Post-COVID microvascular dysfunction in hospitalized [survivors] is associated with [severity] & persistent cognitive complaints, 2025, van der Knaap+

Post-COVID microvascular dysfunction in hospitalized COVID-19 survivors is associated with acute disease severity and persistent cognitive complaints
Noa van der Knaap; Simona Klinkhammer; Alida A. Postma; Johanna M.A. Visser-Meily; Janneke Horn; Caroline M. van Heugten; Paulien H.M. Voorter; Merel M. van der Thiel; Gerhard S. Drenthen; Walter H. Backes; Frank van Rosmalen; Susanne van Santen; Bas C.T. van Bussel; Iwan C.C. van der Horst; David E.J. Linden; Marcel J.H. Ariës; Jacobus F.A. Jansen

OBJECTIVE
Coronavirus disease 2019 (COVID-19) is known to have adverse effects on the brain's vasculature in some patients. After recovery of the infection, vascular abnormalities may persist, but it remains unclear which pathological pathways play a role in post-COVID vascular and cognitive dysfunction and may contribute to post-COVID cognitive complaints.

METHODS
In this observational cohort study, 108 previously hospitalized COVID-19 survivors (general ward: n = 53; intensive care unit (ICU): n = 55) were compared. Cerebral microvascular properties in the cortical gray matter (cGM), normal-appearing white matter (NAWM), and white matter hyperintensities (WMH) were assessed using multi-b-value diffusion MRI around 9 months post-infection and related to acute systemic blood markers and post-COVID cognitive performance and complaints.

RESULTS
A lower microvascular perfusion volume fraction (fmv) and blood flow-related measure (fmv·Dmv) were found in ICU compared to general ward patients in the cGM (p = .032; p = .021), NAWM (p = .008; p = .006), and WMH (p = .014; p = .035). No associations were found between diffusion/perfusion metrics and cognitive performance, but a lower fmv in the NAWM was found in those with more cognitive complaints (p = .047). In ICU survivors, higher median blood lactate levels during ICU admission were associated with lower fmv (p = .031) and fmv·Dmv (p = .044) in the NAWM.

INTERPRETATION
Significantly more widespread post-COVID cerebral microvascular dysfunction was found in COVID-19 ICU compared to general ward survivors. Post-COVID microvascular dysfunction in the NAWM may be due to more severe cerebral tissue hypoxia at time of the infection and is associated with persisting subjective cognitive complaints, even in absence of objective cognitive problems.

HIGHLIGHTS

• Multi-b-value diffusion MRI has potential applications in post-COVID assessment.

• Post-COVID cerebral microvascular dysfunction is more severe in ICU survivors.

• Post-COVID microvascular dysfunction may be a result of acute tissue hypoxia.

• Objective cognition is unaffected by post-COVID cerebral microvascular dysfunction.

• Subjective complaints are related to post-COVID cerebral microvascular dysfunction.


Link | PDF (Journal of the Neurological Sciences) [Open Access]

 

(Presumably related, the lead author's surname is famous in paediatric neurology/neuroradiology, with an eponymous disease.)

 

Yes and I think the key point is that the routine clinical tests for cognitive dysfunction are geared to detecting dementia and not fine-grained enough to pick up mild and non-progressive dysfunction. It's obvious to the person but less clear to an observer.

Clinic evaluation of cognitive impairment in post-COVID syndrome: Performance on legacy pen-and-paper and new digital cognitive tests (2025, Brain, Behavior, & Immunity - Health)

 

Further evidence to —

Spoiler: 6 Related papers

Loss of white matter integrity mediates the association between cortical cerebral microinfarcts and cognitive dysfunction: A longitudinal study (2024, Journal of Cerebral Blood Flow & Metabolism)

Cerebral microstructural alterations in Post-COVID-condition are related to cognitive impairment, olfactory dysfunction and fatigue (2024, Nature Communications)

Macro- and Microstructural White Matter Differences in Neurologic Postacute Sequelae of SARS-CoV-2 Infection (2024, American Journal of Neuroradiology)

Cerebral microstructural alterations in Post-COVID-condition are related to cognitive impairment, olfactory dysfunction and fatigue (2024, Nature Communications)

Microstructural brain abnormalities, fatigue, and cognitive dysfunction after mild COVID-19 (2024, Nature Scientific Reports)

MRI with generalized diffusion encoding reveals damaged white matter in patients previously hospitalized for COVID-19 and with persisting symptoms at follow-up (2023, Brain Communications)

In sum indicating that normal appearing white matter (NAWM) on routine structural imaging —

• can be demonstrated to be abnormal with advanced MRI diffusion-weighted imaging protocols
• which is correlated with subjective cognitive dysfunction (even when routine objective evaluation is normal/insensitive)

I think these white matter microstructural imaging protocols need to move into routine clinical use for targeted assessment (ie indication: brain fog).