LitCovid-sentences  

PMC:7253235 / 27614-36127 JSONTXT 11 Projects

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Id Subject Object Predicate Lexical cue
T178 0-98 Sentence denotes Potential Overlapping Mechanisms in COVID-19 and Cardiovascular Disease and Anti-cancer Treatments
T179 99-277 Sentence denotes Multiple treatments are being assessed in various trials including antivirals, anti-inflammatories, immunotherapies, and cardiovascular medications for the treatment of COVID-19.
T180 278-583 Sentence denotes Although some these therapies have potential to provide benefit, there are numerous potential cardiac toxicities and drug-drug interactions that may be harmful to cardio-oncology patients, which is critically relevant since a high percentage of COVID-19 patients have cardiovascular comorbidities [65–68].
T181 584-743 Sentence denotes An appraisal of these agents and their potential cardiotoxicities—of which there is no current proven efficacy at this time—is beyond the scope of this review.
T182 744-991 Sentence denotes However, some agents are actively used in the treatment of cardiovascular disease and/or cancer-related conditions, and the unique disease states of the cardio-oncology population may yield insights into the mechanisms of COVID-19 pathophysiology.
T183 992-1230 Sentence denotes For instance, the idea of using medications that have already been well-studied and target host responses by boosting host immunity was in discussion during prior significant outbreaks and epidemics including Ebola and influenza [69, 70].
T184 1231-1361 Sentence denotes ACE inhibitors (ACEI), angiotensin-receptor blockers (ARB), and statins are of particular importance during this current pandemic.
T185 1362-1518 Sentence denotes There has been a theoretical uncertainty in regard to the safety of ACEI/ARB use in patients with COVID-19 based on the ACE2 viral entry mechanism [71, 72].
T186 1519-1589 Sentence denotes The virus gains cellular entry by attaching to the ACE2 receptor [72].
T187 1590-1670 Sentence denotes ACE2 expression and activity have shown to be increased in by ACEI/ARB use [73].
T188 1671-1875 Sentence denotes Although there is theoretical risk that ACE2 upregulation may increase the susceptibility of infection, other conflicting evidence indicates that upregulation of ACE2 in fact has a more protective effect.
T189 1876-2055 Sentence denotes Studies in mouse models have shown that ACE2 is protective against acute lung injury and blocking the renin-angiotensin-aldosterone system pathway decreases lung failure [74, 75].
T190 2056-2279 Sentence denotes Based on the review of the literature to date, the Heart Failure Society of America recommends continuation of ACEI/ARB use for patients that are prescribed them for heart failure, hypertension, and ischemic disease [76••].
T191 2280-2439 Sentence denotes Abrupt discontinuation of medications is not recommended and can worsen clinical stability especially in patients with existing cardiovascular conditions [71].
T192 2440-2545 Sentence denotes Additionally, statins have long been shown to have anti-inflammatory properties through multiple studies.
T193 2546-2645 Sentence denotes For instance, simvastatin has been shown to decrease pulmonary inflammation in human subjects [77].
T194 2646-2852 Sentence denotes Although the benefits for cardiovascular patients have been numerous from a lipid lower standpoint, it is important to note that the ability of statins to decrease inflammation also improves mortality [78].
T195 2853-3081 Sentence denotes A retrospective analysis of patients from the Veterans Administration showed that statin use, ACEI use, or ARB use each independently improved 30 day mortality of patients > 65 years old who were hospitalized for pneumonia [79].
T196 3082-3196 Sentence denotes However, in the era of the COVID-19 pandemic, studies are needed to evaluate its role in COVID-19–related illness.
T197 3197-3516 Sentence denotes Although cancer patients have been considered immunosuppressed as a result of their underlying malignancy and cytoreduction therapies, patients that undergo immunotherapy including immune checkpoint inhibitors (ICIs) or CAR-T cell therapy may have different immuno-physiology that responds to COVID-19 differently [80].
T198 3517-3616 Sentence denotes Anti-PD-1/PD-L1 and anti-CTLA-4 ICIs have been approved by the FDA for use in a variety of cancers.
T199 3617-3758 Sentence denotes These drugs primarily work by enhancing a patient’s immune response to tumors through inhibiting negative regulators of T cell function [81].
T200 3759-3870 Sentence denotes CAR-T cell therapy involves reprogramming a patient’s own T cells to directly target their specific tumor [82].
T201 3871-4105 Sentence denotes An adverse effect that can occur with either anti-PD-1 therapy or CAR-T cell therapy involves cytokine release syndrome (CRS) which is similar to the cytokine storm phenomenon that occurs in patients with severe COVID-19 [80, 82, 83].
T202 4106-4307 Sentence denotes CRS occurs as a result of hyperimmune activation in response to tumor death, whereas cytokine storm in COVID-19 patients occurs as a result of T cell hyperactivation from immune dysregulation [80, 84].
