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1.
J Korean Med Sci ; 37(13): e104, 2022 Apr 04.
Article in English | MEDLINE | ID: covidwho-1775638

ABSTRACT

Vaccines have become the mainstay of management against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (coronavirus disease 2019; COVID-19) in the absence of effective antiviral therapy. Various adverse effects of COVID-19 vaccination have been reported, including cardiovascular complications such as myocarditis or pericarditis. Herein, we describe clinical records of a 63-year woman with fulminant myocarditis following ChAdOx1 nCoV-19 vaccination that was salvaged by heart transplantation. She complained chest pain, nausea, vomiting, and fever after the second vaccination. After the heart transplantation, the patient died due to necrotizing pneumonia on the 54th day of onset. Fulminant myocarditis is very rare after ChAdOx1 nCoV-19 vaccination but can be fatal.


Subject(s)
COVID-19 , Heart Transplantation , Myocarditis , COVID-19 Vaccines/adverse effects , Female , Heart Transplantation/adverse effects , Humans , Myocarditis/complications , Myocarditis/etiology , SARS-CoV-2 , Vaccination/adverse effects
2.
Clin Transplant ; 36(4): e14634, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1731123

ABSTRACT

There has been a shift over decades in the diagnostic indications for lung transplantation in children; in particular, there has been a reduction in the proportion of pediatric cystic fibrosis (CF) patients undergoing lung transplantation early in life, and more transplants occurring in other diagnostic groups. Here, we examine trends in pediatric lung transplantation with regards to indications by analyzing data from the United Network of Organ Sharing, the International Society for Heart and Lung Transplantation Thoracic Transplant Registry, and other sources. Over the past two years, there has been a precipitous decline in both the number of transplants due to CF and the proportion of CF cases relative to the total number of transplants, likely not solely due to the COVID-19 pandemic. In 2020, primary pulmonary arterial hypertension for the first-time surpassed CF as main indication for pediatric lung transplantation in the United States, a finding that is also reflected in international data. We discuss the effect of novel CFTR modulator therapies as a major factor leading to this shifting landscape. Based on our trending, pulmonary hypertension-related diagnoses and pediatric interstitial lung diseases are rising indications, for which we suggest adjustments of consensus guidelines around candidate selection criteria.


Subject(s)
COVID-19 , Cystic Fibrosis , Heart Transplantation , Heart-Lung Transplantation , Lung Transplantation , COVID-19/epidemiology , Child , Cystic Fibrosis/surgery , Humans , Lung Transplantation/adverse effects , Pandemics , Survival Rate , Tissue Donors , United States
4.
Transplantation ; 106(3): 641-647, 2022 03 01.
Article in English | MEDLINE | ID: covidwho-1703842

ABSTRACT

BACKGROUND: Heart transplant (HT) recipients may be at higher risk of acquiring SARS-CoV-2 infection and developing critical illness. The aim of this study is to describe characteristics and outcomes of HT recipients infected by SARS-COV-2, from a high-volume transplant center. METHODS: We have described data of all adult HT recipients with confirmed coronavirus disease 2019 by RT-PCR in nasopharyngeal samples from April 5, 2020, to January 5, 2021. Outcomes and follow-up were recorded until February 5, 2021. RESULTS: Forty patients were included. Twenty-four patients (60%) were men; the median age was 53 (40-60) y old; median HT time was 34 mo; and median follow-up time 162 d. The majority needed hospitalization (83%). Immunosuppressive therapy was reduced/withdrawn in the majority of patients, except from steroids, which were maintained. Seventeen patients (42.5%) were classified as having severe disease according to the ordinal scale developed by the World Health Organization Committee. They tended to have lower absolute lymphocyte count (P < 0.001) during follow-up when compared with patients with mild disease. Thirty-day mortality was 12.5%. However, a longer follow-up revealed increased later mortality (27.5%), with median time to death around 35 d. Bacterial nosocomial infections were a leading cause of death. Cardiac allograft rejection (10%) and ventricular dysfunction (12.5%) were also not negligible. CONCLUSIONS: Major findings of this study corroborate other cohorts' results, but it also reports significant rate of later events, suggesting that a strict midterm surveillance is advisable to HT recipients with coronavirus disease 2019.


