CORD-19-Sentences  

CORD-19:6f77139c82e2c2860d7143509613736000284ddb JSONTXT 7 Projects

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Id Subject Object Predicate Lexical cue
TextSentencer_T1 0-24 Sentence denotes Journal Pre-proof Title:
TextSentencer_T2 25-161 Sentence denotes The Cardiovascular Burden of Coronavirus Disease 2019 (COVID-19) with a Focus on Congenital Heart Disease Author Names and Affiliations:
TextSentencer_T3 162-179 Sentence denotes Journal Pre-proof
TextSentencer_T4 181-354 Sentence denotes J o u r n a l P r e -p r o o f 4 making SARS-CoV-2 the seventh member of the coronavirus family that infects humans, as well as the third coronavirus with bat origins (17) .
TextSentencer_T5 355-469 Sentence denotes SARS-CoV-2 has been shown to be transmitted via human-to-human contact with an estimated R 0 of between 2-3 (18) .
TextSentencer_T6 470-660 Sentence denotes The betacoronaviruses mainly infect epithelial cells in the lung (19) , but SARS-CoV-2 has been detected in respiratory, fecal, and blood specimens of patients infected with the virus (14) .
TextSentencer_T7 661-747 Sentence denotes SARS-CoV-2 is spread through droplets, contact, and entry through ocular tissue (20) .
TextSentencer_T8 748-901 Sentence denotes Fecal shedding has been seen in up to 30% of patients for up to 4-5 weeks after onset of symptoms, but it is unclear if this correlates with infectivity.
TextSentencer_T9 902-1161 Sentence denotes Since ACE2 is also expressed in intestinal epithelia and live virus has been detected in the stool of patients with COVID-19, transmission via the fecal-oral route is theoretically possible, but has not been confirmed in epidemiologic studies as of yet (20) .
TextSentencer_T10 1162-1271 Sentence denotes The virus can remain viable as an aerosol for up to 3 hours and on certain surfaces for up to 72 hours (21) .
TextSentencer_T11 1272-1588 Sentence denotes The virus can be detected 1-2 days prior to symptom onset in upper respiratory samples (20) , and with a median incubation period estimate of 5.1 days (95% CI, 4.5 to 5.8 days) (18, 22) , SARS-CoV-2 is thought to be mainly spread via asymptomatic carriers (23, 24) , which makes containment of the disease difficult.
TextSentencer_T12 1589-1724 Sentence denotes Substantial undocumented infections by asymptomatic but infected individuals may explain the rapid geographic spread of COVID-19 (25) .
TextSentencer_T13 1725-1828 Sentence denotes One case report highlights a patient who underwent post-mortem autopsy for pathological analysis (26) .
TextSentencer_T14 1829-2040 Sentence denotes In that study, SARS-CoV-2 was shown to cause direct damage to pneumocytes via a viral cytopathic effect, but also caused acute respiratory distress syndrome (ARDS) characterized by diffuse alveolar damage (26) .
TextSentencer_T15 2041-2118 Sentence denotes No direct damage to heart tissue was noted, but this was only in one patient.
TextSentencer_T16 2119-2378 Sentence denotes Data from multiple studies show that inflammatory markers are increased with SARS-CoV-2 infection, ranging from CRP, IL-6, IFN-γ, to TNF-α (1, 27, 28) , which has been posited to contribute to a sustained inflammatory response and cytokine storm ( Figure 1 ).
TextSentencer_T17 2379-2562 Sentence denotes Lymphopenia is commonly seen in patients who are critically ill (29) , suggesting that SARS-CoV-2 viral particles can invade lymphocytes and cause targeted destruction of these cells.
TextSentencer_T18 2563-2672 Sentence denotes To summarize, SARS-CoV-2 causes direct damage to lung epithelia, which can lead to severe pneumonia and ARDS.
TextSentencer_T19 2673-2864 Sentence denotes The COVID-19 virus also causes an inflammatory response in infected patients, which may lead to multi-organ failure and disseminated intravascular coagulation (DIC) in certain patients (30) .
TextSentencer_T20 2865-3035 Sentence denotes Furthermore, the hypoxia seen in patients with severe pneumonia and ARDS may also lead to further end-organ dysfunction/damage and death in critically-ill patients (29) .
