> top > projects > LitCovid-sentences > docs > PMC:7665480 > annotations
LitCovid-sentences  

PMC:7665480 JSONTXT 10 Projects

Annnotations TAB TSV DIC JSON TextAE

Id Subject Object Predicate Lexical cue
T1 0-98 Sentence denotes Coronavirus disease 2019 (COVID-19) in the heart transplant population: a single-centre experience
T2 100-108 Sentence denotes Abstract
T3 109-117 Sentence denotes Abstract
T4 119-129 Sentence denotes OBJECTIVES
T5 130-305 Sentence denotes Few anecdotal cases have been reported in the literature regarding heart transplant recipients and infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
T6 306-398 Sentence denotes We report our experience with 6 patients hospitalized in Northern Italy during the outbreak.
T7 400-407 Sentence denotes METHODS
T8 408-551 Sentence denotes Of the 396 living heart transplant recipients from 1985 to 2020 included in the study, 6 patients developed the novel 2019 coronavirus disease.
T9 552-710 Sentence denotes Risk factors, last follow-up characteristics, onset presentation, in-hospital course of disease and blood examinations data were collected for these patients.
T10 712-719 Sentence denotes RESULTS
T11 720-822 Sentence denotes All patients were symptomatic and had positive results from a nasopharyngeal swab test for SARS-CoV-2.
T12 823-902 Sentence denotes Of the 6 patients, 5 were hospitalized and 1 remained self-quarantined at home.
T13 903-948 Sentence denotes Two patients died and 3 were discharged home.
T14 949-1005 Sentence denotes Two patients were admittted to the intensive care unit .
T15 1006-1135 Sentence denotes Immunosuppressive therapy was modified with a median reduction comprising doses that were 50% cyclosporine and 50% mycophenolate.
T16 1136-1242 Sentence denotes All patients received a medium-dose of corticosteroids as a bolus medication in addition to their therapy.
T17 1243-1338 Sentence denotes All hospitalized patients received hydroxychloroquine; 2 patients received ritonavir/lopinavir.
T18 1339-1407 Sentence denotes Broad-spectrum antibiotics for prophylaxis were administered to all.
T19 1408-1463 Sentence denotes One patient had an ischaemic stroke and died of sepsis.
T20 1465-1476 Sentence denotes CONCLUSIONS
T21 1477-1683 Sentence denotes In the absence of any strong evidence regarding the treatment of heart transplant recipients infected with SARS-CoV-2, we faced a new challenge in managing viral infection in an immunosuppressed population.
T22 1684-1893 Sentence denotes Because immunomodulation interaction with the infection seems to be crucial for developing severe forms of the disease, we managed to reduce immunosuppressive therapy by adding medium doses of corticosteroids.
T23 1894-2085 Sentence denotes Despite the limited number of affected patients, this report suggests that special considerations should be given to treating coronavirus disease in the heart transplant recipient population.
T24 2087-2337 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.
T25 2339-2351 Sentence denotes INTRODUCTION
T26 2352-2602 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 2603-2746 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 2747-2969 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 2970-3128 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 3129-3214 Sentence denotes Immunosuppression-related issues present the main concern in this special population.
T31 3215-3415 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 3416-3574 Sentence denotes Importantly, it is well established that severe infections in the immunocompromised population dramatically influence both the care and prognosis of patients.
T33 3575-3765 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 3766-3942 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 3943-4052 Sentence denotes This uncertainty has opened up a great debate regarding immunomodulation interaction with the infection [15].
T36 4053-4224 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 4225-4482 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 4483-4557 Sentence denotes Mortality data are only available from case reports and small case series.
T39 4558-4719 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 4720-4915 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 4916-5062 Sentence denotes Moreover, we investigated outcomes from balancing immunosuppression regimen and response to infection through our therapeutic management strategy.
T42 5064-5071 Sentence denotes METHODS
T43 5073-5089 Sentence denotes Study population
T44 5090-5182 Sentence denotes We considered patients who had orthotopic heart transplants in our centre from 1985 to 2020.
T45 5183-5277 Sentence denotes Heart transplant recipients affected with COVID-19 were included in the present investigation.
T46 5278-5441 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 5443-5460 Sentence denotes Ethical statement
T48 5461-5604 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 5605-5858 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 5860-5880 Sentence denotes Statistical analyses
T51 5881-6016 Sentence denotes Continuous variables are expressed as median and interquartile range (IQR); categorical variables are presented as count and frequency.
