LitCovid-sentences  

PMC:7200337 / 54101-70538 JSONTXT 11 Projects

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Id Subject Object Predicate Lexical cue
T296 0-48 Sentence denotes Predictors of COVID-19 Disease Risk and Severity
T297 49-200 Sentence denotes With the rapidly growing number of cases in the first few months, numerous reports on predictors of COVID-19 severity with small cohorts were released.
T298 201-374 Sentence denotes These offered clinicians and immunologists the first understanding of the clinical course and pathological processes that are associated with the novel SARS-CoV-2 infection.
T299 375-514 Sentence denotes This section highlights key findings from those studies, with a major focus on the immune factors associated with disease risk or severity.
T300 516-550 Sentence denotes Susceptibility and Risk Biomarkers
T301 551-682 Sentence denotes There are currently limited known risk factors for susceptibility to COVID-19, although this has been evaluated in several studies.
T302 683-856 Sentence denotes Zhao et al. compared the ABO blood group distribution in a cohort of 2,173 COVID-19 patients to that of healthy controls from the corresponding regions (Zhao et al., 2020b).
T303 857-1030 Sentence denotes They found blood group A to be associated with a higher risk for acquiring COVID-19 when compared to non-A blood groups; blood group O had the lowest risk for the infection.
T304 1031-1251 Sentence denotes Another study demonstrated an identical association (Zietz and Tatonetti, 2020), and similar results have been previously described for other viruses (Lindesmith et al., 2003), including SARS-CoV-1 (Cheng et al., 2005a).
T305 1252-1539 Sentence denotes Several large collaborative efforts are currently underway to generate, share, and analyze genetic data to understand the links between human genetic variation and COVID-19 susceptibility and severity, the most prominent of which is the COVID-19 Host Genetics Initiative (covid19hg.org).
T306 1540-1792 Sentence denotes These studies are supported by previous observations on SARS-CoV-1 that followed the 2003 outbreak, which have identified significant associations between genetic variants and immune phenotypes (Chan et al., 2007, Wang et al., 2011, Zhao et al., 2011).
T307 1793-2069 Sentence denotes Although identifying such polymorphisms and their associated genes and pathways for SARS-CoV-2 will require large cohorts, several studies, which remain to be tested in clinical trials, have already highlighted genetic polymorphisms that may potentially impact susceptibility.
T308 2070-2354 Sentence denotes These studies have focused on genetic variants that may impact the expression or function of genes important in viral entry, namely ACE2 (SARS-CoV-2 receptor) and TMPRSS2 (spike protein activator) (Asselta et al., 2020, Cao et al., 2020c, Renieri et al., 2020, Stawiski et al., 2020).
T309 2355-2589 Sentence denotes Cao et al. identified variants that are potentially expression quantitative trait loci (eQTL) of ACE2 (i.e., they may potentially alter ACE2 gene expression) and analyzed their frequencies in different populations (Cao et al., 2020c).
T310 2590-2784 Sentence denotes Stawiski et al. listed variants that may be critical in ACE2 binding and thereby its function and compared the frequencies of these variants within different populations (Stawiski et al., 2020).
T311 2785-3049 Sentence denotes While there are several limitations to these studies, the major question is whether the utility of these biomarkers is replicable in large populations with COVID-19 clinical outcomes data and in targeted or large-scale genomic analyses that are currently underway.
T312 3050-3195 Sentence denotes In addition, these studies will reveal the potential associations between genetic variants and susceptibility in a gene or loci agnostic fashion.
T313 3197-3225 Sentence denotes Routine Bloodwork Biomarkers
T314 3226-3434 Sentence denotes Several routine blood and serological parameters have been suggested to stratify patients who might be at higher risk for complications to aid in allocation of healthcare resources in the pandemic (Table 1 ).
T315 3435-3573 Sentence denotes Serologic markers from routine bloodwork were reported by comparing patients with mild or moderate symptoms to those with severe symptoms.
