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Covid 19'a Bağlı Hiperinflamasyonda Tocilizumab Tedavisinin Serokonversiyon Üzerine Etkisi

Yıl 2024, Cilt: 8 Sayı: 1, 39 - 44, 30.04.2024
https://doi.org/10.30565/medalanya.1443962

Öz

Amaç:Devam eden COVID-19 pandemisi sürecinde, hastalığa ikincil olarak ortaya çıkan ciddi bir semptom olan hiperinflamasyonun yönetimi büyük bir meydan okuma olarak karşımıza çıkmıştır. İmmünsüpresif bir ilaç olan Tocilizumab, potansiyel bir çözüm sunmaktadır. Ancak, Covid-19'dan iyileşme sonrası antikor oluşumu üzerindeki etkilerini anlamak son derece önemlidir. Bu nedenle, çalışmamız bu spesifik tedaviyi alan hastalarda, enfeksiyon sonrası üçüncü ayda SARS-COV-2 spike toplam antikor seviyelerini ölçerek, tocilizumab tedavisinin antikor üretimi üzerindeki etkilerini araştırmayı amaçlamıştır.

Yöntemler: Çalışmamız, hastaneye yatırıldıkları sırada hiperinflamasyon gösteren ve Covid-19 tanısı almış 48 hastayı içermektedir. Bu hastalar kurumumuza kabul edilmiş, tocilizumab ile tedavi edilmiş ve sonrasında taburcu edilmişlerdir. Bu hastaların 3. ay SARS-COV-2 spike toplam antikor seviyeleri titizlikle belirlenmiştir.

Bulgular: Çalışmanın katılımcıları, ortalama yaşları 52,5 ± 11,6 olan, yaş, cinsiyet, komorbidite ve hastanede kalış süresi ne olursa olsun 3. ayda pozitif SARS-COV-2 spike toplam antikor seviyeleri göstermiştir. Hastaların ortalama antikor seviyeleri 223,58 ± 68,36 U/mL olarak ölçülmüş, aralık 14,2 ile 250 U/mL arasında değişmiştir.
Sonuç: Bulgularımız, tüm hastaların tocilizumab tedavisi sonrası 3 ayda pozitif antikor seviyeleri sergilediklerini ortaya koymaktadır. Bu, hiperinflamasyonun Covid 19'a ikincil yönetiminde tocilizumab uygulamasının, en azından kısa vadede, antikor oluşumunu olumsuz etkilemediğini göstermektedir. Bu, gelecekteki tedavi stratejileri için önemli sonuçlar doğurabilir.

