LitCovid-sentences  

PMC:7665480 / 2339-27614 JSONTXT 5 Projects

Annnotations TAB TSV DIC JSON TextAE

Id Subject Object Predicate Lexical cue
T25 0-12 Sentence denotes INTRODUCTION
T26 13-263 Sentence denotes The worldwide spread of the novel coronavirus disease 2019 (COVID-19) pandemic, first identified in Wuhan, China, has created unprecedented challenges in the diagnosis and medical treatment of affected patients as well as in public health management.
T27 264-407 Sentence denotes Northern Italy was the first Western region to deal with COVID-19 and the first whose organ transplant population had to face the pandemic [1].
T28 408-630 Sentence denotes Despite the significant mitigating measures adopted, as of 4 May 2020, a total of 96,478 cases (46% of the total number of Italian cases) and 15,822 deaths (58%) have been reported in Lombardy and Veneto, respectively [2].
T29 631-789 Sentence denotes Data on patients with heart transplants in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) era are still limited and mostly anecdotal [3–13].
T30 790-875 Sentence denotes Immunosuppression-related issues present the main concern in this special population.
T31 876-1076 Sentence denotes An abnormal inflammatory response has been hypothesized to play a crucial role in acquiring severe forms of COVID-19, mainly due to damage of one's own tissues and microcirculatory thrombophilia [14].
T32 1077-1235 Sentence denotes Importantly, it is well established that severe infections in the immunocompromised population dramatically influence both the care and prognosis of patients.
T33 1236-1426 Sentence denotes Asymptomatic carriers of the virus and patients with mild presentations of COVID-19 have been reported in the transplant recipient population, as have patients with more severe forms [3–13].
T34 1427-1603 Sentence denotes Despite the limited number of reported cases, significant heterogeneity dominates the clinical presentation patterns and challenges remain in fully characterizing risk factors.
T35 1604-1713 Sentence denotes This uncertainty has opened up a great debate regarding immunomodulation interaction with the infection [15].
T36 1714-1885 Sentence denotes Immunomodulated recipients may present higher viral loads and shedding, resulting in greater infectivity and potential spread to other individuals and the transplant team.
T37 1886-2143 Sentence denotes Moreover, drug–drug interactions with immunosuppressant medications need to be carefully evaluated and managed, particularly the interference of antiviral medications with calcineurin inhibitors and mammalian targets of rapamycin inhibitors metabolism [16].
T38 2144-2218 Sentence denotes Mortality data are only available from case reports and small case series.
T39 2219-2380 Sentence denotes The scientific community still has no conclusive evidence as to whether or not outcomes in this population could be worse than those in immunocompetent patients.
T40 2381-2576 Sentence denotes Our goal was to report our single-centre experience related to the COVID-19-affected heart transplant population and our adopted strategies to mitigate the clinical presentation of the infection.
T41 2577-2723 Sentence denotes Moreover, we investigated outcomes from balancing immunosuppression regimen and response to infection through our therapeutic management strategy.
T42 2725-2732 Sentence denotes METHODS
T43 2734-2750 Sentence denotes Study population
T44 2751-2843 Sentence denotes We considered patients who had orthotopic heart transplants in our centre from 1985 to 2020.
T45 2844-2938 Sentence denotes Heart transplant recipients affected with COVID-19 were included in the present investigation.
T46 2939-3102 Sentence denotes We collected data related to risk factors, last follow-up characteristics, COVID-19 onset presentation, in-hospital course of disease and results from blood tests.
T47 3104-3121 Sentence denotes Ethical statement
T48 3122-3265 Sentence denotes The use of data for scientific and research purposes is mentioned in the current informed consent in use at the Cardiac Surgery Unit of Padova.
T49 3266-3519 Sentence denotes We guarantee to respect patient anonymity and professional secrecy, and we use the collected data and the statistical analyses of this study solely for the scientific uses granted in accordance with the law in force (General Data Protection Regulation).
T50 3521-3541 Sentence denotes Statistical analyses
T51 3542-3677 Sentence denotes Continuous variables are expressed as median and interquartile range (IQR); categorical variables are presented as count and frequency.
T52 3678-3799 Sentence denotes All statistical analyses were performed using SPSS software version 20 (IBM SPSS Statistics, IBM Corp., Armonk, NY, USA).
T53 3801-3808 Sentence denotes RESULTS
T54 3809-3849 Sentence denotes All collected data are shown in Table 1.
T55 3850-3905 Sentence denotes To date, 396 heart transplant patients are still alive.