TextSentencer_T21 3036-3091 Sentence denotes There appears to be two clinical stages to the disease.
TextSentencer_T22 3092-3252 Sentence denotes The first stage is the replicative stage, when SARS-CoV-2 is replicating over the course of several days and the patient presents with relatively mild symptoms.
TextSentencer_T23 3253-3384 Sentence denotes Unlike other human coronavirus infections, COVID-19 does not commonly present with upper respiratory symptoms like rhinorrhea (5) .
TextSentencer_T24 3385-3520 Sentence denotes One study showed that a sizeable proportion (18%) of patients who are infected with COVID-19 may not exhibit any symptoms at all (24) .
TextSentencer_T25 3521-3621 Sentence denotes Most symptomatic patients with COVID-19 will present with fever, dry cough, and shortness of breath.
TextSentencer_T26 3622-3754 Sentence denotes They will have J o u r n a l P r e -p r o o f findings of pneumonia on chest x-ray and computed tomography scans of the chest (31) .
TextSentencer_T27 3755-3868 Sentence denotes Most symptomatic patients suffer a mild respiratory infection requiring supportive care like supplemental oxygen.
TextSentencer_T28 3869-3969 Sentence denotes Patients can also develop gastrointestinal symptoms like abdominal pain, nausea, and diarrhea (32) .
TextSentencer_T29 3970-4093 Sentence denotes As mentioned earlier, lymphopenia is seen commonly in patients with COVID-19 and may be a poor prognostic factor (31, 32) .
TextSentencer_T30 4094-4200 Sentence denotes The second stage is the adaptive immunity stage, when the body develops an antibody response to the virus.
TextSentencer_T31 4201-4287 Sentence denotes This leads to falling titers of the virus and resolution of symptoms in most patients.
TextSentencer_T32 4288-4391 Sentence denotes There is a minority of patients, however, that become critically-ill and have a high risk of mortality.
TextSentencer_T33 4392-4482 Sentence denotes Around 10% of patients will have worsening of disease requiring intensive care (Table 1) .
TextSentencer_T34 4483-4601 Sentence denotes They can suffer from ARDS, viremia, acute cardiac injury, multi-organ failure, and secondary bacterial infections (1).
TextSentencer_T35 4602-4705 Sentence denotes The multi-organ dysfunction is believed to be secondary to a marked immune inflammatory response (33) .
TextSentencer_T36 4706-4781 Sentence denotes COVID-19 may result in cardiac injury via multiple mechanisms ( Figure 1 ):
TextSentencer_T37 4782-4784 Sentence denotes 1.
TextSentencer_T38 4785-4906 Sentence denotes COVID-19 may cause cardiac injury indirectly due to an overwhelming immune inflammatory response and cytokine storm (33).
TextSentencer_T39 4907-4909 Sentence denotes 2.
TextSentencer_T40 4910-5046 Sentence denotes SARS-CoV-2 viral invasion of cardiomyocytes and direct damage via this process, but this has not been proven in pathology studies (26) .
TextSentencer_T41 5047-5049 Sentence denotes 3.
TextSentencer_T42 5050-5274 Sentence denotes Severe hypoxia from acute respiratory damage caused by the virus may result in oxidative stress and myocardial injury from increased myocardial oxygen demand in the presence of severe hypoxia due to acute lung injury (ARDS).
TextSentencer_T43 5275-5410 Sentence denotes Furthermore, ACE2 is expressed in the heart, and the SARS-CoV-2 virus uses this enzyme as a receptor for entry into the cell (15, 16) .
TextSentencer_T44 5411-5576 Sentence denotes It is unclear at this time, however, if SARS-CoV-2 binding alters ACE2 expression or causes dysregulation of the RAAS (renin-angiotensin-aldosterone system) pathway.
TextSentencer_T45 5577-5720 Sentence denotes While the mechanism of cardiac injury is not fully described, there are data documenting COVID-19 and its effects on the cardiovascular system.
TextSentencer_T46 5721-5847 Sentence denotes In two studies, cardiac injury (manifested as an increase in troponin levels) was found in 8% of admitted patients (Table 1) .
