Patients who have recovered from COVID-19 develop lower volume fraction of intracellular water (Vic) but do not experience long-term significant decline in cognitive function based on 1-year follow-up, according to a study published in the journal Brain.

Researchers have detected changes in white matter (WM) in patients who have recovered from COVID-19, but status and changes in WM after 1 year in recovered COVID-19 patients are unknown. Prior research has indicated patients without these neurologic manifestations may experience continued central nervous system (CNS) abnormalities after recovery. Patients in the intensive care unit (ICU) have different imaging manifestations in the acute stage and worse cognitive outcomes after discharge compared with individuals not admitted.

The objective of the study was to assess long-term change in WM using 3 diffusion models, assess cognitive function in recovered COVID-19 patients, and investigate correlations with clinical characteristics to explain abnormalities at 1-year follow-up. This is the first study to investigate WM changes at one-year follow-up.

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Twenty-two (11 men, 8 hospitalized in ICU) patients who have recovered from COVID-19 and 21 (5 men) healthy control individuals participated in the study. Baseline clinical characteristics and inflammatory markers were collected. Participants underwent diffusion tensor imaging (DTI), diffusion kurtosis imaging (DKI), and neurite orientation dispersion and density imaging (NODDI). The researchers administered the Weschler Intelligence scale.

Fourteen patients had neurological symptoms in the acute stage, and 9 had symptoms at time of scanning. The 8 patients who were hospitalized in ICU were more likely to have higher C-reactive protein (CRP) compared with patients never in the ICU (P =.025).

As seen through tract-based spatial statistics (TBSS) analysis, patients tended to have lower Vic compared with control individuals. The ICU group had lower fractional anisotropy (FA) compared with the non-ICU group. The bilateral corona radiata (CR), genu of the corpus callosum (CC), and superior longitudinal fasciculus L (SLF) possessed abnormal diffusion metrics.

Vic of both cluster 1 and cluster 2 decreased as length of hospitalization increased and as days of follow-up increased. The correlation dropped following multiple comparison correction.

Study limitations included small sample size, single-center setup, lack of baseline imaging, and moderate-severe WM hyperintensity.

“Lower axonal density with no significant decline in cognitive function were discovered in recovered COVID-19 patients after one year,” the researchers said. “ICU patients had slightly more white matter abnormalities. However, inflammatory storms were not the main cause of these WM changes after one year of recovery. The duration of hospital stay may be a predictor for white 1 matter changes at the one-year follow-up.”


Huang S, Zhou Z, Yang D, et al. Persistent white matter changes in recovered COVID-19 1 patients at the 1-year follow-up. Brain. Published online December 16, 2021. doi:10.1093/brain/awab435