LitCovid-sentences  

PMC:7172841 / 16911-24252 JSONTXT 12 Projects

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Id Subject Object Predicate Lexical cue
T133 0-92 Sentence denotes The IL-6 Blocker Tocilizumab Partially Rescues the Immune Dysregulation Driven by SARS-CoV-2
T134 93-264 Sentence denotes Sepsis-induced immunoparalysis is characterized by profound deficiency of monocytes for cytokine production upon ex vivo stimulation (Giamarellos-Bourboulis et al., 2011).
T135 265-521 Sentence denotes Indeed, production of tumor necrosis factor-α (TNF-α) by LPS-stimulated peripheral blood mononuclear cells (PBMCs) of patients with bacterial CAP classified for immunoparalysis was significantly lower than in patients at an intermediate state (Figure 4 A).
T136 522-681 Sentence denotes That was not the case for patients with pneumonia caused by SARS-CoV-2, in whom PBMCs showed sustained TNF-α production after stimulation with LPS (Figure 4B).
T137 682-856 Sentence denotes The function of PBMCs in patients with SRF caused by 2009H1N1 was also impaired, and there was lower TNF-α production, a pattern different from COVID-19 patients (Figure 4C).
T138 857-1013 Sentence denotes Surprisingly, stimulation of IL-1β was lower among patients with immune dysregulation than among patients with an intermediate immune state (Figures 4D–4F).
T139 1014-1087 Sentence denotes IL-6, however, followed the stimulation pattern of TNF-α (Figures 4G–4I).
T140 1088-1386 Sentence denotes This generated the hypothesis that in the case of SRF-aggravated pneumonia caused by SARS-CoV-2, there is a unique combination of defective antigen presentation and lymphopenia that leads to defective function of lymphoid cells, whereas monocytes remain potent for the production of TNF-α and IL-6.
T141 1387-1467 Sentence denotes Figure 4 Main Features of Immune Dysregulation of Pneumonia Caused by SARS-CoV-2
T142 1468-1625 Sentence denotes (A) Production of TNF-α by PBMCs of patients with sepsis caused by bacterial CAP classified into intermediate state of immune activation and immunoparalysis.
T143 1626-1789 Sentence denotes (B) Production of TNF-α by PBMCs of patients with CAP caused by SARS-CoV-2 classified into three states of immune activation: intermediate, dysregulation, and MAS.
T144 1790-1918 Sentence denotes (C) Production of TNF-α by PBMCs of patients with SRF developing after infection caused by the 2009H1N1 virus and by SARS-CoV-2.
T145 1919-2076 Sentence denotes (D) Production of IL-1β by PBMCs of patients with sepsis caused by bacterial CAP classified into intermediate state of immune activation and immunoparalysis.
T146 2077-2240 Sentence denotes (E) Production of IL-1β by PBMCs of patients with CAP caused by SARS-CoV-2 classified into three states of immune activation: intermediate, dysregulation, and MAS.
T147 2241-2369 Sentence denotes (F) Production of IL-1β by PBMCs of patients with SRF developing after infection caused by the 2009H1N1 virus and by SARS-CoV-2.
T148 2370-2526 Sentence denotes (G) Production of IL-6 by PBMCs of patients with sepsis caused by bacterial CAP classified into intermediate state of immune activation and immunoparalysis.
T149 2527-2682 Sentence denotes (H) Production of IL-6 by PBMCs of patients with CAP caused by SARS-CoV-2 classified into states of immune activation: intermediate, dysregulation and MAS.
T150 2683-2810 Sentence denotes (I) Production of IL-6 by PBMCs of patients with SRF developing after infection caused by the 2009H1N1 virus and by SARS-CoV-2.
T151 2811-2978 Sentence denotes (J–L) Serum amounts of TNF-α, IL-6, and CRP of patients with CAP caused by SARS-CoV-2 classified into states of immune activation: intermediate, dysregulation and MAS.
T152 2979-3042 Sentence denotes Bars in each graphic represent mean values and standard errors.
T153 3043-3169 Sentence denotes Statistical comparisons are indicated by the arrows; ns: non-significant; ∗p < 0.05; ∗∗p < 0.01; ∗∗∗p < 0.001; ∗∗∗∗p < 0.0001.
T154 3170-3267 Sentence denotes Comparisons were done by the Mann-Whitney U test followed by correction for multiple comparisons.
T155 3268-3425 Sentence denotes As a next step, we measured circulating concentrations of TNF-α, interferon-γ (IFN-γ), IL-6, and C-reactive protein (CRP) in patients infected by SARS-CoV-2.
