key: cord-341644-egbahelm authors: Benmarhnia, Tarik title: Linkages Between Air Pollution and the Health Burden from COVID-19: Methodological Challenges and Opportunities date: 2020-07-17 journal: Am J Epidemiol DOI: 10.1093/aje/kwaa148 sha: doc_id: 341644 cord_uid: egbahelm The COVID-19 pandemic revealed and exacerbated existing social and economic health disparities and actionable epidemiological evidence is needed to identify potential vulnerability factors to help inform targeted responses. In this commentary, methodological challenges and opportunities regarding the links between air pollution and COVID-19 are discussed with a focus on: i) the role of differential exposure to air pollution across populations and explain spatio-temporal variability of the epidemic spread and resultant mortality; ii) the indirect impacts of interventions treated as natural experiments to control COVID-19 person-to-person spread on air pollution and population health. I first discuss the potential mechanisms between exposure to air pollution and COVID-19 and the opportunity to clearly formulate causal questions of interest through the target trial framework. Then, I discuss challenges regarding the use of quasi-experimental designs that capitalize on the differential timing of COVID-19 policies including the selection of control groups and potential violations of the common shock assumption. Finally, I discuss environmental justice implications of this many-headed beast of a crisis. In this commentary, I will describe some methodological challenges and opportunities regarding these two types of questions based on the literature (some peer reviewed, some not yet) that is available to date. I will focus on etiological questions, keeping in mind that methodological challenges regarding availability, exhaustiveness and validity of data are definitely an underlying issue (5) . Finally, I will briefly discuss other related topics including environmental justice implications of this many-headed beast of a crisis. Mechanisms through which acute exposure to air pollutants, such as fine particles, may impact respiratory health are well documented and include pulmonary inflammation that may reduce lung function through bronchoconstriction or an alteration of the pulmonary immune system (6, 7) . In parallel, chronic exposure to fine particle pollution notably exacerbates chronic inflammation with cellular proliferation and extracellular matrix reorganization (8) and also weakens pulmonary immune response (9) . Several toxicological studies have described such mechanisms (9, 10) and a vast body of epidemiological evidence confirms the role of acute and chronic exposure to various air pollutants on respiratory hospital admissions, e.g. Chronic obstructive pulmonary disease (COPD) (11) or asthma exacerbation (12) . Furthermore, several papers reported that exposure to air pollution exacerbates the severity of various respiratory infections (13) such as influenza (14) and possibly another coronavirus infection the SARS (15) . A recent study found that chronic exposure to PM2.5 and ozone increases the risk of acute respiratory distress syndrome among older adults in the US (16) . Based on this background knowledge, it is conceivable to suggest that exposure to air pollution may influence the variability in the severity of COVID-19 symptoms or contribute to explaining It is also important to re-emphasize that effect modification is differing levels of air pollution. scale dependent and that for such type of public health prioritization efforts, the additive scale has been shown to be preferable (27) . Another potential approach to better understand the air pollution link for COVID-19 symptoms severity would be to focus on alternative outcomes, such as spatio-temporal changes infection fatality rates instead of counts of COVID-19 cases or deaths. This design would better capture how exposure to air pollutants influence variability in symptoms severity or if the probability of dying from COVID-19 in a given population (with detailed information regarding COVID-19 cases and time in the denominator) is influenced by air pollution levels. Of course, getting accurate statistics and accurate numerators and denominators to estimates population attack or infection fatality rates can be an extremely challenging task (5), but hopefully such surveillance data collection will be improving with time. In this context, the target trial framework (28, 29) can be particularly useful when designing a research question regarding the links between exposure to air pollution and COVID-19. The benefits of using the target trial framework to clarify assumptions, causal contrasts and actionable implications has been demonstrated for other topics (30) (31) (32) (33) by clearly specifying the hypothetical manipulation that is intended in the first place. In this pandemic context with limited available data and time-sensitive actionable evidence (34) , dedicating a preliminary phase to clearly identifying the intended hypothetical manipulation and how targeted actions based on background air pollution levels would maximize potential benefits, may be valuable. and the target trial framework can be a suitable tool. The policies (43) . For instance, it may be challenging to identify an appropriate control group that would have a parallel trend for the outcome of interest given that the timing and intensity of policies are strongly correlated with the spatio-temporal variation of the spread of the disease. Indeed, jurisdictions that may first undertake actions to control COVID-19 person-to-person spread may also suffer from earlier and higher rates which motivates such policies. Given the known timing of the disease incubation period and lagged effects (44, 45) , it is likely to initially observe an increase in the counted cases after the implementation of the policy of interest. This highlights the importance of accounting for both pre-trends and lagged expected effects when designing a study to evaluate the health impact of such policies. It has also been shown that anticipation behaviors may take place where people took social distancing precautions before any official restrictions were in place (46) . Several jurisdictions also implemented various policies at the same time and local communities or institutions such as universities may have implemented additional non-official preventive measures. This could potentially lead to violations of the common shock assumption. Furthermore, some spillover effects are expected where the COVID-19 responses may lead to drastic population mobility (47) or where abatement in traffic emissions may impact other jurisdictions across administrative borders. Given these potential challenges, it is particularly important to design an appropriate identification strategy and adopt various sensitivity analyses and falsification tests. Finally, it is also important to emphasize that exposure to air pollution is not random and may intersect with other social determinants of health. Indeed, differential exposure and susceptibility where socio-economic and race/ethnic minorities bear disproportionate burden from air pollution are well documented (53) (54) (55) (56) . Such environmental justice issues are critical and may contribute to explain the reported differential impacts of COVID-19 on race/ethnic communities in the US Occupational health (59, 60) can also provide critical actionable evidence by identifying highrisk workers given that some workplace conditions (e.g. health care providers and caregivers; water and wastewater sector; construction workers…) may increase severity of health outcomes or interact with other risks such as extreme heat (61) . At the same time, other challenges include the capability to manage compound risks regarding extreme weather events such as extreme heat (62) . 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