Immune-cognitive relationships across viral infections: A transnosological systematic review

The emergence of SARS-CoV-2 has renewed interest in the relationship between immunity and cognition. Despite decades of work, the impact of viral exposure, mainly in the field of HIV, herpes and hepatitis infections, on distinct cognitive processes remains unclear, as most studies use global screening tools (e.g., MoCA) in isolation in each infectious context. This systematic narrative review adopts a transnosological approach, summarizing previously reported immune-cognition relationships across viral infections. Of 931 studies, 32 met inclusion criteria (N = 25,325) spanning SARS-CoV-2, HIV, herpes, hepatitis, Epstein-Barr virus, and multiple infections. Reported studies on immuno-cognitive relationships reveal several consistent findings. Elevated circulating CD14⁺CD16⁺ intermediate monocytes correlated with slower processing speed, reduced episodic memory and mental flexibility. Higher CD4⁺ T cells were associated with better processing speed, while reduced T cells and B cells levels together with elevated IgG predicted deficits in memory and attention. Most proinflammatory cytokines (e.g., IL-6, TNF-α, IFN-γ) were associated with impairments in overlapping cognitive domains (e.g., memory), whereas IL-10, an anti-inflammatory cytokine, consistently supported executive and memory performance.