T52 6017-6138 Sentence denotes All statistical analyses were performed using SPSS software version 20 (IBM SPSS Statistics, IBM Corp., Armonk, NY, USA).
T53 6140-6147 Sentence denotes RESULTS
T54 6148-6188 Sentence denotes All collected data are shown in Table 1.
T55 6189-6244 Sentence denotes To date, 396 heart transplant patients are still alive.
T56 6245-6296 Sentence denotes Six patients developed active SARS-CoV-2 infection:
T57 6297-6388 Sentence denotes 2 of these patients died, 1 of acute respiratory distress syndrome and the other of sepsis.
T58 6389-6605 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 6606-6718 Sentence denotes Of the 6 patients, the only female in the study presented mild symptoms and remained in self-quarantine at home.
T60 6719-6944 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 6945-6953 Sentence denotes Table 1:
T62 6955-7024 Sentence denotes Main characteristics of the 6 heart transplant patients with COVID-19
T63 7025-7089 Sentence denotes Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6
T64 7090-7102 Sentence denotes Demographics
T65 7103-7139 Sentence denotes  Age (years) 69 82 65 71 62 50
T66 7140-7185 Sentence denotes  Gender Male Male Male Male Male Female
T67 7186-7243 Sentence denotes  Time from heart transplant (years) 5 16 11 1 22 13
T68 7244-7257 Sentence denotes  Risk factors
T69 7258-7307 Sentence denotes   BMI (kg/m2) 22.4 23.6 24.5 25.3 32.6 21.5
T70 7308-7349 Sentence denotes   Arterial hypertension − + + + + +
T71 7350-7383 Sentence denotes   Dyslipidaemia − + + − + −
T72 7384-7421 Sentence denotes   Diabetes mellitus − − − − − −
T73 7422-7455 Sentence denotes   Former smoker + − − − − −
T74 7456-7501 Sentence denotes   Extracardiac arteriopathy − − − − − −
T75 7502-7526 Sentence denotes   COPD − − − − − −
T76 7527-7553 Sentence denotes   Stroke − − − − − −
T77 7554-7584 Sentence denotes   Malignancy − − + − − +
T78 7585-7623 Sentence denotes   GFR (ml/min) 80 40 71 82 48 85
T79 7624-7656 Sentence denotes   Previous PCI − + − − − −
T80 7657-7688 Sentence denotes   NYHA class I II I I I I
T81 7689-7724 Sentence denotes  Immunosuppressive therapy (mg/day)
T82 7725-7768 Sentence denotes   Cyclosporine 120 120 160 200 135 70
T83 7769-7814 Sentence denotes   Mycophenolate 1440 − 1440 1440 1440 −
T84 7815-7845 Sentence denotes   Everolimus − − − − − 2
T85 7846-7860 Sentence denotes COVID-19 onset
T86 7861-7881 Sentence denotes  Presenting symptoms
T87 7882-7907 Sentence denotes   Cough + + + + + +
T88 7908-7947 Sentence denotes   Shortness of breath + + + + + +
T89 7948-7975 Sentence denotes   Myalgia − + + + + +
T90 7976-8003 Sentence denotes   Anosmia − − + + + +
T91 8004-8032 Sentence denotes   Headache − − − − + +
T92 8033-8062 Sentence denotes   Sinusitis − − − − − +
T93 8063-8108 Sentence denotes   Gastrointestinal symptoms − − − − + +
T94 8109-8136 Sentence denotes  NPS test + + + + + +
T95 8137-8175 Sentence denotes  X-ray pneumonia signs + + + + −
T96 8176-8228 Sentence denotes  Fever peak (°C) 38.0 38.6 38.0 39.5 38.5 39.2
T97 8229-8263 Sentence denotes  Hospitalization + + + + + −
T98 8264-8306 Sentence denotes  SpO2 at admission (%) 91 85 97 78 85
T99 8307-8365 Sentence denotes  Worst SpO2 during hospitalization (%) 88 75 88 75 65
T100 8366-8398 Sentence denotes  Laboratory results at admission
T101 8399-8459 Sentence denotes   WBC count (cells per 109/l) 10.00 9.24 4.00 7.50 5.90
T102 8460-8501 Sentence denotes   Hb (g/dl) 10.0 13.5 12.0 13.7 13.5
T103 8502-8556 Sentence denotes   Platelets (cells per 109/l) 400 113 215 301 151
T104 8557-8617 Sentence denotes   Lymphocyte (cells per 109/l) 0.35 0.32 0.55 0.90 0.20
T105 8618-8654 Sentence denotes   CRP (mg/dl) 157 140 3.3 72 29
