Email this article CYTOKINE PROFILE OF COVID-19 CONVALESCENT PLASMA AND ITS RELATIONSHIP TO OUTCOME OF TREATED PATIENTS
- Authors: Potapnev M.P.1, Maximovich A.V.1, Dunayev I.A.1, Hushchina L.M.1, Karpenko F.N.1
-
Affiliations:
- Republican Scientific and Practical Center for Transfusiology and Medical Biotechnologies, Minsk, Belarus
- Section: Joint Immunology Forum 2024
- URL: https://rusimmun.ru/jour/article/view/16580
- DOI: https://doi.org/10.46235/1028-7221-16580-CPO
- ID: 16580
Cite item
Full Text
Abstract
Abstract
COVID-19 convalescent plasma (CCP) is considered as an important element of therapy for patients in the initial stages of the disease.The main therapeutic effect of CCP is associated with the presence of specific antiviral antibodies. Additionally, the immunomodulatory effect of CCP is considered as therapeutic where cytokines represented one of the main factors.
The aim of the study was to evaluate the importance of cytokines and cytokine ratio of transfused CCP for the outcome of the disease in patients who received it during inpatient treatment of COVID-19.
Methods: the study included data from 111 patients with COVID-19 who received CCP. The cytokine content in the CCP was measured by enzyme immunoassay
Results: It was found that elevated levels of interleukin-6 (IL-6) and interferon-gamma (IFN-γ), but not IL-1β, IL-8, IL-10, IL-15, IP-10/CXCL10, MCP-1/CCL2 were detected in CCP transfused mainly to patients who had an unfavorable (fatal) outcome of the disease. Values of cytokine ratios of IFN-γ/IL-10, IFN-γ/IP-10, IFN-γ/MCP-1, IL-6/IL-8, IL-6/IL-10, IL-6/IP-10, IL-6/IL-15 were also significantly increased in these CCP series as compared to CCP samples transfused to patients of the recovered group. Low levels of IL-6 and IFN-γ, reduced level of cytokine ratios of IL-6/IP-10, IL-6/IL-15, IFN-γ/MCP-1, IFN-γ/IP-10, IFN-γ/IL-15 were characteristic of CCP, which was transfused to patients, subsequently recovered. The level of IL-6 in the CCP samples transfused to the patients of the recovered group had a strong direct correlation (r= 0.9) with the cytokine ratios of IL-6/IL-10 and IL-6/IP-10, while in the group of the deceased patients there was no strong association (r=0.6). IFN-γ levels in the CCP showed a strong direct correlation with the values of all analyzed cytokine ratios (IFN-γ/ IL-10 (r=0.9), IFN-γ/IP-10 (r=0.9), IFN-γ/MCP-1 (r=0.9)). The level of INF-γ in the CCP transfused to patients of the recovered group had a positive correlation with the cytokine ratios of IFN-γ/IL-10 (r=0.78), IFN-γ/IP-10 (r=0.9), IFN-γ/MCP-1 (r=0.75). The level of INF-γ in the CCP transfused to patients of the deceased group had higher values of positive correlation with ratios of IFN-γ/IL-10 (r=0.96), IFN-γ/IP-10 (r=0.92), IFN-γ/MCP-1 (r=0.92).
Conclusion: The level of cytokines IL-6 and IFN-γ, the cytokine ratios based on them in the CCP may affect the outcome of COVID-19 in patients treated with CCP.
About the authors
Michael Petrovich Potapnev
Republican Scientific and Practical Center for Transfusiology and Medical Biotechnologies, Minsk, Belarus
Email: mpotapnev@yandex.by
ORCID iD: 0000-0002-6805-1782
SPIN-code: 5379-2168
Scopus Author ID: 7004113745
MD, PhD, DSc., Professor, Head the Department of Cellular Biotechnologies, Republican Scientific and Practical Center of Transfusiology and Medical Biotechnologies, Minsk, Belarus
Belarus, Dolginovski tract, 160. 220080. MinskAleksey Vladimirovich Maximovich
Republican Scientific and Practical Center for Transfusiology and Medical Biotechnologies, Minsk, Belarus
Email: max.alex.wf@gmail.com
ORCID iD: 0009-0005-0635-7347
Junior Researcher, Laboratory of biology and genetics of stem cells, Republican Scientific Practical Center of Transfusiology and Medical Biotechnologies, Minsk, Belarus
Russian Federation, Dolginovski tract, 160. 220080. MinskIgor Anatolievich Dunayev
Republican Scientific and Practical Center for Transfusiology and Medical Biotechnologies, Minsk, Belarus
Email: dunaev05@mail.ru
ORCID iD: 0009-0008-8020-2919
MD, PhD., Transfusiologist, Republican Scientific and Practical Center of Transfusiology and Medical Biotechnologies, Minsk, Belarus
Russian Federation, Dolginovski tract, 160. 220080. MinskLarisa Mihailovna Hushchina
Republican Scientific and Practical Center for Transfusiology and Medical Biotechnologies, Minsk, Belarus
Email: gushchina73@mail.ru
ORCID iD: 0000-0002-1434-9639
MD, Deputy Director for Transfusiology, Republican Scientific and Practical Center of Transfusiology and Medical Biotechnologies, Minsk, Belarus
Russian Federation, Dolginovski tract, 160. 220080. MinskFedor Nikolaevich Karpenko
Republican Scientific and Practical Center for Transfusiology and Medical Biotechnologies, Minsk, Belarus
Author for correspondence.
