LitCovid-sentences  

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Id Subject Object Predicate Lexical cue
T23 0-15 Sentence denotes 1 Introduction
T24 16-221 Sentence denotes The emergence of novel coronavirus, officially known as Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2), has presented an unprecedented challenge for the healthcare community across the world.
T25 222-426 Sentence denotes High infectivity, ability to get transmitted even during asymptomatic phase and relatively low virulence have resulted in rapid transmission of this virus beyond geographic regions, leading to a pandemic.
T26 427-571 Sentence denotes The first case of this disease, known as coronavirus disease 2019 (COVID-2019), occurred on December 8, 2019 in the Hubei province of China [1].
T27 572-814 Sentence denotes Since then, within a short span of just over 3 months, the infection has spread to 177 countries/area/territories across the world, with 266073 confirmed cases and 11184 deaths (World Health Organization statistics as on March 21, 2020) [2] .
T28 815-880 Sentence denotes Table 1 Cardiovascular complications in coronavirus disease 2019.
T29 881-912 Sentence denotes Manifestation Incidence Remarks
T30 913-1111 Sentence denotes Acute cardiac injury∗ (most commonly defined as elevation of cardiac troponin I above 99th percentile upper reference limit) 8–12% on average [10] • Most commonly reported cardiovascular abnormality
T31 1112-1187 Sentence denotes • Can result from any of the following mechanisms-•Direct myocardial injury
T32 1188-1210 Sentence denotes •Systemic inflammation
T33 1211-1252 Sentence denotes •Myocardial oxygen demand supply mismatch
T34 1253-1274 Sentence denotes •Acute coronary event
T35 1275-1286 Sentence denotes •Iatrogenic
T36 1287-1320 Sentence denotes • Strong adverse prognostic value
T37 1321-1458 Sentence denotes Acute coronary event Not reported, but appears to be low Potential mechanisms-• Plaque rupture due to inflammation/increased shear stress
T38 1459-1512 Sentence denotes • Aggravation of pre-existing coronary artery disease
T39 1513-1679 Sentence denotes Left ventricular systolic dysfunction Not reported Any of the causes of myocardial dysfunction mentioned above can lead to acute left ventricular systolic dysfunction
T40 1680-1884 Sentence denotes Heart failure Reported in one study- 52% in those who died, 12% in those who recovered and were discharged [5] • Any of the causes of myocardial dysfunction mentioned above can lead to acute heart failure
T41 1885-2003 Sentence denotes • Increased metabolic demand of a systemic disease can cause acute decompensation of pre-existing stable heart failure
T42 2004-2158 Sentence denotes Arrhythmia 16.7% overall; 44.4 in severe illness, 8.9% in mild cases [8] Both tachyarrhythmia and bradyarrhythmia can occur but exact nature not described
T43 2159-2264 Sentence denotes Potential long-term consequences Too early to assess Too early to ascertain for coronavirus disease 2019.
T44 2265-2473 Sentence denotes However, patients recovering from a similar earlier illness- Severe Acute Respiratory Syndrome- continued to have long-term abnormalities of lipid and glucose metabolism and of cardiovascular homeostasis [12]
T45 2474-2704 Sentence denotes ∗ Acute cardiac injury is a non-specific term with significant overlap with other cardiovascular manifestations; however, it is listed here because of how reporting has been done in most of the studies on coronavirus disease 2019.
T46 2705-2898 Sentence denotes Respiratory involvement, presenting as mild flulike illness to potentially lethal acute respiratory distress syndrome or fulminant pneumonia, is the dominant clinical manifestation of COVID-19.
T47 2899-3053 Sentence denotes However, much like any other respiratory tract infection, pre-existing cardiovascular disease (CVD) and CV risk factors enhance vulnerability to COVID-19.
T48 3054-3149 Sentence denotes Further, COVID-19 can worsen underlying CVD and even precipitate de novo cardiac complications.
T49 3150-3259 Sentence denotes This review is aimed at providing overview of various CV manifestations in patients presenting with COVID-19.
T50 3260-3384 Sentence denotes The impact of pre-existing CVD and new onset cardiac complications on clinical outcomes in these patients is also discussed.