T106 8655-8687 Sentence denotes   PCT (ng/ml) 0.26 0.09 0 0
T107 8688-8739 Sentence denotes   Serum creatinine (mg/dl) 1.29 2.1 1.79 1.3 2
T108 8740-8776 Sentence denotes   Troponin I (ng/dl) 34 8 18 24
T109 8777-8806 Sentence denotes  LVEF (%) 55 45 70 55 50
T110 8807-8829 Sentence denotes Treatment and outcomes
T111 8830-8867 Sentence denotes  Hydroxychloroquine + + + + + −
T112 8868-8906 Sentence denotes  Lopinavir/ritonavir + − − − + −
T113 8907-8948 Sentence denotes  Corticosteroid therapy + + + + + −
T114 8949-9010 Sentence denotes  Modification of immunosuppressive therapya + + + + + −
T115 9011-9064 Sentence denotes   % Reduction of cyclosporine 40 100 60 50 40 0
T116 9065-9116 Sentence denotes   % Reduction of mycophenolate 75 0 0 50 50 0
T117 9117-9159 Sentence denotes  Antibiotics prophylaxis + + + + + +
T118 9160-9184 Sentence denotes  ICU stay + − − − +
T119 9185-9221 Sentence denotes   ICU length of stay 18 − − − 2
T120 9222-9250 Sentence denotes  High flow O2 − + − + +
T121 9251-9270 Sentence denotes  NIV − + − + +
T122 9271-9297 Sentence denotes  Intubation + − − − −
T123 9298-9312 Sentence denotes  Complications
T124 9313-9344 Sentence denotes   Respiratory − ARDS − − −
T125 9345-9389 Sentence denotes   Neurological Ischaemic stroke − − − −
T126 9390-9421 Sentence denotes   Infective Sepsis − − − −
T127 9422-9469 Sentence denotes  In-hospital length of stay 24 10 13 27 24
T128 9470-9515 Sentence denotes  Days to negative NPS testb 10 7 15 14c
T129 9516-9541 Sentence denotes  Pronation − − − + +
T130 9542-9568 Sentence denotes  Discharged − − + + +
T131 9569-9592 Sentence denotes  Dead + + − − − −
T132 9593-9675 Sentence denotes a In-hospital percentage reduction from last follow-up dose of immunosuppressant.
T133 9676-9784 Sentence denotes b Days from first positive NPS test to first seriate negative NPS test and clinical resolution of symptoms.
T134 9785-9934 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 9935-10256 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 10257-10394 Sentence denotes New York heart association; PCI: percutaneous coronary intervention; PCT: procalcitonin; SpO2: oxygen saturation; WBC: white blood cells.
T137 10396-10408 Sentence denotes Risk factors
T138 10409-10461 Sentence denotes Data collected on risk factors are shown in Table 1.
T139 10462-10574 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 10575-10704 Sentence denotes Among the patients’ risk factors arterial hypertension was the most frequent, occurring in 83%, followed by dyslipidaemia in 50%.
T141 10705-10730 Sentence denotes Only 1 patient was obese.
T142 10731-10825 Sentence denotes The median glomerular filtration rate was 92 ml/min (IQR 79–133); no patients needed dialysis.
T143 10826-10974 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 10975-11084 Sentence denotes One patient had a previous percutaneous coronary intervention procedure for a cardiac allograft vasculopathy.
T145 11085-11251 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 11252-11457 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 11458-11590 Sentence denotes Immunosuppressive therapy included cyclosporine for all patients, associated with mycophenolate in 4 cases and everolimus in 1 case.
T148 11592-11608 Sentence denotes In-hospital stay
T149 11609-11640 Sentence denotes Data are summarized in Table 1.
T150 11641-11699 Sentence denotes Median in-hospital length of stay was 24 days (IQR 12–26).
T151 11700-11756 Sentence denotes Three patients were discharged home and 2 patients died.
T152 11757-11875 Sentence denotes Median oxygen saturation at admission was 85% (IQR 81–94), the worst level during hospitalization was 75% (IQR 70–88).
