PFAS are found in multiple everyday products, such as cosmetics, outdoor clothing and coated pans. This is because of their special properties. They are heat-resistant, repel water and grease and are extremely resistant. There are thousands of different PFAS compounds and they are found in the soil, water and in the air where they accumulate for long periods. PFAS enter the human body via food, drinking water or the air we breathe and can then accumulate and affect our health. "PFAS are not acutely toxic. But since we encounter them almost everywhere in our surroundings and can hardly escape them, we are essentially subjected to chronic exposure to them. And this is especially problematic for vulnerable groups such as pregnant women, young children or the chronically ill," says Prof Ana Zenclussen, Head of the Department of Environmental Immunology at the UFZ.
Various studies have linked exposure to PFAS to conditions such as obesity, hormonal disorders and cancer. These forever chemicals can also influence the immune system. It is known from epidemiological studies that PFAS exposure has a negative effect on the development of antibodies following vaccination for SARS-CoV-2. In their current study, the researchers aimed to evaluate whether and how PFAS affect the second arm of the immune system, the so-called cellular immune response. This is especially important in the case of an infection with SARS-CoV-2 in order to protect against severe illness outcomes. "And unlike the case for other viruses, a high antibody titer against SARS-CoV-2 is not necessarily indicative of whether the development of the cellular immune response will be adequate upon encountering the virus," explains Ana Zenclussen. "We are therefore closing an important gap with our study."
For the study, the research team used blood samples from women and men who had been vaccinated against SARS-CoV-2 several times and had already been infected with the virus. The scientists cultured the immune cells contained in the blood samples in the laboratory and exposed them to PFAS for 24 hours. "We used a special mixture that realistically reflects 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 concentration a thousand times higher, which corresponds to the exposure of people who work in the production of PFAS.
Dr Oddvar Myhre from the Norwegian Institute of Public Health in Oslo stresses: “The research emphasizes the importance of using a human-relevant PFAS mixture to understand its complex interactions with the immune system, particularly in the context of vaccination responses. This approach reflects real-world exposure scenarios more closely and helps shed light on the potential health risks associated with PFAS contamination."
Following PFAS exposure, the immune cells were exposed to proteins of the SARS-CoV-2 coronavirus. Can the immune cells previously treated with PFAS still react sufficiently to the virus and fight it? Is the immune response worse or significantly different? The research team led by Ana Zenclussen conducted a detailed immune analysis to answer these questions. They employed spectral flow cytometry, a modern method that enables identification, quantification and analysis of multiple immune cell types in a single measurement step. The functionality of the respective cell types can also be determined by measuring the messenger substances released.
In comparison with the unexposed samples, two immune cell types released more inflammatory mediators in response to SARS-CoV-2 proteins in the samples that had previously been exposed to elevated PFAS concentrations. "This suggests an excessive immune response," explains Ana Zenclussen. "It is interesting that this effect was especially pronounced in the immune cells of the male study participants." The situation was different for the female study participants. In this case, proportionally fewer B cells were present following increased PFAS exposure. B cells are immune cells that are crucial for the development of antibodies and long-term immunity. "The fact that high PFAS exposure affects the immune system differently depending on the biological sex is an important result that should be investigated more thoroughly in further studies," says Zenclussen.
The production of immune soluble mediators that play a key role in attracting further immune cells or in wound healing, was negatively affected in both sexes. "Our results show that exposure to high PFAS concentrations clearly alters the immune response to SARS-CoV-2 and may reduce its effectiveness," says Ana Zenclussen. "This could mean that people who are highly exposed to PFAS have a higher risk of poor disease progression or may respond less well to vaccinations. This is important information to adapt and individualise vaccination strategies."
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 Vaccines; Environment International; https://www.sciencedirect.com/science/article/pii/S0160412025001606?via%3Dihub
Further information
Prof Dr Ana Zenclussen
Head of UFZ Department of Environmental Immunology
ana.zenclussen@ufz.de
Dr Oddvar Myhre
Norwegian Institute of Public Health
Oddvar.Myhre@fhi.no