T56 3906-3957 Sentence denotes Six patients developed active SARS-CoV-2 infection:
T57 3958-4049 Sentence denotes 2 of these patients died, 1 of acute respiratory distress syndrome and the other of sepsis.
T58 4050-4266 Sentence denotes All included patients who had heart transplants had the positive reverse transcriptase-polymerase chain reaction nasopharyngeal swab test for SARS-CoV-2 and were symptomatic with fever, cough and shortness of breath.
T59 4267-4379 Sentence denotes Of the 6 patients, the only female in the study presented mild symptoms and remained in self-quarantine at home.
T60 4380-4605 Sentence denotes The rest of our cohort was hospitalized in Northern Italy; they had moderate-to-severe symptoms, such as fever for more than 5 days, oxygen saturation below 90% requiring supportive care and signs of pneumonia on radiographs.
T61 4606-4614 Sentence denotes Table 1:
T62 4616-4685 Sentence denotes Main characteristics of the 6 heart transplant patients with COVID-19
T63 4686-4750 Sentence denotes Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6
T64 4751-4763 Sentence denotes Demographics
T65 4764-4800 Sentence denotes  Age (years) 69 82 65 71 62 50
T66 4801-4846 Sentence denotes  Gender Male Male Male Male Male Female
T67 4847-4904 Sentence denotes  Time from heart transplant (years) 5 16 11 1 22 13
T68 4905-4918 Sentence denotes  Risk factors
T69 4919-4968 Sentence denotes   BMI (kg/m2) 22.4 23.6 24.5 25.3 32.6 21.5
T70 4969-5010 Sentence denotes   Arterial hypertension − + + + + +
T71 5011-5044 Sentence denotes   Dyslipidaemia − + + − + −
T72 5045-5082 Sentence denotes   Diabetes mellitus − − − − − −
T73 5083-5116 Sentence denotes   Former smoker + − − − − −
T74 5117-5162 Sentence denotes   Extracardiac arteriopathy − − − − − −
T75 5163-5187 Sentence denotes   COPD − − − − − −
T76 5188-5214 Sentence denotes   Stroke − − − − − −
T77 5215-5245 Sentence denotes   Malignancy − − + − − +
T78 5246-5284 Sentence denotes   GFR (ml/min) 80 40 71 82 48 85
T79 5285-5317 Sentence denotes   Previous PCI − + − − − −
T80 5318-5349 Sentence denotes   NYHA class I II I I I I
T81 5350-5385 Sentence denotes  Immunosuppressive therapy (mg/day)
T82 5386-5429 Sentence denotes   Cyclosporine 120 120 160 200 135 70
T83 5430-5475 Sentence denotes   Mycophenolate 1440 − 1440 1440 1440 −
T84 5476-5506 Sentence denotes   Everolimus − − − − − 2
T85 5507-5521 Sentence denotes COVID-19 onset
T86 5522-5542 Sentence denotes  Presenting symptoms
T87 5543-5568 Sentence denotes   Cough + + + + + +
T88 5569-5608 Sentence denotes   Shortness of breath + + + + + +
T89 5609-5636 Sentence denotes   Myalgia − + + + + +
T90 5637-5664 Sentence denotes   Anosmia − − + + + +
T91 5665-5693 Sentence denotes   Headache − − − − + +
T92 5694-5723 Sentence denotes   Sinusitis − − − − − +
T93 5724-5769 Sentence denotes   Gastrointestinal symptoms − − − − + +
T94 5770-5797 Sentence denotes  NPS test + + + + + +
T95 5798-5836 Sentence denotes  X-ray pneumonia signs + + + + −
T96 5837-5889 Sentence denotes  Fever peak (°C) 38.0 38.6 38.0 39.5 38.5 39.2
T97 5890-5924 Sentence denotes  Hospitalization + + + + + −
T98 5925-5967 Sentence denotes  SpO2 at admission (%) 91 85 97 78 85
T99 5968-6026 Sentence denotes  Worst SpO2 during hospitalization (%) 88 75 88 75 65
T100 6027-6059 Sentence denotes  Laboratory results at admission
T101 6060-6120 Sentence denotes   WBC count (cells per 109/l) 10.00 9.24 4.00 7.50 5.90
T102 6121-6162 Sentence denotes   Hb (g/dl) 10.0 13.5 12.0 13.7 13.5
T103 6163-6217 Sentence denotes   Platelets (cells per 109/l) 400 113 215 301 151
T104 6218-6278 Sentence denotes   Lymphocyte (cells per 109/l) 0.35 0.32 0.55 0.90 0.20
T105 6279-6315 Sentence denotes   CRP (mg/dl) 157 140 3.3 72 29