T51 3385-3679 Sentence denotes Since our understanding on this subject is only evolving at this stage, the information contained in the subsequent text is based mainly on the limited early experience with COVID-19 and learnings from the previous coronavirus illnesses, namely SARS and Middle-East Respiratory Syndrome (MERS).
T52 3681-3698 Sentence denotes 2 Search methods
T53 3699-3924 Sentence denotes A literature search was done using PubMed and Google search engines for original and review articles, advisories from professional societies, and expert commentaries published since the onset of the current COVID-19 epidemic.
T54 3925-4096 Sentence denotes Search terms “COVID-19” and “coronavirus” were used in combination with “cardiac”, “cardiovascular”, “arrhythmia”, “myocardial infarction”, “troponin” and “heart failure”.
T55 4097-4183 Sentence denotes Relevant cross-references for previous studies about SARS and MERS were also reviewed.
T56 4185-4215 Sentence denotes 2.1 Pathogenic considerations
T57 4216-4279 Sentence denotes SARS-CoV-2 is caused by a novel enveloped RNA beta-coronavirus.
T58 4280-4509 Sentence denotes Seven species of these beta-coronaviruses are known to cause human infections, with four mainly causing mild flulike symptoms and the remaining three resulting in potentially fatal illnesses (SARS, MERS and the ongoing COVID-19).
T59 4510-4628 Sentence denotes Although respiratory tract is the primary target for SARS-CoV-2, CV system may get involved in several different ways.
T60 4629-4718 Sentence denotes Following are the common mechanisms responsible for CV complications in COVID-19 [3,4]-1.
T61 4720-4907 Sentence denotes Direct myocardial injury- SARS-CoV-2 enters human cells by binding to angiotensin-converting enzyme 2 (ACE2), a membrane bound aminopeptidase which is highly expressed in heart and lungs.
T62 4908-5035 Sentence denotes ACE2 plays an important role in neurohumoral regulation of CV system in normal health as well as in various disease conditions.
T63 5036-5173 Sentence denotes The binding of SARS-CoV-2 to ACE2 can result in alteration of ACE2 signaling pathways, leading to acute myocardial and lung injury [3,4].
T64 5174-5176 Sentence denotes 2.
T65 5178-5385 Sentence denotes Systemic inflammation- More severe forms of COVID-19 are characterized by acute systemic inflammatory response and cytokine storm, which can result in injury to multiple organs leading to multiorgan failure.
T66 5386-5506 Sentence denotes Studies have shown high circulatory levels of proinflammatory cytokines in patients with severe/critical COVID-19 [5,6].
T67 5507-5509 Sentence denotes 3.
T68 5511-5772 Sentence denotes Altered myocardial demand-supply ratio- Increased cardiometabolic demand associated with the systemic infection coupled with hypoxia caused by acute respiratory illness can impair myocardial oxygen demand-supply relationship and lead to acute myocardial injury.
T69 5773-5775 Sentence denotes 4.
T70 5777-5982 Sentence denotes Plaque rupture and coronary thrombosis- Systemic inflammation as well as increased shear stress due to increased coronary blood flow can precipitate plaque rupture resulting in acute myocardial infarction.
T71 5983-6064 Sentence denotes Prothrombotic milieu created by systemic inflammation further increases the risk.
T72 6065-6067 Sentence denotes 5.
T73 6069-6246 Sentence denotes Adverse effects of various therapies- Various antiviral drugs, corticosteroids and other therapies aimed at treating COVID-19 can also have deleterious effects on the CV system.
T74 6247-6249 Sentence denotes 6.
T75 6251-6420 Sentence denotes Electrolyte imbalances- Electrolyte imbalances can occur in any critical systemic illness and precipitate arrhythmias, esp. in patients with underlying cardiac disorder.
T76 6421-6559 Sentence denotes There is particular concern about hypokalemia in COVID-19, due to interaction of SARS-CoV-2 with renin-angiotensin-aldosterone system [7].
T77 6560-6624 Sentence denotes Hypokalemia increases vulnerability to various tachyarrhythmias.