Subject(s)
COVID-19 , Heart Transplantation , Adult , Heart Transplantation/adverse effects , Hospitalization , Humans , Male , Middle Aged , SARS-CoV-2 , Transplant Recipients
7.
J Heart Lung Transplant ; 41(4): 492-500, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1654472

ABSTRACT

BACKGROUND: Recent studies have suggested a blunted immune response to messenger RNA vaccines in solid organ transplant (SOT) recipients. Given the paucity of data on adenovirus vector vaccines use in immunosuppressed SOT recipients, we sought to describe the safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine in a heart transplant population. METHODS: Heart transplant recipients aged 18 to 70 years scheduled to receive 2 doses of the ChAdOx1 nCoV-19 vaccine were enrolled into a prospective study involving serum analysis to define their antibody response. An antibody concentration against the spike protein receptor-binding domain of ≥0.8 U/mL was deemed a detectable antibody response. RESULTS: A total of 99 heart transplant recipients (mean age 51 ± 12.5 years, 28% female) were enrolled. No major adverse events were recorded after vaccination; minor symptoms included injection site pain (24%), fatigue (21%) and headache (14%). Of 7 patients with prior SARS-CoV-2 confirmed by PCR testing, all (100%) had detectable antibody responses following first and second vaccine doses. In those with no prior SARS-CoV-2 infection (n = 92), 24% (n = 22) showed an antibody response after dose 1, increasing to 34.8% (n = 32) after dose 2, p < 0.001. Chronic kidney disease (CKD) stage ≥3 (OR 4.7, 95% CI 1.5-15, p = 0.009) and mycophenolate use (OR 4.1, 95% CI 1.2-14, p = 0.02) were independently associated with a nondetectable antibody response. CONCLUSIONS: Almost two-thirds of heart transplant recipients aged 18 to 70 years without a history of prior SARS-CoV-2 infection failed to develop a detectable antibody response following administration of the ChAdOx1 nCoV-19 vaccine. Patient phenotyping may help predict which patients are less likely to develop detectable antibody responses.


Subject(s)
COVID-19 , Heart Transplantation , Adenoviridae/genetics , Adolescent , Adult , Aged , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Female , Humans , Male , Middle Aged , Prospective Studies , SARS-CoV-2 , Transplant Recipients , Vaccination , Young Adult
8.
Sci Rep ; 12(1): 965, 2022 01 19.
Article in English | MEDLINE | ID: covidwho-1638855

ABSTRACT

Hospitalized patients who die from Covid-19 often have pre-existing heart disease. The SARS-CoV-2 virus is dependent on the ACE2 receptor to be able to infect cells. It is possible that the strong link between cardiovascular comorbidities and a poor outcome following a SARS-CoV-2 infection is sometimes due to viral myocarditis. The aim was to examine the expression of ACE2 in normal hearts and hearts from patients with terminal heart failure. The ACE2 expression was measured by global quantitative proteomics and RT-qPCR in left ventricular (LV) tissue from explanted hearts. Immunohistochemistry was used to examine ACE2 expression in cardiomyocytes, fibroblasts and endothelial cells. In total, tissue from 14 organ donors and 11 patients with terminal heart failure were included. ACE2 expression was 2.6 times higher in 4 hearts from patients with terminal heart failure compared with 6 healthy donor hearts. The results were confirmed by immunohistochemistry where more than half of cardiomyocytes or fibroblasts showed expression of ACE2 in hearts from patients with terminal heart failure. In healthy donor hearts ACE2 was not expressed or found in few fibroblasts. A small subpopulation of endothelial cells expressed ACE2 in both groups. Upregulated ACE2 expression in cardiomyocytes may increase the risk of SARS-CoV-2 myocarditis in patients with heart failure.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , Endothelial Cells/pathology , Fibroblasts/pathology , Heart Failure/pathology , Myocytes, Cardiac/pathology , Tissue Donors/supply & distribution , Adult , Aged , Angiotensin-Converting Enzyme 2/genetics , Case-Control Studies , Endothelial Cells/metabolism , Female , Fibroblasts/metabolism , Heart Failure/genetics , Heart Failure/metabolism , Heart Failure/therapy , Heart Transplantation/methods , Humans , Male , Middle Aged , Myocytes, Cardiac/metabolism , Young Adult
10.
Am J Transplant ; 22(4): 1261-1265, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1570333

