COVID-19 and Cardiac Transplant Rejection - Coincidence or Not?

Overlap between the histopathologic changes of acute rejection and viral myocarditis presents a diagnostic dilemma. A 34 year-old female with a past medical history of postpartum cardiomyopathy and subsequent orthotopic heart transplant in December 2019, presented for routine surveillance heart biopsy seven months post-transplant. Her AlloMap was elevated and AlloSure was uptrending, concerning for rejection. Ten days prior to presentation, she tested positive for COVID-19 via polymerase chain reaction (PCR) testing. Her symptoms were fatigue and mild headache for two weeks prior to diagnosis. She did not seek medical attention for her symptoms and received no COVID-19 specific treatment. Endomyocardial biopsy showed grade 2R acute cellular rejection. Her echocardiogram was unchanged with normal left ventricular ejection fraction and right ventricular function. SARS-CoV-2 levels were measured by PCR of ribonucleic acid (RNA) isolated from the biopsy specimen and were undetectable. The patient was treated with two short courses of high dose prednisone which eventually abated her transplant rejection. The patient remained positive on PCR testing for COVID-19 for the next six months. Chest x-ray and computed tomography for follow up after COVID-19 infection showed no evidence of pulmonary fibrosis or superinfection considering ongoing immunosuppression for rejection. Our patient illustrates a case of concomitant COVID-19 infection and presumed transplant rejection, raising the question of whether the findings seen on immunohistochemistry were truly rejection or instead an elevated immune response due to COVID-19 infection. Given that our patient had a predominance of CD3+ T cells and less CD68+ macrophages (the former being more prominent in acute cellular rejection and the latter being more prominent in COVID-19 myocarditis), we are inclined to believe the former. (Figure Presented).

Kidney Biopsy Proven Thrombotic Microangiopathy in a Heart Transplant Recipient

Introduction: Thrombotic Microangiopathy (TMA) after non renal solid organ transplantation is very rare. While few cases of TMA following liver and lung transplants have been published, it has been very rarely reported following orthotopic heart transplant (OHT). We report the first case of kidney biopsy proven De Novo TMA after OHT. Case Description: 58-year-old male with non ischemic cardiomyopathy undergoes OHT in Jan 2021. He had normal renal function pre transplantation. Post-operatively he had pericardial effusion and in that setting developed oliguric AKI from ATN requiring dialysis. His renal function recovered and was discharged without dialysis. He was on tacrolimus, MMF and steroid regimen. Frequent heart biopsies were negative for rejection. In March 2021 the patient was admitted for GI bleed and again noted to have AKI. However, during this episode he developed proteinuria of over 2gm, new compared to previous urine studies. He was discharged with a serum creatinine of 2.6mg/dL. By July 2021 renal function worsened and he underwent a renal biopsy on 7/30/21 which showed acute and chronic TMA, related to calcineurin inhibitor use. Viral causes and other medications were ruled out (CMV, BK, adenovirus, SARs-COV2). Tacrolimus was held and he was initiated on Everolimus. Genetic and complement testing revealed normal complement levels, an elevated SC5b-9 complex, heterozygous for the APOL1 gene mutation (c.[1024A>G;1152T>G] p.[Ser342Gly;Ile384Met] (G1 allele)), and heterozygous for the CFHR5 gene mutation, suggestive for complement mediated TMA. He was initiated on Eculizumab. After two doses of Eculizumab he was again admitted with acute respiratory failure requiring intubation secondary to mTOR induced pneumonitis. His renal function worsened and he was reinitiated on dialysis. After a multidisciplinary discussion, he was transitioned to cyclosporine for immunosuppression. He continues to be on dialysis and cyclosporine with eculizumab without other non-renal findings of TMA. He is currently being evaluated for kidney transplantation. He has no signs of OHT rejection on heart biopsies. Discussion(s): The early identification and treatment of TMA in OHT is important in preventing further complications associated with it. Although rare as compared to other solid organ transplants, it is essential to maintain TMA as a differential diagnosis for AKI following OHT.

A Single Center Experience of Simultaneous Heart-Kidney Transplantation

Purpose: Currently there are no UNOS guidelines regarding the selection criteria required for simultaneous heart-kidney transplant recipients (SHKT). As of 2018 our center has begun performing these dual transplants for appropriate candidates. We report on the criteria devised to guide SHKT candidate selection at our institution and the subsequent clinical outcomes. Method(s): This is a single center, retrospective study of 26 patients who received SHKT at our institution from Dec 2018 to Oct 2021. A multidisciplinary team composed of heart and kidney transplant medical and surgical members determined appropriate recipient-donor SHKT candidate pairs. Selection criteria for SHKT was established by our kidney transplant group and included an evaluation for chronic kidney disease (CKD) or evidence of acute kidney injury (AKI) with a prolonged course or requiring renal replacement therapy (RRT). The surgery was conducted according to our institution's standardized protocols. The majority of patients received IL2-RA and methylprednisolone induction therapy, and all patients received triple immunosuppression therapy with prednisone, mycophenolate mofetil and tacrolimus. Adjustments in long term therapy were made in collaboration between the heart and kidney transplant teams. Result(s): From Dec 2018 to Oct 2021, 26 patients underwent SHKT at our institution. 24 patients (92%) carried a diagnosis of chronic kidney disease (CKD) as defined as an eGFR <60 ml/min/1.73m2 for at least 90 days on at least two separate tests. Clinical risk factors for CKD, the presence of proteinuria, and renal imaging data were also taken into consideration when determining a diagnosis of CKD. Two patients (8%) carried a diagnosis of stage III AKI for at least 4 weeks and required renal replacement therapy during their hospital course. Of our 26 patients, one patient received a DCD donor and 12 patients (46%) received hepatitis C donors. 25 patients (96%) received induction therapy with IL2-RA. During the first 3 months post-transplant, the only patient who received ATG had 7 severe infections;11 patients (44%) and 13 patients (52%) who received IL2 -RA had no infections and <= 4 mild infections, respectively. One patient died due to COVID 19 pneumonia complicated by multisystem organ failure. For a median follow up period of 410 (187-707) days, 8% patients in the IL2-RA induction cohort experienced a 2R/3A heart rejection, 8% patients remained on HD due to primary kidney graft nonfunction, and the survival rate was 96%. Conclusion(s): UNOS guidelines regarding selection criteria for SHKT are an important next step in the care of heart transplant candidates with kidney disease, particularly as the number of SHKT performed yearly increase. Compared to the literature, our data supports the use of standardized criteria for SHKT selection and the use of IL2- RA as an induction strategy with excellent patient survival.

