 (IQR 2.4-5.9) 

    -- PM₁₀ : 6.6 (IQR 4.5-10.4) 

    -- BC: 0.2 (IQR 0.2-0.4) 

    -- NOx: 7.7 (IQR 5.3-12.8) 

 

--for each interquartile increase, short-term exposure was associated with a relative increase of positive SARS-CoV-2 testing: 

    -- PM_2.5 : 6.8% (2.1%-11.8%), with lag of 2 days 

    -- PM₁₀ : 6.9% (2.0%-12.1%), with lag of 2 days 

    -- BC: 5.8% (0.3%-11.6%), with lag of 1 day 

    -- NOx: no association, though a reasonably strong trend, with RR 1.05 (0.97-1.12) 

 

-- no modification of results by taking into account sex, smoking, having asthma, overweight, or self-reported Covid-19 respiratory symptoms 

 

Commentary:

-- air pollution is known to contribute to respiratory infections associated with influenza, SARS, and dengue: hence the likely association with SARS-CoV-2 as well (eg see PM2.5 in Beijing – temporal pattern and its association with influenza | Environmental Health | Full Text (biomedcentral.com) )

-- proposed mechanisms for the association between air pollution and SARS-CoV-2 include: upregulation of proteins critical to viral entry; immune system suppression due to oxidative stress, epithelial damage, and pulmonary inflammation (and the immune dysregulation can be some combination of systemic and locally in the lungs: eg air pollution is associated with cytokine response/systemic inflammation and clinically with higher risk of myocardial infarctions: see http://gmodestmedblogs.blogspot.com/2016/06/air-pollution-and-heart-disease.html 

-- some prior studies on populations have found that pollution is associated with SARS-CoV-2 infections, but one really needs individual data more than community data to determine the actual association (this is called the ecological fallacy: is the relationship between air pollution and covid true for the specific individuals exposed to air pollution? Maybe the ones who got the covid actually had lower air pollution exposure than the average? Eg, maybe these individuals actually had lower pollutant exposure, but were exposed to other toxic chemicals that really caused the increased covid??).

-- there were several findings that supported the conclusion that this relationship between pollutants and covid was from an acute exposure to air pollution, perhaps with altered lung physiology from chronic pollution:

    -- the maximal effects were within 1-2 days after the acute exposure

    -- though there was a pretty high prevalence of asthma (31%) and current smoking (23%), these did not seem to play much of a role in their subgroup analysis

    -- extending the lag interval up to 14 days after the exposure did not alter the results

    -- there was a steeper curve of air pollution-related covid increases in those with lower levels of exposure

-- this study was able to quantify the increased covid risk by acute air pollution, which has been found in several observational studies of groups of people exposed to air pollution

-- a Spanish study of 9605 adults in 2020 found that 18% had SARS-CoV-2 antibodies but  that the incidence of Covid infection was not altered by air pollution (measured by estimated exposure by residential address) as was found in this Swedish study, though the intensity of infection was (see https://ehp.niehs.nih.gov/doi/10.1289/EHP9726 )

 

--one of the important findings of studies like the Swedish one is that it found a pretty clear relationship between air pollution and incidence of Covid, even though the levels of air pollution varied so minimally between the case and control days (all with lots of overlap in the confidence intervals). Finding this mechanistically plausible association provides some insight into the studies finding race/ethnicity to be high covid risk: this study further deflates the issue of race as a significant covid risk factor. the real issue seems not to be so much skin color but social issues that put many of these persons at higher risk (eg, living in inner city neighborhoods with lots of traffic). And, that race is a social construct, not a biological one, but in our society race does elevate important adverse social conditions that predispose people to disease/adverse outcomes

-- another issue is that the covid infections occurred so quickly, with a 1-2 day lag vs the anticipated 4-5 day lag in most studies. What caused this change in viral kinetics? Perhaps this shorter lag time validates the concept that the air pollution creates important immunologic dysfunction leading to faster symptom manifestation. Would be interesting to know the viral loads in those exposed t oair pollutants, or viral replication rates, or specific changes in the virus or host that lead to the faster spread (?epigenetics)…

 

Limitations:

-- though impressive data were collected to be able to justify their conclusions, this was still a young, healthy group. Would these results apply to an older and/or sicker group? What is the interaction between air pollution and age/diabetes or other comorbidities in increasing Covid? would older people with comorbidities have more severe covid infections in the presence of air pollution? (the lack of an association with disease severity in this Swedish stody may well have been because of the healthy young cohort; the Spanish study above suggests that there was increased disease severity in their group, where the mean age was 56 and 35% had a chronic disease)

-- some of their data were not very granular: 23% were smokers (?1 cigarette/week vs 2 packs a day), had asthma (how severe? On meds? Did the meds or level of control matter?), were overweight (?how much, did the BMI level matter?), etc

-- was there a relationship between air pollution and the relative percentage of symptomatic vs asymptomatic Covid? Or the degree of sickness in those who had symptomatic covid?

-- this study involved individual assessment of the various air pollutants. Was there a relationship between the combination of several of them with covid incidence?

-- though there was very specific information on individuals' potential exposure to pollutants, this was not truly individual since it assessed air pollution by the specific area of residence and not by the actual exposure. Were some of the people visiting relatives elsewhere? Or at work where there were perhaps high levels of exposure to other pulmonary toxins? Or indoors in a house with HEPA filters/air conditioners and actually much lower exposure to the pollutants?

-- would be useful to know which of the SARS-CoV-2 variants were involved in the covid  cases, since there could well be important differences in covid risk by variant

-- were  there differences in the relationship between air pollution and covid depending on other community factors, such as population density, numbers of people living in a housing unit, number of smokers at home, use of masks

-- this was not a formal study of community testing but one where data came from individuals who decided to get covid testing. Given the large % who were asymptomatic, it is not possible to generalize these results to the overall community.  Ie, there was a likely selection bias here

 

So, interesting that air pollution had such a significant effect, especially since the levels of air pollution varied so minimally between the case and control days. Which suggests that those exposed to much higher levels of air pollution might have much higher risk of Covid (ie, those living in poorer communities with lots of cars/bus routes, etc.) Which suggests that perhaps a significant component of the observed higher covid risk in people of color may be related to higher air pollution exposure. It was also interesting that the covid test was positive and symptoms present with a lag of only 1-2 days after acute exposure to air pollution: pretty different from the anticipated 4-5 days.

 

geoff

 

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