TOPIC: Transplantation
      TYPE: Medical Student/Resident Case Reports
      INTRODUCTION: The global pandemic of COVID-19 infection has become an unprecedented public health and economic challenge. There is ample research already in the field of COVID-19 to show that patients with diabetes and hypertension are more susceptible to the disease. However, research pertaining to COVID-19 infection in patients with cardiac transplant is scarce; due to this, management of COVID-19 in the heart transplant population, particularly with regard to their immunosuppressive regimen, can be difficult.
      CASE PRESENTATION: A 63-year-old male with history of end-stage ischemic cardiomyopathy status post cardiac transplant, hypertension, and chronic kidney disease presented to the hospital with complaints of fever, dry cough, myalgias, and ageusia for more than 2 weeks. In the outpatient setting, his nasopharyngeal swab was positive for SARS-CoV-2 two weeks prior to presentation. In addition, he also reported several-day duration of worsened diarrhea and mild shortness of breath, prompting him to come to the hospital. On presentation, the patient was afebrile (99.1°F) and tachycardic, with a heart rate of 109 beats/min. His arterial oxygen saturation was 95% on room air on admission. Physical examination demonstrated mild respiratory distress with lungs clear to auscultation bilaterally. Chest X-ray on admission did not show any acute cardiopulmonary process. The RT-PCR result for SARS-CoV-2 returned positive. Labs were notable for leukopenia with WBC of 1.4 with marked neutropenia, supratherapeutic Tacrolimus level of 28.3 pg/mL, significantly elevated creatinine at 4.84 (baseline 1.3), and increased CRP, ferritin, and D-dimer. Transthoracic echo demonstrated left ventricular ejection fraction of 60-65% with no other significant abnormalities. After 2 days of hospital stay, his respiratory status worsened and he was put on supplemental oxygen. Repeat CXR showed peripheral patchy airspace opacities bilaterally. CT chest without contrast was remarkable for diffuse patchy ground-glass opacities at the lung bases. Workup for acute on chronic diarrhea yielded a low level of CMV viremia not requiring treatment, and negative for Cryptosporidium and Clostridium difficile infection. Of note, this case was early in the COVID-19 pandemic, and the current treatment guidelines for COVID-19 were not necessarily all in practice at the time. The patient's neutropenia responded well to Neupogen. His acute renal failure improved drastically with IV fluid supplementation. Due to the supratherapeutic tacrolimus level, the immunosuppression medicines were held the first few days of his hospital stay. However, once the Tacrolimus level reached therapeutic levels, he was maintained on tacrolimus with lower goal of 6-8 and his home regimen of mycophenolate mofetil. Unfortunately, within the first 3 days of hospitalization, the patient's respiratory status/oxygen requirements steadily worsened from nasal cannula to Oxymask and high-flow nasal cannula, and finally, necessitated mechanical ventilation. Along with severe ARDS, he simultaneously developed septic shock requiring pressor support in addition to broad-spectrum antibiotics. Proning and inhaled epoprostenol were initiated. Patient also received one dose of Tociluzimab, one unit of convalescent plasma, 5 days of Remdesivir, and heparin drip. Despite all efforts, the patient passed away on the 13th day of hospitalization.
      DISCUSSION: The paucity of research on COVID-19 infection in the heart transplant population makes appropriate and effective treatment of these patients challenging. Heart transplant patients are at a higher risk of severe infection due to their immunocompromised state, and those with concomitant COVID-19 infection have been shown to have a higher fatality rate of 25% [1]. In addition, there is not much robust data on immunosuppression regimen in heart transplant patients with COVID-19. Some centers are recommending discontinuing all the immunosuppressive medicines or reducing the immunosuppressive regimens in these patients [2]. In our case, the immunosuppressive regimen was reduced, but interestingly, our patient did not show any symptoms of severe cytokine release syndrome initially, possibly due to his supratherapeutic levels of tacrolimus on admission. The patient developed the severe symptoms as the tacrolimus levels dropped lower than the therapeutic range. It is largely just speculation that supratherapeutic levels of immunosuppressive medicines were initially helping our patient. We need more studies to understand the role of the immunosuppression in heart transplant recipients with COVID-19 infection.
      CONCLUSIONS: The current COVID-19 pandemic has spurred an enormous amount of research that has greatly aided in the treatment of patients suffering from COVID-19 infection. The heart transplant population is highly vulnerable to death from severe COVID-19 infection. Therefore, there is tremendous need for further research on not only COVID-19 infection in the cardiac transplant population, but also the role of immunosuppression in their treatment.
      REFERENCE #1: Latif, F et al. Characteristics and Outcomes of Recipients of Heart Transplant With Coronavirus Disease 2019. JAMA Cardiology. 2020; doi: 10.1001/jamacardio.2020.2159
      REFERENCE #2: Siddiqi HK, Mehra, RM. COVID-19 illness in native and immunosuppressed states: A clinical-therapeutic staging proposal. Journal of Heart and Lung Transplantation. 2020; 39(5): 405-407. doi: 10.1016/j.healun.2020.03.012
      DISCLOSURES: No relevant relationships by Praneeth Katrapati, source=Web Response
      No relevant relationships by Munis Raza, source=Web Response
      no disclosure on file for Naresh Solankhi;
      No relevant relationships by Gayatri Suresh Kumar, source=Web Response