Effect of Covid-19 Vaccination on Markers of Rejection in Heart Transplant Recipients

Purpose: Heart transplant recipients have worse survival with COVID-19 than the general population, highlighting the importance of vaccination in these patients. The impact of vaccination on rejection in transplant recipients is not well studied. This study examines the association of vaccination for COVID-19 with changes in markers for and evidence of transplant rejection. Method(s): A retrospective analysis of heart transplant recipients vaccinated for COVID-19 was conducted at a major tertiary care center in the American Midwest. Serial antibody responses were drawn after vaccination to assess vaccine response. Data from routine transplant surveillance was extracted from the electronic medical record. Markers of rejection included Allomap, Allosure, donor specific antibodies (DSA), and endomyocardial biopsies. Only patients with comparative data within 365 days of their first COVID-19 vaccination were included for analysis. Numerical data was assessed using descriptive statistics. Categorical variables were analyzed using Fisher's exact tests. Result(s): Between January 1, 2021 and September 30, 2021, 51 heart transplant recipients had COVID-19 antibody levels checked post-vaccination. There was an increase in the mean Allomap (31.19 +/- 5.27 vs 32.14 +/- 4.30), Allosure (0.04 +/- 0.08 vs 0.11 +/- 0.12%), and biopsy C4d% (3.33 +/- 8.16 vs 10.00 +/- 12.65%) levels post-vaccination compared to those pre-vaccination. Both positive and negative responders to vaccination showed this numerical increase in markers of rejection. There was no change in biopsy grades for acute cellular rejection, nor any changes in class I DSA positivity. One patient who had a positive antibody response to the vaccine had a de novo class II DSA post vaccination. No patients in this cohort had an episode of treated rejection post vaccination. Conclusion(s): Heart transplant recipients receiving COVID-19 vaccination have numerical increases in markers of rejection like Allomap, Allosure, and biopsy C4d%. These subtle changes may suggest a difference in the immunologic environment but are of unclear significance. There was no change in biopsy proven ACR or treated episodes of rejection. Further studies are warranted to investigate the effect of COVID-19 vaccination on transplant rejection. (Table Presented).

COVID-19 Infection in Heart Transplant Recipients: Results of a Six-Month Prospective Survey-Based Study

Solid-organ transplantation recipients were assumed highly vulnerable to coronavirus disease 2019 (COVID-19). However, the results of previous studies in patients with orthotopic heart transplantation (OHT) under immunosuppressive therapy are contradictory. Therefore, we aimed to assess the prevalence of COVID-19 infection and associated risk factors, along with the six-month outcomes in COVID-19 positive OHT patients. This single-center telephone-based survey was conducted on OHT patients. Using a detailed questionnaire, exposure to COVID-19, related symptoms, and preventive self-care measures were collected. Outcomes of COVID-19-positive patients were reassessed using another survey six months later. 118 OHT patients (male: n=87, 73.7%) were included with a mean age of 45.3±13.1 years. Sixteen patients (13.5%) reported one or more symptoms compatible with COVID-19, of whom 12 (10.2%) tested positive. Our results indicated no statistically significant association between COVID-19 and comorbidities. Poor adherence to self-care measures and contact with positive index cases were both significantly associated with COVID-19 infection (P<0.001). A later six months follow-up showed that two out of 12 (16.6%) COVID-19 positive OHT patients died. There was no statistically significant difference between the prevalence of COVID-19 in our patients compared to Iran’s general population (P=251.0). Non-compliance with personal protective protocols and a history of contact with COVID-19 cases were the most risk factors for COVID-19 infection in OHT patients.

Diagnostic challenge of Strongyloides stercoralis hyperinfection syndrome: a case report

Strongyloides stercoralis causes chronic, mostly asymptomatic infections but hyperinfection syndrome may occur in immunosup-pressed patients, especially in those receiving corticosteroids. We report a case of S. stercoralis hyperinfection syndrome in a solid organ transplant recipient that occurred approximately 2.5 months after heart transplantation. The patient presented to the inten-sive care unit with acute respiratory distress, bacteremia, and petechial rash on abdomen and toe. Microbiology testing of respiratory samples excluded infection with Pneumocystis jirovecii, respiratory viruses, pathogenic bacteria and fungi. No eosinophilia was found. Histopathological examination of the skin biopsy of the petechial rash provided the first indication of the diagnosis, revealing the presence of isolated filariform S. stercoralis larvae in the dermis. Subsequent microbiology testing confirmed the diagnosis. This case highlights the role of histopathological examination of a skin rash in diagnosing patients with atypical clinical presentation of Strongyloides hyperinfection syndrome.