T78 6626-6667 Sentence denotes 2.1.1 Role of underling CV comorbidities
T79 6668-6839 Sentence denotes The patients with pre-existing CVD appear to have heightened vulnerability to develop COVID-19 and tend to have more severe disease with worse clinical outcomes [1,4,6,8].
T80 6840-6992 Sentence denotes Various CV risk factors also adversely affect porgnosis of these patients, although they do not seem to increase likleihood of developing the infection.
T81 6993-7203 Sentence denotes A meta-analysis of six published studies from China including 1527 patients with COVID-19 reported 9.7%, 16.4% and 17.1% prevalence of diabetes, cardio-cerebrovascular disease and hypertension respectively [4].
T82 7204-7392 Sentence denotes Although the prevalence of diabetes and hypertension in this cohort was same as in the Chinese general population, the prevalence of cardio-cerebrovascular disease was considerably higher.
T83 7393-7666 Sentence denotes More importantly, the presence of diabetes, cardio-cerebrovascular disease and hypertension was associated with a 2-fold, 3-fold and 2-fold greater risk of severe disease or requiring intensive care unit (ICU) admission, suggesting prognostic impact of these comorbidities.
T84 7667-7816 Sentence denotes A much larger report from the Chinese Center for Disease Control and Prevention described clinical outcomes in 44672 confirmed cases of COVID-19 [1].
T85 7817-7991 Sentence denotes The overall case fatality rate (CFR) was 2.3% in the entire cohort but significantly higher (6%, 7.3% and 10.5% respectively) in patients with hypertension, diabetes and CVD.
T86 7992-8163 Sentence denotes Although data is lacking, the prevalence of various CV comorbidities and their impact on clinical outcomes seem to vary considerably across different geographic locations.
T87 8164-8291 Sentence denotes The CFRs have been lower in China outside Hubei province and many other countries but much higher in some European nations [2].
T88 8292-8414 Sentence denotes A small report including 21 patients from Washington, United States of America presented a particularly grim scenario [9].
T89 8415-8526 Sentence denotes Comorbidities were common in this cohort, with diabetes present in 33.3% and congestive heart failure in 42.9%.
T90 8527-8604 Sentence denotes Acute cardiac dysfunction occurred in 33.3% patients and 52.4% patients died.
T91 8605-8844 Sentence denotes However, the overall CFR in the United States seems to be much lower (201 deaths out of 15219 confirmed cases) [2], although it is likely to rise as many of the patients are currently hospitalized and have not yet had the definite outcome.
T92 8846-8892 Sentence denotes 2.2 Cardiovascular manifestations of COVID-19
T93 8894-8924 Sentence denotes 2.2.1 Acute myocardial injury
T94 8925-9018 Sentence denotes Acute myocardial injury is the most commonly described CV complication in COVID-19 (Table 1).
T95 9019-9210 Sentence denotes Different reports have used different definitions for acute myocardial injury, including rise in cardiac enzymes (different biomarkers and cut-offs) and/or electrocardiographic abnormalities.
T96 9211-9367 Sentence denotes However, an elevation of high-sensitivity cardiac troponin I (cTnI) above 99th percentile upper reference limit is the most commonly used definition.Table 1
T97 9368-9528 Sentence denotes The overall incidence of acute cardiac injury has been variable but roughly 8–12% of the positive cases are known to develop significant elevation of cTnI [10].
T98 9529-9798 Sentence denotes The aforementioned meta-analysis of the Chinese studies [4] reported 8% incidence of acute cardiac injury whereas another study including only those patients who had had a definite outcome (death or discharge from hospital) reported 17% incidence of cTnI elevation [5].
T99 9799-9960 Sentence denotes Regardless of the actual incidence, acute cardiac injury has been consistently shown to be a strong negative prognostic marker in patients with COVID-19 [5,6,8].
T100 9961-10079 Sentence denotes The patients admitted to ICU or having severe/fatal illness have several-fold higher likelihood of troponin elevation.
T101 10080-10218 Sentence denotes In contrast, the incidence of elevated troponin has been very low (only 1–2%) in patients having mild illness not requiring ICU admission.
