Cytokine Filter Experience in Covid-19 Treatment; A Single Center Study

Abstract

Aim: Several studies state that the primary underlying mechanism of severe COVID-19 cases includes the hyperimmune response triggered following SARS-CoV-2 infections and the subsequent cytokine storm. The study aims to examine the effects of cytokine filters on patients with COVID-19 who developed cytokine storms. Material and Methods: This is a retrospective, cross-sectional study. All the patients included in the study had tested positive for COVID-19 in their real-time polymerase chain reaction test. The study included patients with COVID-19 who developed cytokine storms and were treated in the ICU. The patients were divided into two groups those who applied cytokine filter or not. The demographic data and laboratory findings of the patients were recorded. The patient outcomes were categorized as discharged or deceased. Results: The study included 149 patients. Patients’ mean age was 56±29 years, and 125 (83.9%) patients were male. A significant decrease was detected in the levels of fibrinogen, ferritin, lymphocyte count, and CRP after cytokine filtration (p <0.001, <0.001, 0.031, and <0.001, respectively). Age, d-dimer, and lymphocyte count were found independent factors for discharge. Conclusion: The blood filtration method has been found to be useful in the hyperimmune response when administered following early diagnosis in selected cases. When administered following early diagnosis in selected cases, the method can be beneficial in supplementing the effectiveness of primary therapies and preventing secondary cytokine release complications as it controls hyperinflammation.

Keywords

• cytokine storm
• COVID-19
• therapeutics
• interleukin
• blood

Covid-19 Tedavisinde Sitokin Filtresi Deneyimi;Tek Merkezli Bir Çalışma

Öz

Amaç: Yapılan birçok çalışmada şiddetli COVID-19 vakalarının altında yatan ana mekanizmanın, enfeksiyonu takiben tetiklenen hiperimmün yanıt ve ardından gelişen sitokin fırtınası olduğu belirtilmektedir. Çalışmamız sitokin fırtınası gelişen COVID-19 hastalarında, sitokin filtrelerisinin tedavideki etkilerini incelemeyi amaçlamaktadır. Materyal ve Metot: Çalışmamız retrospektif, kesitsel bir çalışmadır. Çalışmaya dahil edilen tüm hastaların gerçek zamanlı polimeraz zincir reaksiyonu ile COVID-19 testi pozitif olan hastalardan oluşmaktadır. Çalışma, sitokin fırtınaları geliştiren ve yoğun bakım ünitesinde tedavi edilen COVID-19 hastalarını içeriyordu. Hastalar sitokin filtresi uygulanan ve uygulanmayanlar olmak üzere iki gruba ayrıldı. Hastaların demografik verileri ve laboratuvar bulguları kaydedildi. Hasta sonuçları taburcu veya ölen olarak kategorize edildi. Bulgular: Çalışmaya 149 hasta dahil edildi. Hastaların yaş ortalaması 56±29 yıl olup 125 (%83,9) hasta erkekti. Sitokin filtrasyonu sonrası fibrinojen, ferritin, lenfosit sayısı ve CRP düzeylerinde anlamlı düşüş tespit edildi (sırasıyla p <0,001, <0,001, 0,031 ve <0,001). Yaş, d-dimer ve lenfosit sayısının taburculuk için bağımsız faktörler olduğu tespit edildi. Sonuç: Seçilmiş olgularda ve erken tanı sonrası kan filtrasyon yöntemlerinin uygulanması hiperimmün yanıt tedavisinde faydalı olduğu bulunmuştur. Seçilmiş vakalarda erken tanının ardından uygulandığında bu yöntem, hiperinflamasyonu kontrol altına aldığı için birincil tedavilerin etkinliğini desteklemede ve sitokin salınımına sekonder gelişen komplikasyonları önlemede faydalı olabilir.