T106 6316-6348 Sentence denotes   PCT (ng/ml) 0.26 0.09 0 0
T107 6349-6400 Sentence denotes   Serum creatinine (mg/dl) 1.29 2.1 1.79 1.3 2
T108 6401-6437 Sentence denotes   Troponin I (ng/dl) 34 8 18 24
T109 6438-6467 Sentence denotes  LVEF (%) 55 45 70 55 50
T110 6468-6490 Sentence denotes Treatment and outcomes
T111 6491-6528 Sentence denotes  Hydroxychloroquine + + + + + −
T112 6529-6567 Sentence denotes  Lopinavir/ritonavir + − − − + −
T113 6568-6609 Sentence denotes  Corticosteroid therapy + + + + + −
T114 6610-6671 Sentence denotes  Modification of immunosuppressive therapya + + + + + −
T115 6672-6725 Sentence denotes   % Reduction of cyclosporine 40 100 60 50 40 0
T116 6726-6777 Sentence denotes   % Reduction of mycophenolate 75 0 0 50 50 0
T117 6778-6820 Sentence denotes  Antibiotics prophylaxis + + + + + +
T118 6821-6845 Sentence denotes  ICU stay + − − − +
T119 6846-6882 Sentence denotes   ICU length of stay 18 − − − 2
T120 6883-6911 Sentence denotes  High flow O2 − + − + +
T121 6912-6931 Sentence denotes  NIV − + − + +
T122 6932-6958 Sentence denotes  Intubation + − − − −
T123 6959-6973 Sentence denotes  Complications
T124 6974-7005 Sentence denotes   Respiratory − ARDS − − −
T125 7006-7050 Sentence denotes   Neurological Ischaemic stroke − − − −
T126 7051-7082 Sentence denotes   Infective Sepsis − − − −
T127 7083-7130 Sentence denotes  In-hospital length of stay 24 10 13 27 24
T128 7131-7176 Sentence denotes  Days to negative NPS testb 10 7 15 14c
T129 7177-7202 Sentence denotes  Pronation − − − + +
T130 7203-7229 Sentence denotes  Discharged − − + + +
T131 7230-7253 Sentence denotes  Dead + + − − − −
T132 7254-7336 Sentence denotes a In-hospital percentage reduction from last follow-up dose of immunosuppressant.
T133 7337-7445 Sentence denotes b Days from first positive NPS test to first seriate negative NPS test and clinical resolution of symptoms.
T134 7446-7595 Sentence denotes c The patient has been asymptomatic since receiving the results of the first NPS test, which was repeated after 14 days, per government regulations.
T135 7596-7917 Sentence denotes ARDS: acute respiratory distress syndrome; BMI: body mass index; CRP: C-reactive protein; COPD: chronic obstructive pulmonary disease; GFR: glomerular filtration rate; Hb: haemoglobin; ICU: intensive care unit; LVEF: left ventricular ejection fraction; NIV: non-invasive ventilation; NPS: naso-pharyngeal swab test; NYHA:
T136 7918-8055 Sentence denotes New York heart association; PCI: percutaneous coronary intervention; PCT: procalcitonin; SpO2: oxygen saturation; WBC: white blood cells.
T137 8057-8069 Sentence denotes Risk factors
T138 8070-8122 Sentence denotes Data collected on risk factors are shown in Table 1.
T139 8123-8235 Sentence denotes The median age was 67 years (IQR 59–74) and the median time from the heart transplant was 12 years (IQR 4–17.5).
T140 8236-8365 Sentence denotes Among the patients’ risk factors arterial hypertension was the most frequent, occurring in 83%, followed by dyslipidaemia in 50%.
T141 8366-8391 Sentence denotes Only 1 patient was obese.
T142 8392-8486 Sentence denotes The median glomerular filtration rate was 92 ml/min (IQR 79–133); no patients needed dialysis.
T143 8487-8635 Sentence denotes At the last follow-up, all patients were classified as New York Heart Association functional class I with the exception of 1 in functional class II.
T144 8636-8745 Sentence denotes One patient had a previous percutaneous coronary intervention procedure for a cardiac allograft vasculopathy.
T145 8746-8912 Sentence denotes Graft function was preserved in all patients as evidenced by the last echocardiographic follow-up with a median left ventricular ejection fraction of 56% (IQR 53–58).
