How long-term metal and lead exposure among foundry workers affect COVID-19 infection outcomes in Jordan.

Foundry workers face a number of occupational health hazards, which may lead to an increased risk of respiratory disease, cancer, and anxiety level and are associated with endocrine, hematologic, renal, and neurological problems in humans. This study aims to evaluated thyroid functions, glutathione level, and the risk of infection with SARS-CoV-2 after vaccinated (two doses of the BNT162b2 mRNA COVID-19 vaccine) foundry workers in Jordan. We examined the efficacy BNT162b2 vaccine by calculating the rate of mortality and the degree of severity from mild to severe respiratory infections in 105 adult males foundry workers occupationally exposed to metals and Pb who had been received two doses, 21 days apart, of the BNT162b2 vaccine. Seventy-five male subjects not exposed to the Pb and who received two shots of the BNT162b2 vaccine (Pfizer-BioNTech) served as the control group. In foundry workers who were infected with COVID-19, the mortality rate (0%) was similar as in the control group (0%), and increased transmission of infection with SARS-CoV-2; the non-hospitalized infections increased nearly 3.4-times and hospitalized infections increased 4.29-times among people exposed to lead and metal contamination compared to the healthy persons control group. Also, among the foundry workers, the blood lead, FT3, and FT4 levels were significantly higher (p < 0.0001) and the levels of glutathione and TSH were significantly decreased (p < 0.0001) compared with the control group. In conclusion, long-term exposure to Pb is associated with a risk of infection with COVID-19 despite the 2 doses of the BNT162b2 vaccine (Pfizer-BioNTech). Also, exposure to Pb is associated with hyperthyroidism and a reduction in glutathione.

Introduction

New and unexplored topics relatively continue to emerge in environmental and sustainability, such as the factors that determine the spread of the 2019 novel coronavirus disease (COVID-19), which produces severe respiratory disease and causes global many people died. Multiple studies have shown that there may be a relationship between an unsustainable environment with severe air pollution and the spread of COVID-19 (Coccia 2020, 2021a, 2021b). In particular, people living in areas with high levels of air pollution are at high risk of developing respiratory diseases, as the mixing of particulate matter with infectious pathogens such as SARS-CoV-2 can negatively affect (Coccia 2020; He et al. 2020). In fact, scientists point out that high levels of air pollution increase the viral infectivity and morbidity and mortality of the COVID-19 (Gupta et al. 2021). Scholars assert that air pollution can be one of the factors that determines the spread of COVID-19 in society. In addition, climatic, environmental, demographic, and geographic factors also affect (Bashir et al. 2020; Coccia 2021b). Several studies have found that the disease spreads more in densely populated urban areas, possibly due to higher rates of social contact between infected and uninfected individuals (Khavarian-Garmsir et al. 2021).

A foundry is a factory that produces metal castings. This involves melting and liquefaction of metals to form molten metal, which is then poured into a mold, with impurities removed from the mold by cooling, and the metal ultimately becomes solid (Ribeiro and Filho 2006). Foundry workers during these operations are exposed to many hazardous substances. These included particulate matter and metals, polycyclic aromatic hydrocarbons (PAH), high heat, silica, and machinery, and even exposure to lead through inhalation or ingestion (Palda 2003). Exposure to these metals leads to an imbalance between oxidants and antioxidants and might mediate the formation of a state of oxidative stress, as the levels of the lipid peroxidation marker malondialdehyde (MDA) increase and the activity of the enzyme glutathione (GSH) decreases (Liu et al. 2009).

Long-term exposure to air pollution has been hypothesized to worsen COVID-19 outcomes because the pollution may be suppressing the early immune responses to infection (Conticini et al. 2020; Hu et al. 2021). Many studies have shown the relation between long-term exposure to air pollution and COVID19 mortality (Cole et al. 2020; Liang et al. 2020). Furthermore, most studies on cumulative deaths were before the vaccination process and in the early stages of the epidemic (Cole et al. 2020; Liang et al. 2020; Travaglio et al. 2021). A major question that arises is how long exposure to metal pollution, especially lead, can affect the diffusion of COVID-19 in foundry workers vaccinated with two dose of COVID-19 vaccine. Therefore, this study aimed to investigate the effect of long exposure to metal pollution, especially lead, on the mortality, infection rate, and the risk of infection with SARS-CoV-2after taking the second dose of Pfizer–BioNTech vaccine; in addition, we studied the effects of long exposure to metal pollution on thyroid functions and glutathione level.

Materials and methods

This study was conducted from July 2021 to January 2022. The study population consisted of 180 men who received two doses of the BNT162b2 messenger RNA vaccine within July 2021 (Pfizer-BioNTech) who did not undergo thyroid surgery or receive any form of thyroid treatment.

