key: cord-0885157-jb3um9sm
authors: Stachel, Maxine W.; Gidea, Claudia G.; Reyentovich, Alex; Mehta, Sapna A.; Moazami, Nader
title: COVID-19 PNEUMONIA IN A DUAL HEART-KIDNEY RECIPIENT
date: 2020-04-18
journal: J Heart Lung Transplant
DOI: 10.1016/j.healun.2020.04.008
sha: 229f12253addb4a613b9ecc9fe36642bce221cae
doc_id: 885157
cord_uid: jb3um9sm

nan

A 61-year-old African American man with history of hypertension, coronary artery disease, end-stage renal disease (on hemodialysis since 2014) and end-stage heart failure secondary to arrhythmogenic right ventricular cardiomyopathy (ARVC) underwent dual organ heart-kidney transplantation in May, 2019.

Approximately two months after transplant mycophenolate was discontinued due to episodes of pancreatitis, leukopenia and detectable BK polyoma virus. Since then, the patient was maintained on tacrolimus (goal level 8 ng/mL) and low-dose prednisone (5mg/day). Eight months after transplant, the patient developed a mild influenza A infection treated with oseltamivir for 10 days. Six weeks later, approximately ten months after heart-kidney transplant, the patient re-presented with cough productive of yellow sputum for three days, associated with pleuritic chest pain, dyspnea, nasal congestion and subjective fevers. He denied travel or exposure to known COVID infected individuals. Initial vital signs were within normal limits and physical exam was unremarkable. The blood oxygen saturation (sPO2) on room air was 96%. Respiratory viral panel was negative and white blood cell count and blood lactate were normal. Absolute lymphocyte count was reduced (700/uL; reference range 1300-3600/uL). C-reactive protein (CRP) was elevated (15.8 mg/L; reference range 0-5 mg/L). The initial chest x-ray revealed multifocal pneumonia (Fig. 1a) . The patient was started empirically on vancomycin, piperacillintazobactam and azithromycin. The baseline immunosuppression was reduced: prednisone was held and tacrolimus dose was decreased to a lower goal level of 6-8 ng/ml. Prophylaxis for opportunistic infection was continued with ganciclovir and atovaquone. An oropharyngeal swab and nasopharyngeal swab were sent for SARS-COV-2 RT-PCR testing, and the patient was admitted to an airborne isolation bed. On hospital day 4, the patient remained clinically stable with sPO2 ~95% on room air, but radiographic worsening was noted (Fig 1b) . His SARS-COV-2 RT-PCR test returned positive and he was started on lopinavir/ritonavir 400/100mg every 12 hours and nitazoxanide 500mg every 12 hours for 7 days. He was also given one dose of 40g intravenous immunoglobulin (IVIG). Tacrolimus levels were followed daily and given the known drug-drug interaction with ritonavir resulted in decreased tacrolimus clearance and no tacrolimus dose was administered or required for a week. Anti-bacterial therapy was discontinued. The patient improved, and by hospital day 14 experienced only intermittent cough with scant sputum production. His CRP decreased to 8.1 mg/L. He was discharged home to self-care.

This patient with COVID-19 disease exhibited a relatively mild form of the disease, remained afebrile and maintained good oxygen saturation throughout his hospital course. His presentation was similar to that reported in non-immunosuppressed patients and similar presentations were reported in 2 COVID-19+ heart transplant recipients from China [1] and 3 COVID-19+ heart transplant recipients from Italy . Since respiratory viral illness represents a significant cause of morbidity and mortality in the aging and immunocompromised transplant population [2] , these patients would likely benefit from early screening and aggressive treatment wherever possible. At this time, there is no proven targeted therapy available for COVID-19. The regimen of lopinavir/ritonavir, nitazoxanide and IVIG was chosen for our patient with history of dual organ transplantation and COVID-19 disease based on in vitro data [3] limited clinical data [4] and drug availability at our institution at the time of this patient's diagnosis. A recent randomized, controlled assessment of lopinavir/ritonavir in adults hospitalized with severe COVID-19

reported no significant benefit [5] . However, it should be emphasized that the patients in this study had relatively few comorbidities and may have received treatment relatively late in the disease process. It is unclear whether these findings can be extrapolated to the transplant population. An important challenge and consideration for use of lopinavir/ritonavir in transplant recipients is significant drug-drug interactions with tacrolimus. There have been limited data supporting use of the antiprotozoal agent nitazoxanide as an antiviral drug and immunomodulator, with several case series reporting positive outcomes in transplant patients with viral illness [6] . Likewise small studies suggest a benefit for using intravenous immunoglobulin replacement in transplant recipients with low level immunoglobulin (Ig) and severe infections [7; our patient's IgG levels were at the lower limit of normal]. Prospective evaluation of potential therapies will be important for tailoring treatment for the COVID-19+ transplant population as the pandemic continues to grow.

First cases of COVID-19 in heart transplantation from China

Post-transplant viral respiratory infections in the transplant patient: epidemiology, diagnosis and management

Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

A trial of lopinavir-ritonavir in adults hospitalized with severe CoVID-19

Severe chronic norovirus diarrheal disease in transplant recipients: clinical features of an under-recognized syndrome

Restoration of humoral immunity after intravenous immunoglobulin replacement therapy in heart transplant recipients with post-transplant antibody deficiency and severe infections

All authors have no conflicts of interest or financial conflicts to disclose. No funding source was provided for this study.

The authors gratefully acknowledge the contributions of Henry J. Neumann, MD, Randal I. Goldberg, MD, Jennifer Pavone, NP, and Bonnie E Lonze, MD, PhD.