Single-nucleus RNA sequencing reveals the shared mechanisms inducing cognitive impairment between COVID-19 and Alzheimer’s disease

Fu, Yifan; Guo, Zhirong; Wang, Yulin; Zhang, Haonan; Zhang, Feifan; Zhang, Xu; Shen, Xianfeng; Roppongi, Reiko T.; Mo, Shaocong; Gu, Wenchao; Nakajima, Takahito; Tsushima, Yoshito

doi:10.3389/fimmu.2022.967356

Cited by 15 publications

(11 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…There is no debate that post-COVID-19 patients can develop a persistent spectrum of cognitive disturbances ( 7 ), which some authors liken to an Alzheimer’s Disease (AD)-type cognitive impairment ( 39 ). In fact, recent studies have pointed out several neuropathological similarities of PASC Cognitive Syndrome with AD ( 26 ); including, numerous elevated AD marker genes (e.g., FERMT2, HLA-DRB1, GNA15, STAB1, ICA1L, COLGALT1, TNFAIP2, ITGAM, VASP, IDLIA, PVR, TECPR1) ( 39 ), several circulatory biomarkers (i.e. GFAP, NFL, P-tau 181, UCH, NSE, and S100B) ( 26 ), and the presence of Apolipoprotein E ϵ4 allele (APOE4) ( 40 , 41 ), consistent with other reports ( 6 ).…”

Section: Discussionmentioning

confidence: 99%

Cognitive impairment in long-COVID and its association with persistent dysregulation in inflammatory markers

et al. 2023

View full text Add to dashboard Cite

ObjectiveTo analyze the potential impact of sociodemographic, clinical and biological factors on the long-term cognitive outcome of patients who survived moderate and severe forms of COVID-19.MethodsWe assessed 710 adult participants (Mean age = 55 ± 14; 48.3% were female) 6 to 11 months after hospital discharge with a complete cognitive battery, as well as a psychiatric, clinical and laboratory evaluation. A large set of inferential statistical methods was used to predict potential variables associated with any long-term cognitive impairment, with a focus on a panel of 28 cytokines and other blood inflammatory and disease severity markers.ResultsConcerning the subjective assessment of cognitive performance, 36.1% reported a slightly poorer overall cognitive performance, and 14.6% reported being severely impacted, compared to their pre-COVID-19 status. Multivariate analysis found sex, age, ethnicity, education, comorbidity, frailty and physical activity associated with general cognition. A bivariate analysis found that G-CSF, IFN-alfa2, IL13, IL15, IL1.RA, EL1.alfa, IL45, IL5, IL6, IL7, TNF-Beta, VEGF, Follow-up C-Reactive Protein, and Follow-up D-Dimer were significantly (p<.05) associated with general cognition. However, a LASSO regression that included all follow-up variables, inflammatory markers and cytokines did not support these findings.ConclusionThough we identified several sociodemographic characteristics that might protect against cognitive impairment following SARS-CoV-2 infection, our data do not support a prominent role for clinical status (both during acute and long-stage of COVID-19) or inflammatory background (also during acute and long-stage of COVID-19) to explain the cognitive deficits that can follow COVID-19 infection.

show abstract

Section: Discussionmentioning

confidence: 99%

Cognitive impairment in long-COVID and its association with persistent dysregulation in inflammatory markers

et al. 2023

View full text Add to dashboard Cite

show abstract

“…Researchers have identified significant similarities in neuronal damage, synaptic dysfunction, and neuroinflammation in both diseases. They presented the role of neural cell adhesion molecule 2 (NCAM2) and ICA1L (AD gene marker) in the process leading to cognitive impairment, which may be a potential target for AD intervention (Fu et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Late neurological consequences of SARS-CoV-2 infection: New challenges for the neurologist

Korchut

Rejdak²

2023

Front. Neurosci.

View full text Add to dashboard Cite

ObjectiveIn this study, a systematic review of the literature was performed to study the frequency of neurological symptoms and diseases in adult patients with COVID-19 that may be late consequences of SARS-CoV-2 infection.MethodsRelevant studies were identified through electronic explorations of Scopus, PubMed, and Google Scholar. We followed PRISMA guidelines. Data were collected from studies where the diagnosis of COVID-19 was confirmed and its late neurological consequences occurred at least 4 weeks after initial SARS-CoV-2 infection. Review articles were excluded from the study. Neurological manifestations were stratified based on frequency (above 5, 10, and 20%), where the number of studies and sample size were significant.ResultsA total of 497 articles were identified for eligible content. This article provides relevant information from 45 studies involving 9,746 patients. Fatigue, cognitive problems, and smell and taste dysfunctions were the most frequently reported long-term neurological symptoms in patients with COVID-19. Other common neurological issues were paresthesia, headache, and dizziness.ConclusionOn a global scale of patients affected with COVID-19, prolonged neurological problems have become increasingly recognized and concerning. Our review might be an additional source of knowledge about potential long-term neurological impacts.

show abstract

“…FindNeighbors and FindCluster were subsequently applied to obtain cell clusters. Next, the single-cell dataset was annotated with known cell markers [24] . To further identify specific subpopulations of plasma cells in UC patients, the plasma cells were redimensionalized and reclustered.…”

Section: Methodsmentioning

confidence: 99%

Single-cell dissection, hdWGCNA and deep learning reveal the role of oxidatively stressed plasma cells in ulcerative colitis

Mo,

Shen,

Huang

et al. 2023

ABBS

Self Cite

View full text Add to dashboard Cite

Ulcerative colitis (UC) develops as a result of complex interactions between various cell types in the mucosal microenvironment. In this study, we aim to elucidate the pathogenesis of ulcerative colitis at the single-cell level and unveil its clinical significance. Using single-cell RNA sequencing and high-dimensional weighted gene co-expression network analysis, we identify a subpopulation of plasma cells (PCs) with significantly increased infiltration in UC colonic mucosa, characterized by pronounced oxidative stress. Combining 10 machine learning approaches, we find that the PC oxidative stress genes accurately distinguish diseased mucosa from normal mucosa (independent external testing AUC=0.991, sensitivity=0.986, specificity=0.909). Using MCPcounter and non-negative matrix factorization, we identify the association between PC oxidative stress genes and immune cell infiltration as well as patient heterogeneity. Spatial transcriptome data is used to verify the infiltration of oxidatively stressed PCs in colitis. Finally, we develop a gene-immune convolutional neural network deep learning model to diagnose UC mucosa in different cohorts (independent external testing AUC=0.984, sensitivity=95.9%, specificity=100%). Our work sheds light on the key pathogenic cell subpopulations in UC and is essential for the development of future clinical disease diagnostic tools.

show abstract

Single-nucleus RNA sequencing reveals the shared mechanisms inducing cognitive impairment between COVID-19 and Alzheimer’s disease

Cited by 15 publications

References 54 publications

Cognitive impairment in long-COVID and its association with persistent dysregulation in inflammatory markers

Cognitive impairment in long-COVID and its association with persistent dysregulation in inflammatory markers

Late neurological consequences of SARS-CoV-2 infection: New challenges for the neurologist

Single-cell dissection, hdWGCNA and deep learning reveal the role of oxidatively stressed plasma cells in ulcerative colitis

Contact Info

Product

Resources

About