Download PDF
CC BY 4.0 · TH Open 2020; 04(03): e271-e279
DOI: 10.1055/s-0040-1716717
Case Report

COVID-19-Induced Cytokine Release Syndrome Associated with Pulmonary Vein Thromboses, Atrial Cardiomyopathy, and Arterial Intima Inflammation

Andreas Goette
1   Department of Cardiology and Intensive Care Medicine, St. Vincenz Hospital, Paderborn, Germany
2   Working Group: Molecular Electrophysiology, University Hospital Magdeburg, Magdeburg, Germany
,
Markus Patscheke
1   Department of Cardiology and Intensive Care Medicine, St. Vincenz Hospital, Paderborn, Germany
,
Frank Henschke
3   Center for Pathology, Paderborn, Germany
,
Matthias Hammwöhner
1   Department of Cardiology and Intensive Care Medicine, St. Vincenz Hospital, Paderborn, Germany
› Author Affiliations
› Further Information
Also available at
   Permissions and Reprints

Abstract

Coronavirus disease 2019 (COVID-19) is a viral disease induced by severe acute respiratory syndrome–coronavirus-2 (SARS-CoV-2), which may cause an acute respiratory distress syndrome (ARDS). First reports have shown that elevated levels of inflammatory cytokines might be involved in the development of organ dysfunction in COVID-19. Here, we can present a case of cytokine release syndrome induced by SARS–CoV-2 causing multiorgan failure and death. Of note, we can report on pulmonary vein thromboses as potential source of cerebrovascular embolic events. Furthermore, we present a specific form of an isolated inflammatory atrial cardiomyopathy encompassing atrial myocardium, perivascular matrix, as well as atrial autonomic nerve ganglia, causing atrial fibrillation, sinus node arrest, as well as atrial clot formation in the right atrial appendage. An associated acute glomerulonephritis caused acute kidney failure. Furthermore, all the described pathologies of organs and vessels were associated with increased local expression of interleukin-6 and monocyte chemoattractant protein-1 (MCP-1). This report provides new evidence about fatal pathologies and summarizes the current knowledge about organ manifestations observed in COVID-19.

Keywords

atria - COVID19 - fibrillation - pathology - stroke


Publication History

Received: 22 June 2020

Accepted: 11 August 2020

Article published online:
26 September 2020

© .

Georg Thieme Verlag KG
Stuttgart · New York

 

