key: cord-345342-04tvuj9f
authors: Kumar, Rebecca N.; Tanna, Sajal D.; Shetty, Aneesha A.; Stosor, Valentina
title: COVID‐19 in an HIV‐positive Kidney Transplant Recipient
date: 2020-05-26
journal: Transpl Infect Dis
DOI: 10.1111/tid.13338
sha: 
doc_id: 345342
cord_uid: 04tvuj9f

We report a case of a 50‐year‐old male with a history of HIV and kidney transplant who presented with SARS‐CoV‐2. We also present a review of COVID‐19 cases in kidney transplant recipients.

Since the first cases of an unusual pneumonia were reported in China in December 2019, coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in an ongoing pandemic 1 . By the beginning of May 2020, the Centers for Disease Control and Prevention reported 1,122,486 cases within the United States alone 2 . Because this is a novel virus, outcomes associated with comorbidities, especially immunosuppressed or compromised states, are still being evaluated. This case describes the clinical course of a symptomatic kidney transplant recipient with HIV who tested positive for SARS-CoV-2.

A 50-year-old HIV+ (CD4 395 cells/µL, CD4% 28%, HIV RNA < 20 copies/mL) African-American male with deceased donor kidney transplantation 14 months earlier for end-stage renal disease secondary to HIV-associated nephropathy (HIVAN)/focal segmental glomerulosclerosis (FSGS) presented to the Emergency Department (ED) complaining of fevers for two days, with temperatures to 101°F, chills, nasal congestion, and mild cough.

The past medical history also includes hypertension, asthma, steatohepatitis, and resolved hepatitis B infection. The patient denied shortness of breath, chest or abdominal pain, diarrhea, or vomiting. He did not have changes in his urine output, pain over the allograft, or dysuria. The patient reported known exposure to COVID-19 at a family gathering seventeen days prior to symptom onset. His husband, who accompanied him to the event, tested positive for SARS-CoV-2 one week prior to onset of the patient's illness.

The transplant history was notable for receipt of a PHS-increased risk, HIV antibodypositive, HIV NAT-negative deceased donor kidney allocated through the HIV Organ Policy Equity (HOPE) Act 3 . He received induction immunosuppression with basiliximab and steroid-sparing maintenance immunosuppression with tacrolimus (target trough 8-10 mcg/L) and mycophenolate mofetil (1250 mg twice daily orally initially followed by 1000 mg twice daily orally after six months post-transplant). Post-transplant course was notable for postoperative perinephric seroma that required drainage. His renal function improved to a

This article is protected by copyright. All rights reserved baseline serum creatinine of 1.9-2.2 mg/dL range post-transplant. The six-month and oneyear surveillance allograft biopsies were negative for acute rejection or recurrent HIVAN/FSGS, and he remained without development of donor-specific antibodies (DSA).

Two days prior to ED evaluation, when patient first reported fever and COVID-19 exposure to the transplant department, the mycophenolate dose was reduced from 1000 mg twice daily to 250 mg twice daily orally due to suspicion for COVID-19 as cause of the patient's illness.

The patient was diagnosed with HIV infection in 1997, initiated antiretroviral therapy (ART) at that time, and has had long-term viral suppression. At and since time of transplant, the ART regimen consisted of dolutegravir, emtricitabine, and tenofovir alafenamide. He was also receiving maraviroc v. placebo as part of a randomized clinical trial (NCT02741323). There have been no opportunistic infections.

In the ED, the patient was hypertensive with blood pressure 172/95 mmHg and tachycardic with heart rate 108/minute, but he appeared well and had temperature 98.9°F and oxygen saturation 100% on room air. A nasopharyngeal swab was obtained, a respiratory viral panel (FilmArray® Respiratory Panel Assay) was negative, and SARS-CoV-2 real time PCR (Northwestern Memorial CDC COVID-19 SARS-CoV-2 detection assay) was positive. No further lab work or imaging was performed. The patient enrolled in the COVID home monitoring program through our medical center and was discharged to home.

The patient had ongoing symptoms reported through the monitoring program including anosmia and ageusia one day after discharge, fatigue, and fevers. Symptoms, including anosmia and ageusia, resolved ten days after illness onset. On a follow-up telehealth visit four weeks later, the patient reported his health was back to baseline. A subsequent laboratory evaluation was notable for white blood cell count 3.7 X 10 3 /µL and serum creatinine 1.93 mg/dL. The HIV RNA remained < 20 copies/mL, and the CD4 count was 435 cells/µL, CD4% 31%, with a CD4/CD8 ratio 0.65 and absolute lymphocyte count of 1413 cells/µL.

This article is protected by copyright. All rights reserved There have been reported cases of COVID-19 in HIV-infected patients and cases of COVID-19 in transplant recipients [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] . However, this case is the first detailed report of an HIVpositive kidney transplant recipient who developed and recovered from COVID-19.

Unlike the case series from Spain where HIV patients with COVID-19 changed regimens to include a boosted protease inhibitor, no modifications were made to our patient's ART regimen 6 . The current regimen was continued due to lack of demonstrated efficacy of lopinavir-ritonavir for COVID-19 in a randomized control trial, as well as avoiding the interactions associated with ritonavir and tacrolimus 16, 17 Overall, our patient did well without experimental antiviral or anti-inflammatory therapies and experienced no serious complications, including need for hospitalization or supplemental oxygenation. In fact, the patient appeared well enough that the ED did not order labs beyond respiratory virus and SARS-CoV-2 testing. Immunosuppression was decreased within 48 hours of symptom onset, but it is unclear if this influenced clinical outcome. As the pandemic progresses and more data becomes available, the clinical spectrum of COVID-19 infections in the transplant population will be better defined and will better inform the management of immunosuppression in this setting. Concern for a potential immune reconstitution inflammatory syndrome (IRIS)-like reaction has made our center's transplant clinicians hesitant to discontinue immunosuppression altogether in the setting of acute infection; COVID-19 increases this concern because of the potential for the heightened

This article is protected by copyright. All rights reserved inflammatory state that occurs with critical illness within the non-immunosuppressed patient 19 .

Maraviroc is currently FDA-approved for treatment of HIV in patients with R-5 virus, because it blocks the C-C chemokine receptor type 5 (CCR-5) receptor and prevents viral entry into CD4 cells. Because of its importance in immune cell response, CCR5 blockade has been suggested as a potential way to reduce allograft loss recipients 20,21 . CCR-5 blockade with leronlimab is currently under investigation in a Phase2b/3 for severely ill COVID-19 patients 22 . In the case series from New York City, six severely ill patients received leronlimab on compassionate use basis; although there was improvement in interleukin-6 levels noted in five patients, only one patient did not require intubation 15 

This article is protected by copyright. All rights reserved therapy. However, we would discourage the complete discontinuation of all immunosuppression to avoid an IRIS type reaction. Consideration for remdesivir or therapies under investigation can be made on an individual basis for those patients who are critically ill or fail to clinically improve. As data emerges in the U.S., it is essential to systematically describe outcomes and identify unique features of patients with both HIV and organ transplants. These populations will also be important to include in clinical trials of COVID therapies.

Cases 

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Accepted Article This article is protected by copyright. All rights reserved 3. Health R, Services Administration DoH, Human S. Organ procurement and transplantation: implementation of the HIV

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American Society of Transplantation Infectious Diseases Community of P. Solid organ transplantation in the HIV-infected patient: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice

This article is protected by copyright. All rights reserved 46 12