T316 3574-3703 Sentence denotes This includes different acute phase proteins, such as SAA (serum amyloid protein) and C-reactive protein (CRP) (Ji et al., 2020).
T317 3704-3818 Sentence denotes Interestingly, elevations in CRP appear to be unique to COVID-19 patients when compared to other viral infections.
T318 3819-4061 Sentence denotes Other consistently reported markers in non-survivors are increased procalcitonin (PCT) and IL-6 levels (Huang et al., 2020d), as well as increased serum urea, creatinine, cystatin C, direct bilirubin, and cholinesterase (Xiang et al., 2020a).
T319 4062-4210 Sentence denotes Overall, inflammatory markers are common in severe cases of COVID-19 and appear to correlate with the severity of the symptoms and clinical outcome.
T320 4211-4392 Sentence denotes Moreover, the extensive damage that occurs in specific organs of severe COVID-19 patients is possibly related to differences in the expression of ACE2 (Figure 5 ) (Du et al., 2020).
T321 4393-4475 Sentence denotes Table 1 Routine Blood and Immunological Prognostic Biomarkers in COVID-19 Patients
T322 4476-4493 Sentence denotes Biomarker Purpose
T323 4494-4925 Sentence denotes Routine Bloodwork Lymphocyte count Predicted the disease severity and the outcomes of hospitalized patients (Tan et al., 2020a).Prognostic value was confirmed in numerous studies (Huang et al., 2020d, Liu et al., 2020b, Song et al., 2020, Wang et al., 2020f, Wynants et al., 2020, Yan et al., 2020b, Yang et al., 2020b, Zhang et al., 2020c, Zhao et al., 2020d).Decreased continuously in non-surviving patients (Wang et al., 2020b).
T324 4926-5199 Sentence denotes N/L Patients with N/L ≥3.13 were reported to be more likely to develop severe illness and to require ICU admission (Liu et al., 2020c).N/L on admission was a risk factor for short-term progression of patients with moderate pneumonia to severe pneumonia (Feng et al., 2020).
T325 5200-5329 Sentence denotes Confirmed to be of prognostic value in COVID-19 in several studies (Song et al., 2020, Wynants et al., 2020, Zhou et al., 2020d).
T326 5330-5406 Sentence denotes CRP Proposed as an early biomarker of disease progression (Ji et al., 2020).
T327 5407-5529 Sentence denotes Even in early stages, CRP levels were positively correlated with lung lesions and reflected disease severity (Wang, 2020).
T328 5530-5680 Sentence denotes Confirmed in numerous studies (Fu et al., 2020, Huang et al., 2020d, Wynants et al., 2020, Yan et al., 2020b, Zhao et al., 2020d, Zhou et al., 2020b).
T329 5681-5765 Sentence denotes Predicted the risk of acute myocardial injury (Liu et al., 2020g, Xu et al., 2020a).
T330 5766-5834 Sentence denotes LDH Higher in severe cases than in mild cases (Xiang et al., 2020a).
T331 5835-5971 Sentence denotes Widely proposed to have prognostic value in COVID-19 (Huang et al., 2020d, Wynants et al., 2020, Yan et al., 2020b, Zhao et al., 2020d).
T332 5972-6082 Sentence denotes D-dimer (and coagulation parameters) Predicted severity independently of other variables (Zhou et al., 2020d).
T333 6083-6190 Sentence denotes Elevated levels and disseminated intravascular coagulation are found in non-survivors (Wang et al., 2020b).
T334 6191-6264 Sentence denotes Identified patients at risk for acute cardiac injury (Liu et al., 2020g).
T335 6265-6468 Sentence denotes Other coagulation parameters, such as fibrin degradation product levels, longer prothrombin time, and activated partial thromboplastin time, were also associated with poor prognosis (Tang et al., 2020a).
T336 6469-6615 Sentence denotes SAA SAA was proposed to be used as an auxiliary index for diagnosis as it was elevated in 80% of the patients in a small cohort (Ji et al., 2020).