T146 8913-9118 Sentence denotes Only 1 patient had a history of cellular-mediated rejection graded as moderate, 2R according to the International Society of Heart and Lung Transplantation classification of 2004, obtained in October 1997.
T147 9119-9251 Sentence denotes Immunosuppressive therapy included cyclosporine for all patients, associated with mycophenolate in 4 cases and everolimus in 1 case.
T148 9253-9269 Sentence denotes In-hospital stay
T149 9270-9301 Sentence denotes Data are summarized in Table 1.
T150 9302-9360 Sentence denotes Median in-hospital length of stay was 24 days (IQR 12–26).
T151 9361-9417 Sentence denotes Three patients were discharged home and 2 patients died.
T152 9418-9536 Sentence denotes Median oxygen saturation at admission was 85% (IQR 81–94), the worst level during hospitalization was 75% (IQR 70–88).
T153 9537-9601 Sentence denotes All hospitalized patients had signs of pneumonia on radiographs.
T154 9602-9677 Sentence denotes Troponin at admission fell consistently within the limits for all patients.
T155 9678-9878 Sentence denotes Two patients needed time in the intensive care unit and invasive ventilation; both of them were then admitted to a ward; in 1 a tracheostomy was performed to wean the patient from ventilatory support.
T156 9879-9925 Sentence denotes Pronation therapy was performed in 2 patients.
T157 9926-10001 Sentence denotes One patient needed 3 days of continuous veno-venous hemofiltration therapy.
T158 10002-10104 Sentence denotes One patient received inotropic drugs with noradrenaline at maximum doses of 0.1 mcg/kg/min for 3 days.
T159 10105-10148 Sentence denotes Extracorporeal life support was never used.
T160 10149-10242 Sentence denotes During the in-hospital stay echocardiographic monitoring was used to evaluate graft function.
T161 10243-10452 Sentence denotes With the exception of a mild reduction in the left ventricular ejection fraction in an older patient with a heart transplant that was more than 20 years old, no patients showed any changes in cardiac function.
T162 10453-10640 Sentence denotes One patient had an ischaemic stroke and a sputum culture that was positive for Pseudomonas; he required targeted antibiotics treatment; unfortunately he developed sepsis and then he died.
T163 10641-10737 Sentence denotes The other patient developed acute respiratory distress syndrome and died of respiratory failure.
T164 10739-10764 Sentence denotes Pharmacological treatment
T165 10765-10804 Sentence denotes Collected data are provided in Table 1.
T166 10805-10928 Sentence denotes During hospitalization hydroxychloroquine and broad-spectrum antibiotics for prophylaxis were administered to all patients.
T167 10929-10974 Sentence denotes Ritonavir/lopinavir were used for 2 patients.
T168 10975-11133 Sentence denotes Our adopted strategy for immunosuppressive therapy comprised a median reduction of 50% (IQR 40–80) of cyclosporine doses and 50% (IQR 13–69) of mycophenolate.
T169 11134-11240 Sentence denotes In all hospitalized patients, a 0.5–1 mg/kg/day bolus of prednisone was administered for the first 7 days.
T170 11241-11345 Sentence denotes Those intubated or in serious condition were given an equivalent intravenous dose of methylprednisolone.
T171 11346-11445 Sentence denotes Progressive tapering then followed, leading to a low maintenance dose of 5–10 mg/day at discharged.
T172 11446-11538 Sentence denotes Immunosuppressive therapy remained reduced until the first outpatient follow-up examination.
T173 11539-11647 Sentence denotes At that time, the original immunosuppressive regime was resumed and corticosteroid therapy was discontinued.
T174 11648-11685 Sentence denotes No graft rejection episodes occurred.
T175 11686-11834 Sentence denotes The patient who self-quarantined at home was treated with a broad-spectrum antibiotic and had a rapid remission of symptoms and resolution of fever.
T176 11835-11938 Sentence denotes No immunosuppressive therapy modifications were made and no anti-inflammatory agents were administered.
T177 11939-12023 Sentence denotes The results of the nasopharyngeal swab test for SARS-CoV-2 at 14 days were negative.
T178 12025-12035 Sentence denotes DISCUSSION
T179 12036-12285 Sentence denotes Chronic immunosuppressive therapy in patients with heart transplants is framed in a well-established protocol that includes calcineurin inhibitors possibly in combination with purine synthesis inhibitors or mammalian targets of rapamycin inhibitors.
T180 12286-12436 Sentence denotes This therapeutic scheme is effective in deactivating the lymphocytes of the adaptive immune response, which is primarily involved in viral infections.