T153 11876-11940 Sentence denotes All hospitalized patients had signs of pneumonia on radiographs.
T154 11941-12016 Sentence denotes Troponin at admission fell consistently within the limits for all patients.
T155 12017-12217 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 12218-12264 Sentence denotes Pronation therapy was performed in 2 patients.
T157 12265-12340 Sentence denotes One patient needed 3 days of continuous veno-venous hemofiltration therapy.
T158 12341-12443 Sentence denotes One patient received inotropic drugs with noradrenaline at maximum doses of 0.1 mcg/kg/min for 3 days.
T159 12444-12487 Sentence denotes Extracorporeal life support was never used.
T160 12488-12581 Sentence denotes During the in-hospital stay echocardiographic monitoring was used to evaluate graft function.
T161 12582-12791 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 12792-12979 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 12980-13076 Sentence denotes The other patient developed acute respiratory distress syndrome and died of respiratory failure.
T164 13078-13103 Sentence denotes Pharmacological treatment
T165 13104-13143 Sentence denotes Collected data are provided in Table 1.
T166 13144-13267 Sentence denotes During hospitalization hydroxychloroquine and broad-spectrum antibiotics for prophylaxis were administered to all patients.
T167 13268-13313 Sentence denotes Ritonavir/lopinavir were used for 2 patients.
T168 13314-13472 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 13473-13579 Sentence denotes In all hospitalized patients, a 0.5–1 mg/kg/day bolus of prednisone was administered for the first 7 days.
T170 13580-13684 Sentence denotes Those intubated or in serious condition were given an equivalent intravenous dose of methylprednisolone.
T171 13685-13784 Sentence denotes Progressive tapering then followed, leading to a low maintenance dose of 5–10 mg/day at discharged.
T172 13785-13877 Sentence denotes Immunosuppressive therapy remained reduced until the first outpatient follow-up examination.
T173 13878-13986 Sentence denotes At that time, the original immunosuppressive regime was resumed and corticosteroid therapy was discontinued.
T174 13987-14024 Sentence denotes No graft rejection episodes occurred.
T175 14025-14173 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 14174-14277 Sentence denotes No immunosuppressive therapy modifications were made and no anti-inflammatory agents were administered.
T177 14278-14362 Sentence denotes The results of the nasopharyngeal swab test for SARS-CoV-2 at 14 days were negative.
T178 14364-14374 Sentence denotes DISCUSSION
T179 14375-14624 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 14625-14775 Sentence denotes This therapeutic scheme is effective in deactivating the lymphocytes of the adaptive immune response, which is primarily involved in viral infections.
T181 14776-14983 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 14984-15179 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 15180-15353 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 15354-15436 Sentence denotes This strategy was adopted due to the lymphocytopenia characterizing this syndrome.
T185 15437-15620 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 15621-15740 Sentence denotes Total suspension of immunosuppression has been proposed in some patients with kidney transplants and COVID-19 [18, 19].
T187 15741-15936 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 15937-16234 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 16235-16405 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 16406-16553 Sentence denotes Conversely, we know that pharmacological interferences occurs between the antiviral drugs used to treat SARS-CoV-2 and calcineurin inhibitors [16].
T191 16554-16709 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 16710-16870 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 16871-16968 Sentence denotes In contrast, the interaction between hydroxychloroquine and calcineurin inhibitors is less clear.
T194 16969-17124 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 17125-17197 Sentence denotes Consequently, close monitoring of immunosuppressant levels is warranted.
T196 17198-17349 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 17350-17453 Sentence denotes First, we tried to reduce the hyperinflammatory state and the overproduction of inflammation mediators.
T198 17454-17594 Sentence denotes However, the use of corticosteroids in SARS-CoV-2 infection for treatment of acute respiratory distress syndrome remains controversial [22].
T199 17595-17824 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 17825-17990 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 17991-18101 Sentence denotes In this regard, supportive therapy with hydroxychloroquine was also administered in all hospitalized patients.
T202 18102-18356 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 18357-18499 Sentence denotes However, despite its common use, efficacy and safety were not confirmed by several dedicated observational studies and randomized trials [24].
T204 18500-18508 Sentence denotes The U.S.
T205 18509-18605 Sentence denotes Food and Drug Administration subsequently revoked emergency use authorization for the drug [25].
T206 18606-18737 Sentence denotes On 17 June 2020, the World Health Organization announced that the hydroxychloroquine arm of the Solidarity Trial was being stopped.