T337 6616-6785 Sentence denotes NT-proBNP (N-terminal pro B type natriuretic peptide) NT-proBNP was an independent risk factor of in-hospital death in patients with severe COVID-19 (Gao et al., 2020b).
T338 6786-6887 Sentence denotes Platelet count High platelet-to-lymphocyte ratio was associated with worse outcome (Qu et al., 2020).
T339 6888-7028 Sentence denotes Thrombocytopenia was associated with poor outcome and with incidence of myocardial injury in COVID-19 (Liu et al., 2020h, Shi et al., 2020).
T340 7029-7171 Sentence denotes Immunological CD4+, CD8+, and NK cell counts Lower CD4+, CD8+, and NK cells in PBMCs correlated with severity of COVID-19 (Nie et al., 2020b).
T341 7172-7243 Sentence denotes Validated by several studies (Wang et al., 2020f, Zheng et al., 2020b).
T342 7244-7435 Sentence denotes PD-1 and Tim-3 expression on T cells Increasing PD-1 and Tim-3 expression on T cells could be detected as patients progressed from prodromal to overtly symptomatic stages (Diao et al., 2020).
T343 7436-7587 Sentence denotes Expression was higher in infected patients versus healthy controls and in ICU versus non-ICU patients in both CD4 and CD8 T cells (Zhou et al., 2020b).
T344 7588-7912 Sentence denotes phenotypic changes in peripheral blood monocytes The presence of a distinct population of monocytes with high forward scatter (CD11b+, CD14+, CD16+, CD68+, CD80+, CD163+, and CD206+, which secrete IL-6, IL-10, and TNF-α) was identified in patients requiring prolonged hospitalization and ICU admission (Zhang et al., 2020c).
T345 7913-7990 Sentence denotes CD14+CD16+IL-6+ monocytes are increased in ICU patients (Zhou et al., 2020b).
T346 7991-8207 Sentence denotes IP-10, MCP-3, and IL-1ra IP-10, MCP-3, and IL-1ra were, among 48 examined cytokines, the only ones that closely associated with disease severity and outcome of COVID-19 in a study by Yang et al. (Yang et al., 2020b).
T347 8208-8401 Sentence denotes IL-6 Associated with disease severity (hospitalization and ICU admission) and poor prognosis (Chen et al., 2020g, Huang et al., 2020b, Liu et al., 2020b, Liu et al., 2020f, Wang et al., 2020b).
T348 8402-8495 Sentence denotes Increased levels were associated with higher risk of respiratory failure (Yao et al., 2020b).
T349 8496-8636 Sentence denotes IL-8 Positively correlated with disease severity (Chen et al., 2020e, Gong et al., 2020), with severe cases showing the highest IL-8 levels.
T350 8637-8854 Sentence denotes IL-10 Increased in severe or critical patients as compared to mild patients (Gong et al., 2020, Zhou et al., 2020d) without a statistically significant difference between severe and critical cases (Gong et al., 2020).
T351 8855-9048 Sentence denotes IL-2R Associated with disease severity in a study that, among other cytokines, also associated ferroprotein levels, PCT levels, and eosinophil counts with COVID-19 severity (Gong et al., 2020).
T352 9049-9228 Sentence denotes IL-1β CD14+IL-1β+ monocytes are abundant in early-recovery patients as shown in a single-cell RNA-seq analysis and thought to be associated with cytokine storm (Wen et al., 2020).
T353 9229-9363 Sentence denotes IL-1β did not correlate with disease severity in a cross-sectional study with mild, severe, and critical patients (Gong et al., 2020).
T354 9364-9508 Sentence denotes IL-4 IL-4 was associated with impaired lung lesions (Fu et al., 2020), but some reports point to a potential mediator effect (Wen et al., 2020).
T355 9509-9740 Sentence denotes IL-18 In modeling immune cell interaction between DCs and B cells in late recovery COVID-19 patients, IL-18 was found to be important in B cell production of antibodies, which suggests its importance in recovery (Wen et al., 2020).
