Environmental Pollutants PM2.5, PM10, Nitrogen Dioxide (NO2), and Ozone (O3) Association with the Incidence of Monkeypox Cases in European Countries

Background Monkeypox, also known as monkeypox disease, is caused by the monkeypox virus (MPXV), which is a zoonotic infection. The swift spread of human monkeypox cases has caused an alarming situation worldwide. This novel study aimed to investigate the association of particulate matter air pollutants PM2.5, PM10, Nitrogen dioxide (NO2), and Ozone (O3) on the incidence of monkeypox cases from May 1, 2022, to July 15, 2022. Methods The data on air pollutants PM2.5, PM10, NO2, and O3 and monkeypox cases were recorded from the date of occurrence of the first case of monkeypox in the United Kingdom, Spain, France, Germany, Italy, the Netherlands, Switzerland, and Portugal from May 1, 2022, to July 15, 2022. The daily concentrations of PM2.5, PM10, NO2, and O3 were recorded from the metrological website “Air Quality Index-AQI,” and daily human monkeypox cases were recorded from the official website of “Our World in Data.” The mean values along with simple, multiple, and Spearman Rho correlations were performed to investigate the relationship and strength of association between the concentrations of air pollutants and cases of monkeypox. Results The environmental pollutants PM2.5, PM10, NO2, and O3 were positively associated with monkeypox cases in the United Kingdom, Spain, France, Germany, Italy, the Netherlands, Switzerland, and Portugal. The analysis further revealed that for each 10-unit increase in PM2.5, PM10, and NO2, levels, the number of monkeypox cases was significantly augmented by 29.6%, 9.7%, 13%, and 80.6%, respectively. Conclusions Environmental pollutants PM2.5, PM10, NO2, and O3 have been positively linked to the number of daily monkeypox cases in European countries. Environmental pollution is a risk factor for the increasing incidence of monkeypox daily cases. The regional and international authorities must implement policies to curtail air pollution to combat the cases of monkeypox in European countries and worldwide.


Introduction
Te human monkeypox disease is caused by the monkeypox virus (MPXV), which is a zoonotic infection most commonly found in African countries. Te MPXV belongs to the "genus Orthopoxvirus, subfamily Chordopoxvirinae and family poxviridae" [1,2]. Te monkeypox virus was found for the frst time in 1958 after the occurrence of a pox-like ailment in monkeys, which were housed in the research institute in Copenhagen, Denmark. Hence the disease endemic 07 African countries and 40,971 cases from 87 nonendemic countries in Europe, North and South America, Australia, and Asia [8]. On July 23, 2022, the World Health Organization (WHO) declared the monkeypox outbreak to be a global public health emergency of worldwide concern [9]. Te swift spread of monkeypox cases has caused an alarming situation globally [10]. Te possible routes of transmission of MPXV are animal-to-human and humanto-human. Respiratory droplets, direct or indirect contact with body fuids, skin lesions of an infected person, and contaminated surfaces in a patient's environment have been associated with interhuman transmission [2,[11][12][13].
Te world is witnessing that viral infections have a transmission linkage with environmental conditions. Since December 2019, the transmission of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been highly associated with exposure to environmental pollutants [14,15]. Te science community has been trying to identify a possible linkage between the spread of human monkeypox cases and its association with environmental pollution. Tis study is aimed at investigating the association between environmental pollutants PM2.5, PM10, CO, O 3 , and NO 2 and daily cases of monkeypox disease in European countries.

Materials and Methods
Te present study was conducted in the "Department of Physiology, College of Medicine, King Saud University, Riyadh, Saudi Arabia." Tis study investigated the association of four environmental pollutants, namely particulate matter PM2.5, PM10, NO 2 , and O 3 , in eight countries in Europe and their association with monkeypox cases. Te eight selected European countries were the United Kingdom, Spain, France, Germany, Italy, the Netherlands, Switzerland, and Portugal ( Figure 1). Te daily number of cases and concentrations of environmental pollutants in these countries were recorded from May 1, 2022, to July 15, 2022.

Measurements of Air Pollutants and Monkeypox Cases.
Data for the daily number of monkeypox cases were recorded from the ofcial website of "Our World in Data, 2022" [16]. Te daily concentrations of PM2.5, PM10, NO 2 , and O 3 were obtained from the metrological website, "Real-Time Air Quality Index-AQI" [17]. Te data was obtained starting from the frst case of human monkeypox in these regions (May 1, 2022) to July 15, 2022. Te research team members visited the metrological website "Air Quality Index-AQI" and found day-to-day detailed information on air pollutants. AQI provided information about measurement protocols. Air pollutants were measured hourly over 24 hours each day. Te AQI monitoring stations used high-tech laser particle sensors to measure real-time environmental pollution. One investigator obtained day-to-day information on air pollutants, PM 2.5, PM 10, NO 2 , and O 3 concentrations, from the metrological websites ("Air Quality Index-AQI, 2021"). Also, another research team member checked the data on air pollutants daily concentration. Te same research team members also recorded the human monkeypox daily cases from the ofcial website of "Our World in Data." However, for the confrmation of the data, another research team member rechecked the monkeypox cases in European countries.

