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Time Course of the Development of Immunothrombosis during COVID-19 Hospitalization

J. Oliveira1, G. Vieira-Damiani1,2, G. Locachevic3, J. Mariolano3, K. Soares3, A. Santos1, B. Jacintho1, C. Vaz1, G. Mesquita1, E. Paula4,5, F. Orsi4,3

1School of Medical Sciences, Department of Clinical Medicine, University of Campinas, Campinas, Brazil, 2Federal Institute of Education Science and Technology of São Paulo, Capivari-SP. Department of Biology, Campinas, Brazil, 3School of Medical Sciences, Department of Clinical Pathology, University of Campinas, Campinas, Brazil, 4Hematology and Hemotherapy Center, University of Campinas, Campinas, Brazil, 5School of Medical Sciences, University of Campinas, Campinas, Brazil

Abstract Number: PB0142

Meeting: ISTH 2021 Congress

Theme: COVID and Coagulation » COVID and Coagulation, Basic Science

Background: Hypercoagulability in COVID-19 has been attributed to immunothrombosis, a process that involves the formation of neutrophils extracellular traps (NETs). The moment of the COVID-19 evolution in which immunothrombosis mechanisms are triggered is not established.

Aims: To describe the association of the kinetics of NETs release during COVID-19 hospitalization with death and thrombosis.

Methods: We quantified markers of NETs (citrullinated H3) and inflammatory cytokines (TNF-α, IL-6) on 4 time points during COVID-19 hospitalization (admission, day 4, day 8 and last day) between May and July 2020. The association between changes in these markers levels and clinical outcomes was determined.

Results: Table 1 summarizes the patients characteristics. 101 patients were included, 59% were critically ill, 11% had a thrombotic event and 21% died. Figure 1 illustrates the changes in citH3, IL-6 and TNF- α levels during hospitalization. IL-6 levels were high on admission in survivors (median 25.32, IQR 24.19-28.15) and non-survivors (median 24.19, IQR 12.51-27.19), but gradually decreased after day 4 in survivors. TNF-α levels remained 2 times higher in non-survivors than in survivors during the entire hospitalization period. CitH3 levels were similar between non-survivors and survivors until day 4. On day 8, citH3 increased by 3-fold (median 3.80, IQR 1.98-10.15) in non-survivors and 2-fold (median 2.60, IQR 1.22-5.01) in survivors. While IL-6 and TNF-α levels were similar between patients with and without thrombosis, citH3 levels increased shortly before the occurrence of a thrombotic event.  

Figure 1
Change in citH3, IL-6 and TNF- α levels during hospitalization by clinical outcomes of 101 COVID-19 patients hospitalized between May and July 2020 at the UNICAMP University Hospital in Campinas, Brazil. Patients are groups as survivors (indicated in blue and “0”) and non-survivors (indicated in green and as “1”)

Table 2

  Patients (n=101)
Age in years, median (SD)  58 (13.72)
Men, n (%)                                    63 (62.4)
Days in-hospital, median (SD)  15 (25.68)
Days in ICU, median (SD) 20 (17.47)
Obesity (BMI>30kg/m2), n (%)                                                                      27 (26.7%)
Diabetes, n (%)                                     44 (43.6)
Hypertension, n (%) 54 (53.5)
Pacients with a thrombotic event during hospitalization, n (%) 11 (10.9)
Death during hospitalization, n (%) 21 (20.9)

Clinical characteristics at baseline and main outcomes during hospitalization of 101 COVID-19 patients hospitalized between May and July 2020 at the UNICAMP University Hospital in Campinas, Brazil

Conclusions: Markers of inflammation and immunothrombosis were associated with poor outcomes in COVID-19; however, these disorders were detected in different moments during COVID-19 course. While an increased inflammatory response was observed since the beginning of hospitalization, markers of immunothrombosis arose latter during the course of the disease. Acknowledgment of the time-course of immunothrombosis development in COVID-19 is important for planning therapeutic strategies against this pathological process.    

To cite this abstract in AMA style:

Oliveira J, Vieira-Damiani G, Locachevic G, Mariolano J, Soares K, Santos A, Jacintho B, Vaz C, Mesquita G, Paula E, Orsi F. Time Course of the Development of Immunothrombosis during COVID-19 Hospitalization [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/time-course-of-the-development-of-immunothrombosis-during-covid-19-hospitalization/. Accessed November 29, 2023.

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