  • References

  • 1 Lee DW, Gardner R, Porter DL. et al. Current concepts in the diagnosis and management of cytokine release syndrome. Blood 2014; 124 (02) 188-195
    CrossrefPubMedGoogle Scholar
  • 2 Lundemose JB, Smith H, Sweet C. Cytokine release from human peripheral blood leucocytes incubated with endotoxin with and without prior infection with influenza virus: relevance to the sudden infant death syndrome. Int J Exp Pathol 1993; 74 (03) 291-297
    PubMedGoogle Scholar
  • 3 Duan E, Wang D, Luo R. et al. Porcine reproductive and respiratory syndrome virus infection triggers HMGB1 release to promote inflammatory cytokine production. Virology 2014; 468-470: 1-9
    CrossrefPubMedGoogle Scholar
  • 4 Hirano T, Murakami M. COVID-19: a new virus, but a familiar receptor and cytokine release syndrome. Immunity 2020; 52 (05) 731-733
    CrossrefPubMedGoogle Scholar
  • 5 Moore JB, June CH. Cytokine release syndrome in severe COVID-19. Science 2020; 368 (6490): 473-474
    CrossrefPubMedGoogle Scholar
  • 6 Zhang C, Wu Z, Li JW, Zhao H, Wang GQ. Cytokine release syndrome in severe COVID-19: interleukin-6 receptor antagonist tocilizumab may be the key to reduce mortality. Int J Antimicrob Agents 2020; 55 (05) 105954
    CrossrefPubMedGoogle Scholar
  • 7 Schaller T, Hirschbühl K, Burkhardt K. et al. Postmortem examination of patients with COVID-19. JAMA 2020; (e-pub ahead of print). DOI: 10.1001/jama/2020.8907.
    CrossrefPubMedGoogle Scholar
  • 8 Namendys-Silva SA. ECMO for ARDS due to COVID-19. Heart Lung 2020; 49 (04) 348-349
    CrossrefPubMedGoogle Scholar
  • 9 Ellinghaus D, Degenhardt F, Bujanda L. et al. The ABO blood group locus and a chromosome 3 gene cluster associate with SARS CoV-2 respiratory failure in an Italian-Spanish genome-wide association analysis. MedRxiv 2020; DOI: 10.1101/2020.05.31.20114991.
    CrossrefPubMedGoogle Scholar
  • 10 Giannis D, Ziogas IA, Gianni P. Coagulation disorders in coronavirus infected patients: COVID-19, SARS-CoV-1, MERS-CoV and lessons from the past. J Clin Virol 2020; 127: 104362
    CrossrefPubMedGoogle Scholar
  • 11 Ranucci M, Ballotta A, Di Dedda U. et al. The procoagulant pattern of patients with COVID-19 acute respiratory distress syndrome. J Thromb Haemost 2020; 18 (07) 1747-1751
    CrossrefPubMedGoogle Scholar
  • 12 Bukowska A, Schild L, Bornfleth P. et al. Activated clotting factor X mediates mitochondrial alterations and inflammatory responses via protease-activated receptor signaling in alveolar epithelial cells. Eur J Pharmacol 2020; 869: 172875
    CrossrefPubMedGoogle Scholar
  • 13 Campbell CM, Kahwash R. Will complement inhibition be the new target in treating COVID-19-related systemic thrombosis?. Circulation 2020; 141 (22) 1739-1741
    CrossrefPubMedGoogle Scholar
  • 14 Delabranche X, Helms J, Meziani F. Immunohaemostasis: a new view on haemostasis during sepsis. Ann Intensive Care 2017; 7 (01) 117
    CrossrefPubMedGoogle Scholar
  • 15 Jackson SP, Darbousset R, Schoenwaelder SM. Thromboinflammation: challenges of therapeutically targeting coagulation and other host defense mechanisms. Blood 2019; 133 (09) 906-918
    CrossrefPubMedGoogle Scholar
  • 16 Bikdeli B, Madhavan MV, Jimenez D. et al. COVID-19 and thrombotic or thromboembolic disease: implications for prevention, antithrombotic therapy, and follow-up. J Am Coll Cardiol 2020; 75 (23) 2950-2973
    CrossrefPubMedGoogle Scholar
  • 17 Smith SA, Mutch NJ, Baskar D, Rohloff P, Docampo R, Morrissey JH. Polyphosphate modulates blood coagulation and fibrinolysis. Proc Natl Acad Sci U S A 2006; 103 (04) 903-908
    CrossrefPubMedGoogle Scholar
  • 18 Iba T, Levy JH. Inflammation and thrombosis: roles of neutrophils, platelets and endothelial cells and their interactions in thrombus formation during sepsis. J Thromb Haemost 2018; 16 (02) 231-241
    CrossrefPubMedGoogle Scholar
  • 19 Iba T, Levy JH. Derangement of the endothelial glycocalyx in sepsis. J Thromb Haemost 2019; 17 (02) 283-294
    CrossrefPubMedGoogle Scholar
  • 20 Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost 2020; 18 (04) 844-847
    CrossrefPubMedGoogle Scholar
  • 21 Tang N, Bai H, Chen X, Gong J, Li D, Sun Z. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost 2020; 18 (05) 1094-1099
    CrossrefPubMedGoogle Scholar