Kaynakça

  • 1. Fang X, Li S, Yu H, Wang P, Zhang Y, Chen Z, et al. Epidemiological, comorbidity factors with severity and prognosis of COVID-19: a systematic review and meta-analysis. Aging (albany NY) 2020;12:2493. doi: 10.18632/aging.103579.
  • 2. Lighter J, Phillips M, Hochman S, Sterling S, Johnson D, Francois F, et al. Obesity in patients younger than 60 years is a risk factor for Covid-19 hospital admission. Clin Infect Dis 2020;71: 896-7. doi: 10.1093/cid/ciaa415.
  • 3. Ozturk S, Turgutalp K, Arici M, Odabas AR, Altiparmak MR, Cebeci E, et al. Mortality analysis of COVID-19 infection in chronic kidney disease, haemodialysis and renal transplant patients compared with patients without kidney disease: a nationwide analysis from Turkey. Nephrol Dial Transplant. 2020;35:2083-95. doi: 10.1093/ndt/gfaa271.
  • 4. Gustine JN and Jones D. Immunopathology of Hyperinflammation in COVID-19. Am Jf Pathol. 2021;191:4-17. doi: 10.1016/j.ajpath.2020.08.009
  • 5. Manson JJ, Crooks C, Naja M, Ledlie A, Goulden B, Liddle T, et al. COVID-19-associated hyperinflammation and escalation of patient care: a retrospective longitudinal cohort study. Lancet Rheumatol. 2020;2:e594-e602. doi: 10.1016/S2665-9913(20)30275-7.
  • 6. Tufan A, Güler AA and Matucci-Cerinic M. COVID-19, immune system response, hyperinflammation and repurposingantirheumatic drugs. Turk J Med Sci. 2020;50:620-32. doi: 10.3906/sag-2004-168 .
  • 7. Liu B, Li M, Zhou Z, Guan X and Xiang Y. Can we use interleukin-6 (IL-6) blockade for coronavirus disease 2019 (COVID-19)-induced cytokine release syndrome (CRS)? J Autoimmun. 2020;111:102452. doi: 10.1016/j.jaut.2020.102452.
  • 8. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020;395:1054-62. doi: 10.1016/S0140-6736(20)30566-3.
  • 9. Guan W-j, Ni Z-y, Hu Y, Liang W, Ou C, He J, et al. Clinical characteristics of coronavirus disease 2019 in China. N Eng J Med. 2020;382:1708-20. doi: 10.1056/NEJMoa2002032.
  • 10. Toniati P, Piva S, Cattalini M, Garrafa E, Regola F, Castelli F, et al. Tocilizumab for the treatment of severe COVID-19 pneumonia with hyperinflammatory syndrome and acute respiratory failure: a single center study of 100 patients in Brescia, Italy. Autoimmun Rev. 2020;19:102568. doi: 10.1016/j.autrev.2020.102568.
  • 11. Ejazi SA, Ghosh S and Ali N. Antibody detection assays for COVID‐19 diagnosis: an early overview. Immunol Cell Biol. 2021;99:21-33. doi: 10.1111/imcb.12397.
  • 12. Xiao AT, Gao C and Zhang S. Profile of specific antibodies to SARS-CoV-2: the first report. J Infect. 2020;81:147-78. doi: 10.1016/j.jinf.2020.03.012.
  • 13. Fidecicchi T, Fruzzetti F, Lete Lasa LI and Calaf J. COVID-19, gender and estroprogestins, what do we know? Eur J Contracep Reprod Health Care. 2022;27:67-74. doi: 10.1080/13625187.2021.2000959.
  • 14. Savoia C, Volpe M and Kreutz R. Hypertension, a moving target in COVID-19: current views and perspectives. Circ Res. 2021;128:1062-79. doi: 10.1161/CIRCRESAHA.121.318054.
  • 15. Rosas IO, Bräu N, Waters M, Go RC, Hunter BD, Bhagani S, et al. Tocilizumab in hospitalized patients with severe Covid-19 pneumonia. N Engl J Med. 2021;384(16):1503-16. doi: 10.1056/NEJMoa2028700.
  • 16. Hamaoka T, Ono S. Regulation of B-cell differentiation: interactions of factors and corresponding receptors. Annu Rev Immunol. 1986;4:167-204. doi: 10.1146/annurev.iy.04.040186.001123. 17. Sheppard M, Laskou F, Stapleton PP, Hadavi S and Dasgupta B. Tocilizumab (actemra). Hum Vaccin Immunother. 2017;13:1972-88. doi: 10.1080/21645515.2017.1316909.
  • 18. Tanaka T, Narazaki M and Kishimoto T. IL-6 in inflammation, immunity, and disease. Cold Spring Harb Perspect Biol. 2014;6:a016295. doi: 10.1101/cshperspect.a016295.
  • 19. Capra R, De Rossi N, Mattioli F, Romanelli G, Scarpazza C, Sormani MP, et al. Impact of low dose tocilizumab on mortality rate in patients with COVID-19 related pneumonia. Eur J İntern Med. 2020;76:31-5. doi: 10.1016/j.ejim.2020.05.009.
  • 20. Eşkazan AE, Balkan İİ, Demirbaş KC, Ar MC, Karali R, Sekibağ Y, et al. Tocilizumab in COVID-19: the Cerrahpaşa-PREDICT score. J Infect Chemother. 2021;27:1329-35. doi: 10.1016/j.jiac.2021.05.007.
  • 21. Zhang C, Wu Z, Li J-W, Zhao H and 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(5):105954. doi: 10.1016/j.ijantimicag.2020.105954.
  • 22. Antisitokin-antiinflamatuar tedaviler, koagülopati yönetimi. T.C. Sağlık Bakanlığı. 2021. https://covid19.saglik.gov.tr/Eklenti/39296/0/covid-19rehberiantisitokin-antiinflamatuartedavilerkoagulopatiyonetimipdf.pdf
  • 23. Ciotti JR, Valtcheva MV and Cross AH. Effects of MS disease-modifying therapies on responses to vaccinations: A review. Mult Scler Relat Disord. 2020;45:102439. doi: 10.1016/j.msard.2020.102439.
  • 24. Long Q-X, Liu B-Z, Deng H-J, Wu GC, Deng K, Chen YK, et al. Antibody responses to SARS-CoV-2 in patients with COVID-19. Nat Med. 2020;26:845-8. doi: 10.1038/s41591-020-0897-1.
  • 25. Maine GN, Lao KM, Krishnan SM, Oloye OA, Fatemi S, Kumar S, et al. Longitudinal characterization of the IgM and IgG humoral response in symptomatic COVID-19 patients using the Abbott Architect. J Clin Virol. 2020;133:104663. doi: 10.1016/j.jcv.2020.104663.

