Impaired immune cell cytotoxicity in severe COVID-19 is IL-6 dependent
Alessio Mazzoni, … , Francesco Annunziato, Lorenzo Cosmi
Alessio Mazzoni, … , Francesco Annunziato, Lorenzo Cosmi
Published May 28, 2020
Citation Information: J Clin Invest. 2020;130(9):4694-4703. https://doi.org/10.1172/JCI138554.
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Clinical Medicine Immunology Infectious disease

Impaired immune cell cytotoxicity in severe COVID-19 is IL-6 dependent

Abstract

BACKGROUND Coronavirus disease 19 (COVID-19) is an emerging infectious disease caused by SARS-CoV-2. Antiviral immune response is crucial to achieve pathogen clearance; however, in some patients an excessive and aberrant host immune response can lead to an acute respiratory distress syndrome. The comprehension of the mechanisms that regulate pathogen elimination, immunity, and pathology is essential to better characterize disease progression and widen the spectrum of therapeutic options.METHODS We performed a flow cytometric characterization of immune cell subsets from 30 patients with COVID-19 and correlated these data with clinical outcomes.RESULTS Patients with COVID-19 showed decreased numbers of circulating T, B, and NK cells and exhibited a skewing of CD8+ T cells toward a terminally differentiated/senescent phenotype. In agreement, CD4+ T and CD8+ T, but also NK cells, displayed reduced antiviral cytokine production capability. Moreover, a reduced cytotoxic potential was identified in patients with COVID-19, particularly in those who required intensive care. The latter group of patients also showed increased serum IL-6 levels that inversely correlated to the frequency of granzyme A–expressing NK cells. Off-label treatment with tocilizumab restored the cytotoxic potential of NK cells.CONCLUSION The association between IL-6 serum levels and the impairment of cytotoxic activity suggests the possibility that targeting this cytokine may restore antiviral mechanisms.FUNDING This study was supported by funds from the Department of Experimental and Clinical Medicine of University of Florence (the ex-60% fund and the “Excellence Departments 2018–2022 Project”) derived from Ministero dell’Istruzione, dell’Università e della Ricerca (Italy).

Authors

Alessio Mazzoni, Lorenzo Salvati, Laura Maggi, Manuela Capone, Anna Vanni, Michele Spinicci, Jessica Mencarini, Roberto Caporale, Benedetta Peruzzi, Alberto Antonelli, Michele Trotta, Lorenzo Zammarchi, Luca Ciani, Leonardo Gori, Chiara Lazzeri, Andrea Matucci, Alessandra Vultaggio, Oliviero Rossi, Fabio Almerigogna, Paola Parronchi, Paolo Fontanari, Federico Lavorini, Adriano Peris, Gian Maria Rossolini, Alessandro Bartoloni, Sergio Romagnani, Francesco Liotta, Francesco Annunziato, Lorenzo Cosmi

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Figure 3

Functional characterization of CD4+ and CD8+ T cells and NK cells in patients with COVID-19.

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Functional characterization of CD4+ and CD8+ T cells and NK cells in pat...
(A) Frequency of IL-2–secreting cells among CD4+ and CD8+ T cells after in vitro polyclonal stimulation in healthy donors (black dots) and COVID-19 patients (gray dots). Frequency of IFN-γ–secreting cells (B) and TNF-α– secreting cells (C) among CD4+ and CD8+ T cells and NK cells after in vitro polyclonal stimulation in healthy donors (black dots) and COVID-19 patients (gray dots). Frequency of perforin-expressing cells (D) and granzyme A–expressing cells (E) among CD4+ and CD8+ T cells and NK cells in healthy donors (black dots) and COVID-19 patients (gray dots). Data obtained from 30 healthy controls and 30 COVID-19 patients. Red lines represent mean values for each population. *P < 0.05; ***P < 0.001; calculated with Student’s t test.