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The COVID-19 pandemic caused by SARS-CoV-2 continues to spread rapidly due to its virulence and ability to be transmitted by asymptomatic infected persons. If they are present, the symptoms of COVID-19 may include rhinorrhea (runny nose), headache, cough, and fever. Up to 5% of affected persons may experience more severe COVID-19 illness, including severe coagulopathy, acute respiratory distress syndrome (ARDS) characterized by respiratory failure that requires supplementary oxygen and mechanical ventilation, and multi-organ failure. Interestingly, clinical evidence has highlighted the distinction between COVID-19-associated coagulopathy (CAC) and disseminated intravascular coagulation (DIC). Patients with CAC exhibit different laboratory values than DIC patients for activated partial thromboplastin time (aPTT) and prothrombin time (PT) which may be normal or shortened, varying platelet counts, altered red blood cell morphology, unique bleeding complications, a lack of schistocytes in the peripheral blood, and no decrease in fibrinogen levels. In this review, we consider the search for 1) laboratory results that can diagnose or predict development of CAC, including serum levels of D-dimers, fibrinogen, interleukin-6 (IL-6) and the growth factor angiopoietin-2 (Ang-2), 2) mechanisms of CAC induction, and 3) novel therapeutic regimens that will successfully treat COVID-19 before development of CAC., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)