Effect of Tocilizumab Treatment on Seroconversion in Hyperinflammation Secondary to Covid 19

Yıl 2024, Cilt: 8 Sayı: 1, 39 - 44, 30.04.2024
https://doi.org/10.30565/medalanya.1443962

Öz

Aim:During the ongoing COVID-19 pandemic, the management of hyperinflammation, a serious symptom that occurs secondary to the disease, has emerged as a major challenge. Tocilizumab, an immunosuppressive drug, offers a potential solution. However, it is extremely important to understand its effects on antibody formation after recovery from Covid-19. Therefore, our study aimed to investigate the effects of tocilizumab treatment on antibody production by measuring SARS-COV-2 spike total antibody levels at the third month post-infection in patients receiving this specific treatment.

Materyal and Methods:Our study incorporated 48 patients diagnosed with Covid 19 who presented with hyperinflammation during hospitalization. These patients, admitted to our institution, were treated with tocilizumab and subsequently discharged. We meticulously determined the 3rd month SARS-COV-2 spike total antibody levels in these patients.

Results:The participants of the study, characterized by a mean age of 52.5 ± 11.6 years, demonstrated positive SARS-COV-2 spike total antibody levels at 3 months, irrespective of age, gender, comorbidity, and length of hospital stay. The mean antibody levels in the patient population were quantified to be 223.58 ± 68.36 U/mL, with a range from 14.2 to 250 U/mL.

Conclusion: Our findings reveal that all patients exhibited positive antibody levels at 3 months following tocilizumab treatment.This suggests that the administration of tocilizumab in the management of hyperinflammation secondary to Covid 19 does not adversely affect antibody formation, at least in the short term. This could have substantial implications for future treatment strategies.