TextSentencer_T47 5848-5947 Sentence denotes While an uncommon finding overall, cardiac injury was more common in critically-ill patients (32) .
TextSentencer_T48 5948-6117 Sentence denotes Two studies of critically-ill patients demonstrated that 23% (n=12) of patients developed cardiac injury (29) and 33% (n=7) of patients developed a cardiomyopathy (34) .
TextSentencer_T49 6118-6365 Sentence denotes Another study documented that among a group of patients (n = 120) with COVID-19, elevations in troponin levels (n = 12, 10%) and N-terminal pro B-type natriuretic peptide levels (n = 33, 27.5%) were detected, signaling cardiovascular injury (35) .
TextSentencer_T50 6366-6480 Sentence denotes One analysis of patients who died from COVID-19 demonstrated that patients had two different time points of death.
TextSentencer_T51 6481-6600 Sentence denotes A group of patients died around 14 days after onset of disease and another group died around 22 days after onset (27) .
TextSentencer_T52 6601-6794 Sentence denotes The authors hypothesized that the initial group died of respiratory failure, but the second group had myocardial damage and significant cardiovascular collapse concerning for myocarditis (27) .
TextSentencer_T53 6795-6887 Sentence denotes There have been a few case reports documenting clinical myocarditis with COVID-19 (36, 37) .
TextSentencer_T54 6888-7000 Sentence denotes This is consistent with previous reports of myocarditis caused by coronaviruses, including MERS (7, 8, 27, 38) .
TextSentencer_T55 7001-7369 Sentence denotes Given the increased elevations of cytokine levels noted in patients with severe COVID-J o u r n a l P r e -p r o o f 19 infection, as well as the observation that some patients with COVID-19 deteriorate rapidly with multiorgan failure and cardiogenic shock, more studies should be performed to investigate COVID-19 and its possible role in fulminant myocarditis (35) .
TextSentencer_T56 7370-7482 Sentence denotes While most patients who contract COVID-19 recover (39) , there are those who develop severe or critical illness.
TextSentencer_T57 7483-7807 Sentence denotes Unfortunately, multiple studies have shown that patients with underlying cardiovascular comorbidities, such as hypertension and coronary artery disease, are more likely to suffer from a severe COVID-19 infection that requires ICU care, have complications like ARDS, which in turn may result in death (27) (28) (29) 32, 40) .
TextSentencer_T58 7808-8001 Sentence denotes One study showed that patients infected with COVID-19 who had underlying hypertension had increased odds of death (OR 3.05 [95% CI 1.57-5.92, p < 0.001]) compared to those without hypertension.
TextSentencer_T59 8002-8128 Sentence denotes Similarly, coronary artery disease was associated with increased odds (OR 21.4 [95% CI 4.64-98.7, p < 0.0001]) of death (40) .
TextSentencer_T60 8129-8336 Sentence denotes In one meta-analysis, COVID-19 patients with hypertension had a relative risk ratio of 2.03 (95% CI 1.54-2.68, p < 0.00001) of having severe disease/requiring ICU care compared to those without hypertension.
TextSentencer_T61 8337-8563 Sentence denotes Patients with coronary artery disease/cerebrovascular disease had a relative risk ratio of 3.3 (95% CI 2.03-5.36, p < 0.00001) of having severe disease/requiring ICU care compared to those without cardiovascular disease (41) .
TextSentencer_T62 8564-8932 Sentence denotes When analyzing the largest case series to date (44,672 confirmed COVID-19 cases), the Chinese Center for Disease Control and Prevention reported that patients with cardiovascular disease had a case fatality rate of 10.5% and those with hypertension had a case fatality rate of 6%, both of which were higher than the overall case fatality rate of 2.3% (39) (Figure 2 ).
TextSentencer_T63 8933-9046 Sentence denotes Patients with hypertension accounted for 13% of the COVID-19 cases but they comprised 32% of the COVID-19 deaths.
TextSentencer_T64 9047-9192 Sentence denotes Patients with cardiovascular disease made up 4.2% of the COVID-19 cases, but were responsible for 18.3% of the COVID-19 deaths ((42), Figure 2 ).
