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Covid-19: a puzzle with many missing pieces

BMJ 2020; 368 doi: (Published 19 February 2020) Cite this as: BMJ 2020;368:m627

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Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2)

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Re: Air pollution and Covid19: how to compose the puzzle

Dear Editor
Dear Editor
In Italy, the debate on Covid-19 has been extended to its possible link with air pollution, above all due to the high concentration of Covid-19 in the Po Valley, which is recognized as one of the most polluted large geographical areas in Europe. A BMJ rapid-response letter on February 26 2020, in response to a previous one published on 19 February 2020 (BMJ 2020;368:m627), had already urged for studing exposure–response relationship between air pollutant concentrations and Covid-19 cases during the current outbreak.

Covid-19 affects many organs of the human system, including the upper respiratory tract and lungs.
Of the 5,542 deaths in Italy due to Covid-19, 7 out of 10 were male, the majority were elderly (median age 78 years), compared to a median of 63 years of live patients with positive test [1].
The medical records of 514 deceased patients show that over two thirds had two or more diseases: ischemic heart disease (24.5%), hypertension (74.7%), renal failure (23.2%), diabetes (30.5%), and COPD (19.1%). There is an increasing focus on the comorbidity in terms both of managing Covid-19 patients and not slowing down the prevention and treatment of comorbidities.
Most of the diseases involved, especially respiratory and cardiovascular diseases, have also been shown to be associated with exposure to air pollution [2].
These findings have undoubtedly increased the public concern, largely amplified by media and social media, and the need to investigate the relationship between diseases, pollution and Covid-19.
To contribute to knowledge advancement, study proposals should take into account the strength of the evidence on environment-health relationships and the potential link with Covid-19.
Evidence of a causal link between air pollution and many diseases are robust [3], with estimates of disease risk and premature death from various causes [4-7].
Evidence that long-term exposure to atmospheric particulates decreases the body's defences against bacterial and viral pathogens appear sufficient, particularly by altering the response of bronchial epithelial cells via inflammatory processes and endothelial dysfunction, and exacerbating the conditions of chronically ill patients, particularly those with COPD and asthma [8-14], and children with acute respiratory infections [15].
Knowledge concerning how atmospheric particulates facilitate the transport of pathogens is weaker [16 – 20], and needs to be strengthened.
Assessing the effects of air pollution on the spread of COVID-19 is challenging as it entails considering all of, or at least the main, local conditions relating to air quality trends, the characteristics of the resident communities, the pre-existing state of health and co-factors linked to both pollution and diseases (e.g. age and socio-economic conditions), and possibly also information on the adopted Covid-19 containment measures and indicators of a decrease in ordinary disease prevention and control during the critical phase. In the dramatic current phase, we believe that this is not the time for ecological studies, involving work and resources, leading to the classic conclusion "further studies are needed". Instead, studies with etiological design to investigate the influence of pollution on Covid-19 and on other related recognized diseases should be carried out. Such studies should take into account the trend of Covid-19 indicators and of the concentration of air particulates in the epidemic period, as well as the related (confounding) factors. These studies should be carried out on small geographical areas or, where possible, by individual residential data.
This type of study is complex, requiring the collaboration of many disciplines - other than environmental epidemiology. The Italian Environment and Health Network funded by the Ministry of Health (RIAS project) should also be involved, as it brings together the principle actors operating in the health field and in the national system of environmental agencies Non-profit associations and citizen’s committees should also be included, thus giving full meaning to the concept of citizen science, which is often lauded but rarely practiced.
Our institutes have presented a proposal to the National Research Council to study the relationship between air pollution and viral transmission in the human population, exploiting the current information on health flows and integrating them with the spatial and temporal modeling of data on concentrations of air pollutants, obtained both from terrestrial monitoring stations and from satellite models. By comparing different geographical areas and taking into account all the confounding factors, our aim is to provide key evidence on whether air pollution facilitates viral transport and thus inter-human contagion.
In support of the Covid-19 containment measures established by law, while we wait to begin the research investigations, we aim to promote recommendations regarding environmental and individual risk factors. In addition to maintaining the high focus on outdoor pollution, given the amount of time spent in the home, tobacco smoke - the greatest risk for the respiratory system - should be avoided or at least limited, and all environments should be adequately ventilated.

Fabrizio Bianchi (PhD, epidemiologist) 1 and Fabio Cibella (MD, epidemiologis) 2
1 Environmental Epidemiology Unit, Institute of Clinical Physiology, National Research Council, Pisa, Italy
2 Institute for Biomedical Research and Innovationa, National Research Council, Palermo, Italy

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4. Schraufnagel DE, Balmes JR, Cowl CT, De Matteis S, Jung SH, Mortimer K, Perez-Padilla R, Rice MB, Riojas-Rodriguez H, Sood A, Thurston GD, To T, Vanker A, Wuebbles DJ. Air Pollution and Noncommunicable Diseases: A Review by the Forum of International Respiratory Societies' Environmental Committee, Part 2: Air Pollution and Organ Systems. Chest. 2019 Feb;155(2):417-426. doi:10.1016/j.chest.2018.10.041
5. Chen S, Bloom DE. The macroeconomic burden of noncommunicable diseases associated with air pollution in China. PLoS One. 2019 Apr 18;14(4):e0215663. doi: 10.1371/journal.pone.0215663
6. Campbell-Lendrum D, Prüss-Ustün A. Climate change, air pollution and noncommunicable diseases. Bull World Health Organ. 2019 Feb 1;97(2):160-161. doi:10.2471/BLT.18.224295
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16. Khare P, Marr LC. Simulation of vertical concentration gradient of influenza viruses in dust resuspended by walking. Indoor Air. 2015 Aug;25(4):428-40. Alonso et al. Concentration, Size Distribution, and Infectivity of Airborne Particles Carrying Swine Viruses. PLoS One. 2015 Aug;25(4):428-40.
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18. Chen G, Zhang W, Li S, Williams G, Liu C, Morgan GG, Jaakkola JJK, Guo Y. Is short-term exposure to ambient fine particles associated with measles incidence in China? A multi-city study. Environ Res. 2017 Jul;156:306-311. doi:10.1016/j.envres.2017.03.046.
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Competing interests: No competing interests

28 March 2020
Fabrizio Bianchi
Director of research
Cibella Fabio
Environmental epidemiology unit, Institute of Clinical Physiology, National Research Council, Pisa, Italy