Synergy of SARS-CoV-2 and HIV-1 Infections in the Human Brain

TL;DR

This review examines how SARS-CoV-2 and HIV-1 infections interact in the brain, causing similar neurological effects and highlighting the need for better treatments.

Contribution

The paper identifies parallels in microglial and neuroinflammatory responses between SARS-CoV-2 and HIV-1 infections in the brain.

Findings

SARS-CoV-2 and HIV-1 both cause microglial activation and neuroinflammation in the brain.

PWH experience higher Long-COVID prevalence and overlapping cognitive and mental health issues.

Similar astrogliosis and microglial nodules are observed in both infections.

Abstract

This review explores the interplay between SARS-CoV-2 and HIV-1 infections within the human brain, highlighting the significant neurological implications of these viral infections. SARS-CoV-2 can infect the central nervous system (CNS), with evidence of the virus detected in various brain regions, including the hypothalamus, cerebellum, and olfactory bulb. This infection is linked to microglial activation and neuroinflammation, which can lead to severe neurological outcomes in affected individuals. Autopsy studies revealed microglial changes, including downregulation of the P2RY12 receptor, indicating a shift from homeostatic to inflammatory phenotype. Similar changes in microglia are found in the brains of people with HIV-1 (PWH). In SARS-CoV-2, the correlation between inflammatory cytokines, such as IL-1, IL-6, and MCP-1, found in cerebrospinal fluid and brain tissues, indicates significant neurovascular inflammation. Astrogliosis and microglial nodules were observed, further emphasizing the inflammatory response triggered by the viral infections, again in parallel to those found in the brains of PWH. Epidemiologic data indicate that although SARS-CoV-2 infection rates in PWH mirror those in People without HIV (PWoH) populations, Long-COVID prevalence is markedly higher among PWH. Evidence of overlapping cognitive impairment, mental health burden, and persistent neuroinflammation highlights diagnostic complexity and therapeutic gaps. Despite plausible mechanistic synergy, direct neuropathological confirmation remains scarce, warranting longitudinal, biomarker-driven studies. Understanding these interactions is critical for developing targeted interventions to mitigate CNS injury and improve outcomes.

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