The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.
Impaired immune cell cytotoxicity in severe COVID-19 is IL-6 dependent
Open accessAbstract
BACKGROUNDCoronavirus 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.METHODSWe performed a flow cytometric characterization of immune cell subsets from 30 patients with COVID-19 and correlated these data with clinical outcomes.RESULTSPatients 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.CONCLUSIONThe association between IL-6 serum levels and the impairment of cytotoxic activity suggests the possibility that targeting this cytokine may restore antiviral mechanisms.FUNDINGThis 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).
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“For CD8+ T cells, there are reports of diminished CD8+ cytotoxicity and cytokine production in severe cases126,132, while others report the opposite141, and still others find no differences142.”
From SARS-CoV-2, COVID-19 and the aging immune system (2021) · cites this paper as [142]
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“Some studies have found reduced effector functions for CD4+ T cells, i.e. IFNγ/IL-2/TNFα production, in patients with severe disease141, while others have seen no differences142.”
From SARS-CoV-2, COVID-19 and the aging immune system (2021) · cites this paper as [142]
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Cujba, A.-M., Aguilar-Fernández, S., Antoinette, A., Said, W., Müller, M., Kock, K. H., Nestor, J., Sonthalia, R., Buyamin, E. V., Rawat, P., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.09.21.749940
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Next-generation natural killer cell therapy: bench to bedside and beyond
Zhao, A., Xu, J., Deng, W., Zhang, M., Shao, Y., Liu, Y., Liang, A., Wang, X., Niu, T., & Qian, W. (2026) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-026-02911-1
Herpesvirus reactivation in COVID-19: clinical evidence, mechanistic insights, and research gaps
Yoo, J., Park, J. S., Kim, J., Lee, S., & Choi, U. Y. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1954424
Metadata
- Authors
- Mazzoni, A., Salvati, L., Maggi, L., Capone, M., Vanni, A., Spinicci, M., Mencarini, J., Caporale, R., Peruzzi, B., Antonelli, A., Trotta, M., Zammarchi, L., Ciani, L., Gori, L., Lazzeri, C., Matucci, A., Vultaggio, A., Rossi, O., Almerigogna, F., Parronchi, P., Fontanari, P., Lavorini, F., Peris, A., Rossolini, G. M., Bartoloni, A., Romagnani, S., Liotta, F., Annunziato, F., & Cosmi, L.
- Affiliations
- University of Florence (IT)
- Corresponding author
- Annunziato, Francesco
- ORCID
- Mazzoni, Alessio
- Salvati, Lorenzo
- Maggi, Laura
- Capone, Manuela
- Vanni, Anna
- Spinicci, Michele
- Mencarini, Jessica
- Peruzzi, Benedetta
- Antonelli, Alberto
- Trotta, Michele
- Zammarchi, Lorenzo
- Gori, Leonardo
- Lazzeri, Chiara
- Matucci, Andrea
- Vultaggio, Alessandra
- Parronchi, Paola
- Lavorini, Federico
- Peris, Adriano
- Bartoloni, Alessandro
- Liotta, Francesco
- Annunziato, Francesco
- Cosmi, Lorenzo
- Venue
- Journal of Clinical Investigation
- Published
- 2020-08-04
- Volume
- 130
- Issue
- 9
- Pages
- 4694-4703
- ISSN
- 0021-9738 (ISSN-L)
- 1558-8238
- PMC
- PMC7456250
- OpenAlex
- W3032533580
- Cited by
- 502
- References
- 45
- Citations by year
- 2026: 12 · 2025: 17 · 2024: 47 · 2023: 70 · 2022: 105 · 2021: 181 · 2020: 70
- FWCI
- 14.01
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Florence Research (University of Florence) (submittedVersion, other-oa)
- Funders
- Università degli Studi di Firenze
- Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi di Firenze
- Topics
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
- Keywords
- COVID-19 pandemic, SARS-CoV-2, interleukin-6, natural killer cells, CD8+ T cells, CD4+ T cells, granzyme A, T cell senescence, tocilizumab, cytokine storm, acute respiratory distress syndrome, intensive care
- MeSH terms
- Betacoronavirus, COVID-19, SARS-CoV-2, Adult, Aged, Aged, 80 and over, B-Lymphocytes, Critical Care, Cytotoxicity, Immunologic, Female, Humans, Killer Cells, Natural, Male, Middle Aged, Pneumonia, Viral, CD4-Positive T-Lymphocytes, Interleukin-6, Cytokines, Coronavirus Infections, CD8-Positive T-Lymphocytes, Models, Immunological, Granzymes, Pandemics
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