TextSentencer_T65 9193-9648 Sentence denotes This may be due to the fact that patients with history of coronary artery disease or acute coronary syndromes may have reduced or impaired cardiovascular functional reserve, and the COVID-19 infection may either precipitate a myocardial infarction (type 1 myocardial infarction), increase myocardial demand leading to worsening ischemia and necrosis (type 2 myocardial infarction), or increase metabolic demand that leads to heart failure and death (43) .
TextSentencer_T66 9649-9736 Sentence denotes There is a case series of patients with heart transplants and COVID-19 infection (44) .
TextSentencer_T67 9737-9908 Sentence denotes It appears that although these patients are immunosuppressed, they seem to have similar outcomes compared to patients without heart transplantation and COVID-19 infection.
TextSentencer_T68 9909-10027 Sentence denotes The number of patients was very small (n=2), and thus results cannot obviously be extrapolated to a larger population.
TextSentencer_T69 10028-10274 Sentence denotes What was remarkable, however, was that of the 200 heart transplant patients in the Hubei province, only three were infected with COVID-19, which speaks to the importance of proper hygiene, social distancing and other public health measures (44) .
TextSentencer_T70 10275-10411 Sentence denotes To date, there are no published reports of patients with congenital heart disease and COVID-19 infection, albeit they are bound to come.
TextSentencer_T71 10412-10501 Sentence denotes There is only limited data detailing the effects of COVID-19 on the pediatric population.
TextSentencer_T72 10502-10676 Sentence denotes A review of 72,314 cases by the Chinese Center for Disease Control and Prevention showed that less than 1% of COVID-19 cases were in children younger than 10 years old (39) .
TextSentencer_T73 10677-10868 Sentence denotes Based on a single epidemiological study of 2,143 pediatric patients evaluated and treated for COVID-19, there were 731 cases confirmed via RT-J o u r n a l P r e -p r o o f PCR testing (45) .
TextSentencer_T74 10869-10965 Sentence denotes Children of all ages were infected, with the median age being 7 years (range 1 day to 18 years).
TextSentencer_T75 10966-11015 Sentence denotes 56% of the infected pediatric patients were male.
TextSentencer_T76 11016-11110 Sentence denotes Compared to adult patients, children diagnosed with COVID-19 seem to have less severe disease.
TextSentencer_T77 11111-11165 Sentence denotes Over 90% of the cases were mild or moderate in nature.
TextSentencer_T78 11166-11347 Sentence denotes Young children, especially infants, however, seemed to be more susceptible to severe disease than older children; 10% of patients under 1 year of age had severe or critical disease.
TextSentencer_T79 11348-11406 Sentence denotes The only death in the series was a 14 year-old male (45) .
TextSentencer_T80 11407-11549 Sentence denotes In another study of 1,391 children under 16 years of age assessed and tested for COVID-19, 171 (12.3%) were positive for SARS-CoV-2 infection.
TextSentencer_T81 11550-11600 Sentence denotes The median age of infected children was 6.7 years.
TextSentencer_T82 11601-11657 Sentence denotes 15.8% of patients had no symptoms or signs of pneumonia.
TextSentencer_T83 11658-11784 Sentence denotes Three (1.8%) children required intensive care and mechanical ventilatory support, but all had pre-existing medical conditions.
TextSentencer_T84 11785-11835 Sentence denotes Lymphopenia was present in only 6 (3.5%) patients.
TextSentencer_T85 11836-11966 Sentence denotes A 10-month-old child with history of intussusception died from multiorgan failure, and this was the only death in the study (46) .
TextSentencer_T86 11967-12029 Sentence denotes A third study examined 366 children under the age of 17 years.
TextSentencer_T87 12030-12097 Sentence denotes In that group, only 6 (1.6%) patients tested positive for COVID-19.
TextSentencer_T88 12098-12225 Sentence denotes The median age of infected patients was 3 years old (range 1-7 years), and none of the infected children had any comorbidities.
TextSentencer_T89 12226-12317 Sentence denotes All six of the pediatric patients had fever and cough at diagnosis, as well as lymphopenia.
