| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T179 |
0-10 |
Sentence |
denotes |
Discussion |
| T180 |
11-346 |
Sentence |
denotes |
All patients with pneumonia caused by SARS-CoV-2 who develop SRF display hyper-inflammatory responses with features of either immune dysregulation or MAS, both of which are characterized by pro-inflammatory cytokines: the immune dysregulation described here, which is driven by IL-6 and not by IL-1β, and MAS, which is driven by IL-1β. |
| T181 |
347-565 |
Sentence |
denotes |
There are two key features of this immune dysregulation: over-production of pro-inflammatory cytokines by monocytes and dysregulation of lymphocytes characterized by CD4 lymphopenia and subsequently B cell lymphopenia. |
| T182 |
566-688 |
Sentence |
denotes |
In parallel, the absolute natural killer (NK) cell count is depleted, probably as result of the rapidly propagating virus. |
| T183 |
689-896 |
Sentence |
denotes |
It was previously shown that the addition of IL-6 in the growth medium of healthy dendritic cells attenuated HLA-DR membrane expression and decreased the production of IFN-γ by CD4 cells (Ohno et al., 2016). |
| T184 |
897-1385 |
Sentence |
denotes |
Three findings of our study are compatible with the proposal that IL-6 is one of the drivers of decreased HLA-DR on the CD14 monocytes: (1) IL-6 concentrations in the blood is inversely associated with HLA-DR expression (Figure 5A), (2) the addition of Tocilizumab in the plasma-enriched medium of cells partially restored the expression of HLA-DR on cell membranes (Figures 5E and 5F), and (3) absolute lymphocyte counts of six patients increased after Tocilizumab treatment (Figure 5G). |
| T185 |
1386-1561 |
Sentence |
denotes |
Our findings are indirectly supported by the increase of circulating HLA-DR+ cells during convalescence of one case of COVID-19 of moderate severity (Thevarajan et al., 2020). |
| T186 |
1562-1916 |
Sentence |
denotes |
In conclusion, we identified a unique signature of immune dysregulation in the patients with SARS-CoV-2, characterized on the one hand by normal or high cytokine production capacity and increased circulating cytokines (especially IL-6) and on the other hand by defects in the lymphoid function associated with IL-6-mediated decrease in HLA-DR expression. |
| T187 |
1917-2206 |
Sentence |
denotes |
These findings support the rationale of launched clinical trials on the efficacy of Anakinra, Sarilumab, Siltuximab, and Tocilizumab (Clinicaltrials.gov NCT04330638, NCT04317092, and NCT04315298 and EudraCT number 2020-001039-29) to elaborate anti-inflammatory responses in these patients. |
