PFAS Influence Cellular Immune Response to Coronavirus

Per- and polyfluoroalkyl substances (PFAS) are ubiquitous, accumulate in the environment, and are difficult to break down. They are referred to as "forever chemicals." PFAS can impair the immune system and human health. Researchers at the Helmholtz Centre for Environmental Research (UFZ) show in their current study that high PFAS exposure negatively affects the cellular immune response to the coronavirus SARS-CoV-2. People exposed to high levels of PFAS may respond less well to vaccinations, the scientists suspect. The study was conducted in close cooperation with the Norwegian Institute of Public Health in Oslo and has been published in the journal Environment International.

*PFAS seem to play a role not only in the development of various civilization diseases but also influence the cellular immune response to the coronavirus. Photo: ©angellodeco / AdobeStock*

PFAS are incorporated into many everyday products, such as cosmetics, outdoor clothing, or coated pans. This is due to their special properties. They are heat resistant, water- and grease-repellent, and extremely durable. There are thousands of different PFAS compounds. They can be found in soils, waters, and air. They enter the human body through food, drinking water, or inhaled air, where they accumulate and can affect our health. "PFAS are not acutely toxic. This is particularly problematic for vulnerable groups such as pregnant women, small children, or chronically ill patients," says Prof. Ana Zenclussen, head of the Department of Environmental Immunology at UFZ.

Exposure to PFAS has been linked in various studies to obesity, hormonal disorders, or cancer. They can also affect the immune system. Epidemiological studies have shown that PFAS negatively impact the development of antibodies following vaccination against SARS-CoV-2. With their current study, the researchers aimed to find out whether and how PFAS affect the second axis of the immune system, known as the cellular immune response. This response is particularly important in protecting against severe disease progression when infected with SARS-CoV-2. "Unlike other viruses, a high antibody titer against SARS-CoV-2 in the blood does not necessarily indicate that the development of the cellular immune response was adequate," explains Ana Zenclussen. "Thus, our study fills an important gap."

For their study, the research team used blood samples from women and men who were vaccinated multiple times against SARS-CoV-2 and had already experienced an infection with the virus. The immune cells contained in the blood samples were cultured in the laboratory and exposed to PFAS for 24 hours. "For this, we used a specific mixture that realistically represents the PFAS exposure of the European population," explains Ana Zenclussen. The PFAS mixture was developed by the Norwegian cooperation partners based on a large cohort study. In addition to a realistic PFAS concentration, the researchers also exposed the immune cells to higher concentrations of the PFAS mixture in further experiments – up to a thousand-fold increased concentration, which corresponds to the exposure of people working in the PFAS manufacturing sector.

Dr. Oddvar Myhre from the Norwegian Institute of Public Health in Oslo emphasizes: "To understand the complex interactions with the immune system, especially in relation to the response to vaccinations, it was essential to use a PFAS mixture that is relevant to humans. This approach accurately reflects real exposure scenarios and thus helps clarify the potential health risks associated with PFAS contamination."

Following PFAS exposure, the immune cells were exposed to components of the SARS-CoV-2 coronavirus. Can the immune cells previously treated with PFAS still respond adequately to the virus and combat it? Or is the immune response worse or markedly different? To answer these questions, the research team led by Ana Zenclussen conducted a detailed immune analysis. They used a method called spectral flow cytometry – a modern technique that allows for the identification, quantification, and analysis of the immune cell types contained in a sample in a single measurement step. It can also determine the functionality of the respective cell types by measuring secreted signaling molecules.

Compared to the untreated samples, two immune cell types in the samples exposed to elevated PFAS concentrations secreted pro-inflammatory signaling molecules in greater quantities. "This indicates an exaggerated immune reaction," explains Ana Zenclussen. "Interestingly, this effect was particularly observed in the immune cells of male study participants." For female study participants, a different picture emerged. Here, after increased PFAS exposure, relatively fewer B cells were present. B cells are immune cells that are crucial for developing antibodies and establishing long-term immunity. "That high PFAS exposure affects the immune system differently depending on gender is an important finding that should be further investigated in future studies," says Zenclussen.

For both genders, the production of signaling molecules important for the immune response, which are critical for attracting additional immune cells or wound healing, was generally downregulated. "Our results show that exposure to high PFAS concentrations alters the immune response to SARS-CoV-2 and may reduce its effectiveness," says Ana Zenclussen. "This could mean that people with high PFAS exposure may have a higher risk of adverse disease progression or respond less effectively to vaccinations. "

Publication:
H.S. Ayuk, A. Pierzchalski, T. Tal, O. Myhre, B. Lindeman, V. Stojanovska, A. Zenclussen: Evaluating PFAS-Induced Modulation of Peripheral Blood Mononuclear Cells (PBMCs) Immune Response to SARS-CoV-2 Spike in COVID-19 Vaccinees; Environment International; https://www.sciencedirect.com/science/article/pii/S0160412025001606?via%3Dihub

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