TextSentencer_T90 12318-12414 Sentence denotes One of the patients required intensive care unit (ICU) admission, but there were no mortalities.
TextSentencer_T91 12415-12535 Sentence denotes The mechanism by which children seem less susceptible to severe infection caused by SARS-CoV-2 has yet to be elucidated.
TextSentencer_T92 12536-12707 Sentence denotes It has been theorized that the ACE2 (the binding protein for SARS-CoV-2) in children is not as functional as it is in adults, and thus SARS-CoV-2 is less infectious (45) .
TextSentencer_T93 12708-12873 Sentence denotes None of the studies described children with congenital heart disease and COVID-19, and thus the effect of the virus on this specific patient population is not clear.
TextSentencer_T94 12874-12950 Sentence denotes Nevertheless, children seem less vulnerable to COVID-19 than adults overall.
TextSentencer_T95 12951-13287 Sentence denotes A review of pregnant women infected with COVID-19 revealed that pregnant women are not at increased risk of poor outcomes when compared to the general adult population (47) , and there seems to be no evidence of vertical transmission of the SARS-CoV-2 virus from mother to baby during birth or during breastfeeding at present (20, 47) .
TextSentencer_T96 13288-13479 Sentence denotes All the women who gave birth with COVID-19 had cesarean sections, so there is no data about vertical transmission for women who are infected earlier in the pregnancy or who deliver vaginally.
TextSentencer_T97 13480-13572 Sentence denotes More studies are clearly warranted to examine the potential impact of COVID-19 on pregnancy.
TextSentencer_T98 13573-13673 Sentence denotes To date, there are no published studies on COVID-19 in adult patients with congenital heart disease.
TextSentencer_T99 13674-13851 Sentence denotes Thus, all of the current management strategies are extrapolated from what is known about the effect of COVID-19 on adult patients and adult patients with cardiovascular disease.
TextSentencer_T100 13852-14156 Sentence denotes That being said, efforts are under way through the Adult Congenital Heart Association and the International Society of Adult Congenital Heart Disease to gather data on the number of suspected and confirmed cases both in the United States and globally and to better understand outcomes in this population.
TextSentencer_T101 14157-14360 Sentence denotes In the absence of data to help guide care it is difficult to make any definitive recommendations, however, there are some sensible steps that can be taken while we await the building of an evidence base.
TextSentencer_T102 14361-14495 Sentence denotes Diagnosis When a patient with congenital heart disease is suspected of having COVID-19, the first step is confirmation of the disease.
TextSentencer_T103 14496-14601 Sentence denotes Nasopharyngeal swab and RT-PCR is the recommended initial test, but it is only about 75% sensitive (48) .
TextSentencer_T104 14602-14678 Sentence denotes If the clinical suspicion is high enough, a CT chest may be warranted (49) .
TextSentencer_T105 14679-14824 Sentence denotes Proper isolation measures should be taken and providers should wear appropriate personal protective equipment, regardless of the diagnostic test.
TextSentencer_T106 14825-14988 Sentence denotes It should be noted that there are cases of negative initial testing that later repeated as positive, as this may be due to low viral titers early in the infection.
TextSentencer_T107 14989-15122 Sentence denotes One shocking reality is that in many countries, including Western nations like the United States, lack widespread testing capability.
TextSentencer_T108 15123-15304 Sentence denotes At the time of the writing of this manuscript in the third week of March 2020, testing in Los Angeles is woefully unavailable for the vast majority of potentially infected patients.
TextSentencer_T109 15305-15416 Sentence denotes Drive-through testing is not available for days and in-hospital testing is limited to the highest risk subsets.
TextSentencer_T110 15417-15561 Sentence denotes This situation must be remedied and quickly for us to have a realistic chance of accounting for and tracking the degree of spread of this virus.
TextSentencer_T111 15562-15697 Sentence denotes Patients with underlying cardiovascular comorbidities are at increased risk of morbidity and mortality from SARS-CoV-2 infection (39) .
TextSentencer_T112 15698-15889 Sentence denotes Studies so far have not detailed in a granular fashion the risk of individual cardiovascular complications in patients with underlying cardiovascular disease who are infected with SARS-CoV-2.
