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1.
Sci Rep ; 12(1): 18126, 2022 Oct 28.
Article in English | MEDLINE | ID: covidwho-2096796

ABSTRACT

The development of tools that provide early triage of COVID-19 patients with minimal use of diagnostic tests, based on easily accessible data, can be of vital importance in reducing COVID-19 mortality rates during high-incidence scenarios. This work proposes a machine learning model to predict mortality and risk of hospitalization using both 2 simple demographic features and 19 comorbidities obtained from 86,867 electronic medical records of COVID-19 patients, and a new method (LR-IPIP) designed to deal with data imbalance problems. The model was able to predict with high accuracy (90-93%, ROC-AUC = 0.94) the patient's final status (deceased or discharged), while its accuracy was medium (71-73%, ROC-AUC = 0.75) with respect to the risk of hospitalization. The most relevant characteristics for these models were age, sex, number of comorbidities, osteoarthritis, obesity, depression, and renal failure. Finally, to facilitate its use by clinicians, a user-friendly website has been developed ( https://alejandrocisterna.shinyapps.io/PROVIA ).


Subject(s)
COVID-19 , Humans , COVID-19/epidemiology , Retrospective Studies , ROC Curve , Hospitalization , Triage/methods
2.
Brain ; 144(12): 3727-3741, 2021 12 31.
Article in English | MEDLINE | ID: covidwho-1455243

ABSTRACT

Recently, we reported oligoadenylate synthetase 1 (OAS1) contributed to the risk of Alzheimer's disease, by its enrichment in transcriptional networks expressed by microglia. However, the function of OAS1 within microglia was not known. Using genotyping from 1313 individuals with sporadic Alzheimer's disease and 1234 control individuals, we confirm the OAS1 variant, rs1131454, is associated with increased risk for Alzheimer's disease. The same OAS1 locus has been recently associated with severe coronavirus disease 2019 (COVID-19) outcomes, linking risk for both diseases. The single nucleotide polymorphisms rs1131454(A) and rs4766676(T) are associated with Alzheimer's disease, and rs10735079(A) and rs6489867(T) are associated with severe COVID-19, where the risk alleles are linked with decreased OAS1 expression. Analysing single-cell RNA-sequencing data of myeloid cells from Alzheimer's disease and COVID-19 patients, we identify co-expression networks containing interferon (IFN)-responsive genes, including OAS1, which are significantly upregulated with age and both diseases. In human induced pluripotent stem cell-derived microglia with lowered OAS1 expression, we show exaggerated production of TNF-α with IFN-γ stimulation, indicating OAS1 is required to limit the pro-inflammatory response of myeloid cells. Collectively, our data support a link between genetic risk for Alzheimer's disease and susceptibility to critical illness with COVID-19 centred on OAS1, a finding with potential implications for future treatments of Alzheimer's disease and COVID-19, and development of biomarkers to track disease progression.


Subject(s)
2',5'-Oligoadenylate Synthetase/genetics , Alzheimer Disease/genetics , COVID-19/genetics , Genetic Linkage/genetics , Genetic Predisposition to Disease/genetics , Patient Acuity , Adolescent , Aged , Aged, 80 and over , Alzheimer Disease/diagnosis , Alzheimer Disease/epidemiology , COVID-19/diagnosis , COVID-19/epidemiology , Cells, Cultured , Female , Gene Regulatory Networks/genetics , Genetic Predisposition to Disease/epidemiology , Humans , Induced Pluripotent Stem Cells/physiology , Male , Middle Aged , Polymorphism, Single Nucleotide/genetics , Young Adult
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