Statistical Analysis.
Te results were analyzed using the "SPSS software version 22.0 for Microsoft windows." Te mean and SEM values were calculated using a paired sample t test. Te linear and multiple regression analyses were performed to model the association of the air pollutants PM2.5, PM10, NO 2 , and O 3 on the number of monkeypox day-to-day cases. Te Spearman-Rho correlation was also used to assess the relationship, strength, and direction of the correlation between the pollutants and monkeypox cases. A p value <0.05 was considered statistically signifcant.

Ethical Statement.
For this study, the data on the daily new cases of human monkeypox and particulate matter PM2.5, PM10, CO, NO 2 , and O 3 -related information were obtained from publicly available databases; hence, ethical approval was not required.
Te country with the second highest overall levels of air pollutants was the United Kingdom, with PM2.5 (68.0 ± 3.1), PM10 (27.8 ± 1.4), NO 2 (39.6 ± 1.2), O 3 (22.4 ± 0.7), and mean monkeypox cases were (64.0 ± 12.7). However, the lowest levels of air pollutants and lowest number of cases were found in Switzerland, where PM2.5 was (2.3 ± 0.1), PM10 was (15.2 ± 0.9), NO 2 was (8.9 ± 0.3), and O 3 was (34.0 ± 0.9), and monkeypox cases were (5.8 ± 1.0) ( Table 1). Te air pollutants and monkeypox cases data for other countries including Germany, France, the Netherlands, Italy, and Portugal, are also presented in Table 2. Table 2 shows the combined mean values for air pollutants PM2.5, PM10, NO 2 , and O 3 , and monkeypox cases in the United Kingdom and the European continental countries ( Figure 1). Te highest overall concentration of all air pollutants, PM2.5, PM10, NO 2 , and O 3 was found in Spain (45.0), which had the highest mean number of monkeypox cases (101.3). Furthermore, the overall combined lowest level of all air pollutants, PM2.5, PM10, NO 2 , and O 3 was found in Switzerland (15.1) with the lowest mean number of monkeypox cases (5.8) during the study period (  (13.5). Te correlation coefcient was signifcant between the air pollutants and cases (p � 0.329).
A simple regression analysis was used to determine the efects of PM2.5, PM10, NO 2 , O 3 , and levels on monkeypox cases. Te simple regression analysis results indicated that PM2.5 (p < 0.001), PM10 (p < 0.001), NO 2 (p < 0.05) and O 3 (p < 0.03) had a signifcant relationship with the number of daily monkeypox cases in the European countries ( Table 3). Furthermore, multivariate regression analysis indicated that PM2.5 (p < 0.001) and O 3 (p < 0.002) each had a signifcant efect on the number of daily monkeypox cases. Terefore, in both simple and multiple regression analyses, the results indicated that both PM2.5 (p < 0.001), and O 3 (p < 0.002) had a signifcant efect on the number of daily monkeypox cases in European countries (Table 3).
In addition to simple and multiple linear regression analysis, Spearman's "Rho" correlation was executed to assess the strength and direction of the relationship between the air pollutant concentrations and the number of monkeypox cases. Te Rho correlation analysis results are presented in Table 4. Te results show that PM2.5, PM10, and NO 2 had a signifcant linkage on the number of monkeypox cases PM2.5 (p < 0.001), PM10 (p < 0.001), and NO 2 (p < 0.001) (Table 4). However, O 3 was borderline associated with an increased number of monkeypox cases (p � 0.06) ( Table 4). Te overall results reveal that the environmental pollutants PM2.5, PM10, and NO 2 had a signifcant relationship with increased monkeypox cases (Table 4).