TextSentencer_T113 15890-16104 Sentence denotes While no studies on COVID-19 have included patients with congenital heart disease, it stands to reason that patients with congenital heart disease could be considered at higher risk for complications from COVID-19.
TextSentencer_T114 16105-16203 Sentence denotes Certain adult patients with congenital heart disease (ACHD) are likely at higher risk than others.
TextSentencer_T115 16204-16523 Sentence denotes Based on the ACHD Anatomy and Physiological Stage Classification, any patient with complex congenital heart disease (Anatomy Stage III) or Physiological Stage B, C, or D symptoms could be considered high risk for complications related to COVID-19 infection on the basis of decreased functional reserve (50) ( Table 2) .
TextSentencer_T116 16524-16678 Sentence denotes Those with reduced immunity, including Down syndrome, DiGeorge syndrome and asplenia may be at even higher risk for poor outcomes with COVID-19 infection.
TextSentencer_T117 16679-16891 Sentence denotes Studies have tried to risk-stratify patients suffering from a viral pneumonia (51) , and the MuLBSTA score may be a tool providers can use to see which patients are at high risk of decompensation and death (31) .
TextSentencer_T118 16892-17059 Sentence denotes Since patients with underlying cardiovascular disease are at higher risk of morbidity and mortality, patients with ACHD should take great care in preventing infection.
TextSentencer_T119 17060-17263 Sentence denotes This includes frequent handwashing, social distancing measures, proper and appropriate use of masks and other personal protective equipment, and cleaning and disinfecting commonly touched surfaces (52) .
TextSentencer_T120 17264-17379 Sentence denotes Patients with congenital heart disease should be vaccinated against influenza and pneumococcal pneumonia (11, 12) .
TextSentencer_T121 17380-17542 Sentence denotes If possible, regularly scheduled clinic visits should be converted to telehealth visits to minimize risk of acquiring an infection in the nosocomial setting (53).
TextSentencer_T122 17543-17742 Sentence denotes This desire to minimize risk of infection must obviously be weighed against the necessity of in-person visits for some patients, e.g. those with decompensated congestive heart failure or arrhythmias.
TextSentencer_T123 17743-17934 Sentence denotes The advent of wearable technology and wide availability of blood pressure, heart rate, and oximetry equipment for home use can be a reasonable substitute for inclinic vital sign measurements.
TextSentencer_T124 17935-18150 Sentence denotes Additionally, the video function can allow a clinician to inspect the J o u r n a l P r e -p r o o f patient visually, albeit in a far less comprehensive manner when compared to the traditional physical examination.
TextSentencer_T125 18151-18368 Sentence denotes Hand-held and easily sterilized echocardiographic equipment can also be a 'handy' substitute for traditional comprehensive echocardiography, and the inevitably higher rate of exposure in a frequently visited echo lab.
TextSentencer_T126 18369-18523 Sentence denotes At least in the short term, these social distancing approaches to the practice of clinical medicine will have to suffice for the majority of our patients.
TextSentencer_T127 18524-18683 Sentence denotes Our early experience with telehealth at the UCLA ACHD clinic has been positive and we have been able to safely diminish our physical clinic walkthrough volume.
TextSentencer_T128 18684-18806 Sentence denotes Once a patient with ACHD is diagnosed with COVID-19, the management of the infection is similar to the general population.
TextSentencer_T129 18807-18936 Sentence denotes Most COVID-19 patients (close to 80% in the Chinese experience) can be managed expectantly at home with self-care measures (39) .
TextSentencer_T130 18937-19061 Sentence denotes The initial data from the United States are similar, and estimates are that 20-30% of patients are being hospitalized (54) .
TextSentencer_T131 19062-19230 Sentence denotes For those that need to be admitted, the treatment is mainly supportive and should follow the World Health Organization (WHO) guidelines on management of COVID-19 (55) .
TextSentencer_T132 19231-19366 Sentence denotes Symptomatic relief with antipyretics, use of supplemental oxygen and management of comorbid conditions are the cornerstones of therapy.
TextSentencer_T133 19367-19481 Sentence denotes The use of antiviral, immune modulating, or antibiotic therapies is at this point not considered standard of care.
