Plasma ADRD Biomarkers are Altered in COVID‐19 ICU Survivors

Abstract

AbstractBackgroundLong Covid, which features cognitive symptoms in some people, affects an estimated 23.3 million Americans. Older adult survivors of COVID‐19‐associated critical illness are more likely to experience the cognitive symptoms of Long Covid, including deficits in attention, memory, and executive functioning. We sought to evaluate Alzheimer’s disease and related dementia (ADRD) plasma biomarkers in pilot study of older ICU survivors of COVID‐19‐related critical illness and non‐COVID critical illness.Method17 ICU survivors (13 COVID‐19, 4 non‐COVID) underwent clinical and cognitive testing, a blood sample, and a structural MRI approximately 2 months after ICU discharge. Plasma from the blood sample was extracted, and SIMOA assays were used to measure Aβ42, Aβ40, glial fibrillar acidic protein (GFAP), neurofilament light chain (NfL), and phosphorylated tau (pTau181). Structural MRI scans were processed using Freesurfer version 6 to measure brain atrophy (mean global cortical thickness). Plasma analyte values over three standard deviations outside the mean of the whole group were excluded (1 NfL and 1 pTau). Two‐sample t‐tests were used to compare plasma analytes between ICU groups. Pearson or Spearman correlation models were used to evaluate the relationship of target analytes with brain volumes. Covariates were tested but did not change the results.ResultSignificantly lower Aβ42/40 ratio and Aβ42 levels were observed in COVID‐19 ICU survivors relative to non‐COVID ICU survivors (Figure 1). Across all participants Aβ42/40 ratio was not associated with mean global cortical thickness, while NfL and GFAP levels were negatively associated with cortical thickness (Figure 2). However, when limited to only the COVID‐19 ICU survivors, a more ADRD‐like pattern was observed, with a trend for a positive association of Aβ42/40 ratio with cortical thickness and negative association of GFAP and NfL with cortical thickness (Figure 3).ConclusionCognitive impairment in COVID‐19 critical illness may be related to ADRD pathophysiology. Future studies in larger samples of COVID‐19 ICU survivors, as well as those with Long Covid symptoms with a history of mild to moderate COVID‐19 infection are needed to better understand these relationships.