  • 22 Chen T, Dai Z, Mo P. et al. Clinical characteristics and outcomes of older patients with coronavirus disease 2019 (COVID-19) in Wuhan, China (2019): a single-centered, retrospective study. J Gerontol A Biol Sci Med Sci 2020; (e-pub ahead of print). DOI: 10.1093/gerona/glaa089.
    CrossrefPubMedGoogle Scholar
  • 23 Huang C, Wang Y, Li X. et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395 (10223): 497-506
    CrossrefPubMedGoogle Scholar
  • 24 Iba T, Levy JH, Wada H, Thachil J, Warkentin TE, Levi M. Subcommittee on Disseminated Intravascular Coagulation. Differential diagnoses for sepsis-induced disseminated intravascular coagulation: communication from the SSC of the ISTH. J Thromb Haemost 2019; 17 (02) 415-419
    CrossrefPubMedGoogle Scholar
  • 25 Levi M, Scully M. How I treat disseminated intravascular coagulation. Blood 2018; 131 (08) 845-854
    CrossrefPubMedGoogle Scholar
  • 26 Lippi G, Bonfanti L, Saccenti C, Cervellin G. Causes of elevated D-dimer in patients admitted to a large urban emergency department. Eur J Intern Med 2014; 25 (01) 45-48
    CrossrefPubMedGoogle Scholar
  • 27 Zhang Y, Xiao M, Zhang S. et al. Coagulopathy and antiphospholipid antibodies in patients with COVID-19. N Engl J Med 2020; 382 (17) e38
    CrossrefPubMedGoogle Scholar
  • 28 Schnittler HJ, Feldmann H. Viral hemorrhagic fever--a vascular disease?. Thromb Haemost 2003; 89 (06) 967-972
    Article in Thieme ConnectPubMedGoogle Scholar
  • 29 Varga Z, Flammer AJ, Steiger P. et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet 2020; 395 (10234): 1417-1418
    CrossrefPubMedGoogle Scholar
  • 30 Connors JM, Levy JH. COVID-19 and its implications for thrombosis and anticoagulation. Blood 2020; 135 (23) 2033-2040
    CrossrefPubMedGoogle Scholar
  • 31 Goette A, Kalman JM, Aguinaga L. et al. Document Reviewers. EHRA/HRS/APHRS/SOLAECE expert consensus on atrial cardiomyopathies: definition, characterization, and clinical implication. Europace 2016; 18 (10) 1455-1490
    CrossrefPubMedGoogle Scholar
  • 32 Inciardi RM, Lupi L, Zaccone G. et al. Cardiac involvement in a patient with coronavirus disease 2019 (COVID-19). JAMA Cardiol 2020; (e-pub ahead of print). DOI: 10.1001/jamacardio.2020.1096.
    CrossrefPubMedGoogle Scholar
  • 33 Mao L, Jin H, Wang M. et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol 2020; (e-pub ahead of print). DOI: 10.1001/jamaneurol.2020.1127.
    CrossrefPubMedGoogle Scholar
  • 34 Chamarthy MR, Park H, Sutphin P. et al. Pulmonary arteriovenous malformations: endovascular therapy. Cardiovasc Diagn Ther 2018; 8 (03) 338-349
    CrossrefPubMedGoogle Scholar
  • 35 Amawi H, Abu Deiab GI, Aljabali AAA, Dua K, Tambuwala MM. COVID-19 pandemic: an overview of epidemiology, pathogenesis, diagnostics and potential vaccines and therapeutics. Ther Deliv 2020; 11 (04) 245-268
    CrossrefPubMedGoogle Scholar
  • 36 Dixon DL, Van Tassell BW, Vecchié A. et al. Cardiovascular considerations in treating patients with coronavirus disease 2019 (COVID-19). J Cardiovasc Pharmacol 2020; 75 (05) 359-367
    CrossrefPubMedGoogle Scholar
  • 37 Grein J, Ohmagari N, Shin D. et al. Compassionate use of remdesivir for patients with severe COVID-19. N Engl J Med 2020; 382: 2327-2336
    CrossrefPubMedGoogle Scholar
  • 38 Hung IF, Lung KC, Tso EY. et al. Triple combination of interferon beta-1b, lopinavir-ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial. Lancet 2020; 395 (10238): 1695-1704
    CrossrefPubMedGoogle Scholar
  • 39 Zhagn S, Li D, Chen H. et al. [Dynamic inflammatory response in a critically ill COVID-19 patient treated with corticosteroids] (in Chinese). Zhejiang Da Xue Xue Bao Yi Xue Ban 2020; 49 (02) 220-226
    PubMedGoogle Scholar
  • 40 van Kraaij TD, Mostard RL, Ramiro S. et al. Tocilizumab in severe COVID-19 pneumonia and concomitant cytokine release syndrome. Eur J Case Rep Intern Med 2020; 7 (05) 001675
    PubMedGoogle Scholar
  • 41 Amlani A, Barber C, Fifi-Mah A, Monzon J. Successful treatment of cytokine release syndrome with IL-6 blockade in a patient transitioning from immune-checkpoint to MEK/BRAF inhibition: a case report and review of literature. Oncologist 2020; 25 (07) e1120-e1123
    CrossrefPubMedGoogle Scholar
  • 42 Alattar R, Ibrahim TBH, Shaar SH. et al. Tocilizumab for the treatment of severe coronavirus disease 2019. J Med Virol 2020; (e-pub ahead of print). DOI: 10.1002/jmv.25964.
    CrossrefPubMedGoogle Scholar