T356 9741-9813 Sentence denotes GM-CSF GM-CSF+IFN-γ+ T cells are higher in ICU than in non-ICU patients.
T357 9814-9927 Sentence denotes CD14+CD16+GM-CSF+ monocytes are higher in COVID-19 patients as compared to healthy controls (Zhou et al., 2020b).
T358 9928-10028 Sentence denotes IL-2 and IFN-γ IL-2 and IFN-γ levels were shown to be increased in severe cases (Liu et al., 2020b).
T359 10029-10174 Sentence denotes anti-SARS-CoV-2 antibody levels Prolonged SARS-CoV-2 IgM positivity could be utilized as a predictive factor for poor recovery (Fu et al., 2020).
T360 10175-10287 Sentence denotes Higher anti-SARS-CoV-2 IgG levels and higher N/L were more commonly found in severe cases (Zhang et al., 2020a).
T361 10288-10387 Sentence denotes Figure 5 ACE2 Expression in Organs and Systems Most Frequently Implicated in COVID-19 Complications
T362 10388-10470 Sentence denotes The gastrointestinal tract, kidneys, and testis have the highest ACE2 expressions.
T363 10471-10829 Sentence denotes In some organs, different cell types have remarkably distinct expressions; e.g., in the lungs, alveolar epithelial cells have higher ACE2 expression levels than bronchial epithelial cells; in the liver, ACE2 is not expressed in hepatocytes, Kupffer cells, or endothelial cells but is detected in cholangiocytes, which can explain liver injury to some extent.
T364 10830-10931 Sentence denotes Furthermore, ACE2 expression is enriched on enterocytes of the small intestine compared to the colon.
T365 10932-11149 Sentence denotes ACE2, angiotensin-converting enzyme 2; BNP, B-type natriuretic peptide; CRP, C-reactive protein; IL, interleukin; N/L, neutrophil-to-lymphocyte ratio; PT, prothrombin time; aPTT, activated partial thromboplastin time.
T366 11150-11326 Sentence denotes Lymphopenia is the most frequently described prognostic marker in COVID-19 (Table 1), and it appears to predict morbidity and mortality even at early stages (Fei et al., 2020).
T367 11327-11582 Sentence denotes Tan et al. proposed a prognostic model based on lymphocyte counts at two time points: patients with less than 20% lymphocytes at days 10–12 from the onset of symptoms and less than 5% at days 17–19 had the worst outcomes in this study (Tan et al., 2020a).
T368 11583-11835 Sentence denotes Wynants et al. compared predictors of disease severity across seven studies (>1,330 patients), highlighting CRP, neutrophil-to-lymphocyte ratio (N/L), and lactate dehydrogenase (LDH) as the most significant predictive biomarkers (Wynants et al., 2020).
T369 11836-12009 Sentence denotes Furthermore, a meta-analysis of 30 COVID-19 studies with a total of 53,000 patients also attempted to identify early-stage patients with poor prognosis (Zhao et al., 2020d).
T370 12010-12213 Sentence denotes The most consistent findings across the different studies were elevated levels of CRP, LDH, and D-dimer, as well as decreased blood platelet and lymphocyte counts (Yan et al., 2020b, Zhou et al., 2020d).
T371 12214-12612 Sentence denotes Systemic and pulmonary thrombi have been reported with activation of the extrinsic coagulation cascade, involving dysfunctional endothelium and monocytic infiltration (Poor et al., 2020, Varga et al., 2020); thrombocytopenia and elevated D-dimer levels may be indicative of these coagulopathies in COVID-19 patients with important therapeutic implications (Fogarty et al., 2020, Poor et al., 2020).
T372 12614-12662 Sentence denotes Immunological Biomarkers in the Peripheral Blood
T373 12663-12815 Sentence denotes Immunological biomarkers are particularly important, as immunopathology has been suggested as a primary driver of morbidity and mortality with COVID-19.
