Cerebral Vascular Pathology of COVID-19

Introduction: Long-term adverse outcomes of Long COVID can affect all major systems of the body, including the immune system, respiratory system (lung fibrosis and pulmonary thromboembolism), cardiovascular system (cardiomyopathy and coagulopathy), and the neurological system, along with cutaneous and gastrointestinal complications, impaired hepatic and renal function, and impaired mental health. In the present study, we investigated the longitudinal impact of the intersection of the coinfection of HIV-1 and SARS-CoV-2 on circulating markers of systemic inflammation, neurogenesis, and BBB biomarkers.

Objective: While acute COVID-19 does not appear to markedly differ by HIV status, the long-term impact of COVID-19 in people with HIV (PWH) remains unclear.

Methods: Samples from forty-four participants with or without HIV were obtained approximately 10 days after the initial COVID diagnosis (t=0) and then three (t=1) and six (t=2) months later. Biomarkers of blood brain barrier (BBB) and vascular dysfunction, neurogenesis, and inflammatory responses were assessed by multiplex profiling and ELISA.

Results: The majority of inflammatory biomarkers either decreased or remained unchanged over the evaluated time frame. Notable exceptions were IL-9, TNF-α, and CCL-4, which increased at t=2 compared to earlier time points. The BBB disruption and vascular dysfunction biomarkers (S100β and soluble ICAM1, respectively) increased at t=1 and then returned to basal levels, suggesting transient loss of BBB integrity. No significant changes were observed between people without HIV (PWOH) and PWH across studied inflammatory and BBB markers. Among biomarkers of neurogenesis, eotaxin/CCL11 was not altered, FGF-2 was transiently decreased at t=1 in PHW, and G-CSF was elevated at t=2 in PWH when compared to the previous time-points.

Conclusion/Discussion: BBB and vascular dysfunction occur after COVID-19 and may be implicated in the development of post-COVID conditions. HIV-1 infection may potentiate post COVID-induced neuropathology by impairing neurogenesis.

Key Topics:

• Biomarker, in-depth phenotyping assays and in vitro studies using tissue and other biospecimens
• Studies of vascular injury, thrombosis, and other potential mechanisms of Long COVID