T203 4308-4494 Sentence denotes Similar markers are elevated in both phenomena, including IL-6, TNF-alpha, and IFN-λ, of which IL-6 has also been shown to be a mortality predictor in COVID-19 patients [27, 64, 80, 84].
T204 4495-4614 Sentence denotes COVID-19 patients that develop cytokine storm syndrome are at risk of developing ARDS and multi-organ failure [84, 85].
T205 4615-4735 Sentence denotes Immunosuppression with tocilizumab, an IL-6 inhibitor, is used to treat CRS associated with CAR-T cell therapy [80, 86].
T206 4736-4953 Sentence denotes Additionally, tocilizumab immunosuppression is used to treat immune-related adverse events (irAEs) from PD-1 inhibitors that are refractory to steroids; irAEs also occur as a result of hyperimmune activation [80, 87].
T207 4954-5152 Sentence denotes Moreover, the cytokine storm observed with COVID-19 has also been noted to be similar to that of secondary hemophagocytic lymphohistiocytosis (HLH) which is also treated with immunosuppression [64].
T208 5153-5278 Sentence denotes Current trials are underway with using tocilizumab and sarilumab (another IL-6 inhibitor) to treat COVID-19 patients [88–90].
T209 5279-5504 Sentence denotes Although immunotherapy may be thought to reinstate a cancer patient’s immunocompetence, there is potential for synergy from CRS and the COVID-19 cytokine storm pathogenesis which can further worsen a patient’s mortality risk.
T210 5505-5700 Sentence denotes Further unfavorable synergy between ICI immune-related adverse events (irAEs) can also be seen potentially between the pneumonitis that ICIs can cause and the lung involvement with COVID-19 [80].
T211 5701-5832 Sentence denotes Pneumonitis occurs in < 10% of patients being treated with anti-CTLA-4 and anti-PD-1 ICIs and is potentially life-threatening [81].
T212 5833-5939 Sentence denotes Therefore, if combined with lung injury from COVID-19, there is a theoretical potential for poor outcomes.
T213 5940-6098 Sentence denotes There are potential cancer treatments that may counteract the pathogenesis of COVID-19, such as CCR5 treatments and tyrosine kinase inhibitors (TKIs) [91–93].
T214 6099-6295 Sentence denotes The CCR5 receptor is a G protein–coupled receptor selectively expressed on macrophages, T cells, eosinophils, dendritic cells, and microglia and is implicated in chemokine-mediated signaling [94].
T215 6296-6543 Sentence denotes This receptor has historically been targeted for HIV antiviral therapy, in the setting of disrupting viral entry, specifically through small molecule inhibition with maraviroc and vicriviroc, and monoclonal antibody treatment with leronlimab [95].
T216 6544-6664 Sentence denotes Moreover, multiple cancers have been shown to overexpress CCR5 which has been linked to a cancer’s metastatic potential.
T217 6665-6761 Sentence denotes CCR5 therapies are currently being studied in metastatic colorectal and breast cancers [91, 94].
T218 6762-6913 Sentence denotes Due to its immune system restorative properties, leronlimab is being investigated for compassionate use in the treatment of COVID-19 patients [96, 97].
T219 6914-7086 Sentence denotes Studies examining receptor blockade in leronlimab preliminarily have shown decreases in IL-6, restoration of CD4/CD8 ratios, and reduction in overall COVID-19 viremia [98].
T220 7087-7291 Sentence denotes These collective findings suggest possible therapeutic role in establishing immune reconstitution in patients that are critically ill and may provide dual benefit in patients with shared cancer diagnoses.
T221 7292-7451 Sentence denotes TKIs like sunitinib and erlotinib that specifically inhibit AAK1, a protein regulator that allows passage of the virus into cells, have theorized utility [92].
T222 7452-7599 Sentence denotes Sunitinib is an anti-vascular endothelial growth factor (VEGF) TKI which is used in first-line for treatment of advanced renal cell carcinoma [99].
T223 7600-7763 Sentence denotes Erlotinib is an anti-epidermal growth factor receptor (EGFR) TKI which is used in first-line treatment for metastatic EGFR-mutant non-small cell lung cancer [100].
T224 7764-7941 Sentence denotes Both these TKIs have shown to reduce the infectivity of Dengue and Ebola through in vivo studies with murine models which showed decreased viremia and mortality with treatments.
T225 7942-8118 Sentence denotes Moreover, in vitro studies in cultured cells and hepatitis C in this same study showed that use of these TKIs reduced intracellular trafficking and inhibited viral entry [101].
T226 8119-8225 Sentence denotes However, the high doses required to achieve this effect may potentially exhibit harm to patients [92, 93].
T227 8226-8383 Sentence denotes Regardless, there is potential for cancer patients receiving these therapies to achieve dual benefit as referenced before, but warrant further investigation.
T228 8384-8513 Sentence denotes Further studies are warranted in tracking the outcomes of cancer patients with COVID-19 and the type of treatments they received.