Anahtar Kelimeler

• sitokin fırtınası
• Covid-19
• terapötik
• interlökin
• kan

References

1. 1. Coronaviridae Study Group of the International Committee on Taxonomy of Viruses. The species severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat Microbiol. 2020;5(4):536-544. doi:10.1038/s41564-020-0695-z
2. 2. L. Lin, L. Lu, W. Cao, T. Li Hypothesis for potential pathogenesis of SARS-CoV-2 infection-a review of immune changes in patients with viral pneumonia Emerg. Microb. Infect. 2020; 9:727-32. doi:10.1080/22221751.2020.1746199
3. 3. Spina S, Marrazzo F, Migliari M, Stucchi R, Sforza A, Fumagalli R. The response of Milan’s Emergency Medical System to the COVID-19 outbreak in Italy. Lancet 2020;395: e49-50. doi:10.1016/S0140-6736(20)30493-1
4. 4. Tang Y, Liu J, Zhang D, Xu Z, Ji J, Wen C. Cytokine Storm in COVID-19: The Current Evidence and Treatment Strategies. Front Immunol. 2020;11: 1708. doi:10.3389/fimmu.2020.01708
5. 5. Law HK, Cheung CY, Ng HY. et al. Chemokine upregulation in sars-coronavirus–infected, monocyte-derived human dendritic cells. Blood 2005;106: 2366-74. doi:10.1182/blood-2004-10-4166
6. 6. Abbas AK, Lichtman AH, Pillai SP Chapter 4: Innate Immunity, Cellular and Molecular Immunology, 9th Ed.-International Edition, Philadelphia, Saunders-Elsevier Science, 2018, p.57-95.
7. 7. Channappanavar R, Perlman S. Pathogenic human coronavirus infections causes and consequences of cytokine storm and immunopathology. Semin Immunopathol. 2017;39(5): 529‐39. doi:10.1007/s00281-017-0629-x
8. 8. Yao XH, He ZC, Li TY, et al. Pathological evidence for residual SARSCoV‐ 2 in pulmonary tissues of a ready‐for‐discharge patient. Cell Res. 2020;30: 541‐3. doi:10.1038/s41422-020-0318-5

9. 9. Hojyo S, Uchida M, Tanaka K, et al. How COVID-19 induces cytokine storm with high mortality. Inflamm Regen. 2020;40: 37. doi:10.1186/s41232-020-00146-3
10. 10. Tay MZ, Poh CM, Renia L, MacAry PA, Ng LFP. The trinity of COVID-19: immunity, inflammation, and intervention. Nat Rev Immunol. 2020;20(6): 363-74. doi:10.1038/s41577-020-0311-8
11. 11. Bonavia A, Groff A, Karamchandani K, Singbartl K. Clinical utility of extracorporeal cytokine hemoadsorption therapy: a literature review. Blood Purif. 2018;46(4): 337-49. doi:10.1159/000492379
12. 12. Villa G, Zaragoza JJ, Sharma A, Neri M, De Gaudio AR, Ronco C. Cytokine removal with high cut-off membrane: review of literature. Blood Purif. 2014; 38(3-4): 167-73. doi:10.1159/000369155
13. 13. Kogelmann K, Jarczak D, Scheller M, Drüner M. Hemoadsorption by CytoSorb in septic patients: a case series. Crit Care. 2017;21(1): 74. doi:10.1186/s13054-017-1662-9
14. 14. Rimmelé T, Kellum JA. Clinical review: blood purification for sepsis. Crit Care. 2011;15(1): 205. doi:10.1186/cc9411
15. 15. Hetz, H, Berger R, Recknagel P, Steltzer H. Septic shock secondary to β-hemolytic streptococcus-induced necrotizing fasciitis treated with a novel cytokine adsorption therapy. Int J Artif Organs. 2014; 37(5): 422-6. doi:10.5301/ijao.5000315
16. 16. Taniguchi T, Hirai F, Takemoto Y, et al. A novel adsorbent of circulating bacterial toxins and cytokines: the effect of direct hemoperfusion with CTR column for the treatment of experimental endotoxemia. Crit Care Med. 2006;34(3): 800-6. doi:10.1097/01.ccm.0000202449.15027.ae
17. 17. AL Shareef K, Bakouri M. Cytokine Blood Filtration Responses in COVID-19; Blood Purif 2021;50: 141-9. doi:10.1159/000508278
18. 18. Ruiz-Rodríguez JC, Molnar Z, Deliargyris EN, Ferrer R. The Use of CytoSorb Therapy in Critically Ill COVID-19 Patients: Review of the Rationale and Current Clinical Experiences. Crit Care Res Pract. 2021;2021: 7769516. doi:10.1155/2021/7769516
19. 19. Berlot G, Tomasini A, Pognuz ER. et al. The combined use of tocilizumab and hemoadsorption in a patient with SARS-COV-2-19-associated pneumonia: a case report. Nephron. 2020;144(9): 459–62. doi:10.1159/000509738
20. 20. Mehta Y, Mehta C, Nanda S, Kochar G, George JV, Singh MK. Use of CytoSorb therapy to treat critically ill coronavirus disease 2019 patients: a case series; Med Case Reports 2021;15: 476. doi:10.1186/s13256-021-03021-y
21. 21. Friesecke S, Stecher SS, Gross S, Felix SB, Nierhaus A. Extracorporeal cytokine elimination as rescue therapy in refractory septic shock: a prospective single-center study. J Artif Organs. 2017;20(3): 252-9. doi:10.1007/s10047-017-0967-4
22. 22. Brouwer WP, Duran S, Kuijper M, Ince C. Hemoadsorption with CytoSorb shows a decreased observed versus expected 28-day all-cause mortality in ICU patients with septic shock: a propensity-score-weighted retrospective study. Crit Care. 2019;23(1): 317. doi:10.1186/s13054-019-2588-1