T207 18738-18935 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 18936-19020 Sentence denotes Only 2 of our 5 hospitalized patients were treated with ritonavir/lopinavir therapy.
T209 19021-19200 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 19201-19345 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 19346-19644 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 19645-19721 Sentence denotes As a result, we have abandoned their use in our heart transplant population.
T213 19722-19854 Sentence denotes Second, by introducing corticosteroids, we lowered the risk of graft failure due to the reduction in the dose of immunosuppressants.
T214 19855-19987 Sentence denotes Nevertheless, given the debated effects of corticosteroids, the dose introduced was of medium proportion, as already suggested [23].
T215 19988-20181 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 20182-20459 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 20460-20523 Sentence denotes We mainly opted for broad spectrum beta-lactams and macrolides.
T218 20524-20673 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 20674-20758 Sentence denotes The nasopharyngeal swab test was performed when the person was already asymptomatic.
T220 20759-20853 Sentence denotes This patient was the only one on everolimus due to a high number of Epstein-Barr virus copies.
T221 20854-20997 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 20998-21127 Sentence denotes Some authors claim a possible beneficial effect for everolimus as therapy for COVID-19 due to its immunomodulatory activity [27].
T223 21128-21422 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 21423-21550 Sentence denotes Table 2 summarizes the available data on SARS-COV-2 infections in heart transplant recipients from reported case series [3–13].
T225 21551-21623 Sentence denotes When we analysed the overall data, the case-fatality-rate was about 20%.
T226 21624-21714 Sentence denotes More than 80% of the patients were hospitalized, and half required intensive care support.
T227 21715-21824 Sentence denotes The best immunosuppressive strategy is still being debated, in accordance with 60% of dosage reduction cases.
T228 21825-21833 Sentence denotes Table 2:
T229 21835-21916 Sentence denotes Summary of available data on SARS-COV-2 infections in heart transplant recipients
T230 21917-22138 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 22139-22195 Sentence denotes Number of patients 2 1 2 1 28 4 1 1 4 4 6 54
T232 22196-22220 Sentence denotes Baseline characteristics
T233 22221-22349 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 22350-22494 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 22495-22550 Sentence denotes  Male gender 2 1 1 1 22 3 1 1 4 1 5 42 (78)
T236 22551-22618 Sentence denotes  Arterial hypertension 0 1 2 1 20 NA NA 0 2 0 5 31 (63)
T237 22619-22682 Sentence denotes  Diabetes mellitus 0 1 2 1 17 NA NA 0 1 0 0 22 (45)
T238 22683-22752 Sentence denotes  Chronic kidney diseasea 0 1 2 0 10 NA NA 0 0 0 0 13 (27)
T239 22753-22811 Sentence denotes  Lung disease 0 0 0 1 10 NA NA 1 1 0 0 13 (27)
T240 22812-22868 Sentence denotes  PCI for CAV 0 1 0 0 NA NA NA 0 1 0 1 3 (14)
T241 22869-22922 Sentence denotes  BMI >30 0 0 0 1 NA NA NA 0 NA 0 1 2 (12)
T242 22923-22946 Sentence denotes COVID-19 onset symptoms
T243 22947-22997 Sentence denotes  Fever 2 0 2 0 19 NA 1 1 4 3 6 38 (78)
T244 22998-23052 Sentence denotes  Chest pain 0 0 0 1 5 NA 0 0 0 1 NA 7 (16)
