LitCovid-sentences  

PMC:7534795 / 16899-24588 JSONTXT 11 Projects

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Id Subject Object Predicate Lexical cue
T103 0-112 Sentence denotes Inflammation plays an important role in the development of cardiovascular impairment in the setting of COVID-19.
T104 113-397 Sentence denotes Similar to SARS-CoV and MERS-CoV infection, SARS-CoV-2 infection can also trigger excessive host immune responses, leading to extensive and uncontrolled release of proinflammatory cytokines termed as cytokine storm (Restrepo & Reyes, 2018; Zumla, Hui, Azhar, Memish, & Maeurer, 2020).
T105 398-510 Sentence denotes Cytokines play a pivotal role in the immune response to defend against different bacterial and viral infections.
T106 511-791 Sentence denotes However, it has also been established that dysregulated, amplified and uncontrolled immune responses may cause immunopathology leading to systematic self-attack contributing to multiple organ damage and cardiovascular injury secondary to SARS-CoV-2 infection (Zhang et al., 2020).
T107 792-1372 Sentence denotes A plethora of studies have shown increased amounts of cytokines, such as interleukin-6 (IL-6), IL-7, IL-8, IL-9, IL-10, IL-1β, IL-1RA, tumor necrosis factor-alpha (TNF-α), granulocyte-macrophage colony-stimulating factor, fibroblast growth factor, macrophage inflammatory protein 1 alpha, platelet-derived growth factor, monocyte chemoattractant protein and vascular endothelial growth factor in the serum of COVID-19 patients, especially in ICU patients (Chen, Zhou, et al., 2020; Conti et al., 2020; Huang et al., 2020; Wang, Hu, et al., 2020; Zhang, Zhao, Zhang, et al., 2020).
T108 1373-1492 Sentence denotes Importantly, there is a strong correlation between serum cytokine levels and mortality rates in patients with COVID-19.
T109 1493-1607 Sentence denotes The amplified and uncontrolled inflammatory response induces cellular apoptosis or necrosis of the affected cells.
T110 1608-1839 Sentence denotes This is followed by increased permeability of blood vessels leading to the accumulation of inflammatory monocytes, macrophages and neutrophils in different body organs fueling the inflammatory cascade (Channappanavar et al., 2016).
T111 1840-2008 Sentence denotes The vicious circle intensifies the situation as the cytokine storm is further stimulated and the regulation of immune response is lost resulting in severe consequences.
T112 2009-2149 Sentence denotes Collectively, this indicates the uncontrolled inflammatory response is a major factor in the adverse response observed in COVID-19 patients.
T113 2150-2313 Sentence denotes In that sense, it would seem reasonable that ameliorating the exaggerated immune response would improve the clinical outcomes in patients with COVID-19 (Table 3 ).
T114 2314-2512 Sentence denotes Table 3 Overview of the pharmacological approaches under investigation for ameliorating cytokine storm, hyperinflammatory state and the associated secondary organ complications in COVID-19 patients.
T115 2513-2619 Sentence denotes Pharmacological intervention Sample size and criteria Treatment protocol Key findings Conclusion Reference
T116 2620-2716 Sentence denotes • Tocilizumab for IL-6 cytokine release syndrome • Multicenter Randomized controlled trial (RCT)
T117 2717-2745 Sentence denotes • Severe COVID-19 infections
T118 2746-2766 Sentence denotes • 18–85 years of age
T119 2767-2788 Sentence denotes • Elevated serum IL-6
T120 2789-2829 Sentence denotes • N = 94 standard therapy + tocilizumab
T121 2830-2890 Sentence denotes • N = 94 standard therapy • 4–8 mg/kg tocilizumab i.v. once
T122 2891-3022 Sentence denotes • Additional dose if fever persists in 24 h after first dose • First phase showed normalization of fever within 24 h of tocilizumab
T123 3023-3128 Sentence denotes • Improved respiratory function, oxygenation, and pulmonary lesions • Phase 4 study completed in May 2020
T124 3129-3146 Sentence denotes • Results pending
T125 3147-3296 Sentence denotes • Tocilizumab may be a promising investigative therapy to reduce cytokine release syndrome and associated multi-organ damage (ChiCTR2000029765, 2020)
T126 3297-3395 Sentence denotes • Tocilizumab to mitigate cytokine storm and associated complications • Retrospective cohort study
T127 3396-3414 Sentence denotes • >18 years of age
T128 3415-3467 Sentence denotes • Intensive care unit (ICU) COVID-19 hospitalization
T129 3468-3516 Sentence denotes • Primary endpoint of hospital-related mortality
T130 3517-3555 Sentence denotes • N = 210 standard care + tocilizumab
T131 3556-3624 Sentence denotes • N = 420 standard care • 400 mg single dose or 8 mg/kg tocilizumab
T132 3625-3779 Sentence denotes • 88% required 1 infusion, 12% received a second infusion • Hazard ratio (HR) 0.71 for hospital related mortality (95% confidence interval (CI) 0.56–0.89)
T133 3780-3862 Sentence denotes • Treatment was more effective in patients with C-reactive protein (CRP) >15 mg/dL
T134 3863-4073 Sentence denotes • HR 0.48 (95% CI 0.30–0.77) than those with CRP <15 mg/dL HR 0.92 (95% CI 0.57–1.48) • Tocilizumab treatment is associated with a lower rate of mortality, particularly in those with enhanced inflammatory state