ABSTRACT

An unvaccinated adult male heart transplant recipient patient with recalcitrant COVID-19 due to SARS-CoV-2 delta variant with rising nasopharyngeal quantitative viral load was successfully treated with ALVR109, an off-the-shelf SARS-CoV-2-specific T cell therapy. Background immunosuppression included 0.1 mg/kg prednisone, tacrolimus, and mycophenolate mofetil 1 gm twice daily for historical antibody-mediated rejection. Prior therapies included remdesivir, corticosteroids, and tocilizumab, with requirement for high-flow nasal oxygen. Lack of clinical improvement and acutely rising nasopharyngeal viral RNA more than 3 weeks into illness prompted the request of ALVR109 through an emergency IND. The day following the first ALVR109 infusion, the patient's nasopharyngeal SARS-CoV-2 RNA declined from 7.43 to 5.02 log10 RNA copies/ml. On post-infusion day 4, the patient transitioned to low-flow oxygen. Two subsequent infusions of ALVR109 were administered 10 and 26 days after the first; nasopharyngeal SARS-CoV-2 RNA became undetectable on Day 11, and he was discharged the following day on low-flow oxygen 5 weeks after the initial diagnosis of COVID-19. The clinical and virologic improvements observed in this patient following administration of ALVR109 suggest a potential benefit that warrants further exploration in clinical trials.


Subject(s)
COVID-19 , Heart Transplantation , Adult , Cell- and Tissue-Based Therapy , Humans , Male , RNA, Viral/genetics , SARS-CoV-2
12.
ESC Heart Fail ; 9(1): 219-223, 2022 02.
Article in English | MEDLINE | ID: covidwho-1530139

ABSTRACT

While severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection primarily causes inflammation in the respiratory system, there is growing evidence of extrapulmonary tissue damage mediated by the host innate immune system in children and adults. A cytokine storm can manifest as a viral-induced haemophagocytic lymphohistiocytosis (HLH). Here, we present a previously healthy 8-year-old boy with newly diagnosed cardiac injury and COVID-19-related HLH syndrome with haemophagocytosis in bone marrow biopsy. After remission of inflammation, the patient underwent a heart transplant due to persistent cardiac failure. The histology of the explanted heart showed only a focal subtle subendocardial inflammation. Three days after transplant, he developed progressive acute respiratory distress syndrome (ARDS) with the rise of inflammatory markers. He unfortunately died after 20 days because of disseminated intravascular coagulation (DIC). For the first time, we described a child with COVID-19-related HLH and severe cardiac failure, which had a poor prognosis despite a heart transplant.


Subject(s)
COVID-19 , Heart Transplantation , Lymphohistiocytosis, Hemophagocytic , Adult , Child , Cytokine Release Syndrome , Humans , Lymphohistiocytosis, Hemophagocytic/complications , Lymphohistiocytosis, Hemophagocytic/diagnosis , Male , SARS-CoV-2
13.
J Heart Lung Transplant ; 41(3): 327-333, 2022 03.
Article in English | MEDLINE | ID: covidwho-1520991

ABSTRACT

BACKGROUND: Reports focused on adult heart transplant (HTx) recipients with COVID-19 suggest an increased risk of severe disease, however; it is unclear if this holds true for pediatric HTx patients, given the typically milder course of illness in children in general with COVID-19. We sought to rapidly implement a system for multi-center data collection on pediatric HTx candidates and recipients, with the aim of describing the patient population and infection related outcomes. METHODS: The Pediatric Heart Transplant Society (PHTS) is a multi-center collaboration that seeks to improve the outcomes of children who are listed and undergo HTx. The society consists of pediatric HTx centers in North America (n = 53), UK (n = 2), and Brazil (n = 1). In response to the pandemic, PHTS developed a web-based platform to collect COVID-19 specific data on pediatric HTx candidates and recipients. Non-PHTS centers were also invited to submit data. Data fields included pre-and post-HTx patient characteristics, presumed versus documented infection, need for hospitalization (including ICU and ventilator use), treatments administered, and 30-day outcome (resolution, death, sequelae, and or unresolved) RESULTS: Data collection was initiated on 4/30/20. As of 03/15/21 there were 225 patients [19 pre-HTx and 206 post-HTx, median age 14 years (IQR 7, 18)] reported from 41 centers. Hospitalization occurred in 42% (n = 8) of the pre-HTx and 21% (n=43) of the post-HTx patients. Among the patients listed for HTx, 21% (n = 4) required ICU and 10.5% (n = 2) were mechanically ventilated. Among post-HTx patients, 7% (n = 14) required ICU and 1% (n = 3) were mechanically ventilated. At 30 days, the majority of patients had resolution of symptoms (94.7% pre-HTx, 95.6% post-HTx). One death was reported in a post-HTx patient prior to 30 days from onset of COVID-19 illness. CONCLUSIONS: These data demonstrate the ability to rapidly adapt the PHTS data collection infrastructure in response to a novel infection and represent the first known multi-center report of characteristics and early outcomes for patients listed and following pediatric HTx with COVID-19. Hospitalization appears to be more common for both candidates and recipients due to COVID-19 than for the general pediatric population though stays were short and mortality minimal.


