https://doi.org/10.4081/itjm.2023.1650

STAT3 eye-opener in COVID-19

Vol. 17 No. 3 (2023)
Published: 28 November 2023
COVID-19, STAT3, IL-6, circulating cells, vitamin D
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Authors

Chiara Mozzini
chiara.mozzini@asst-mantova.it
https://orcid.org/0000-0002-4414-6576
Department of Medicine, ASST Mantova, C. Poma Hospital, Mantova, Italy.
Giuseppe Lucchini
Biostatistic Unit, ASST Mantova, C. Poma Hospital, Mantova, Italy.
Mauro Pagani
Department of Medicine, ASST Mantova, C. Poma Hospital, Mantova, Italy.

Among the elevated inflammatory mediators, blood Interleukin-6 (IL-6) level is highly correlated with COVID-19 mortality and predicts the need for mechanical ventilation. IL-6 is the major activator of signal transducers and activators of transcription-3 (STAT3) during inflammatory responses. The primary objective of the study is to explore STAT3 activation in different subsets of circulating cells derived from 25 COVID-19 patients (patients) admitted to an Internal Medicine department compared to 25 healthy donors (HD). Higher percentages of classical and intermediate monocytes were observed in patients, compared to HD (respectively P<0.01 and P<0.001). The active form of STAT3, phosphorylated STAT3 (pSTAT3) was significantly higher in patients, compared to HD, both in non-classical and in intermediate monocytes (P<0.001). Low-density neutrophils (LDN) count was significantly higher in patients compared to HD (P<0.001). The pSTAT3 was significantly higher in LDN derived from patients (P<0.05). High pSTAT3 was significantly directly related to d-dimer and inversely related to vitamin D levels (P<0.01). This study gives information about STAT3 activation and the possible role of Vitamin D as a tool against COVID-19.