Email: director@blood.by
ORCID iD: 0009-0009-7890-5495
MD, PhD., Director, Republican Scientific and Practical Center of Transfusiology and Medical Biotechnologies, Minsk, Belarus
Russian Federation, Dolginovski tract, 160. 220080. MinskReferences
- Максимович А.В., Потапнев М.П., Дунаев И.А., Гущина Л.М., Карпенко Ф.Н. Особенности цитокинового профиля и противовоспалительной активности in vitro плазмы иммунной анти-COVID-19 // Иммунопатология, аллергология, инфектология, 2023, № 2, с.46-51. doi: 10.14427/jipai.2023.2.46 [Maksimovich A.V., Potapnev M.P., Dunayeu I.A., Hushchina L.M., Karpenko F.N. Cytokine profile and anti-inflammatory activity in vitro of Covid-19 convalescent plasma. Immunopatologiya, allergologiya, infektologiya = Immunopathology, allergology, infectology, 2023, no.2, pp.46-51. (In Russ.)]
- Первакова М.Ю., Потапенко В.Г., Ткаченко О.Ю., Волчкова Е.В., Титова О.Н., Лапин С.В., Суркова Е.А., Блинова Т.В., Холопова И.В., Кузнецова Д.А., Мошникова А.Н., Мазинг А.В., Куликов А.Н., Полушин Ю.С., Афанасьев А.А., Шлык И.В., Гаврилова Е.Г., Климович А.В., Медведева Н.В., Эмануэль В.Л. Цитокиновые паттерны летальных гипервоспалительных состояний, индуцированных вторичным гемофагоцитарным синдромом, бактериальным сепсисом и COVID-19 //Иммунология, 2022, Т. 43, №. 2, С. 174-187. https://orcid.org/0000-0001-9630-257X [Pervakova M.Yu., Potapenko V.G., Tkachenko O.Yu., Volchkova E.V., Titova O.N., Lapin S.V., Surkova E.A., Blinova T.V., Kholopova I.V., Kuznetsova D.A., Moshnikova A.N., Mazing A.V., Kulikov A.N., Polushin Yu.S.,Afanasyev A.A., Shlyk I.V., Gavrilova E.G., Klimovich A.V., Medvedeva N.V., EmanuelV.L. Cytokine patterns of fatal hyperinflammatory conditions, caused by secondary hemophagocytic lymphohistiocytosis, bacterial sepsis and COVID-19. Immunologiya. 2022, Vol. 43, no.2, pp. 174–187. (in Russ.)]
- Потапнев М.П. Цитокиновый шторм. Причины и последствия // Иммунология. 2021, Т. 42, №. 2, С. 175-188. DOI: https://doi.org/10.33029/ 0206-4952-2021-42-2-175-188 [Potapnev M.P. Cytokine storm. Causes and consequences. Immunologiya. 2021, Vol. 42, no. 2, pp.175–88. (in Russ.)]
- Acosta-Ampudia Y., Monsalve D.M., Rojas M., Rodriguez Y., Gallo J.E., Salazar-Uribe J.C., Santander M.J., Gala M.P., Zapata W., Zapata M.I., Manrique R., Pardo-Oviedo J.M., Camacho B., Ramfrez-Santana C., Anaya J.-M. , the CP-COVID-19 group. J. Autoimmunity 2021; 118: 102598. https:/doi.org./10.1016/j.jaut.2021.102598
- Agarwal A., Mukherjee A., Kumar G., Chatterjee P., Bhatnagar T., Malhotra P. (2020). Convalescent plasma in the management of moderate covid-19 in adults in India: open label phase II multicentre randomised controlled trial (PLACID Trial). BMJ. 2020; 371:m3939. http:// dx.doi.org/10.1136/mbj.m3939
- Bandopadhyay P., D’Rozario R., Lahiri A., Sarif J., Paul S.R., Roy R., Maiti R., Chaudhuri K., Bagchi S., Maiti A., PerwezM.M., Sarkar B.S., Roy D., Chakraborthy R., Vasudevan J.S., Sharma S., Biswas D., Maiti C., Saha B., Bhattacharya P., Pandey R., Chatterjee S., Paul S., Ganguly D. Nature and dimensions of systemic hyperinflammation and its attenuation by convalescent plasma in severe COVID-19. J. Infect. Diseases. 2021;224: 565 doi: 10.1093/infdis/jiab010
- Bonny T.S., Patel E.U., Zhu X., Bloch E.M., Grabowski M.K., Abraham A.G., Littlefield K., Shrestha R., Benner S.E., Laeyendecker O., Shoham S., Sullivan D., Quinn T.C., Casadevall A., Pekosz A., Redd A.D., Tobian A.A.R. Cytokine and chemokine levels in coronavirus disease 2019 convalescent plasma . In Open Forum Infectious Diseases.- US: Oxford University Press, 2021- 8 (2). C.ofaa574 doi: 10.1093/ofid/ofaa574
- Briggs N., Gormally, M. V., Li F., Browning S. L., Treggiari M. M., Morrison A.., Laurent-Rolle M., Deng Y., Hendrickson J.E., Tormey C.A., Desruisseaux, M. S. (2021). Early but not late convalescent plasma is associated with better survival in moderate-to-severe COVID-19. PLoS One, 16(7), e0254453.
