Precision Medicine and Machine Learning to predict critical disease and death due to Coronavirus disease 2019 (COVID-19).
Júnior WLDT, Danelli T, Tano ZN, Cassela PLCS, Trigo GL, Cardoso KM, Loni LP, Ahrens TM, Espinosa BR, Fernandes AJ, Almeida ERD, Lozovoy MAB, Reiche EMV, Maes M, Simão ANC
•papers•Jun 16 2025The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes Coronavirus Disease 2019 (COVID-19) and induces activation of inflammatory pathways, including the inflammasome. The aim was to construct Machine Learning (ML) models to predict critical disease and death in patients with COVID-19. A total of 528 individuals with SARS-CoV-2 infection were included, comprising 308 with critical and 220 with non-critical COVID-19. The ML models included imaging, demographic, inflammatory biomarkers, NLRP3 (rs10754558 and rs10157379) and IL18 (rs360717 and rs187238) inflammasome variants. Individuals with critical COVID-19 were older, higher male/female ratio, body mass index (BMI), rate of type 2 diabetes mellitus (T2DM), hypertension, inflammatory biomarkers, need of orotracheal intubation, intensive care unit admission, incidence of death, and sickness symptom complex (SSC) scores and lower peripheral oxygen saturation (SpO<sub>2</sub>) compared to those with non-critical disease. We found that 49.5 % of the variance in the severity of critical COVID-19 was explained by SpO<sub>2</sub> and SSC (negatively associated), chest computed tomography alterations (CCTA), inflammatory biomarkers, severe acute respiratory syndrome (SARS), BMI, T2DM, and age (positively associated). In this model, the NLRP3/IL18 variants showed indirect effects on critical COVID-19 that were mediated by inflammatory biomarkers, SARS, and SSC. Neural network models yielded a prediction of critical disease and death due to COVID-19 with an area under the receiving operating characteristic curve of 0.930 and 0.927, respectively. These ML methods increase the accuracy of predicting severity, critical illness, and mortality caused by COVID-19 and show that the genetic variants contribute to the predictive power of the ML models.