COVID-19: room for treating T cell exhaustion?

• Published in: Critical care (London, England) Vol. 24; no. 1; p. 229
• Main Authors: Riva, Giovanni, Nasillo, Vincenzo, Tagliafico, Enrico, Trenti, Tommaso, Luppi, Mario
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 15.05.2020; BioMed Central; BMC
• Subjects: Antiviral agents; Betacoronavirus; Coronavirus Infections; Coronaviruses; COVID-19; Critical care; Cytokines; Health aspects; Humans; Immunotherapy; Letter; Lymphocytes; Pandemics; Pneumonia, Viral; SARS-CoV-2; Sepsis; Severe acute respiratory syndrome coronavirus 2; T cells
• ISSN: 1364-8535; 1466-609X; 1364-8535; 1366-609X
• DOI: 10.1186/s13054-020-02960-0

In critically ill COVID-19 patients, indeed, massive cytokine storms (including IL-6, TNF-α, and other inflammatory biomarkers), as well as increments of circulating neutrophils and monocyte activation, are typically observed together with low T lymphocyte counts and functional exhaustion of effector T cell responses [1, 3, 4]. [...]ineffective and detrimental expansions of innate/humoral responses, alongside T cell suppression, are reminiscent of classical features of sepsis, which is currently defined as a life-threatening organ dysfunction induced by dysregulated host response to infection, being characterized not only by systemic hyperinflammation (SIRS) with related endothelial and organ damage, but also by impairment of adaptive T cell immunity. [...]the relevant coagulation disorders observed in end-stage COVID-19 could also well fit with the idea that severe COVID-19 possibly represents a peculiar clinicopathologic manifestation of viral sepsis. Importantly, immune checkpoint inhibitors (ICIs), such as anti-PD-1 and anti-PD-L1 monoclonal antibodies, originally developed to improve antineoplastic T cell immunity, are undergoing clinical investigation in septic patients [5]. [...]it should be conceivable that, also in COVID-19 patients, ICIs may be tested to restore immune competence of exhausted T cell subsets and, in this context, to specifically improve the pivotal process of virus elimination, likely blunted in severe COVID-19.