1. Role of Innate and Adaptive Cytokines in the Survival of COVID-19 Patients
- Author
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Monserrat, Jorge, Gómez Lahoz, Ana, Ortega, Miguel, Sanz, José, Muñoz, Benjamin, Arévalo Serrano, Juan, Rodríguez, José, Gasalla, Jose, Gasulla, Óscar, Arranz, Alberto, Fortuny Profitós, Jordi, Mazaira Font, Ferran, Teixidó Román, Miguel, Martínez A, Carlos, Balomenos, Dimitri, Asunsolo, Angel, Álvarez Mon, Melchor, On Behalf Of The Covid-19 Hupa Group, Comunidad de Madrid, Universidad de Alcalá, Monserrat, Jorge [0000-0003-1775-4645], Ortega, Miguel Ángel [0000-0003-2588-1708], Sanz, José [0000-0003-3180-184X], Arévalo Serrano, Juan [0000-0003-2563-7860], Rodríguez Frade, José Miguel [0000-0002-8446-3373], Fortuny-Profitós, Jordi [0000-0002-4181-1593], Martínez-A, Carlos [0000-0002-2121-189X], Asúnsolo, Ángel [0000-0001-7898-4685], Álvarez-Mon, Melchor [0000-0003-1309-7510], Monserrat, Jorge, Ortega, Miguel Ángel, Sanz, José, Arévalo Serrano, Juan, Rodríguez Frade, José Miguel, Fortuny-Profitós, Jordi, Martínez-A, Carlos, Asúnsolo, Ángel, and Álvarez-Mon, Melchor
- Subjects
Interleukin-27 ,Pronòstic mèdic ,COVID-19 (Malaltia) ,Catalysis ,Inorganic Chemistry ,COVID-19 (Disease) ,Granulocyte Colony-Stimulating Factor ,Humans ,Physical and Theoretical Chemistry ,Chemokine CCL5 ,Molecular Biology ,Spectroscopy ,Interleukin-15 ,Epidermal Growth Factor ,Chemokine CX3CL1 ,Interleukin-12 Subunit p40 ,Interleukin-6 ,SARS-CoV-2 ,Tumor Necrosis Factor-alpha ,Macrophage Colony-Stimulating Factor ,Interleukin-17 ,Interleukin-8 ,Enginyeria biomèdica [Àrees temàtiques de la UPC] ,Organic Chemistry ,Interleukin-18 ,Granulocyte-Macrophage Colony-Stimulating Factor ,COVID-19 ,General Medicine ,Transforming Growth Factor alpha ,Prognosis ,innate and adaptive cytokines ,chemokines ,growth factors ,prognosis ,biomarkers ,Interleukin-10 ,Computer Science Applications ,Chemokine CXCL10 ,Interleukin 1 Receptor Antagonist Protein ,Innate and adaptive cytokines ,Citocines ,Cytokines ,Fibroblast Growth Factor 2 ,Chemokines ,Growth factors ,Biomarkers - Abstract
SARS-CoV-2 is a new coronavirus characterized by a high infection and transmission capacity. A significant number of patients develop inadequate immune responses that produce massive releases of cytokines that compromise their survival. Soluble factors are clinically and pathologically relevant in COVID-19 survival but remain only partially characterized. The objective of this work was to simultaneously study 62 circulating soluble factors, including innate and adaptive cytokines and their soluble receptors, chemokines and growth and wound-healing/repair factors, in severe COVID-19 patients who survived compared to those with fatal outcomes. Serum samples were obtained from 286 COVID-19 patients and 40 healthy controls. The 62 circulating soluble factors were quantified using a Luminex Milliplex assay. Results. The patients who survived had decreased levels of the following 30 soluble factors of the 62 studied compared to those with fatal outcomes, therefore, these decreases were observed for cytokines and receptors predominantly produced by the innate immune system—IL-1α, IL-1α, IL-18, IL-15, IL-12p40, IL-6, IL-27, IL-1Ra, IL-1RI, IL-1RII, TNFα, TGFα, IL-10, sRAGE, sTNF-RI and sTNF-RII—for the chemokines IL-8, IP-10, MCP-1, MCP-3, MIG and fractalkine; for the growth factors M-CSF and the soluble receptor sIL2Ra; for the cytokines involved in the adaptive immune system IFNγ, IL-17 and sIL-4R; and for the wound-repair factor FGF2. On the other hand, the patients who survived had elevated levels of the soluble factors TNFβ, sCD40L, MDC, RANTES, G-CSF, GM-CSF, EGF, PDGFAA and PDGFABBB compared to those who died. Conclusions. Increases in the circulating levels of the sCD40L cytokine; MDC and RANTES chemokines; the G-CSF and GM-CSF growth factors, EGF, PDGFAA and PDGFABBB; and tissue-repair factors are strongly associated with survival. By contrast, large increases in IL-15, IL-6, IL-18, IL-27 and IL-10; the sIL-1RI, sIL1RII and sTNF-RII receptors; the MCP3, IL-8, MIG and IP-10 chemokines; the M-CSF and sIL-2Ra growth factors; and the wound-healing factor FGF2 favor fatal outcomes of the disease, This research was coordinated by ProA Capital and Startlite Foundation, Programa de Actividades de I+D de la Comunidad de Madrid en Biomedicina (B2020/MITICAD-CM), Halekulani S.L., MJR; and Universidad de Alcala COVID-19 UAH 2019/00003/016/001/026 and COVID-19 2021-2020/00003/016/001/027
- Published
- 2022
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