Subject(s)
COVID-19/epidemiology , Heart Transplantation , Postoperative Complications/epidemiology , Postoperative Complications/virology , Adolescent , Child , Child, Preschool , Cohort Studies , Female , Humans , Male
14.
J Heart Lung Transplant ; 41(2): 133-136, 2022 02.
Article in English | MEDLINE | ID: covidwho-1509806

ABSTRACT

BACKGROUND: BACKGROUND: There is a paucity of data regarding the antibody response to SARS-CoV-2 vaccination in children after solid organ transplant. METHODS: We retrospectively reviewed the SARS-CoV-2 Anti-Spike IgG antibodies measured following SARS-CoV-2 vaccination at our pediatric heart transplant (HTx) center. RESULTS: Among patients (median age 17.1 years) in whom antibody testing was performed (median 118 days post-vaccine completion), a SARS-CoV-2 Anti-Spike IgG antibody was detected in 28 of 40 (70%) post-HTx recipients (median antibody level 10.9 AU/ml). Neutropenia, diabetes mellitus, and previous use of rituximab were associated with absence of a detectable antibody. All 7 post-HTx patients with a known pre-vaccination SARS-CoV-2 viral infection had a detectable SARS-CoV-2 Anti-Spike IgG. All 12 vaccinated pre-HTx patients had a detectable antibody (median antibody level 11.6 AU/ml) including 5 patients that maintained detectable antibodies post-HTx. There were no cases of myocarditis among the total of 17 pre-HTx and 81 post-HTx patients that underwent SARS-CoV-2 vaccination. CONCLUSION: Our data suggest that a significant proportion of pediatric HTx recipients have no detectable antibody response after SARS-CoV-2 vaccination and support the recommendation to complete the vaccination series prior to HTx in those pediatric patients waiting for HTx.


Subject(s)
Antibodies, Viral/blood , COVID-19 Vaccines , COVID-19/prevention & control , Heart Transplantation , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Adolescent , Age Factors , Antibody Formation , COVID-19/blood , Child , Female , Humans , Male , Retrospective Studies , Young Adult
15.
J Heart Lung Transplant ; 41(2): 158-160, 2022 02.
Article in English | MEDLINE | ID: covidwho-1499889
16.
ESC Heart Fail ; 8(6): 5568-5571, 2021 12.
Article in English | MEDLINE | ID: covidwho-1449922

ABSTRACT

Adequate immune response to vaccination remains a challenge in patients after solid organ transplantation. We report a case of a 61-year-old male patient who received a left ventricular assist device as a bridge to transplant therapy. Three months before transplantation, he suffered mild SARS-CoV-2 infection and was successfully discharged thereafter. Eight days before his successful heart transplantation, he received mRNA BNT 162b2 vaccination. Immediately after transplantation, we detected sufficient rise of nucleocapsid and spike antibodies despite immune suppression therapy. We suspect potential booster effects of the previous SARS-CoV-2 infection giving rise to adequate immune response following single vaccination.