TextSentencer_T134 19482-19601 Sentence denotes Controlled trials are ongoing, and we are all anxiously awaiting results and recommendations for treatment of COVID-19.
TextSentencer_T135 19602-19780 Sentence denotes Some patients with COVID-19 may experience cardiac injury and arrhythmias (32) , and employment of echocardiography and cardiac enzymes would seem paramount in this setting (53).
TextSentencer_T136 19781-20066 Sentence denotes Myocardial injury may occur due to a variety of mechanisms, from direct viral invasion of cardiomyocytes, hypoxia due to severe pneumonia leading to ischemic cardiac tissue, or an overwhelming inflammatory response leading to cytokine storm and myocardial dysfunction (Figure 1) (41) .
TextSentencer_T137 20067-20145 Sentence denotes This leads to troponin leak and elevations in brain natriuretic peptide (BNP).
TextSentencer_T138 20146-20455 Sentence denotes While laboratory assessment for cardiac injury is not recommended on a routine basis, patients who show signs and symptoms of myocardial injury (STsegment changes on an electrocardiogram for example), acute coronary syndrome (chest pain), unstable arrhythmias, or heart failure should be evaluated thoroughly.
TextSentencer_T139 20456-20687 Sentence denotes Differentiation between normal cardiac function with increased metabolic demand, acute coronary syndrome, and fulminant myocarditis will be important as each of these clinical scenarios will require a different treatment algorithm.
TextSentencer_T140 20688-20925 Sentence denotes For patients who are deteriorating, judicious use of fluid resuscitation, vasopressors, mechanical ventilation and extracorporeal membrane oxygenation (ECMO) have been successful at supporting patients through critical illness (29, 55) .
TextSentencer_T141 20926-21146 Sentence denotes While the use of steroids has not been recommended in the general treatment of COVID-19 (55) , there have been reports of patients recovering from fulminant myocarditis with intravenous immunoglobulin and steroids (36) .
TextSentencer_T142 21147-21241 Sentence denotes More studies will be needed to help parse out which patients will benefit from such therapies.
TextSentencer_T143 21242-21429 Sentence denotes In terms of medical treatment options, there are currently over 50 studies in various stages of development related to treatment of COVID-19 (clinicaltrials.gov, accessed March 20, 2020).
TextSentencer_T144 21430-21701 Sentence denotes Given the novel nature of the SARS-CoV-2 virus, there are no known effective therapies at this time, but the therapies being studied include antiviral (remdesivir, lopinavir/ritonavir, chloroquine, hydroxychloroquine) and anti-inflammatory (tocilizumab, steroids) agents.
TextSentencer_T145 21702-21907 Sentence denotes The only trial published so far assesses the use of lopinavir-ritonavir in adults hospitalized with COVID-19, and this therapy showed no J o u r n a l P r e -p r o o f benefit beyond standard of care (56).
TextSentencer_T146 21908-22061 Sentence denotes Many of these therapies have cardiovascular side effects, however, and caution must be used when applying them to patients with congenital heart disease.
TextSentencer_T147 22062-22161 Sentence denotes Vaccine development is also underway and is one of the priorities for the WHO moving forward (14) .
TextSentencer_T148 22162-22330 Sentence denotes If patients suffer cardiovascular complications from COVID-19 requiring either percutaneous or surgical intervention, each case must be assessed on an individual basis.
TextSentencer_T149 22331-22475 Sentence denotes Each institution should develop protocols for appropriate triage, isolation, and treatment of COVID-19 patients who may need such interventions.
TextSentencer_T150 22476-22694 Sentence denotes In China, the preference has been to use thrombolytic therapy for patients with acute coronary syndromes (i.e. ST-elevation myocardial infarction) (57) , but this has not been the standard of care in the United States.
TextSentencer_T151 22695-22889 Sentence denotes As the pandemic progresses and resources start to become strained, we may be asked to ration certain measures such as intensive care unit beds, mechanical ventilation and extracorporeal support.
TextSentencer_T152 22890-22972 Sentence denotes It is our sincere hope that it will not come to this in the majority of countries.
