Beyond the virus: ecotoxicological and reproductive impacts of SARS-CoV-2 lysate protein in C57Bl/6j female mice

Since the establishment of the COVID-19 pandemic, a range of studies have been developed to understand the pathogenesis of SARS-CoV-2 infection, vaccine development, and therapeutic testing. However, the possible impacts that these viruses can have on non-target organisms have been explored little, and our knowledge of the consequences of the COVID-19 pandemic for biota is still very limited. Thus, the current study aimed to address this knowledge gap by evaluating the possible impacts of oral exposure of C57Bl/6 J female mice to SARS-CoV-2 lysate protein (at 20 µg/L) for 30 days, using multiple methods, including behavioral assessments, biochemical analyses, and histopathological examinations. Although we did not have evidence of hematological, mutagenic, or genotoxic effects, we noted that the ingestion of SARS-CoV-2 lysate protein-induced behavioral disorders (hypoactivity, anxiety-like behavior, and short-term memory deficit), which were associated with oxidative stress and dopaminergic and cholinesterase imbalance in the animal brain. Furthermore, the elevation of bilirubin levels and lactate dehydrogenase levels in these animals suggests the occurrence of hepatic changes, and the redox imbalance, nitrosative stress, and elevated production of IFN-γ and inflammatory infiltration in the duodenum, disrupted follicular structure, and presence of vacuoles in granulosa cells, in ovarian, indicate that the SARS-CoV-2-exposed group showed significant toxicity. Principal component analysis (PCA) and cluster analysis confirmed that the groups were clearly separated and showed that the largest changes upon SARS-CoV-2 exposure were related to ROS, MDA, nitrite, IFN-γ/IL-10 levels and SOD and catalase activity in the ovary; IFN-γ/IL-10 production and SOD activity in the duodenum; BChE activity in the brain; bilirubin levels and lactate dehydrogenase activity in the serum; number of primary follicles in the ovary. In conclusion, our study provides new insights into the toxicity of SARS-CoV-2 lysate proteins in a non-target terrestrial organism of infection and, therefore, expands our understanding of the real extent of the ecological/environmental impact of the COVID-19 pandemic.