T374 12816-12921 Sentence denotes Several cytokines and other immunologic parameters have been correlated with COVID-19 severity (Table 1).
T375 12922-13192 Sentence denotes Most notably, elevated IL-6 levels were detected in hospitalized patients, especially critically ill patients, in several studies and are associated with ICU admission, respiratory failure, and poor prognosis (Chen et al., 2020g, Huang et al., 2020b, Liu et al., 2020f).
T376 13193-13443 Sentence denotes Increased IL-2R, IL-8, IL-10, and GM-CSF have been associated with disease severity as well, but studies are limited, and further studies with larger cohorts of patients are needed to indicate predictive power (Gong et al., 2020, Zhou et al., 2020b).
T377 13444-13563 Sentence denotes Conflicting results regarding IL-1β and IL-4 have been reported (Fu et al., 2020, Gong et al., 2020, Wen et al., 2020).
T378 13564-13855 Sentence denotes Although elevated cytokine concentrations have been widely described in COVID-19 patients, the vast majority (including IL-6, IL-10, IL-18, CTACK, and IFN-γ) do not seem to have prognostic value, because they do not always differentiate moderate cases from severe cases (Yang et al., 2020b).
T379 13856-13919 Sentence denotes This stratification was possible with IP-10, MCP-3, and IL-1ra.
T380 13920-14247 Sentence denotes While there are reports that levels of IL-6 at first assessment might predict respiratory failure (Herold et al., 2020), other publications with longitudinal analyses demonstrated that IL-6 increases fairly late during the disease’s course, consequently compromising its prognostic value at earlier stages (Zhou et al., 2020a).
T381 14248-14545 Sentence denotes Liu et al. developed a web-based tool using k-means clustering to predict prognosis in terms of death or hospital discharge of COVID-19 patients using age, comorbidities (binary), and baseline log helper T cell count (TH), log suppressor T cell count (TS), and log TH/TS ratio (Liu et al., 2020e).
T382 14546-14754 Sentence denotes Total T cell, helper T cell, and suppressor T cell counts were significantly lower and the TH/TS ratio was significantly higher in patients who died from infection as compared to patients who were discharged.
T383 14755-15005 Sentence denotes Importantly, most serological and immunological changes observed in severe cases are associated with disease severity but cannot necessarily serve as predictive factors, as they may not have utility in early identification of patients at higher risk.
T384 15006-15214 Sentence denotes Discovery of truly predictive biomarkers and potential drivers of hyperinflammatory processes requires comprehensive profiling of asymptomatic and mild cases and longitudinal studies that are limited to date.
T385 15215-15324 Sentence denotes Confounding variables including age, gender, and comorbidities may dramatically affect associations observed.
T386 15325-15600 Sentence denotes In addition, direct correlation with patient viral load will be important to provide a greater understanding of underlying causes of morbidity and mortality in COVID-19 and the contribution of viral infectivity, hyperinflammation, and host tolerance (Medzhitov et al., 2012).
T387 15601-15808 Sentence denotes In summary, lymphopenia, increases in proinflammatory markers and cytokines, and potential blood hypercoagulability characterize severe COVID-19 cases with features reminiscent of cytokine release syndromes.
T388 15809-15913 Sentence denotes This correlates with a diverse clinical spectrum ranging from asymptomatic to severe and critical cases.
T389 15914-16038 Sentence denotes During the incubation period and early phase of the disease, leukocyte and lymphocyte counts are normal or slightly reduced.
T390 16039-16202 Sentence denotes After SARS-CoV-2 binds to ACE2 overexpressing organs, such as the gastrointestinal tracts and kidneys, increases in non-specific inflammation markers are observed.
T391 16203-16437 Sentence denotes In more severe cases, a marked systemic release of inflammatory mediators and cytokines occurs, with corresponding worsening of lymphopenia and potential atrophy of lymphoid organs, impairing lymphocyte turnover (Terpos et al., 2020).