2019-20 coronavirus outbreak

Philosophy

Intensive care unit

ARDS

Respiratory distress

Betacoronavirus

Surgery

Virology

China

Archaeology

Endothelial activation

Zhàng

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

Outbreak

Coronavirus disease 2019 (COVID-19)

Immunology

Von Willebrand factor

Inflammation

Infectious disease (medical specialty)

Internal medicine

Pathological

Coronavirus Infections

Medicine

Coagulopathy

Gastroenterology

Theology

Disease

Severity of illness

Lung

Platelet

History

Thrombosis Research

Mounting evidence supports the strong prognostic importance of D-dimers and the impact of coagulopathy in COVID-19 patients [[1]F.A. Klok, M.J.H.A. Kruip, N.J.M. van der Meer, M.S. Arbous, D.A.M.P.J. Gommers, K.M. Kant, F.H.J. Kaptein, J. van Paassen, M.A.M. Stals, M.V. Huisman, H. Endeman, Incidence of thrombotic complications in critically ill ICU patients with COVID-19, Thromb. Res. (n.d.). doi:https://doi.org/10.1016/j.thromres.2020.04.013.Google Scholar,[2]Zhou F. Yu T. Du R. Fan G. Liu Y. Liu Z. Xiang J. Wang Y. Song B. Gu X. Guan L. Wei Y. Li H. Wu X. Xu J. Tu S. Zhang Y. Chen H. Cao B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study.Lancet. 2020; : 0https://doi.org/10.1016/S0140-6736(20)30566-3Abstract Full Text Full Text PDF Scopus (16717) Google Scholar,[3]Zhang Y. Xiao M. Zhang S. Xia P. Cao W. Jiang W. Chen H. Ding X. Zhao H. Zhang H. Wang C. Zhao J. Sun X. Tian R. Wu W. Wu D. Ma J. Chen Y. Zhang D. Xie J. Yan X. Zhou X. Liu Z. Wang J. Du B. Qin Y. Gao P. Qin X. Xu Y. Zhang W. Li T. Zhang F. Zhao Y. Li Y. Zhang S. Coagulopathy and antiphospholipid antibodies in patients with Covid-19.N. Engl. J. Med. 2020; https://doi.org/10.1056/NEJMc2007575Crossref Scopus (1465) Google Scholar]. We would like to emphasize the significance of anticoagulation in severe COVID-19 disease, by adding our observation of highly pathological data on anti-phospholipid-antibodies, von Willebrand Factor (VWF) and Factor VIII. We observed a 72-year-old previously healthy male patient admitted to our hospital 6 days after the onset of respiratory symptoms and fever. Six days after admission, following a rapid deterioration of his clinical condition with development of acute respiratory distress syndrome, acute renal insufficiency and altered mental status, he was transferred to the intensive care unit (ICU). Supportive care with intubation, positive pressure ventilation and renal replacement therapy led to a stabilization of his condition. During the ICU stay, a continual increase of D-dimers was observed, from initially 0.69 mg/L to 2.55 mg/L on day 4, 2.81 mg/L on day 11 to 20.63 mg/L on day 21. At this time, IgG anti-cardiolipin antibodies (ACA) and anti-beta2-glycoprotein I (anti-β2-GPI) were negative, but IgM ACA elevated at 121.9 CU (normal <20 CU) and IgM anti-β2-GPI elevated at 275.3 CU (normal <20 CU). Furthermore, on day 21, we also observed a concurrent massive elevation of VWF, with VWF:antigen 555% (normal 42–136%) and VWF:activity 520% (normal 42–168%), accompanied by an increase of Factor VIII clotting activity of 369% (normal 55–164%). The increased VWF points towards massive endothelial stimulation and damage with release of VWF from Weibel-Palade bodies. Interestingly, endothelial cells express ACE2, the receptor for SARS-CoV-2, thus possibly mediating endothelial activation [[4]Hamming I. Timens W. Bulthuis M.L.C. Lely A.T. Navis G.J. van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis.J. Pathol. 2004; 203: 631-637Crossref PubMed Scopus (3784) Google Scholar]. The patient received prophylactic anticoagulation with dalteparin 5000 U s.c. daily from admission to hospital. We increased the dose to therapeutic anticoagulation with unfractionated heparin on day 21, without hemorrhagic complication. Since then, the patient is steadily improving, ventilation and hemodialysis could be successfully withdrawn, and he has been transferred from the ICU to a general ward. D-dimers decreased to 6.26 mg/L on day 24 and to 1.94 mg/L on day 29. Considering the high levels of VWF and factor VIII, we strongly suggest administering higher, possibly therapeutic doses of anticoagulation to these patients. The role of antiphospholipid antibodies, VWF and FVIII needs further study.

Severe COVID-19 infection associated with endothelial activation