T181 12437-12644 Sentence denotes Lacking any strong evidence regarding the treatment of patients with a heart transplant infected with SARS-CoV-2, we faced a new challenge in managing the viral infection in this immunosuppressed population.
T182 12645-12840 Sentence denotes Strengthened by our experience with other viral infections in patients with heart transplants, especially cytomegalovirus, we followed the same management protocol in patients with COVID-19 [17].
T183 12841-13014 Sentence denotes Our first steps consisted of reducing immunosuppressive therapy in the patients with severe clinical forms of COVID-19, i.e. those with hypoxia who required hospitalization.
T184 13015-13097 Sentence denotes This strategy was adopted due to the lymphocytopenia characterizing this syndrome.
T185 13098-13281 Sentence denotes For the milder form of the disease (i.e. the patient in self-quarantine at home), we opted not to reduce immunosuppression, instead implementing a close telephone monitoring protocol.
T186 13282-13401 Sentence denotes Total suspension of immunosuppression has been proposed in some patients with kidney transplants and COVID-19 [18, 19].
T187 13402-13597 Sentence denotes However, we were concerned that suspending immunosuppression could lead to graft failure due to rebound activation of immunological memory, potentially exacerbated by the hyperinflammatory state.
T188 13598-13895 Sentence denotes Furthermore, we do not yet know if the anti-inflammatory effect of chronic immunosuppressive therapy plays an undetermined role in the ‘cell damage cascade’ triggered by an uncontrolled cytokine storm and lymphocyte–macrophage activation, as has already been speculated in the literature [20, 21].
T189 13896-14066 Sentence denotes Indeed, some evidence suggests that lung damage in the severe forms of the disease is essentially due to immune hyperactivation rather than viral pathogenesis per se [6].
T190 14067-14214 Sentence denotes Conversely, we know that pharmacological interferences occurs between the antiviral drugs used to treat SARS-CoV-2 and calcineurin inhibitors [16].
T191 14215-14370 Sentence denotes The main issue of drug–drug interactions is an increased in immunosuppressant plasma concentrations due to their shared metabolism via cytochrome-P450-3A4.
T192 14371-14531 Sentence denotes In particular, the interaction between lopinavir and calcineurin inhibitors has already been characterized as being based on suppression of cytochrome-P450-3A4.
T193 14532-14629 Sentence denotes In contrast, the interaction between hydroxychloroquine and calcineurin inhibitors is less clear.
T194 14630-14785 Sentence denotes Its metabolism via cytochrome-P450-3A4, as well as via cytochrome-P450-2C8, might theoretically increase the plasma concentration of the immunosuppressant.
T195 14786-14858 Sentence denotes Consequently, close monitoring of immunosuppressant levels is warranted.
T196 14859-15010 Sentence denotes Therefore, on one hand we chose to reduce chronic immunosuppressive therapy; on the other, we introduced corticosteroid therapy for 2 critical reasons.
T197 15011-15114 Sentence denotes First, we tried to reduce the hyperinflammatory state and the overproduction of inflammation mediators.
T198 15115-15255 Sentence denotes However, the use of corticosteroids in SARS-CoV-2 infection for treatment of acute respiratory distress syndrome remains controversial [22].
T199 15256-15485 Sentence denotes A retrospective analysis by Wang et al. in a Wuhan cohort showed that administration of early, low-dose and short-term corticosteroids was associated with faster improvement of clinical symptoms and absorption of lung focus [23].
T200 15486-15651 Sentence denotes Moreover, Siddiqi and Mehra [20] proposed the use of corticosteroids in immunosuppressed states when hypoxia is highlighted in moderate to severe clinical scenarios.
T201 15652-15762 Sentence denotes In this regard, supportive therapy with hydroxychloroquine was also administered in all hospitalized patients.
T202 15763-16017 Sentence denotes At the beginning of the COVID-19 pandemic, first reports and many national treatment guidelines suggested the use of hydroxychloroquine due to the anti-inflammatory and broad-spectrum antiviral effects observed with the severe acute respiratory syndrome.
T203 16018-16160 Sentence denotes However, despite its common use, efficacy and safety were not confirmed by several dedicated observational studies and randomized trials [24].
T204 16161-16169 Sentence denotes The U.S.
T205 16170-16266 Sentence denotes Food and Drug Administration subsequently revoked emergency use authorization for the drug [25].
T206 16267-16398 Sentence denotes On 17 June 2020, the World Health Organization announced that the hydroxychloroquine arm of the Solidarity Trial was being stopped.
