ABSTRACT
Background The aim of our study was to investigate the prevalence and associations of cognitive impairment in COVID‐19 survivors in the post‐acute setting. Method Our study is conducted in three post‐COVID‐19 outpatient clinics in tertiary hospitals in Greece. Eligible subjects included previously hospitalized COVID‐19 survivors with mild to moderate disease, returning for follow‐up at least two months post‐discharge. Exclusion criteria included intensive care unit admission, intubation, a history of neurodegenerative disease and other significant comorbidities. Study measurements included demographics, clinical evaluation, medical, family history, anthropometrics, 6‐minute walk test (6MWT), 30 seconds sit‐to‐stand (30STS), handgrip strength, spirometry, Pittsburgh Sleep Quality Index (PSQI), the Montreal Cognitive Assessment (MoCA), reactive oxygen metabolites (dROMs) and plasma antioxidant capacity (PAT). Cognitive impairment was considered on MoCA ≤24. Result 142 COVID‐19 survivors were included in the study (110 Male, 32 Female;Mean age of 56.16±10.92). A total of 47.2% presented with cognitive decline (CD) as indicated by a MoCA score ≤24. Cognitive decline prevalence by SARS‐CoV‐2 variant of concern (VOC) was 39.5%, 50% and 62.5% for Alpha, Beta and Delta, correspondingly. A binary logistic regression model controlling for age, gender and VOC indicated that the diffusing capacity for carbon monoxide (DLCO) was independently associated with MoCA ≤24 (p = 0.014, OR = 0.669, 95%CI: 0.484‐0.923). Compared to severe untreated OSAS (n = 28), distinct domains but similar prevalence of cognitive impairment was noted. Conclusion Diffusion capacity abnormalities for carbon monoxide in COVID‐19 survivors as noted in other studies, may be implicated in the development of cognitive impairment.
ABSTRACT
Type I interferon (IFN-I) signalling represents a major target for modulation in a virus' bid for latency. IFN-I perturbations are also present in such as Alzheimer's disease (AD) and multiple sclerosis (MS), where viral infections are known to increase symptomatic burden. IFN-I modulation such as via IFNß-1a, an established MS treatment, has been researched to a limited extent to both AD and COVID-19. In this mini review, we present emerging research on trained immunity as a pathogenetic basis for Alzheimer's disease and the emerging context for IFNß-1a repositioning, via mechanisms shared with multiple sclerosis and induced by viral infections.
Subject(s)
Alzheimer Disease , COVID-19 , Multiple Sclerosis , Virus Diseases , Humans , Interferon-betaABSTRACT
Introduction (IFITM3) is an innate immune protein that has been identified as a novel γ-secretase (γs) modulator. FYN is a kinase that stabilizes IFITM3 on the membrane, primes APP for amyloidogenic γs processing and mediates tau oligomerization. The purpose of this study is to explore the role of FYN and IFITM3 in AD and COVID-19, expanding on previous research from our group. Methods A 520 gene signature containing FYN and IFITM3 (termed Ia) was extracted from a previously published meta-analysis of Alzheimer's disease (AD) bulk- and single nuclei sequencing data. Exploratory analyses involved meta-analysis of bulk and single cell RNA data for IFITM3 and FYN differential expression per CNS site and cellular type. Confirmatory analyses, gene set enrichment analysis (GSEA) on Ia was performed to detect overlapping enriched biological networks between COVID-19 with AD. Results Bulk RNA data analysis revealed that IFITM3 and FYN were overexpressed in two CNS regions in AD vs. Controls: the temporal cortex Wilcoxon p-value=1.3e-6) and the parahippocampal cortex Wilcoxon p-value=0.012). Correspondingly, single cell RNA analysis of IFITM3 and FYN revealed that it was differentially expressed in neurons, glial and endothelial cells donated b AD patients, when compared to controls. Discussion IFITM3 and FYN were found as interactors within biological networks overlapping between AD and SARS-CoV-2 infection. Within the context of SARS-CoV-2 induced tau aggregation and interactions between tau and Ab1-42, the FYN – IFITM3 regulome may outline an important innate immunity element responsive to viral infection and IFN-I signalling in both AD and COVID-19.