Kaynakça

  • 1. Fang X, Li S, Yu H, Wang P, Zhang Y, Chen Z, et al. Epidemiological, comorbidity factors with severity and prognosis of COVID-19: a systematic review and meta-analysis. Aging (albany NY) 2020;12:2493. doi: 10.18632/aging.103579.
  • 2. Lighter J, Phillips M, Hochman S, Sterling S, Johnson D, Francois F, et al. Obesity in patients younger than 60 years is a risk factor for Covid-19 hospital admission. Clin Infect Dis 2020;71: 896-7. doi: 10.1093/cid/ciaa415.
  • 3. Ozturk S, Turgutalp K, Arici M, Odabas AR, Altiparmak MR, Cebeci E, et al. Mortality analysis of COVID-19 infection in chronic kidney disease, haemodialysis and renal transplant patients compared with patients without kidney disease: a nationwide analysis from Turkey. Nephrol Dial Transplant. 2020;35:2083-95. doi: 10.1093/ndt/gfaa271.
  • 4. Gustine JN and Jones D. Immunopathology of Hyperinflammation in COVID-19. Am Jf Pathol. 2021;191:4-17. doi: 10.1016/j.ajpath.2020.08.009
  • 5. Manson JJ, Crooks C, Naja M, Ledlie A, Goulden B, Liddle T, et al. COVID-19-associated hyperinflammation and escalation of patient care: a retrospective longitudinal cohort study. Lancet Rheumatol. 2020;2:e594-e602. doi: 10.1016/S2665-9913(20)30275-7.
  • 6. Tufan A, Güler AA and Matucci-Cerinic M. COVID-19, immune system response, hyperinflammation and repurposingantirheumatic drugs. Turk J Med Sci. 2020;50:620-32. doi: 10.3906/sag-2004-168 .
  • 7. Liu B, Li M, Zhou Z, Guan X and Xiang Y. Can we use interleukin-6 (IL-6) blockade for coronavirus disease 2019 (COVID-19)-induced cytokine release syndrome (CRS)? J Autoimmun. 2020;111:102452. doi: 10.1016/j.jaut.2020.102452.
  • 8. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020;395:1054-62. doi: 10.1016/S0140-6736(20)30566-3.
  • 9. Guan W-j, Ni Z-y, Hu Y, Liang W, Ou C, He J, et al. Clinical characteristics of coronavirus disease 2019 in China. N Eng J Med. 2020;382:1708-20. doi: 10.1056/NEJMoa2002032.
  • 10. Toniati P, Piva S, Cattalini M, Garrafa E, Regola F, Castelli F, et al. Tocilizumab for the treatment of severe COVID-19 pneumonia with hyperinflammatory syndrome and acute respiratory failure: a single center study of 100 patients in Brescia, Italy. Autoimmun Rev. 2020;19:102568. doi: 10.1016/j.autrev.2020.102568.
  • 11. Ejazi SA, Ghosh S and Ali N. Antibody detection assays for COVID‐19 diagnosis: an early overview. Immunol Cell Biol. 2021;99:21-33. doi: 10.1111/imcb.12397.
  • 12. Xiao AT, Gao C and Zhang S. Profile of specific antibodies to SARS-CoV-2: the first report. J Infect. 2020;81:147-78. doi: 10.1016/j.jinf.2020.03.012.
  • 13. Fidecicchi T, Fruzzetti F, Lete Lasa LI and Calaf J. COVID-19, gender and estroprogestins, what do we know? Eur J Contracep Reprod Health Care. 2022;27:67-74. doi: 10.1080/13625187.2021.2000959.
  • 14. Savoia C, Volpe M and Kreutz R. Hypertension, a moving target in COVID-19: current views and perspectives. Circ Res. 2021;128:1062-79. doi: 10.1161/CIRCRESAHA.121.318054.
  • 15. Rosas IO, Bräu N, Waters M, Go RC, Hunter BD, Bhagani S, et al. Tocilizumab in hospitalized patients with severe Covid-19 pneumonia. N Engl J Med. 2021;384(16):1503-16. doi: 10.1056/NEJMoa2028700.
  • 16. Hamaoka T, Ono S. Regulation of B-cell differentiation: interactions of factors and corresponding receptors. Annu Rev Immunol. 1986;4:167-204. doi: 10.1146/annurev.iy.04.040186.001123. 17. Sheppard M, Laskou F, Stapleton PP, Hadavi S and Dasgupta B. Tocilizumab (actemra). Hum Vaccin Immunother. 2017;13:1972-88. doi: 10.1080/21645515.2017.1316909.
  • 18. Tanaka T, Narazaki M and Kishimoto T. IL-6 in inflammation, immunity, and disease. Cold Spring Harb Perspect Biol. 2014;6:a016295. doi: 10.1101/cshperspect.a016295.
  • 19. Capra R, De Rossi N, Mattioli F, Romanelli G, Scarpazza C, Sormani MP, et al. Impact of low dose tocilizumab on mortality rate in patients with COVID-19 related pneumonia. Eur J İntern Med. 2020;76:31-5. doi: 10.1016/j.ejim.2020.05.009.
  • 20. Eşkazan AE, Balkan İİ, Demirbaş KC, Ar MC, Karali R, Sekibağ Y, et al. Tocilizumab in COVID-19: the Cerrahpaşa-PREDICT score. J Infect Chemother. 2021;27:1329-35. doi: 10.1016/j.jiac.2021.05.007.
  • 21. Zhang C, Wu Z, Li J-W, Zhao H and 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(5):105954. doi: 10.1016/j.ijantimicag.2020.105954.
  • 22. Antisitokin-antiinflamatuar tedaviler, koagülopati yönetimi. T.C. Sağlık Bakanlığı. 2021. https://covid19.saglik.gov.tr/Eklenti/39296/0/covid-19rehberiantisitokin-antiinflamatuartedavilerkoagulopatiyonetimipdf.pdf
  • 23. Ciotti JR, Valtcheva MV and Cross AH. Effects of MS disease-modifying therapies on responses to vaccinations: A review. Mult Scler Relat Disord. 2020;45:102439. doi: 10.1016/j.msard.2020.102439.
  • 24. Long Q-X, Liu B-Z, Deng H-J, Wu GC, Deng K, Chen YK, et al. Antibody responses to SARS-CoV-2 in patients with COVID-19. Nat Med. 2020;26:845-8. doi: 10.1038/s41591-020-0897-1.
  • 25. Maine GN, Lao KM, Krishnan SM, Oloye OA, Fatemi S, Kumar S, et al. Longitudinal characterization of the IgM and IgG humoral response in symptomatic COVID-19 patients using the Abbott Architect. J Clin Virol. 2020;133:104663. doi: 10.1016/j.jcv.2020.104663.
Toplam 24 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular İç Hastalıkları, Klinik Kimya, Klinik Mikrobiyoloji
Bölüm Araştırma Makalesi
Yazarlar

Faruk Karandere 0000-0002-7423-0170

Deniz Yılmaz 0000-0001-9870-5305

Felemez Arslan 0000-0001-8318-1860

Ezgi Şahin 0000-0001-6162-8983

Hakan Koçoğlu 0000-0002-9208-2693

Nilgün Işıksaçan 0000-0002-0230-6500

Yayımlanma Tarihi 30 Nisan 2024
Gönderilme Tarihi 27 Şubat 2024
Kabul Tarihi 23 Mart 2024
Yayımlandığı Sayı Yıl 2024 Cilt: 8 Sayı: 1

Kaynak Göster

Vancouver Karandere F, Yılmaz D, Arslan F, Şahin E, Koçoğlu H, Işıksaçan N. Effect of Tocilizumab Treatment on Seroconversion in Hyperinflammation Secondary to Covid 19. Acta Med. Alanya. 2024;8(1):39-44.

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