- Chavda V. P., Bezbaruah R., Dolia S., Shah N., Verma S., Savale S., Ray S. Convalescent plasma (hyperimmune immunoglobulin) for COVID-19 management: An update. Process Biochemistry . 2023; 127: 66-81. https:doi.org.10.1016/j.procbio.2023.01.018
- Hakim S.M., Chikhouni G. M.A., Ammar M.A., Amer A.M. Effec t of convalescent plasma transfusion on outcome of coronavirus disease 2019: a meta- analysis with trial sequential analysis . J. Anethesia. 2023; 1-14. https://doi.org/10.1007/s00540-023-03171-x
- Kandula U. R., Tuji T. S., Gudeta D. B., Bulbula K. L., Mohammad A. A., Wari K. D., Abbas A. (2023). Effectiveness of COVID-19 Convalescent Plasma (CCP) During the Pandemic Era: A Literature Review. J Blood Med, 159-187. https://doi.org/10.2147/JBM.S397722
- Pouladzadeh M., Safdarian M., Eshghi P., Abolghasemi H., Ghorbanibavani A., Sheibani B., Choghakabodi P.M., Feghhi A., Boroujerdnia M.G., Forouzan A., Far M.A.J., Kaydani G.A., Rajaei E., Amin M., Torabizadeh M., Yousefi F., Hadaddezfuli R. A randomized clinical trial evaluating the immunomodulatory effect of convalescent plasma on COVID-19 – related cytokine storm. Internal and Emerg. Medicine. 2021; 16: 2181-2191. https://doi.org/10.1007/s11739-021-02734-8
- Rabaan A.A., Al-ahmed S.H., Muhammad J., Khan A., Sule A.A., Tirupathi R., Mutair A.A., Alhumaid S., Al-Omari A., Dhawan M., Tiwari R. Sharun K., Mohapatra R.K., Mitra S., Bilal M., Alyami S.A., Emran T.B., Moni M.A., Dhama K. Role of inflammatory cytokines in COVID-19 patients: A review on molecular mechanisms, immune functions, immunopathology and immunomodulatory drugs to counter cytokine storm. Vaccines. 2021; 9: 436. https://doi.org/10.3390/vaccines9050436
- Royas M., Rodriguez Y., Monsalve D.M., Acosta-Ampudia Y., Camacho B., Gallo J.E., Royas-Villarraga A., Ramirez-Santana C., Diaz-Coronado J.C., Manrique R., Mantilla R.D., Shoenfeld Y., Anaya J-M. Convalescent plasma in Covid-19:Possible mechanisms of action. Autoimmunity Reviews. 2020; 19: 102554. https:/doi.org/10.1016/j.autrev.2020.102554.
- Simonovich VA, Burgos Pratx LD, Scibona P, Beruto MV, Vallone MG, Vázquez C, Savoy N., Giunta D.H., Pérez L.G., Sánchez M.L., Gamarnik A.V., . Ojeda D.S., Santoro D.M., Camino P.J., Antelo S., Rainero K., Vidiella G.P., Miyazaki E.A., Cornistein W., Trabadelo O.A., Ross F.M., Spotti M., Funtowicz G., Scordo W.E., Losso M.H., Ferniot I., Pardo P.E., Rodriguez E., Rucci P., Pasquali P. , Fuentes N.A., Esperatti M., Speroni G.A., Nannini E.C., Matteaccio A., Michelangelo H.G., Follmann D., Lane H.C., Belloso W.H., for the PlasmAr Study Group. A Randomized Trial of Convalescent Plasma in Covid-19 Severe Pneumonia. N Engl J Med. 2021; 384(7): 619–29. https://doi.org/10.1056/ NEJMoa2031304.
Supplementary files
СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).