T245 23053-23126 Sentence denotes  Shortness of breath or cough 0 1 2 1 21 NA 1 1 4 2 6 39 (80)
T246 23127-23197 Sentence denotes  Gastrointestinal symptoms 1 0 2 0 11 NA 0 0 1 1 2 18 (37)
T247 23198-23216 Sentence denotes Treatment regimens
T248 23217-23247 Sentence denotes  Maintenance immunosuppression
T249 23248-23304 Sentence denotes   Cyclosporine 0 0 1 0 5 1 0 1 3 2 6 19 (35)
T250 23305-23372 Sentence denotes   Mycophenolate  mofetil 2 1 2 1 19 2 0 1 4 1 4 37 (69)
T251 23373-23428 Sentence denotes   Tacrolimus 2 0 1 1 22 3 1 0 1 1 0 32 (59)
T252 23429-23506 Sentence denotes   Proliferation sig-  nal inhibitors 0 1 0 0 5 1 0 0 0 0 1 8 (15)
T253 23507-23561 Sentence denotes   Azathioprine 0 0 0 0 0 0 0 0 0 2 0 2 (4)
T254 23562-23617 Sentence denotes   Prednisone 0 0 0 1 19 2 0 1 4 2 0 29 (54)
T255 23618-23657 Sentence denotes Number of immunosuppressive medications
T256 23658-23700 Sentence denotes  1 0 0 0 0 3 0 1 0 0 0 1 2 (8)
T257 23701-23745 Sentence denotes  2 2 1 2 0 8 3 0 0 0 1 5 14 (14)
T258 23746-23790 Sentence denotes  3 0 0 0 1 16 1 0 1 4 2 0 9 (35)
T259 23791-23833 Sentence denotes  4 0 0 0 0 1 0 0 0 0 0 0 0 (0)
T260 23834-23852 Sentence denotes COVID-19 treatment
T261 23853-23915 Sentence denotes  Hydroxychloroquine 0 1 2 1 18 3 0 1 4 1 5 36 (67)
T262 23916-23976 Sentence denotes  Lopinavir/ritonavir 0 0 1 0 0 0 0 0 2 0 2 5 (9)
T263 23977-24036 Sentence denotes  Remdesivir/placebo 0 0 0 1 0 0 0 0 0 0 0 1 (2)
T264 24037-24088 Sentence denotes  Umifenovir 1 0 0 0 0 0 0 0 0 0 0 1 (2)
T265 24089-24141 Sentence denotes  Oseltamivir 0 0 1 0 0 0 0 0 0 0 0 1 (2)
T266 24142-24192 Sentence denotes  Ribavirin 1 0 0 0 0 0 0 0 0 0 0 1 (2)
T267 24193-24239 Sentence denotes  IFN-b 0 0 0 0 0 0 0 0 1 0 0 1 (2)
T268 24240-24292 Sentence denotes  Ganciclovir 2 1 0 0 0 0 0 0 0 0 0 3 (6)
T269 24293-24346 Sentence denotes  Tocilizumab 0 0 2 0 6 0 0 0 0 0 0 8 (15)
T270 24347-24403 Sentence denotes  Steroid bolus 1 0 1 0 8 0 0 1 0 1 5 17 (31)
T271 24404-24449 Sentence denotes  IVIG 1 0 1 0 0 0 0 0 0 0 0 2 (4)
T272 24450-24476 Sentence denotes Immunosuppressant strategy
T273 24477-24535 Sentence denotes  Dose reduction 0 0 0 0 6 NA 0 0 0 1 5 12 (24)
T274 24536-24602 Sentence denotes  At least 1 withdrawal 1 1 2 1 16 NA 0 0 4 1 1 27 (55)
T275 24603-24665 Sentence denotes Acute graft rejection 0 0 0 0 0 NA 0 0 0 0 0 0 (0)
T276 24666-24680 Sentence denotes Major outcomes
T277 24681-24738 Sentence denotes  Hospitalized 2 1 2 1 22 NA 0 1 4 2 5 40 (82)
T278 24739-24800 Sentence denotes  Need for ICU stay 0 1 1 1 NA NA 0 0 2 0 2 7 (33)
T279 24801-24865 Sentence denotes  Invasive ventilation 0 0 1 0 NA NA 0 0 2 0 1 4 (19)
T280 24866-24934 Sentence denotes  Self quarantined at home 0 0 0 0 6 NA 1 0 0 2 1 10 (20)
T281 24935-24983 Sentence denotes  Death 0 0 0 0 7 1 0 0 1 0 2 11 (20)
T282 24984-25039 Sentence denotes  Discharged 2 1 1 1 11 NA 0 0 2 2 3 23 (47)
T283 25040-25104 Sentence denotes  Remained hospitalized 0 0 1 0 4 NA 0 1 1 0 0 7 (14)
T284 25105-25391 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 25392-25480 Sentence denotes a Defined by a glomerular filtration rate ˂30 ml/min and the presence of haemodialysis.
T286 25481-25558 Sentence denotes The mortality rate remains higher compared to that of the overall population.
T287 25559-25659 Sentence denotes It is still unclear whether any of the adopted approaches actually influence prognosis and survival.