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Citations

Crossref
Scopus
Google Scholar
Europe PMC
Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395:497-506. DOI: https://doi.org/10.1016/S0140-6736(20)30183-5
Liu B, Li M, Zhou Z, et al. Can we use interleukin-6 (IL-6) blockade for coronavirus disease 2019 (COVID-19)-induced cytokine release syndrome (CRS)? J Autoimmun 2020;111:102452.
Zhong Z, Wen Z, Darnell JE. STAT3: a STAT family member activated by tyrosine phosphorylation in response to epidermal growth factor and interleukin-6. Science 1994;264:95-8. DOI: https://doi.org/10.1126/science.8140422
Narasimhan PB, Marcovecchio P, Hamers AAJ, Hedrick CC. Nonclassical Monocytes in Health and Disease. Ann Rev Immunol 2019;37:439-56. DOI: https://doi.org/10.1146/annurev-immunol-042617-053119
Sagiv JY, Michaeli J, Assi S, et al. Phenotypic diversity and plasticity in circulating neutrophil subpopulations in cancer. Cell Rep 2015;10:562-73. DOI: https://doi.org/10.1016/j.celrep.2014.12.039
Gatti A, Rsdrizzani D, Viganò P, et al. Decrease of nonclassical and intermediate monocyte subsets in severe acute SARS-CoV-2 infection. Cytometry 2020;97:887-90. DOI: https://doi.org/10.1002/cyto.a.24188
Morrissey SM, Geller AE, Hu X, et al. Emergence of Low-density Inflammatory Neutrophils Correlates with Hypercoagulable State and Disease Severity in COVID-19 Patients. MedRxiv 2020. DOI: https://doi.org/10.1101/2020.05.22.20106724
Cignarella A, Tedesco S, Cappellari R, Fadini GP. The continuum of monocyte phenotypes: experimental evidence and prognostic utility in assessing cardiovascular risk. J Leukoc Biol 2018;103:1021-8. DOI: https://doi.org/10.1002/JLB.5RU1217-477RR
Akaishi H, Takeda K, Kaisho T, et al. Defective IL-2 mediated IL-2 receptor alpha chain expression on STAT3 deficient T lymphocytes. Int Immunol 1998;10:1747-51. DOI: https://doi.org/10.1093/intimm/10.11.1747
Matsuyama T, Kubli SP, Yoshinaga SK, et al. An aberrant STAT pathway is central to COVID-19. Cell Death Differ 2020;27:3209-25. DOI: https://doi.org/10.1038/s41418-020-00633-7
Liu B, Li M, Zhou Z, et al. 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: https://doi.org/10.1016/j.jaut.2020.102452
Hirano T, Murakami M. COVID-19: A New Virus, but a Familiar Receptor and Cytokine Release Syndrome. Immunity 2020;52:731-5. DOI: https://doi.org/10.1016/j.immuni.2020.04.003
Hojyo S, Hojyo, Uchida M, et al. How COVID-19 induces cytokine storm with high mortality. Inflamm Regen 2020;40:37-44. DOI: https://doi.org/10.1186/s41232-020-00146-3
Lin X, Lin B-W, Chen X-L, et al. PAI-1/PIAS3/Stat3/miR-34a forms a positive feedback loop to promote EMT-mediated metastasis through Stat3 signalling in Non-small cell lung cancer. Biochem Biophys Res Commun 2017;493:1464-70. DOI: https://doi.org/10.1016/j.bbrc.2017.10.014
Klok FA, Kruip MJHA, van der Meer NJM, et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res 2020;191:145-7. DOI: https://doi.org/10.1016/j.thromres.2020.04.013
Tang N, Bai H, Chen X. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost 2020;18:1094-9. DOI: https://doi.org/10.1111/jth.14817
Mozzini C, Girelli D. The role of Neutrophil Extracellular Traps in COVID-19: Only an hypothesis or a potential new field of research? Thromb Res 2020;191:26-7. DOI: https://doi.org/10.1016/j.thromres.2020.04.031
Zuo Y, Yalavarthi S, Shi H, et al. Neutrophil extracellular traps in COVID-19. JCI Insight 2020;5:e138999. DOI: https://doi.org/10.1172/jci.insight.138999
Radermecker C, Detrembleur N, Guiot J, et al. Neutrophil extracellular traps infiltrate the lung airway, interstitial, and vascular compartments in severe COVID-19. J Exp Med 2020;217:e20201012. DOI: https://doi.org/10.1084/jem.20201012
Mc Donald PP, Bald A, Cassatella MA. Activation of the NF-kappaB pathway by inflammatory stimuli in human neutrophils. Blood 1997;89:3421-33. DOI: https://doi.org/10.1182/blood.V89.9.3421
Yang CY, Leung PS, Adamopoulos IE, Gershwin ME. The implication of vitamin D and autoimmunity: a comprehensive review, Clin Rev Allergy Immunol 2013;45:217-26. DOI: https://doi.org/10.1007/s12016-013-8361-3
Olson K, Kulling P, Olson T, et al. Vitamin D decreases STAT phosphorylation and inflammatory cytokine output in T-LGL leukaemia. Cancer Biol Ther 2017;18:290-303. DOI: https://doi.org/10.1080/15384047.2016.1235669
Gopinath SD. Inhibition of STAT3 signalling ameliorates atrophy of the soleus muscles in mice lacking the vitamin D receptor. Skelet Muscle 2017;7:2-19. DOI: https://doi.org/10.1186/s13395-017-0121-2
D’Avolio A, Avataneo V, Manca A, et al. 25-Hydroxyvitamin D concentrations are lower in patients with positive PCR for SARS-CoV-2. Nutrients 2020;12:1359. DOI: https://doi.org/10.3390/nu12051359
Annweiler G, Corvaisier M, Gautier J, et al. Vitamin D supplementation associated to better survival in hospitalized frail elderly COVID-19 patients: the GERIACOVID quasi-experimental study. Nutrients 2020;12:E3377. DOI: https://doi.org/10.3390/nu12113377
Annweiler C, Hanotte B, Grandin de l’Eprevier C, et al. Vitamin D and survival in COVID-19 patients: a quasiexperimental study. J Steroid Biochem Mol Biol 2020;204:105771. DOI: https://doi.org/10.1016/j.jsbmb.2020.105771
Ahmed F. A Network-Based Analysis Reveals the Mechanism Underlying Vitamin D in Suppressing Cytokine Storm and Virus in SARS CoV-2 Infection. Front Immunol 2020;11:590459. DOI: https://doi.org/10.3389/fimmu.2020.590459
Cannell JJ, Grant WB, Holick MF. Vitamin D and inflammation. Dermatoendocrinol 2015;6:e983401. DOI: https://doi.org/10.4161/19381980.2014.983401
Silberstein S. Correlation between premorbid IL-6 levels and COVID-19 mortality: Potential role for Vitamin D. Int Immunopharmacol 2020;88:106995. DOI: https://doi.org/10.1016/j.intimp.2020.106995
Annweiler C, Beaudenon M, Gautier J, et al. COVID-19 and high-dose VITamin D supplementation TRIAL in high-risk older patients (COVIT-TRIAL): study protocol for a randomized controlled trial. Trials 2020; 21:1031-34. DOI: https://doi.org/10.1186/s13063-020-04928-5

How to Cite

Mozzini, C., Lucchini, G., & Pagani, M. (2023). STAT3 eye-opener in COVID-19. Italian Journal of Medicine, 17(3). https://doi.org/10.4081/itjm.2023.1650
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