T102 10219-10346 Sentence denotes Any of the mechanisms described above can lead to acute cardiac injury and rise in cardiac troponins in patients with COVID-19.
T103 10347-10571 Sentence denotes The relative role of these different mechanisms has not been described but direct (i.e. non-coronary) myocardial injury due to viral myocarditis or the effect of systemic inflammation appear to be the most common mechanisms.
T104 10572-10708 Sentence denotes These observations are supported by a previous autopsy study in patients who had died due to SARS during the Toronto SARS outbreak [11].
T105 10709-10870 Sentence denotes In this study, the viral ribonucleic acid was detected in 35% of the autopsied human heart samples, providing evidence for direct myocardial injury by the virus.
T106 10871-10992 Sentence denotes No study has described the incidence of ST-segment elevation myocardial infarction in COVID-19, but it appears to be low.
T107 10993-11142 Sentence denotes Similarly, the incidence of left ventricular systolic dysfunction, acute left ventricular failure and cardiogenic shock have also not been described.
T108 11143-11227 Sentence denotes Only one Chinese study reported incidence of heart failure in COVID-19 patients [5].
T109 11228-11365 Sentence denotes Heart failure had occurred in 52% of the patients who subsequently died and in 12% of the patients who were discharged from the hospital.
T110 11367-11385 Sentence denotes 2.2.2 Arrhythmias
T111 11386-11451 Sentence denotes Both tachy- and brady-arrhythmias are known to occur in COVID-19.
T112 11452-11582 Sentence denotes A study describing clinical profile and outcomes in 138 Chinese patients with COVID-19 reported 16.7% incidence of arrhythmia [8].
T113 11583-11710 Sentence denotes The incidence was much higher (44.4%) in those requiring ICU admission as compared to those not requiring ICU admission (8.9%).
T114 11711-11752 Sentence denotes The type of arrhythmia was not described.
T115 11754-11793 Sentence denotes 2.2.3 Potential long-term consequences
T116 11794-11932 Sentence denotes COVID-19 has emerged only a few months ago and it is too early to predict long-term outcome of the patients who recover from this illness.
T117 11933-12090 Sentence denotes However, some important messages can be gleaned from previous experiences with SARS, caused by SARS-CoV which shares considerable similarity with SARS-CoV-2.
T118 12091-12315 Sentence denotes It was reported that among patients who had recovered from SARS, 68% continued to have abnormalities of lipid metabolism at 12-years follow-up; CV abnormalities were present in 40% and altered glucose metabolism in 60% [12].
T119 12316-12425 Sentence denotes Similar findings have also been reported in patients recovering from other respiratory tract infections [13].
T120 12426-12629 Sentence denotes Considering this, careful follow-up of those recovering from the current COVID-19 would be important to understand the long-term impact of this illness and also to protect these patients from future CVD.
T121 12631-12659 Sentence denotes 2.3 Management implications
T122 12660-12841 Sentence denotes The overall management principles for patients presenting with COVID-19 who develop CV complications or who have pre-existing CVD are same as for any other patient without COVID-19.
T123 12842-12910 Sentence denotes However, there are a few important points that need consideration-1.
T124 12911-13031 Sentence denotes As caregivers, it is our utmost responsibility to protect ourselves from getting infected while managing these patients.
T125 13032-13156 Sentence denotes Therefore, all heathcare personnel engaged in the care of COVID-19 patients must observe necessary precautions at all times.
T126 13157-13307 Sentence denotes All of them should be trained in donning, usage, and doffing of the personal protective equipment in accordance with the existing practice guidelines.
T127 13308-13310 Sentence denotes 2.
T128 13311-13471 Sentence denotes The hospital systems need to ensure preparedness for dealing with large volume of COVID-19 patients, many of whom would need ICU care and/or acute cardiac care.
T129 13472-13631 Sentence denotes Appropriate protocols for rapid diagnosis, triage, isolation, and management of COVID-19 patients with CV complications should be developed and well-rehearsed.
T130 13632-13800 Sentence denotes Rapid triaging and management of these patients is crucial, not only to allow efficient utilization of healthcare resources but also to minimize exposure to caregivers.
