Efeitos ecotoxicológicos e reprodutivos do SARS-CoV-2: um estudo experimental com implicações para a conservação de espécies terrestres

Abstract

SARS-CoV-2, the etiological agent of COVID-19, is an emerging biological contaminant that has had pandemic repercussions, impacting human society, especially the poorest. It is known that the virus can interact with the environment in ways that are not yet fully understood and that it has negatively influenced the biology of various aquatic organisms. However, the possible impacts that this virus can have on non-target organisms have been little explored, limiting our knowledge of its consequences for biota. To determine the effects of SARS-CoV-2 on terrestrial mammals to anticipate mitigation actions, we evaluated the possible negative impacts associated with exposure to viral lysate on the health and reproductive capacity of sexually maturing female C57BL/6J mice, and whether there was an influence on the health of the offspring. To this end, a two-stage experiment was carried out. The first consisted of exposing pre-reproductive animals (orally) to SARS-CoV-2 lysate (concentration: 20µg viral protein/L) for 30 days. Subsequently, the possible effects of exposure on the behavior of the females were assessed (via the open field test, object recognition test and tail suspension test) and whether there was an induction of mutagenic effects (via the micronucleus test in peripheral blood), genotoxic effects (via the comet assay), hematological and biochemical effects (in the blood and in different organs, using different biomarkers). There were no hematological, mutagenic or genotoxic effects, but there were behavioral disturbances (hypoactivity, anxiety-like behavior and short-term memory deficit), which were associated with oxidative stress and dopaminergic and cholinesterase imbalance in the animals' brains. In addition, the elevation of bilirubin and lactate dehydrogenase levels in these animals suggests liver alterations, and the redox imbalance, nitrosative stress and elevated production of IFN-γ and the inflammatory infiltrate in the duodenum, the disturbed follicular structure and the presence of vacuoles in the granulosa cells in the ovary indicate that the group exposed to SARS-CoV-2 showed significant toxicity with potential reproductive effects. The second phase consisted of mating the remaining females for a maximum of five days and evaluating data on pregnancy, litter size, pup biomass and toxicity biomarkers. No significant changes were observed in gestation length, litter size or offspring biomass, indicating that reproductive parameters were not affected. However, exposure resulted in significant neurobehavioral changes (anxiety-like behavior and changes in maternal care), associated with elevated dopamine levels and altered cholinesterase activity in key regions of the central nervous system. In addition, oxidative and nitrosative stress markers (ROS and NO) were elevated in mammary and ovarian tissues, suggesting a persistent inflammatory response. Therefore, this study provides new insights into the toxicity of SARS-CoV-2 lysate proteins in a terrestrial organism not targeted by the infection and demonstrates that the neurochemical and behavioral changes observed can have long-lasting effects. This, in natural environments, could pose a significant risk to population survival and stability, mainly through the modulation of neurochemical pathways and stress responses in non-target species.