COVID-19: room for treating T cell exhaustion?

Riva, Giovanni; Nasillo, Vincenzo; Tagliafico, Enrico; Trenti, Tommaso; Luppi, Mario

doi:10.1186/s13054-020-02960-0

Cited by 23 publications

(29 citation statements)

References 5 publications

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“…Serum iron was lower when compared with other cohorts of non-COVID-19 ICU patients reported previously, including those with sepsis [4]. The association of serum iron with lymphocyte counts could reflect the requirement of the adaptive immune response for iron [5] and may contribute to possible T cell dysfunction reported in COVID-19 [6].…”

Section: Discussionmentioning

confidence: 62%

“…Hypoferremia is likely to be due at least in part to inflammation-driven increases in hepcidin concentrations [2]. Anti-inflammatory drugs such as tocilizumab will likely suppress hepcidin synthesis through inhibition of interleukin-6 (IL-6) [6] and so increase serum iron. Other potential therapeutic strategies include hepcidin antagonists and hypoxia-inducible factor inhibitors.…”

Section: Discussionmentioning

confidence: 99%

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Systemic hypoferremia and severity of hypoxemic respiratory failure in COVID-19

et al. 2020

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Dear Editor, Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory coronavirus 2 (SARS-CoV-2) was declared a pandemic on March 11, 2020 [1]. Risk factors associated with respiratory failure in patients with COVID-19 include older age, neutrophilia and elevated inflammatory and coagulation markers [1]. Inflammation is often accompanied by systemic hypoferremia and low iron levels may impair hypoxia sensing and immunity [2], and increase the risk of thromboembolic complications [3]-which are all of significant concern in COVID-19. However, the iron status of COVID-19 patients is unclear. Therefore, we sought to characterise iron parameters, including serum iron, in COVID-19 intensive care unit (ICU) patients and relate these to disease severity. Methods We retrospectively evaluated any serum iron profiles that were measured in critically ill patients with COVID-19 within 24 h of admission to the ICU, John Radcliffe Hospital, Oxford, UK, between March 31, 2020, and April 25, 2020. Relevant clinical and laboratory data were extracted from routine datasets. The number of patients who had died, had been discharged, and were still in ICU as of May 12, 2020 was recorded. We stratified patients according to severity of hypoxemic respiratory failure on admission to ICU-severe (PaO 2 /FiO 2 ratio < 100 mmHg) versus non-severe (PaO 2 /FiO 2 ratio 100-300 mmHg). All patients with severe hypoxemia required invasive mechanical ventilation and prone positioning. Mann-Whitney rank

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Section: Discussionmentioning

confidence: 62%

Section: Discussionmentioning

confidence: 99%

Systemic hypoferremia and severity of hypoxemic respiratory failure in COVID-19

et al. 2020

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“…3 Department of Anesthesiology and Intensive Care Medicine, SRH Wald-Klinikum Gera, Straße des Friedens 122, 07548 Gera, Germany. 4 Septomics Research Center, Jena University Hospital, 07745 Jena, Germany. 5 Center for Sepsis Control and Care, Jena University Hospital, Am Klinikum 1, 07747 Jena, Germany.…”

Section: Acknowledgementsmentioning

confidence: 99%

“…Recently, Neurath argued for a protective effect of tumor necrosis factor (TNF) inhibitors in severe COVID-19 [ 2 ]. Specifically, TNF may aggravate lymphopenia through direct killing via TNF/TNFR1 signaling in T cells [ 3 ], and T cell dysfunction reflects an important yet underestimated target for immunomodulatory interventions [ 4 ]. Thus, anti-TNF strategies may be an interesting option in severe COVID-19.…”

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confidence: 99%

Infliximab against severe COVID-19-induced cytokine storm syndrome with organ failure—a cautionary case series

et al. 2020

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The severe acute respiratory coronavirus 2 (SARS-CoV-2) pandemic has prompted search for therapeutics tackling both the pathogen and the overwhelming host response, on an unprecedented scale. In a minority of patients, the disease may cause frequently lethal complications from acute respiratory distress syndrome to multisystem organ failure presumably driven by a cytokine storm [1]. Therefore, anti-cytokine therapies may be helpful to prevent tissue injury. However, these antiinflammatory drugs constitute double-edged swords; while they can prevent organ damage, they increase the risk of concomitant (super)infection. Recently, Neurath argued for a protective effect of tumor necrosis factor (TNF) inhibitors in severe COVID-19 [2]. Specifically, TNF may aggravate lymphopenia through direct killing via TNF/TNFR1 signaling in T cells [3], and T cell dysfunction reflects an important yet underestimated target for immunomodulatory interventions [4]. Thus, anti-TNF strategies may be an interesting option in severe COVID-19. This is supported by data from patients with inflammatory bowel disease (IBD) already on anti-TNF treatment. As of June 16, 2020, outcome data from 1511 IBD patients with COVID-19, among them, 433 patients on anti-TNF, are available from the SECURE-IBD registry [5]. Of these, 16% were hospitalized but only three patients (0.7%) died. Compared to other anti-inflammatory drugs such appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material.

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“…More recently, COVID-19 clinical syndrome and related immunopathogenesis have been compared with sepsis, recalling the need to target the underlying and shared impairment of protective T cell immunity, while suppressing the emergent cytokine storm [ 7 – 9 ]. In fact, severe COVID-19 has appeared as a peculiar clinicopathologic entity—yet poorly understood from a mechanistic viewpoint—which however, by definition, may represent a novel form of viral sepsis, being characterized by (a) T cell deficiencies , with early and progressive lymphopenia; (b) systemic hyperinflammation , with a peculiar time-course, often increasing at a late phase, when coagulopathy and fatal organ damage may eventually occur; and (c) COVID-19-associated coagulopathy , displaying some unique clinical and laboratory findings, compared with either disseminated intravascular coagulation or sepsis-induced coagulopathy [ 10 ].…”

Section: Introductionmentioning

confidence: 99%