key: cord-0973602-iyt8bhph
authors: Zhao, Channa; Fang, Xinyu; Feng, Yating; Fang, Xuehui; He, Jun; Pan, Haifeng
title: Emerging role of air pollution and meteorological parameters in COVID‐19
date: 2021-05-18
journal: J Evid Based Med
DOI: 10.1111/jebm.12430
sha: 05cac84e21e7064d3ab0aedd0c56d2417f49d230
doc_id: 973602
cord_uid: iyt8bhph

Exposure to air pollutants has been associated with respiratory viral infections. Epidemiological studies have shown that air pollution exposure is related to increased cases of SARS‐COV‐2 infection and COVID‐19‐associated mortality. In addition, the changes of meteorological parameters have also been implicated in the occurrence and development of COVID‐19. However, the molecular mechanisms by which pollutant exposure and changes of meteorological parameters affects COVID‐19 remains unknown. This review summarizes the biology of COVID‐19 and the route of viral transmission, and elaborates on the relationship between air pollution and climate indicators and COVID‐19. Finally, we envisaged the potential roles of air pollution and meteorological parameters in COVID‐19.

The incubation period of COVID-19 is typically 3-7 days (range: 1-5′ and 3′ UTR sequence. 8 Coded proteins include S, envelope (E), membrane (M) and N proteins. 9 Among these proteins, spinous proteins are essential for the binding of virus to host, and mediate the entry of virus into host cells. The spinous process of coronavirus consists of three fractions: a large outer domain, a one-way transmembrane anchor, and a short intracellular tail. The outer domain is composed of receptor binding subunit S1 and membrane fusion subunit S2. 10 Entry of coronaviruses into host cells is a two-step process mediated by the virion spike proteins that modify the virus particles. S1 domain is in charge of receptor binding, S2 domain is in charge of membrane fusion. 11 COVs replication and transcription occur in the cytoplasm of invaded cells and are mediated by replication transcript (RTC). In COVs genome replication, continuous negative RNA synthesis is designed to produce full-length complementary templates, which are then replicated into multiple positive offspring genomes. 12 

SARS-COV-2 infection activates innate and adaptive immune responses, which can lead to immune system damage, such as lymphopenia, lymphocyte activation and dysfunction, abnormal granulocyte and monocyte, high cytokine level and high antibody level. 13, 14 Innate immune cells trigger a series of inflammation. 15 The interaction between SARS-COV-2 and hosts is initiated by the single stranded RNA (ssRNA) and double-stranded RNA (dsRNA) of SARS-COV-2 through the cytoplasmic RIG pattern recognition receptors. 16 PRR senses the viral replication process and forms abnormal RNA structure, and activates IRFs and NF-αβ. 17, 18 Activated PRR triggers cytokine secretion via downstream signal transduction cascades. 16 A large body of clinical evidences suggested critical roles of a wide range of cytokines in the nosogenesis of COVID-19. 19 It has been confirmed that there is an uncontrolled "cytokine storm" in patients with poor prognosis, which is characterized by local and systemic pro-inflammatory factors, including interleukin (IL)−6, tumor necrosis factor-α (TNF-α) and IL-1β. [20] [21] [22] [23] [24] The adaptive immune system is mainly composed of B cells, CD4 + T cells (helper T cells) and CD8 + T cells (cytotoxic or killer cells), which react to pathogens in an antigen-specific way and produce protective immunity. 25 Acute respiratory distress syndrome (ARDS) is an important manifestation of COVID-19. Macrophages participate in epithelial injury during ARDS. 26 When recognizing damage associated molecular pattern (DAMP) or pathogen associated molecular pattern (PAMP) in the process of COVID-19, macrophages are activated via TLRs, NLRP3/inflammasome or triggering cytoplasmic DNA sensors. Subsequent signal transduction stimulates the secretion of cytokines and activates the antiviral gene expression program in adjacent cells. 27, 28 4

The average incubation period of COVID-19 is 6.4 days and could range from 2.1 to 11.1 days. 29 The pathogenesis of SARS-COV-2 infection is akin to that of SARS-COV infection. 30 Nasal epithelial cells are the primary site of SARS-COV-2 infection; lower respiratory tract infection may be caused by inhalation-mediated virus seeding into the lung. 31 Patients infected with SARS coronavirus initially show fever, sore throat, cough, and dyspnea. 32, 33 In addition to respiratory symptoms, some infected patients also have gastrointestinal symptoms, such as stomachache, diarrhea, inappetence, nausea, and vomiting. [34] [35] [36] The gastrointestinal tropism of SARS-COV-2 coronavirus has also been confirmed by biopsy specimens and fecal virus test. 37 AQI: air quality index.