TextSentencer_T153 22973-23207 Sentence denotes This concern further underscores the dire importance of slowing the spread of SARS-CoV-2 to allow health care systems to appropriately prepare and manage this crisis without having to resort to rationing of the highest levels of care.
TextSentencer_T154 23208-23434 Sentence denotes Importantly, the clinical need for imaging, invasive and surgical interventions must be weighed against the risk of infecting healthcare workers who may lack the appropriate personal protective equipment at this point in time.
TextSentencer_T155 23435-23601 Sentence denotes Standard operating procedures for use of personal protective equipment and sterilization of catheterization labs and operating rooms should also be developed (53,58).
TextSentencer_T156 23602-23930 Sentence denotes The SARS-CoV-2 virus uses ACE2 as a receptor to enter and infect cells (15), and since ACE2 is expressed in many tissues including vascular endothelium and cardiac tissue (16) , there has been some hypotheses that the use of ACE-inhibitors and angiotensin receptor 1 blockers (ARBs) may have an effect on the course of COVID-19.
TextSentencer_T157 23931-24031 Sentence denotes ACE2 inactivates angiotensin II, and generates angiotensin 1-7, which is a potent vasodilator (59) .
TextSentencer_T158 24032-24153 Sentence denotes In animal models, the ARBs have been shown to increase cardiac ACE2 expression after chronic (> 28 days) treatment (59) .
TextSentencer_T159 24154-24498 Sentence denotes Based on studies of the original SARS coronavirus, viral binding to ACE2 leads to ACE2 downregulation, which results in excessive production of angiotensin II by angiotensin converting enzyme (ACE) and decreased quantities of the vasodilator heptapeptide angiotensin 1-7, which can contribute to lung injury and stimulation of the RAAS pathway.
TextSentencer_T160 24499-24776 Sentence denotes Counterintuitively, while ARBs increase the number of ACE2 receptors available for SARS-CoV-2 binding, the overall effect of ARBs may protect against lung injury by reducing angiotensin II production by ACE and by increasing the production of vasodilator angiotensin 1-7 (59) .
TextSentencer_T161 24777-24880 Sentence denotes The effect of ACE-inhibitors and ARBs in patients with COVID- 19 are not yet known and remain unproven.
TextSentencer_T162 24881-25007 Sentence denotes More studies are required before any recommendations are made about starting or withdrawing ACE-inhibitor and ARB medications.
TextSentencer_T163 25008-25437 Sentence denotes As such, the Heart Failure Society of America, American College of Cardiology, and American Heart Association released a statement recommending continuation of RAAS inhibitors for patients currently taking them for "indications for which these agents are known to be beneficial, such as heart failure, hypertension, or ischemic heart disease (60) ." This position has also been echoed by the European Society of Cardiology (61) .
TextSentencer_T164 25438-25579 Sentence denotes The global pandemic caused by COVID-19 is just beginning and the number of people infected by the virus is increasing at an exponential rate.
TextSentencer_T165 25580-25873 Sentence denotes While there are no studies currently documenting COVID-19 infections in patients with congenital heart disease, it is highly likely that with over 300,000 cases diagnosed world-wide (as of 3/22/2020) there have already been a number of congenital heart disease patients infected by SARS-CoV-2.
TextSentencer_T166 25874-26110 Sentence denotes It is imperative that individual programs, in concert with regional, national, and global organizations, work together to ensure data are gathered on the number of patients tested, those diagnosed with the infection, and their outcomes.
TextSentencer_T167 26111-26215 Sentence denotes Congenital cardiology programs need to be ready to enroll these patients in study registries and trials.
TextSentencer_T168 26216-26458 Sentence denotes In the words of Winston Churchill, "never 'worry' about action, but only about inaction." We need to be meticulous in our study of this disease, voracious in our appetite to learn its secrets, and tireless in our efforts to combat its spread.
TextSentencer_T169 26459-26806 Sentence denotes J o u r n a l P r e -p r o o f  COVID-19 results in respiratory illness, but some patients can have cardiac injury.  Patients with underlying cardiac disease have worse outcomes with COVID-19  ACHD patients may be at increased risk of worse outcomes with COVID-19  No treatment exists currently, the focus is on supportive care and prevention.