T131 13801-13955 Sentence denotes There are already reports highlighting delays in delivering acute cardiac care due to extra precautions that need to be observed in view of COVID-19 [14].
T132 13956-14003 Sentence denotes Efforts should be made to minimize such delays.
T133 14004-14006 Sentence denotes 3.
T134 14007-14147 Sentence denotes Strong emphasis should be placed on avoiding unwarranted diagnostic tests (e.g. cardiac troponin, echocardiography, etc.) in these patients.
T135 14148-14381 Sentence denotes This is required to minimize unwarranted downstream diagnostic/therapeutic procedures which would further strain the already stretched healthcare resources and would also subject caregivers to added risk of exposure to the infection.
T136 14382-14544 Sentence denotes The American College of Cardiology has released an advisory discouraging random measurement of cardiac biomarkers such as troponins and natriuretic peptides [15].
T137 14545-14709 Sentence denotes It urges all the clinicians to reserve these assays for circumstances in which they would actually meaningfully add to the management of the patients with COVID-19.
T138 14710-14847 Sentence denotes The American Society of Echocardiography has also issued a similar advisory regarding the use of echocardiography in these patients [16].
T139 14848-14850 Sentence denotes 4.
T140 14851-15062 Sentence denotes The individual hospitals may also have to reconsider risk-benefit ratio of primary percutaneous intervention vs fibrinolysis in patients with COVID-19 who present with ST-segment elevation myocardial infarction.
T141 15063-15065 Sentence denotes 5.
T142 15066-15214 Sentence denotes There has been a concern regarding the safety of ACE inhibitors (ACEi) and angiotensin receptor blockers (ARB) during the ongoing COVID-19 pandemic.
T143 15215-15311 Sentence denotes These agents upregulate expression of ACE2 in various tissues, including on cardiomyocytes [17].
T144 15312-15536 Sentence denotes Since SARS-CoV-2 binds to ACE2 to gain entry into human cells, there is a potentially increased risk of developing COVID-19 or developing more severe disease in patients who are already on background treatment with ACEi/ARB.
T145 15537-15627 Sentence denotes However, to date, no experimental or clinical data have emerged to support these concerns.
T146 15628-15704 Sentence denotes At the same time, the risks of discontinuing these therapies are well known.
T147 15705-15883 Sentence denotes Therefore, several leading professional societies have strongly urged to not discontinue clinically-indicated ACEi/ARB therapy in the event the patient develops COVID-19 [18,19].
T148 15884-15886 Sentence denotes 6.
T149 15887-16044 Sentence denotes Clinicians caring for these patients also need to be fully aware of the potential CV side-effects of various therapies used for treating the viral infection.
T150 16045-16206 Sentence denotes Additionally, various anti-retroviral drugs have significant interactions with cardiac drugs, which need to be considered and appropriate dose modification done.
T151 16207-16358 Sentence denotes More recently, chloroquine/hydroxychloroquine and azathioprine have been proposed as potential therapeutic options, based on preliminary evidence [20].
T152 16359-16473 Sentence denotes Both these drugs are known to prolong QT interval and due caution must be exercised when prescribing these agents.
T153 16474-16756 Sentence denotes Their combination is best avoided and even when using chloroquine/hydroxychloroquine alone, daily electrocardiogram for monitoring QT interval is warranted, esp. in patients with hepatic or renal dysfunction and in those receiving another drug with potential to prolong QT interval.
T154 16758-16790 Sentence denotes 3 Summary and future directions
T155 16791-17068 Sentence denotes Although respiratory illness is the dominant clinical manifestation of COVID-19, the shear burden of the illness implies that a large number of patients with COVID-19 would present with pre-existing CVD or develop new-onset cardiac dysfunction during the course of the illness.
T156 17069-17180 Sentence denotes Considering this, the current understanding about the interplay between CVD and COVID-19 is grossly inadequate.
T157 17181-17381 Sentence denotes It is therefore highly desirable that the future studies on COVID-19 specifically describe the incidence, mechanisms, clinical presentation and outcomes of various CV manifestations in these patients.
T158 17382-17507 Sentence denotes The diagnostic and therapeutic challenges posed by the concurrence of these two illnesses also need to be adequately studied.