Subject(s)
COVID-19 , Heart Transplantation , Antibodies, Viral , Humans , Immunity , Male , Middle Aged , SARS-CoV-2 , Vaccination
17.
Transplant Proc ; 53(9): 2743-2746, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1447201

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a viral infectious disease caused by the severe acute respiratory syndrome coronavirus 2 virus that is affecting the entire world population. The objective of this study was to analyze the repercussion of the disease in a group of patients at risk such as heart transplant recipients. METHODS: From February 2020 to February 2021, heart transplant recipients diagnosed with COVID-19 were consecutively included. The total number of transplant recipients in outpatient follow-up at that time was 381. Three levels of infection were determined: group A: asymptomatic patients or with trivial symptoms without the need for hospital admission (6 patients); group B: patients admitted to the hospital for respiratory symptoms (12 patients); and group C: patients with severe symptoms and need for admission to the critical care unit (2 patients). At each risk level, medical performance was different: group A: close control, no therapeutic modification; group B: reduction of calcineurin inhibitor and substitution of mycophenolate mofetil for everolimus; group C: reduction of calcineurin inhibitor and withdrawal of mycophenolate mofetil. RESULTS: The prevalence of infection in the series was 5.2%. Most patients admitted had a pathologic chest x-ray with fever, cough, dyspnea, or vomiting. The change in immunosuppression performed in patients in group 2 was well tolerated and there was no graft rejection. Antiviral treatment was little used. However, boluses of steroids and some antibiotics were used frequently. The need for supplemental oxygen was 50% in group 2 and 100% in group 3. CONCLUSIONS: A significant number of transplant recipients will be affected by COVID-19 (5.3%). Management of the infection will depend on the severity of the infection and must be based on a balance between reduction and adjustment of immunosuppression, strict control of the cardiologic situation, and treatment of the infection.


Subject(s)
COVID-19 , Heart Transplantation , Kidney Transplantation , Heart Transplantation/adverse effects , Humans , Immunosuppressive Agents/adverse effects , SARS-CoV-2 , Tertiary Care Centers , Transplant Recipients
18.
Circ J ; 85(10): 1906-1917, 2021 09 24.
Article in English | MEDLINE | ID: covidwho-1440968

ABSTRACT

Destination therapy (DT) is the indication to implant a left ventricular assist device (LVAD) in a patient with stage D heart failure who is not a candidate for heart transplantation. The implantable LVAD has been utilized in Japan since 2011 under the indication of bridge to transplant (BTT). After almost 10 year lag, DT has finally been approved and reimbursed in May 2021 in Japan. To initiate the DT program in Japan, revision of the LVAD indication from BTT is necessary. Also, in-depth discussion of caregiver issues as well as end-of-life care is indispensable. For that purpose, we assembled a DT committee of multidisciplinary members in August 2020, and started monthly discussions via web-based communication during the COVID-19 pandemic. This is a summary of the consensus reached after 6 months' discussion, and we have included as many relevant topics as possible. Clinical application of DT has just started, and we are willing to revise this consensus to meet the forthcoming issues raised during real-world clinical experience.


Subject(s)
COVID-19/epidemiology , Consensus , Heart Failure/therapy , Heart Transplantation , Heart-Assist Devices , Pandemics , SARS-CoV-2 , Heart Failure/epidemiology , Humans , Japan/epidemiology
20.
J Med Case Rep ; 15(1): 453, 2021 Sep 13.
Article in English | MEDLINE | ID: covidwho-1413220

ABSTRACT

BACKGROUND: With the rapidly expanding pandemic of severe acute respiratory syndrome coronavirus-2, a chronic immunosuppressed state in solid organ transplant recipients is a concern. We reported coronavirus disease 2019 in heart transplant recipients and described the patients' course from diagnosis to either hospital admission or improvement in symptoms. CASE PRESENTATION: This study retrospectively identified 13 white (Iranian) heart transplant patients with coronavirus disease 2019 between December 2019 and October 2020. The mean age of patients was 43.7 years (19-65 years); seven (70%) were men. Laboratory and treatment data were collected for those admitted or managed as outpatients. Outcomes were also recorded for all patients. This report demonstrates a range of symptoms, clinical severity, and disease course in heart transplant recipients with coronavirus disease 2019, including ten hospitalized patients and three patients, managed entirely in the outpatient setting. One patient passed away, and none of them experienced an episode of clinically overt rejection. CONCLUSIONS: We would like to emphasize the importance of being alert in these patients to consider testing in a broad range of clinical presentations and gathering more data for better management.


Subject(s)
COVID-19 , Heart Transplantation , Adult , Heart Transplantation/adverse effects , Humans , Immunosuppressive Agents , Iran , Male , Retrospective Studies , SARS-CoV-2
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