Cell-free DNA maps COVID-19 tissue injury and risk of death and can cause tissue injury. Integrating plasma cell-free DNA with clinical laboratory results enhances the prediction of critically ill patients with COVID-19 at hospital admission Dear Editor, Owing to the substantial clinical heterogeneity of patients infected with SARS-CoV-2,1,2 factors primarily relying upon clinical and/or laboratory parameters are yet inadequate to accurately predict COVID-19 patients evolving to severe or critical illness at early stage.3,4 Recent studies have revealed an elevated level of cell-free DNA (cfDNA) in plasma in severe COVID-19 patients due to massive cell death or irreversible multiorgan injuries during pathological conditions.5,6 Therefore, the utilization of cfDNA profiling may benefit improving the COVID-19 prediction and help understand molecular characteristics of the life-threatening disease.7,8 Herein, we developed an M2Model, a LightGBM-based9 machine learning model with focal loss as an objective function to predict critical COVID-19 at admission by jointly analysing multimodal data, including laboratory parameters and cfDNA profiles. Laboratory results and blood samples were collected from a total of 399 consecutive hospitalized patients with COVID-19 (345 noncritical and 54 critical patients; Table S1). [Extracted from the article]