COVID-19 and pneumonia: a role for the uPA/uPAR system

•The hCoVs induce inflammatory pneumonia, which in turn may cause ALI and ARDS.•The inflammatory process may be caused by dysregulated uPA/uPAR system.•Serum suPAR levels could represent a potential biomarker of disease progression.•Drugs targeting the uPA/uPAR system may be used for the treatment of hCoV infections. Here, we highlight recent findings on the urokinase plasminogen activator (uPA)/uPA receptor (uPAR) system that suggest its potential role as a main orchestrator of fatal progression to pulmonary, kidney, and heart failure in patients with coronavirus. Patients with prolonged background inflammation can present aberrant inflammatory reactions, well recognized as the main factors that can result in death and probably sustained by a dysregulated uPA/uPAR system. SuPAR, the soluble form of uPAR, represents a biomarker of disease progression, and its levels correlate well with comorbidities associated with the death of patients with coronavirus. New drugs that regulate the uPA/uPAR system could help treat the severe complications of highly pathogenic human coronaviruses (hCoVs), including pandemic coronavirus 2019 (COVID-19). A dysregulated uPA/uPAR system is present in several pathologies, including the comorbidities of patients with COVID-19. Thus, drugs regulating the uPA/uPAR system could reduce the mortality of pandemic COVID-19.