T207 16399-16596 Sentence denotes Data from major ongoing randomized clinical trials showed that hydroxychloroquine does not result in a reduction in mortality of hospitalized COVID-19 patients, when compared with standard of care.
T208 16597-16681 Sentence denotes Only 2 of our 5 hospitalized patients were treated with ritonavir/lopinavir therapy.
T209 16682-16861 Sentence denotes At the beginning of the Northern Italy pandemic, the Italian government agency for the regulation of drugs developed several protocols for off-label usage of antiretrovirals [26].
T210 16862-17006 Sentence denotes These 2 patients had fulfilled inclusion criteria for enrolment in one of the first randomized clinical trials for these drugs against COVID-19.
T211 17007-17305 Sentence denotes With increasing evidence of both the absence of clinical benefit from ritonavir/lopinavir in the more seriously ill patients and the risk of toxicity associated with the combined administration of hydroxychloroquine and azithromycin, their usage in the general COVID-19 population has been limited.
T212 17306-17382 Sentence denotes As a result, we have abandoned their use in our heart transplant population.
T213 17383-17515 Sentence denotes Second, by introducing corticosteroids, we lowered the risk of graft failure due to the reduction in the dose of immunosuppressants.
T214 17516-17648 Sentence denotes Nevertheless, given the debated effects of corticosteroids, the dose introduced was of medium proportion, as already suggested [23].
T215 17649-17842 Sentence denotes Therefore, we hypothesize that the broad-spectrum immunomodulatory effect of corticosteroids can help in the clinical management of transplant recipients affected with severe forms of COVID-19.
T216 17843-18120 Sentence denotes Not least, we considered the administration of broad-spectrum antibiotic therapy to avoid superimposed bacterial infections that would have a detrimental effect on the prognosis due to immunosuppression and corticosteroids, and the reduction of defenses due to lymphocytopenia.
T217 18121-18184 Sentence denotes We mainly opted for broad spectrum beta-lactams and macrolides.
T218 18185-18334 Sentence denotes The patient who self-quarantined at home, despite presenting with similar onset symptoms, experienced a mild course of infection of shorter duration.
T219 18335-18419 Sentence denotes The nasopharyngeal swab test was performed when the person was already asymptomatic.
T220 18420-18514 Sentence denotes This patient was the only one on everolimus due to a high number of Epstein-Barr virus copies.
T221 18515-18658 Sentence denotes Although there are speculations about this drug’s antiviral activity in relation to SARS-CoV-2, no conclusions can be drawn from a single case.
T222 18659-18788 Sentence denotes Some authors claim a possible beneficial effect for everolimus as therapy for COVID-19 due to its immunomodulatory activity [27].
T223 18789-19083 Sentence denotes Moreover, the anti-replicative effect of controlling the spread of Epstein–Barr virus or cytomegalovirus can also be promising in SARS-CoV-2 infection on the basis of its ability to reduce mRNA translation, ribosome biogenesis, protein synthesis, mitochondrial metabolism and viral replication.
T224 19084-19211 Sentence denotes Table 2 summarizes the available data on SARS-COV-2 infections in heart transplant recipients from reported case series [3–13].
T225 19212-19284 Sentence denotes When we analysed the overall data, the case-fatality-rate was about 20%.
T226 19285-19375 Sentence denotes More than 80% of the patients were hospitalized, and half required intensive care support.
T227 19376-19485 Sentence denotes The best immunosuppressive strategy is still being debated, in accordance with 60% of dosage reduction cases.
