Neurodegeneration blood markers in largely Hispanic and non‐Hispanic Black COVID‐19 patients: from acute hospitalization to long‐term PASC with/without brain fog

Abstract Background Understanding the effect of COVID‐19 and Post‐Acute Sequelae of SARS CoV‐2 infection (PASC) on neurodegeneration using accessible blood biomarkers of neurofilament light (NfL) and phosphorylated tau 181 (p‐tau‐181) is of critical importance. Few studies to date have explored levels of neurodegenerative markers in COVID‐19 and PASC among race and ethnic minority populations. Method NfL and p‐tau181 blood levels were measured using highly sensitive Simoa technology across three cohorts: (1) 102 Hispanic and non‐Hispanic Black non‐intubated COVID‐19 inpatients (75 +/‐9yo) treated in NYC March to June 2020, 95 of whom had serial samples with a second sample average 17d later; (2) 96 contemporaneously sampled outpatient controls, pre‐vaccination era, without history of COVID‐19, matched for age, sex and race/ethnicity (72+/‐8yo) and (3) 119 PASC diverse outpatients examined at least three months after acute infection, including 55 with brain fog (47+/‐14yo) and 64 without (41+/‐15yo). Associations with clinically‐obtained inflammatory markers (C‐reactive protein [CRP], ferritin, interleukin‐6 [IL‐6], ESR, LDH) were explored. An external quality control allowed direct comparison of NfL and p‐tau‐181 across the groups. Result When controlling for age, NfL was significantly elevated in hospitalized COVID‐19 patients vs matched non‐COVID patients, but neither NfL nor p‐tau‐181 levels were significantly elevated in long‐term PASC outpatients with and without cognitive symptoms. NfL, but not p‐tau‐181, increased significantly between time points 1 and 2. At the second time‐point in the hospitalization, but not initially, NfL was significantly associated with CRP, ferritin, IL‐6; p‐tau‐181 was significantly associated with ferritin and IL‐6. There were no associations between NfL or p‐tau181 with either LDH or ESR. Conclusion Plasma NfL, but not p‐tau‐181, was elevated in hospitalized non‐intubated COVID‐19 patients in an aged cohort; after controlling for age, neither neurodegenerative marker was identifiable in PASC in middle aged adults. NfL increased significantly after prolonged hospitalization, and persistently elevated inflammatory markers correlated with NfL and p‐tau‐181 after a prolonged hospitalization period. The relationships between NfL, p‐tau‐181, and markers of systemic inflammation during acute COVID‐19 support other pathobiological models for neurodegenerative sequelae in older adults following COVID‐19 infection, but provide some reassurance for PASC brain fog sufferers.