Clinicopathological Profile of Disseminated Intravascular Coagulopathy (DIC) in Natural Course of Moderate COVID-19 Patients

Abstract

Background: Timely and accurately identification of thrombotic complications seems to become an important issue in patients suffering from coronavirus disease 2019 (COVID-19). Preliminary reports on critical ill COVID-19 patients include thrombocytopenia, abnormal coagulation tests, and disseminated intravascular coagulation. While the COVID-19 pandemic is spreading worldwide, the progression of DIC in the natural course of COVID-19 remains unpredictable and enigmatic. Methods: Out of a total of 694 COVID-19 inpatients, we selected 332 adults (≥18 - <65 years old) without any comorbidities from twelve hospitals (Wenzhou, China). The patients were divided into mild, moderate and severe groups, depending on the degree of disease severity. According to patient’s onset time of the first symptoms before admission, the natural course of COVID-19 was categorized at 3-day intervals for analysis, as follows: 1-3 days (D1-3), D4-6, D7-9 and D10-14. Demographic, clinical, treatment, and laboratory data were extracted from electronic medical records and compared between groups at different stages of COVID-19 course. Findings: The nature course of COVID-19 can be classified into two or four stages depending on patients with or without pneumonia. Mild patients without pneumonia showed two stages: virus infection stage (day 1-3) and recovery stage (day 4-6). In contrast, moderate and severe patients with pneumonia had four stages: virus infection stage (day 1-3); inflammation stage (day 4-6) characterized by c-reactive protein (CRP) >10 mg/L and fibrinogen >4 g/L; early stage of DIC (day 7-9) characterized by high fibrinogen levels and d-dimer >500 µg/L; and the stage of overt DIC (day 10-14) characterized by platelet >300×109, high fibrinogen and high d-dimer levels. These data showed that natural course of COVID-19 closely linked with the occurrence and progression of DIC might be one of the major causes for the progression of the disease and the occurrence of events. Interpretation: To elucidate the natural course of COVID-19 accompanying the DIC progression can help clinicians quickly and accurately identify the stage of the disease, make the correct diagnosis and treatment, promote patient recovery and survival. Funding Statement: This work was supported by the National Natural Science Foundation of China (grant 81670336) , the Wenzhou Grant for Scientific Talents, Wenzhou Science and Technology Bureau (RX2016003); the Key Research and Development Program of Zhejiang Province (2019C03011); and Special Project for Significant New Drug Research and Development in the Major National Science and Technology Projects of China (2020ZX09201002);Wenzhou Science and Technology Key problem program (ZY2020001); The Key Research and Development Program of Zhejiang Province (2019C03011). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The Ethics Committee of the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University waived the need for a written informed consent.