T156 3426-3568 Sentence denotes IFN-γ was below the limit of detection in all patients (data not shown), indicating that Th1 responses do not contribute to over-inflammation.
T157 3569-3714 Sentence denotes No differences of circulating TNF-α concentrations were found between COVID-19 patients at the three states of immune classification (Figure 4J).
T158 3715-3909 Sentence denotes In contrast, IL-6 and CRP concentrations were significantly higher among patients with immune dysregulation than among patients at an intermediate state of immune activation (Figures 4K and 4L).
T159 3910-4138 Sentence denotes Given that IL-6 was below the limit of detection in some patients with immune dysregulation, we divided them into two groups as follows: seven patients with IL-6 below the limit of detection and 14 patients with detectable IL-6.
T160 4139-4309 Sentence denotes Their severity was similar given that SOFA score and pneumonia severity indexes were similar (p values of comparisons were 0.937 and 0.877, respectively; data not shown).
T161 4310-4500 Sentence denotes IL-6 is known to inhibit HLA-DR expression (Ohno et al., 2016), leading to the hypothesis that IL-6 over-production mediates the low HLA-DR expression on CD14 monocytes of COVID-19 patients.
T162 4501-4820 Sentence denotes In agreement with this, negative correlation was found between serum amounts of IL-6 and the absolute number of HLA-DR molecules on CD14 monocytes of patients with COVID-19 but also between the absolute lymphocyte count and the absolute number of mHLA-DR on CD14 monocytes of patients with COVID-19 (Figures 5A and 5B).
T163 4821-4999 Sentence denotes Furthermore, PBMCs from patients with immune dysregulation were cultured overnight in the presence of plasma of the COVID-19 patients, which was already shown to be rich in IL-6.
T164 5000-5410 Sentence denotes The expression of HLA-DR on CD14 monocytes was strongly inhibited by COVID-19 plasma from patients with immune dysregulation but not by plasma from patients with an intermediate immune state of activation (Figures 5C–5F); the addition of the specific blocker of the IL-6 pathway Tocilizumab partially restored the expression of HLA-DR on monocytes of all patients with immune dysregulation (Figures 5E and 5F).
T165 5411-5555 Sentence denotes Treatment with Tocilizumab in six patients was accompanied by increase of the absolute lymphocyte blood count within the first 24 h (Figure 5G).
T166 5556-5635 Sentence denotes IL-6 was produced partly by CD14 monocytes and partly by CD4 cells (Figure 5H).
T167 5636-5706 Sentence denotes Figure 5 Immune Dysregulation Caused by SARS-CoV-2 Is Mediated by IL-6
T168 5707-5820 Sentence denotes (A) Negative correlation between serum amounts of IL-6 and the absolute numbers of the mHLA-DR on CD14 monocytes.
T169 5821-5909 Sentence denotes The Spearman’s (rs) co-efficient of correlation and the respective p value are provided.
T170 5910-6018 Sentence denotes (B) Correlation between the absolute lymphocyte count and the absolute numbers of mHLA-DR on CD14 monocytes.
T171 6019-6094 Sentence denotes The rs co-efficient of correlation and the respective p value are provided.
T172 6095-6291 Sentence denotes (C) Changes of the absolute numbers of mHLA-DR on CD14 monocytes of four patients infected by SARS-CoV-2 with intermediate state of immune activation after incubation with medium and their plasma.
T173 6292-6474 Sentence denotes (D) Changes of the MFI of HLA-DR on CD14 monocytes of four patients infected by SARS-CoV-2 with intermediate state of immune activation after incubation with medium and their plasma.
T174 6475-6736 Sentence denotes (E) Changes of the absolute numbers of mHLA-DR on CD14 monocytes of eight patients infected by SARS-CoV-2 with immune dysregulation after incubation with medium and their plasma; modulation by the addition of the specific IL-6 blocker Tocilizumab is also shown.
T175 6737-6984 Sentence denotes (F) Changes of the MFI of HLA-DR on CD14 monocytes of eight patients infected by SARS-CoV-2 with immune dysregulation after incubation with medium and their plasma; modulation by the addition of the specific IL-6 blocker tocilizumab is also shown.
T176 6985-7099 Sentence denotes (G) Changes of the absolute lymphocyte count of six patients before and after start of treatment with Tocilizumab.
T177 7100-7244 Sentence denotes (H) Intracellular staining for IL-6 in CD14 monocytes and in CD4 lymphocytes of three patients infected by SARS-CoV-2 with immune dysregulation.
T178 7245-7341 Sentence denotes Statistical comparisons are indicated by the arrows; ns: non-significant; ∗p < 0.05; ∗∗p < 0.01.