T288 25660-25816 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 25817-25964 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 25965-26102 Sentence denotes Available data show a higher mortality rate among older male patients with cardiovascular comorbidities who are infected with SARS-CoV-2.
T291 26103-26274 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 26275-26426 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 26427-26579 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 26580-26747 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 26748-26952 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 26953-27044 Sentence denotes Further investigations are needed to understand the aetiopathogenesis of this complication.
T297 27046-27057 Sentence denotes Limitations
T298 27058-27161 Sentence denotes The major limitations regarding our experience are related to the small size of the population studied.
T299 27162-27311 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 27312-27446 Sentence denotes More studies are needed to evaluate and correlate clinical and laboratory data to support our immunosuppressive modification strategy.
T301 27447-27614 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.
T302 27616-27626 Sentence denotes CONCLUSION
T303 27627-27762 Sentence denotes To date, few anecdotal results have been reported in the literature regarding infection with SARS-CoV-2 in heart transplant recipients.
T304 27763-27979 Sentence denotes Our strategy primarily consisted of lowering the dose of their immunosuppressive therapy facing the viral infection and introducing corticosteroids to reduce the hyperinflammatory state and the risk of graft failure.
T305 27980-28141 Sentence denotes Despite the limited number of affected patients, this report suggests that special considerations should be given to COVID-19 in the heart transplant population.
T306 28142-28335 Sentence denotes Given the information available in the literature, the case fatality rate for this vulnerable cohort is doubled that of the overall population and the best therapeutic strategy remains unclear.
T307 28336-28501 Sentence denotes Prompt referral to a transplant centre following onset of first symptoms is required in order to treat the disease immediately and avoid progression to severe forms.
T308 28502-28538 Sentence denotes Conflict of interest: none declared.
T309 28540-28560 Sentence denotes Author contributions
T310 28561-28577 Sentence denotes Raphael Caraffa:
T311 28578-28601 Sentence denotes Writing—original draft.
T312 28602-28618 Sentence denotes Lorenzo Bagozzi:
T313 28619-28633 Sentence denotes Data curation.
T314 28634-28652 Sentence denotes Alessandro Fiocco:
T315 28653-28676 Sentence denotes Writing—original draft.
T316 28677-28693 Sentence denotes Olimpia Bifulco:
T317 28694-28710 Sentence denotes Formal analysis.
T318 28711-28725 Sentence denotes Matteo Nadali:
T319 28726-28738 Sentence denotes Methodology.
T320 28739-28754 Sentence denotes Matteo Ponzoni:
T321 28755-28769 Sentence denotes Data curation.
T322 28770-28794 Sentence denotes Massimiliano Carrozzini:
T323 28795-28807 Sentence denotes Supervision.
T324 28808-28825 Sentence denotes Giuseppe Toscano:
T325 28826-28837 Sentence denotes Validation.
T326 28838-28860 Sentence denotes Angela Pompea Fraiese:
T327 28861-28872 Sentence denotes Validation.
T328 28873-28885 Sentence denotes Marco Metra:
T329 28886-28911 Sentence denotes Writing—review & editing.
T330 28912-28933 Sentence denotes Carlo Maria Lombardi:
T331 28934-28959 Sentence denotes Writing—review & editing.
T332 28960-28979 Sentence denotes Francesco Serafini:
T333 28980-28994 Sentence denotes Data curation.
T334 28995-29009 Sentence denotes Angela Ribola:
T335 29010-29024 Sentence denotes Data curation.
T336 29025-29038 Sentence denotes Vjola Jorgji:
T337 29039-29064 Sentence denotes Writing—review & editing.
T338 29065-29079 Sentence denotes Tomaso Bottio:
T339 29080-29124 Sentence denotes Conceptualization; Writing—review & editing.
T340 29125-29137 Sentence denotes Gino Gerosa:
T341 29138-29156 Sentence denotes Conceptualization.
T342 29158-29178 Sentence denotes Reviewer information
T343 29179-29344 Sentence denotes European Journal of Cardio-Thoracic Surgery thanks Sai Bhagra and the other, anonymous reviewer(s) for their contribution to the peer review process of this article.
T344 29346-29359 Sentence denotes Abbreviations
T345 29360-29393 Sentence denotes COVID-19 Coronavirus disease 2019
T346 29394-29417 Sentence denotes IQR Interquartile range
T347 29418-29476 Sentence denotes SARS-CoV-2 Severe acute respiratory syndrome coronavirus-2