Studies have analyzed the association between COVID-19 and air quality index (AQI), and found that there were significant relationship between air quality and daily new cases, total cases, and mortality [42] [43] [44] [45] [46] [47] [48] ( 

Many studies have examined the association between NO 2 and COVID-19. 66,10-74 NO 2 , an endogenously generated oxidant, has a potential impact on COV19 epidemic transmission. 75 increase in the daily counts of confirmed cases. 49 The causal links between NO 2 and COVID-19 deaths were also verified in India by a study using machine learning method. 51 However, two other studies showed that ground level NO 2 was inversely correlated with COVID-19 infections and the basic reproductive ratio(R 0 ). 71, 78 In an ML experiment by Mele et al, when NO 2 exceeded the threshold level, the number of deaths from COVID-19 increased. 75 Overall, NO 2 renders the respiratory system more susceptible to COVID-19 75 (Table 3 ).

A 10 μg/m 3 increase (lag 0-14) in O 3 was associated with a 4.76%

increase in the daily counts of confirmed cases. 49 Liu et al evaluated the (Table 4 ).

CO and CO 2 24-hour concentrations were positively correlated with R 0 and newly confirmed cases. 47 46 the correlation between CO and daily incidence was positive in Wuhan City but negative in Xiaogan and Huanggang City 64 (Table 5 ).

Study has shown that SO 2 increased the propagation speed of COVID-19 infection, especially in Korea and China. 2 SO 2 is positively correlated with newly confirmed cases and deaths. 47, 63 However, negative associations have also been found. 46 In a study by Zhu et al, the number of confirmed COVID-19 cases reduced by 7.79% with every 10μg/m 3 increase in SO 2 (lag time: 0-14 days). 49 In addition, Jiang et al did not find correlation between SO 2 and daily incidence. 64 In conclusion, SO 2 may also play an important role in the spread of COVID-19 (Table 6 ).

Several studies have shown negative correlation between temperature and daily incidence. 44 (Table 7) . 

Several studies analyzed the effects of relative humidity on COVID-19, but the results are inconsistent. Three studies showed that relative humidity was positively associated with daily new COVID-19 cases and R 0 . 64, 78, 79 The other three studies failed to observe the association between relative humidity and COVID-19 45, 71, 81 ( Table 8) .

Elevated wind speed (m/s) has been associated with increased daily new COVID-19 cases. 79 But several other studies reported opposite findings: mean wind speed was inversely correlated with R 0 coronavirus infection, 45, 78 indicating that higher wind speed may decrease the risk of coronavirus infection because of its ability in clearing the fine particles and modulating the dynamics of various vectors and pathogens (Table 8) .

Increase in the moving average of cloud has also been associated with increased daily new COVID-19 cases. 79 For air pressure, in provinces with medium flow, mean/maximum/minimum air pressure was inversely correlated with R 0 78 (Table 8 ). to the oxidized form (R-S-S-R), which directly prevents the virus from fusing with cells. 115 In addition, through the nuclear factor activated T cells (NFAT) and activated protein 1 (AP-1) signaling pathways, O 3 can stimulate cellular and humoral immunity. 115 

Temperature is implicated through a variety of mechanisms. Firstly, immune system function may be repressed under low temperature.

Cold stress decreases the phagocytic function of pulmonary alveolar macrophages, secretion of proinflammatory cytokines (eg, IL-6, IL-8, IL-10, MCP-1), and the number of neutrophilic granulocytes, 123,124 which in turn are required for SARS-COV-2 clearance. 125 Temperature variation could also influence local immune responses. Exposure to cold air leads and subsequent temperature reduction of the respiratory epithelium compromise local immune responses both in upper airway and nasal mucociliary clearance. 126 Second, patients with existing cardiovascular and/or nervous system diseases have higher risk of developing severe COVID-19. 127 Compared to moderate temperature, cold and heat stress can exacerbate the underlying cardiovascular and nervous system diseases due to increased sympathetic activity and circulation regulation as well as the heat-induced dehydration and systemic inflammation. 128, 129 Lung function could also be jeopardized under low temperature. Previous study suggested the forced expiratory volume in one second was declined in cold environment. 130 Breathing cold air can cause bronchoconstriction and mucus hyper-secretion, which in turn increase the susceptibility to pulmonary infection. 131, 132 A positive correlation has been shown between outdoor tempera- 

The authors declare no conflict of interest.

Haifeng Pan https://orcid.org/0000-0001-8218-5747

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