These participants were classified into two main groups. Group 1: Including 105 (men) foundry workers (n = 105) with a mean age of 38.7 ± 7.06 years who worked in non-ferrous metal foundry for 18 ± 6.3 years in Amman, Jordan. Group 2: Including healthy men (n = 75) with a mean age of 39.4 ± 5.04 years who did not live in areas close to factories in Amman, Jordan, and not worked in non-ferrous metal foundry as control group (Table 1).

Table 1

Basic demographic data

Variable	Foundry workers (n = 105)	Healthy people (control) (n = 75)
Age	38.7 ± 7.06	39.4 ± 5.04
Gender	100% male	100% male
Duration in work in non-ferrous metal foundry plant	18 ± 6.3 years	Not worked in non-ferrous metal foundry
Smoker	44 (41.9%)	30 (40%)
Nationality	Jordanian	Jordanian

The health records for 7 months after vaccination for all the population study were used to evaluate the following outcome measures for COVID-19: infection rates (symptomatic), hospitalization rates, and mortality rates. Simple descriptive statistics were used to calculate the percentage of patients with symptomatic infection, requiring hospitalization, or dying as a result of COVID-19.

The blood samples from each foundry worker (n = 105) and from control group (n = 75) were collected when starting this study using a dry plastic disposable syringe and divided into two parts: the first part (3 ml) was collected into K2EDTA tubes for blood of lead level (BLL), glutathione (GSH) evaluation, the second part (3 ml) was collected into serum vacationer tubes for measurements thyroid-stimulating hormone (TSH), free T4 (FT4), and free T3 (FT3) tests. The BLL, GSH, TSH, FT4, and FT3 level in foundary workers were compared with the control group.

Biochemical analysis

Lead in the blood

An inductively coupled plasma mass spectrometer Agilent ICP-MS (7700 series, Agilent Technologies, Tokyo, Japan) was used to determine lead levels in blood samples (Nakata et al. 2021). Analytical quality control was performed using the certified reference material of Seronorm™ Trace Elements Whole Blood L-2 (Sero, Billingstad, Norway).

Thyroid blood test

Samples were centrifuged at 3000 rpm for 10 min after at least half an hour. Then, the serum was used for analysis. The measurements of TSH, FT3, and FT4 were conducted by electrochemical luminescence (ECLIA) on Cobas 8000 (Roche Diagnostics, Germany).

Glutathione blood test

GSH was measured following the method described by Beutler et al. (1963) using a kit from Biodiagnostic Co., Egypt. The procedure was described in the insert of the kit.

Statistical analysis

Data analyses were performed using Graph Pad Prism and SPSS programs. Based on normality distribution, variable levels were expressed as mean ± SD. Qualitative data was expressed as absolute numbers. For differences assessments, ANOVA, chi-squared (Χ2), or Kruskal–Wallis tests were appropriately used follwed by LSD as post hoc test. P ˂ 0.05 is significant.

Results

Relative to the control group with a mean age of 39.4 ± 5.04 years (healthy peoples were not exposed to metals pollution and lead), foundry workers (n = 105) with a mean age of 38.7 ± 7.06 years who worked in non-ferrous metal foundry plant for 18 ± 6.3 years, especially lead, had significantly increased in blood level of lead (15.9 ± 1.65 vs. 10.7 ± 1.12 µg/dL; p ˂ 0.0001), FT3 (3.7 ± 1.73 vs. 2.2 ± 0.75 pg/mL; p ˂ 0.0001), and FT4 (1.91 ± 0.49 vs. 1.43 ± 0.49 ng/dL; p ˂ 0.0001), and a significant decreased in TSH (1.72 ± 0.41 vs. 2.5 ± 0.92 mIU/L; p ˂ 0.0001) and GSH (20.85 ± 4.95 vs. 29.01 ± 4.1 mg/dL; p ˂ 0.0001) (Fig. 1).

Fig. 1

The effect of exposure to metal pollution for foundry workers on the level of BLL, GSH, TSH, FT3, and FT4 compared to healthy people who were not exposed to metals pollution

In this study, we monitored both groups (foundry workers and the control population) for COVID-19 infections for 7 months. We show an increase in deaths (0 vs. 0%), non-hospitalized infections (22.85 vs. 6.66%), and hospitalized infections (5.71 vs. 1.33%) respectively (Table 2).