T228 19486-19494 Sentence denotes Table 2:
T229 19496-19577 Sentence denotes Summary of available data on SARS-COV-2 infections in heart transplant recipients
T230 19578-19799 Sentence denotes Li et al. [3] Mathies et al. [5] Holzhauser et al. [6] Hsu et al. [7] Latif et al. [8] Hoek et al. [9] Kates et al. [10] Decker et al. [11] Fernandez- Ruiz et al. [12] Lee et al. [13] Caraffa et al Total, n (%)
T231 19800-19856 Sentence denotes Number of patients 2 1 2 1 28 4 1 1 4 4 6 54
T232 19857-19881 Sentence denotes Baseline characteristics
T233 19882-20010 Sentence denotes  Age (years) 51; 43 77 59; 75 39 64 (53.3–70.5) 75; 65; 51; 50 74 62 64; 67; 63; 38 15; 25; 1.1; 2.4 67 (59–74) 59.1
T234 20011-20155 Sentence denotes  Time from HTx (years) 16.2; 2.6 17 8; 20 3 8.6 (4.2–14.5) 21; 10; 10; 6 23 0.4 13.8; 10; 17.9; 8.7 0.4; 3; 0.5; 2 12 (4.0–17.5) 9.4
T235 20156-20211 Sentence denotes  Male gender 2 1 1 1 22 3 1 1 4 1 5 42 (78)
T236 20212-20279 Sentence denotes  Arterial hypertension 0 1 2 1 20 NA NA 0 2 0 5 31 (63)
T237 20280-20343 Sentence denotes  Diabetes mellitus 0 1 2 1 17 NA NA 0 1 0 0 22 (45)
T238 20344-20413 Sentence denotes  Chronic kidney diseasea 0 1 2 0 10 NA NA 0 0 0 0 13 (27)
T239 20414-20472 Sentence denotes  Lung disease 0 0 0 1 10 NA NA 1 1 0 0 13 (27)
T240 20473-20529 Sentence denotes  PCI for CAV 0 1 0 0 NA NA NA 0 1 0 1 3 (14)
T241 20530-20583 Sentence denotes  BMI >30 0 0 0 1 NA NA NA 0 NA 0 1 2 (12)
T242 20584-20607 Sentence denotes COVID-19 onset symptoms
T243 20608-20658 Sentence denotes  Fever 2 0 2 0 19 NA 1 1 4 3 6 38 (78)
T244 20659-20713 Sentence denotes  Chest pain 0 0 0 1 5 NA 0 0 0 1 NA 7 (16)
T245 20714-20787 Sentence denotes  Shortness of breath or cough 0 1 2 1 21 NA 1 1 4 2 6 39 (80)
T246 20788-20858 Sentence denotes  Gastrointestinal symptoms 1 0 2 0 11 NA 0 0 1 1 2 18 (37)
T247 20859-20877 Sentence denotes Treatment regimens
T248 20878-20908 Sentence denotes  Maintenance immunosuppression
T249 20909-20965 Sentence denotes   Cyclosporine 0 0 1 0 5 1 0 1 3 2 6 19 (35)
T250 20966-21033 Sentence denotes   Mycophenolate  mofetil 2 1 2 1 19 2 0 1 4 1 4 37 (69)
T251 21034-21089 Sentence denotes   Tacrolimus 2 0 1 1 22 3 1 0 1 1 0 32 (59)
T252 21090-21167 Sentence denotes   Proliferation sig-  nal inhibitors 0 1 0 0 5 1 0 0 0 0 1 8 (15)
T253 21168-21222 Sentence denotes   Azathioprine 0 0 0 0 0 0 0 0 0 2 0 2 (4)
T254 21223-21278 Sentence denotes   Prednisone 0 0 0 1 19 2 0 1 4 2 0 29 (54)
T255 21279-21318 Sentence denotes Number of immunosuppressive medications
T256 21319-21361 Sentence denotes  1 0 0 0 0 3 0 1 0 0 0 1 2 (8)
T257 21362-21406 Sentence denotes  2 2 1 2 0 8 3 0 0 0 1 5 14 (14)
T258 21407-21451 Sentence denotes  3 0 0 0 1 16 1 0 1 4 2 0 9 (35)
T259 21452-21494 Sentence denotes  4 0 0 0 0 1 0 0 0 0 0 0 0 (0)
T260 21495-21513 Sentence denotes COVID-19 treatment
T261 21514-21576 Sentence denotes  Hydroxychloroquine 0 1 2 1 18 3 0 1 4 1 5 36 (67)
T262 21577-21637 Sentence denotes  Lopinavir/ritonavir 0 0 1 0 0 0 0 0 2 0 2 5 (9)
T263 21638-21697 Sentence denotes  Remdesivir/placebo 0 0 0 1 0 0 0 0 0 0 0 1 (2)
T264 21698-21749 Sentence denotes  Umifenovir 1 0 0 0 0 0 0 0 0 0 0 1 (2)
T265 21750-21802 Sentence denotes  Oseltamivir 0 0 1 0 0 0 0 0 0 0 0 1 (2)
T266 21803-21853 Sentence denotes  Ribavirin 1 0 0 0 0 0 0 0 0 0 0 1 (2)
T267 21854-21900 Sentence denotes  IFN-b 0 0 0 0 0 0 0 0 1 0 0 1 (2)
T268 21901-21953 Sentence denotes  Ganciclovir 2 1 0 0 0 0 0 0 0 0 0 3 (6)
T269 21954-22007 Sentence denotes  Tocilizumab 0 0 2 0 6 0 0 0 0 0 0 8 (15)
T270 22008-22064 Sentence denotes  Steroid bolus 1 0 1 0 8 0 0 1 0 1 5 17 (31)
T271 22065-22110 Sentence denotes  IVIG 1 0 1 0 0 0 0 0 0 0 0 2 (4)
T272 22111-22137 Sentence denotes Immunosuppressant strategy
T273 22138-22196 Sentence denotes  Dose reduction 0 0 0 0 6 NA 0 0 0 1 5 12 (24)
