Neuroinflammation in long COVID: the role of the Val16Ala polymorphism of SOD2 and cognitive impairment

Abstract

Long COVID (LC) includes persistent behavioral and cognitive deficits, impacting quality of life. Neuroinflammation plays a key role in these alterations, with genetic factors influencing susceptibility. The MnSOD Val16Ala SNP is associated with neuroinflammation and cognitive dysfunction, but its role in LC remains unclear. This study investigated the relationship between the SOD2 Val16Ala polymorphism and neurocognitive alterations in young adults post-SARS-CoV-2 infection. Neurocognitive performance was assessed using the Neupsilin test in individuals with and without prior COVID-19. Blood samples were collected for the quantification of cytokines (IL-1, IL-6, TNF-α, and IFN-γ) and for the genotyping of the SOD2 Val16Ala polymorphism. The COVID-19 group showed worse cognitive performance and higher cytokine levels than controls, particularly in memory and executive function. Val allele carriers (Val/Ala and Val/Val) exhibited increased pro-inflammatory cytokine levels compared to Ala/Ala carriers. These findings suggest a potential interaction between genetic susceptibility and inflammatory response in post-COVID neurocognitive alterations. Young adults post-COVID-19 presented an exacerbated neuroinflammatory response, likely influencing cognition. The presence of the Val allele was associated with greater susceptibility to inflammatory events, suggesting a genetic component in LC-related neurological dysfunction. These results reinforce the role of neuroinflammation in LC and highlight the importance of genetic factors in determining cognitive outcomes. Understanding these mechanisms may help identify individuals at higher risk and support future therapeutic strategies.