Table 2

All subjects received the two doses from the BNT162b2 messenger RNA vaccine (Pfizer–BioNTech). The percentage (%) of foundry workers and controls who died were not admitted to the hospital and who entered the hospital were recorded during the 6 months after receiving the two doses from the BNT162b2 messenger RNA vaccine (Pfizer–BioNTech)

Foundry workers (n = 105)			Control (n = 75)
Death	Infected, non-hospitalization	Infected, hospitalization	Death	Infected, non-hospitalization	Infected, hospitalization
0 (0%)	24 (22.85%)	6 (5.71%)	0 (0%)	5 (6.66%)	1 (1.33%)

Discussion

Heavy metal fumes are released into the air of non-ferrous alloy foundries during the manufacturing operations, and foundry workers are exposed to them (Peixe et al. 2014). Therefore, blood is used to screen and monitor Pb exposure assessment (Barbosa et al. 2005).

Our study focuses on the percentage of mortality, hospitalization, and non-hospitalization among foundry workers who were infected with SARS-CoV-2 after taking the second dose of BNT162b2 messenger RNA vaccine (Pfizer-BioNTech); the mortality rate was similar (0%) for both foundry workers and control group (0%). Non-hospitalized infections were increased nearly 3.4-times, and hospitalized infections increased 4.29-times foundry workers compared with control group. Exposure to pollutants can lead to immune suppression, which leads to an increase in infections (Woodby et al. 2021). This leads to a worse diagnosis and a wider spread of COVID-19, as recent studies have suggested that PM2.5 can proliferate COVID-19 transmission (Bianconi et al. 2020).

Lead can enhance the number of immunoglobulins by modulating the immune system by targeting the humoral as well as innate immune cells, causing variation in the numbers of lymphocytes, peripheral blood mononuclear cells (PBMCs), and macrophages, as well as impaired responses to mitogens and depression of neutrophil functions (Başaran and Ündeğer 2000; Metryka et al. 2021). Although the mechanism of the Pb effect on the immune system is unclear in humans, many studies have shown that lead can enhance Th2 cell growth and influence Th1 cell proliferation. Therefore, lead can induce differential activation of Th subsets through modulation of antigen density, expression of costimulatory molecules on APC, and modification of APC membrane fluidity (Heo et al. 1996). Lead affects the cellular and humoral immune response and reduces host resistance through the effect of lead on the production and activity of other cells, such as granulocytes and monocytes, regulated by a set of cytokines and nitric oxide (McCabe et al. 1999).

Occupational exposure to metal pollution has been observed to have several adverse health effects based on the intensity and duration of exposure. Several studies have shown that occupational and environmental exposure to heavy metals, such as mercury, cadmium, chromium, arsenic, nickel, and lead, can cause oxidative damage and disrupt various proteins’ activity in the reproductive and endocrine systems (Kim et al. 2004; Patra et al. 2011; Jomova and Valko 2011).

The antioxidants in cells, such as glutathione, which work to remove the toxicity in the cell, strengthen the immune system, and prevent oxidative processes in the body, are depleted due to exposure to toxic metals, especially lead (Patra et al. 2011; Jomova and Valko 2011).

In this study, a significant correlation was observed between the high level of lead in people exposed to lead compared to those not exposed to metal contamination. In addition to the fact that exposure to lead and metal pollution increases reactive oxygen species (ROS) (Patra et al. 2011; Sevcikova et al. 2011), it also leads to a significant deficiency of glutathione. ROS can lead to cell damage through the oxidation of RNA, DNA, proteins, lipids, and other macromolecules, leading to human diseases, including cancers, neurodegenerative disorders, cardiovascular disease, and aging (Cadenas and Davies 2000; Patra et al. 2011). The disulfide bond in the active site of the glutathione reductase interferes with lead, and this enzyme becomes inactive, and hence, this inhibition prevents the production of the reduced form of glutathione, so lead depletes the main antioxidants of cells, increases the production of oxygen species, and causes a state of oxidative stress (Ercal et al. 2001). In this study, we observed a significant decrease in the level of GSH in the blood during exposure to Pb and metal contamination at work.

There was no significant difference for FT4 between groups, while there was a strong relationship (p < 0.001) between FT3 levels and lead exposure (Yılmaz et al. 2012). There was a non-significant decrease in TSH with a strong significance to an increase in FT4 that was observed in workers exposed to Pb (Dursun and Tutus 1999). One study reports a drastic decrease in thyroid function tests in Pb-exposed workers (Wu et al. 2011). Another occupational study showed that Pb-exposed workers had a significant increase in thyroid function tests and decrease in TSH (Fahim et al. 2020). Our study found a significant decrease in TSH and a significant increase in TF3 and FT4 in Pb-exposed workers.

Conclusions

This study finds that long-term exposure to metal pollution and lead in non-ferrous metal foundry may have supported increase both the transmission and risk with COVID-19 infection despite vaccination with the 2 doses of BNT162b2 messenger RNA vaccine (Pfizer-BioNTech). Also, exposure to the pollution is associated with hyperthyroidism and a reduction in glutathione.