Discussion
Te swift spread of human monkeypox viral infection has caused a challenging situation of global concern [10]. Te present study explores the association of environmental pollutants PM 2.5, PM10, O 3 , and NO 2 with the prevalence of monkeypox cases in European countries. We noted that PM2.5, PM10, O 3 , and NO 2 were signifcantly associated with the number of monkeypox cases in eight European countries. Tis study also provides an understanding of the relationship between environmental pollutants and the occurrence of monkeypox cases.
Te microorganisms, including bacteria, bacterial spores, viruses, and yeast are spread from infected patients to  the inanimate environment, particularly to areas adjacent to patients and surfaces frequently touched by hands which we designate as "high-touch surfaces" [18]. Human MPXV transmission happens in two ways: either from animal to human or human to human. Monkeypox can spread from person to person through contact with an infected person's lesions or scabs that may be found on the skin or mucosal surfaces. Aerosol transmission has been demonstrated between animal populations [19]. Moreover, contact with an ill patient's respiratory droplets, secretions, lesion materials, body fuids, and polluted personal objects can contaminate the environment and result in the virus spreading among people [20]. Te incubation period of human monkeypox diseases is about 7 days, ranging from 3-20 days [21]. Te pox virus can remain active on linens, clothing, and environmental surfaces, particularly in dark, cool, and low-humidity environments. Te virus can be contagious for about 15 days, and other closely related orthopoxviruses can persist in an environment similar to a household for weeks or months. Te porous materials, bedding, and clothing may harbour the virus for longer periods than nonporous materials such as plastic, glass, and metal surfaces [22].
In the preprint literature (ahead of peer review) Susan et al. [23] reported that the monkeypox virus DNA lies on surfaces in hospitals and households. Te monkeypox virus was found in air and dust samples that were collected during a bed linen change in rooms used to isolate monkeypox patients. Te authors found widespread MPXV DNA contamination of the environment occupied by the infected and symptomatic individuals. Lin et al. [24] demonstrated that to control the spread of monkeypox disease in various regions or states, it is important to implement preventive and control measures for the isolation of patients and the appropriate disposal of pollutants. Tis study highlights the signifcance of pollutants which may spread diseases.
Tere is no available literature that can demonstrate the impact of particulate matter air pollutants on the incidence of monkeypox cases. To our knowledge, this is the frst reported study to establish a relationship between air pollutants and the increasing number of monkeypox cases in European countries. It is worthwhile to consider the role of air pollutants in the spread of the SARS-CoV-2 virus during the COVID-19 pandemic. Te SARS-CoV-2 virus is transmitted through various air pollutants. Te medical literature indicates that environmental pollutants, including MP2.5, PM10, CO, NO 2 , and O 3 , can contribute to the spread of SARS-CoV-2 disease. Studies published from various regions of the globe including the United States of America [25], the United Kingdom [15], Italy [26], Saudi    Journal of Tropical Medicine Arabia [27], and India [28], all have established a link between environmental pollution and an increased incidence of SARS-CoV-2.
Te present study analysis demonstrates the strong infuence of levels of particulate matter concentrations, positively associated with the number of daily cases of monkeypox in eight European countries. In the present study, it was identifed that monkeypox cases were linked to some air pollutants (PM2.5, PM10, NO 2 , and O 3 ) in eight diferent countries in Europe. Te study fndings favour the hypothesis that environmental pollutants are associated with increased daily cases of monkeypox in various countries.

Pathway between Air Pollutants and the Spread of Monkeypox Cases.
Tis study has established plausible pathways to understand the relationship between increased air pollutants and increased cases of monkeypox in European countries. Te monkeypox virus is inanimate but can be carried by air, dust, fne particles, ultrafne particles, and Earth substances. Environmental pollutants can carry the infected particles from surfaces and transport them over a long distance. Once the substances contaminated with monkeypox enter the environment, they can come into close contact with humans, enter the body, and infect people. Te present study fndings provide evidence that air pollutants can transport vectors for the monkeypox virus, promote viral entry into the body, and cause infection. Tese mechanisms are consistent with the hypothesis that air pollutants have resulted in an increased number of monkeypox cases in European countries.

Study Strengths and Limitations
Tis is the frst novel study investigating the relationship between air pollutants and the number of monkeypox cases in European countries. Te levels of air pollutants "PM2.5, PM10, O 3 , NO 2 , and monkeypox cases were temporally documented from the appearance of the frst case of human monkeypox in eight European countries from May 1, 2022, to July 15, 2022. Tis study's fndings established an association between environmental air pollutants and monkeypox cases. Tis study also has a few limitations. Te frst limitation of this study is that we were unable to collect the data for other pollutants, which may also be linked to affecting the dynamics of the monkeypox cases. Another limitation is that the number of monkeypox cases can fuctuate for reasons besides environmental pollutants. Tese reasons could include temperature, humidity, changes in societal patterns, gatherings, or noncompliance with preventive measures.

Conclusions
Te levels of environmental pollutants, PM2.5, PM10, NO 2 , and O 3 were signifcantly associated with an increased incidence of monkeypox cases in European countries. Tis is the frst novel study that has established a linkage between air pollutants and monkeypox cases. Tese fndings send a vital message to health authorities both at regional and global levels: take immediate measures to minimize environmental pollution to combat monkeypox disease.

Data Availability
Data may be provided on reasonable request to the corresponding author.

Ethical Approval
Te data were obtained from publicly available websites; hence ethical approval was not required.