T135 4074-4165 Sentence denotes • Double blind RCT recently completed with results pending NCT04320615 (Biran et al., 2020)
T136 4166-4240 Sentence denotes • Tocilizumab to mitigate cytokine storm • Prospective observational study
T137 4241-4280 Sentence denotes • Severe or critical COVID-19 infection
T138 4281-4304 Sentence denotes • 25 to 88 years of age
T139 4305-4345 Sentence denotes • N = 21 tocilizumab + standard therapy
T140 4346-4405 Sentence denotes • 42.9% had CVD • 4–8 mg/kg or 400 mg tocilizumab i.v. once
T141 4406-4534 Sentence denotes • 85.7% received single dose of tocilizumab, 14.3% required second dose within 12 h of first dose • Fever normalized within 24 h
T142 4535-4568 Sentence denotes • Reduced O2 therapy requirements
T143 4569-4605 Sentence denotes • Minimal improvement in IL-6 levels
T144 4606-4634 Sentence denotes • CT lung lesion improvement
T145 4635-4703 Sentence denotes • All patients discharged • Limited sample size and no control group
T146 4704-4827 Sentence denotes • Tocilizumab treatment in severe COVID-19 cases may improve clinical symptoms in hyperinflammatory state (Xu et al., 2020)
T147 4828-4949 Sentence denotes • Intensive methylprednisolone regimen +/− tocilizumab for management of cytokine storm • Prospective observational study
T148 4950-5005 Sentence denotes • O2 sat ≤ 94% OR tachypnea, elevated CRP, high D-dimer
T149 5006-5069 Sentence denotes • Primary outcome of hospital discharge or clinical improvement
T150 5070-5114 Sentence denotes • N = 86 methylprednisolone +/− tocilizumab
T151 5115-5148 Sentence denotes • N = 86 standard care • Stage 1:
T152 5149-5222 Sentence denotes Immediate methylprednisolone 250 mg i.v. on day 1, then 80 mg on days 2–5
T153 5223-5296 Sentence denotes • Stage 2 (lack of clinical improvement or worsening respiratory status):
T154 5297-5410 Sentence denotes Add tocilizumab 8 mg/kg i.v. once between days 2–5 • Improvement in respiratory status HR 1.79 (95% CI 1.20–2.67)
T155 5411-5462 Sentence denotes • Improvement reached in a shorter time vs. control
T156 5463-5691 Sentence denotes • Reduced hospital mortality and need for mechanical ventilation • Short duration of intensive immunosuppressive therapy is associated with improved clinical outcomes in patients with hyperinflammaory state (Ramiro et al., 2020)
T157 5692-5788 Sentence denotes • Ruxolitinib treatment for elevated cytokine levels and inflammatory response • Prospective RCT
T158 5789-5834 Sentence denotes • 18 to 75 years of age with severe infection
T159 5835-5884 Sentence denotes • Primary outcome of time to clinical improvement
T160 5885-5922 Sentence denotes • N = 20 ruxolitinib + standard care
T161 5923-5987 Sentence denotes • N = 21 placebo + standard care • Ruxolitinib 5 mg twice daily
T162 5988-6092 Sentence denotes • Placebo vitamin C 100 mg twice daily • No difference in primary endpoint HR 1.669 (95% CI 0.836–3.335)
T163 6093-6149 Sentence denotes • Improvement in lung computerized tomography (CT) scans
T164 6150-6319 Sentence denotes • Significantly reduced cytokine levels and CRP by day 3 • Ruxolitinib may hasten time of chest CT scan improvement and mitigate systemic inflammation (Cao et al., 2020)
T165 6320-6425 Sentence denotes • Anakinra for targeting the cytokine inflammatory cascade through IL-1 blockade • Open label case series
T166 6426-6446 Sentence denotes • Elevated CRP N = 9
T167 6447-6494 Sentence denotes • 6/9 with CVD risk factors (diabetes, obesity)
T168 6495-6564 Sentence denotes • 3/9 with hypertension • Anakinra 100 mg every 12 h s.c. on days 1–3
T169 6565-6637 Sentence denotes • Anakinra 100 mg once daily s.c. on days 4–10 • Fever subsided by day 3
T170 6638-6678 Sentence denotes • CRP normalized in 5 patients by day 11
T171 6679-6718 Sentence denotes • Halted progression of CT lung lesions
T172 6719-6789 Sentence denotes • 100% survival • Small case series, potential for confounding factors
T173 6790-6840 Sentence denotes • Potential therapy to target inflammatory cascade
T174 6841-6937 Sentence denotes • Positive results in patients with hypertension and other CVD risk factors (Aouba et al., 2020)
T175 6938-6955 Sentence denotes • Ana-COVID study
T176 6956-7044 Sentence denotes • Anakinra for COVID-19 hyperinflammatory state • Prospective/retrospective cohort study
T177 7045-7094 Sentence denotes • Hospitalized adults with critical lung function
T178 7095-7148 Sentence denotes • Cohort with CVD (hypertension, stroke, cardiopathy)
T179 7149-7220 Sentence denotes • Primary outcome of ICU admission with mechanical ventilation or death
T180 7221-7255 Sentence denotes • N = 52 anakinra + standard care
T181 7256-7325 Sentence denotes • N = 44 standard care • Anakinra 100 mg s.c. twice daily for 3 days
T182 7326-7618 Sentence denotes • Then anakinra 100 mg s.c. once daily for 7 days • Significantly reduced need for mechanical ventilation or death HR 0.22 (0.11–0.41) • Anakinra may be associated with improved outcomes in patients with severe COVID-19 infection, including those with CVD and history of cardiovascular events
T183 7619-7689 Sentence denotes • May be due to mitigation of inflammatory cascade (Huet et al., 2020)