T274 22197-22263 Sentence denotes  At least 1 withdrawal 1 1 2 1 16 NA 0 0 4 1 1 27 (55)
T275 22264-22326 Sentence denotes Acute graft rejection 0 0 0 0 0 NA 0 0 0 0 0 0 (0)
T276 22327-22341 Sentence denotes Major outcomes
T277 22342-22399 Sentence denotes  Hospitalized 2 1 2 1 22 NA 0 1 4 2 5 40 (82)
T278 22400-22461 Sentence denotes  Need for ICU stay 0 1 1 1 NA NA 0 0 2 0 2 7 (33)
T279 22462-22526 Sentence denotes  Invasive ventilation 0 0 1 0 NA NA 0 0 2 0 1 4 (19)
T280 22527-22595 Sentence denotes  Self quarantined at home 0 0 0 0 6 NA 1 0 0 2 1 10 (20)
T281 22596-22644 Sentence denotes  Death 0 0 0 0 7 1 0 0 1 0 2 11 (20)
T282 22645-22700 Sentence denotes  Discharged 2 1 1 1 11 NA 0 0 2 2 3 23 (47)
T283 22701-22765 Sentence denotes  Remained hospitalized 0 0 1 0 4 NA 0 1 1 0 0 7 (14)
T284 22766-23052 Sentence denotes BMI: body mass index; CAV: cardiac allograft vasculopathy; HTx: heart transplant; IFN-b: interferon-beta; ICU: intensive care unit; IVIG: intravenous gamma globulin; NA: not available; PCI: percutaneous coronary intervention; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2.
T285 23053-23141 Sentence denotes a Defined by a glomerular filtration rate ˂30 ml/min and the presence of haemodialysis.
T286 23142-23219 Sentence denotes The mortality rate remains higher compared to that of the overall population.
T287 23220-23320 Sentence denotes It is still unclear whether any of the adopted approaches actually influence prognosis and survival.
T288 23321-23477 Sentence denotes Our adopted therapeutic strategy resulted in one-third mortality in this particular population at risk of severe illness from infection with the SARS-CoV-2.
T289 23478-23625 Sentence denotes One patient of advanced age with an already documented cardiac allograft vasculopathy did not overcome the disease, having developed a severe form.
T290 23626-23763 Sentence denotes Available data show a higher mortality rate among older male patients with cardiovascular comorbidities who are infected with SARS-CoV-2.
T291 23764-23935 Sentence denotes Furthermore, we must consider that during the outbreak the maximum standard of care was not achievable for all due to the limited availability of intensive care unit beds.
T292 23936-24087 Sentence denotes The other death was the consequence of a complicated course of hospitalization for a patient not responsive to antibiotic therapy who developed sepsis.
T293 24088-24240 Sentence denotes In addition, in 1 case we even managed to treat the infection at home in an unprecedented era in which healthcare resources are limited by the pandemic.
T294 24241-24408 Sentence denotes Apart from a bacterial superinfection and progression of respiratory disease, the only major complication that occurred during hospitalization was an ischaemic stroke.
T295 24409-24613 Sentence denotes Anecdotal cases regarding neurological events in patients with COVID-19 have been reported in the literature to date [28] and evidenced shows a hypercoagulability state in patients with severe forms [29].
T296 24614-24705 Sentence denotes Further investigations are needed to understand the aetiopathogenesis of this complication.
T297 24707-24718 Sentence denotes Limitations
T298 24719-24822 Sentence denotes The major limitations regarding our experience are related to the small size of the population studied.
T299 24823-24972 Sentence denotes Months after the beginning of the pandemic, mounting evidence is emerging for therapy and supportive care practices for managing COVID-19 infections.
T300 24973-25107 Sentence denotes More studies are needed to evaluate and correlate clinical and laboratory data to support our immunosuppressive modification strategy.
T301 25108-25275 Sentence denotes The cohort of heart transplant recipients makes up a minimal part of the affected population and the need to collect patients in a multicentre study remains essential.