ABSTRACT
T cells are key players in the resolution of the infection by SARS-CoV-2. A delay in their activation can lead to severe COVID-19. The present work aimed to identify differences in cytokine release by T cells ex-vivo between COVID-19 patients in the acute phase, showing diverse disease severity. Concentrations of IFNγ, Granzyme B, IL-6, IL-10, IL-17A, IL-18, IP-10, MCP-1, and TNFα were evaluated after stimulation ex-vivo of whole blood samples with peptides from SARS-CoV-2 spike protein and a mitogen as well as without stimulation. Samples derived from hospitalized COVID-19 patients and SARS-CoV-2 vaccinated controls (CTR). Patients were classified on disease severity considering the necessity of non-invasive ventilation (NIV). Samples from patients requiring NIV revealed a similar release of cytokines compared with patients without NIV. COVID-19 patients showed higher spontaneous production of IFNγ and IP-10, lower production of MCP-1 after SARS-CoV-2 peptide stimulation and lower production of IFNγ, IL-10, IL-17A, Granzyme B, IP-10 after mitogenic stimulus compared with CTR. In conclusion, differences in T cell responses evaluated ex-vivo by a whole blood-based cytokine release assay do not appear to explain the need for non-invasive ventilation in COVID-19 patients.
Subject(s)
COVID-19 , Noninvasive Ventilation , Spike Glycoprotein, Coronavirus , Humans , COVID-19/therapy , Cytokines , SARS-CoV-2 , Interleukin-10 , Granzymes , Interleukin-17 , Chemokine CXCL10ABSTRACT
Abstract Objective To estimate the effect of tocilizumab or glucocorticoids in preventing death and intubation in patients hospitalized with SARS-CoV-2 pneumonia. Methods This was a retrospective cohort study enrolling all consecutive patients hospitalized at Reggio Emilia AUSL between February the 11th and April 14th 2020 for severe COVID-19 and treated with tocilizumab or glucocorticoids (at least 80 mg/day of methylprednisolone or equivalent for at least 3 days). The primary outcome was death within 30 days from the start of the considered therapies. The secondary outcome was a composite outcome of death and/or intubation. All patients have been followed-up until May 19th 2020, with a follow-up of at least 30 days for every patient. To reduce confounding due to potential non-comparability of the two groups, those receiving tocilizumab and those receiving glucocorticoids, a propensity score was calculated as the inverse probability weighting of receiving treatment conditional on the baseline covariates. Results and conclusion Therapy with tocilizumab alone was associated with a reduction of deaths (OR 0.49, 95% CI 0.21-1.17) and of the composite outcome death/intubation (OR 0.35, 95% CI 0.13-0.90) compared to glucocorticoids alone. Nevertheless, this result should be cautiously interpreted due to a potential prescription bias.