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Letters to the Editor

COVID-19 in Solid Organ Transplant Recipients: Observations From Connecticut

Kutzler, Heather L. PharmD1; Poulos, Constantine M. MD2; Cheema, Faiqa MD1,3; O’Sullivan, David M. PhD4; Ali, Ayyaz MD1,3,5; Ebcioglu, Zeynep MD1,3; Einstein, Michael MD1,3; Feingold, Andrew D. MD1,3,5; Gluck, Jason MD1,3,5; Hammond, Jonathan A. MD1,2,5; Jaiswal, Abhishek MD1,3,5; Lawlor, Michael T. MD1,3; Morgan, Glyn MD1,2; Radojevic, Joseph A. MD1,3,5; Rochon, Caroline MD1,2; Sheiner, Patricia MD1,2; Singh, Joseph U. MD1,3; Sotil, Eva U. MD1,3; Swales, Colin MD1,3; Ye, Xiaoyi MD1,3; Serrano, Oscar K. MD1,2

Author Information
doi: 10.1097/TP.0000000000003495
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To the Editor:

Our knowledge about the effects of COVID-19 on the solid organ transplant (SOT) population is characterized by remarkable heterogeneity in the treatment and outcomes of SOT recipients infected with SARS-CoV-2. As one of the earliest COVID-19 hotspots in the United States, we present our outcomes on 16 SOT (13 kidney, 2 liver, and 1 simultaneous heart-kidney) recipients with COVID-19 between March 30, 2020, and May 7, 2020, at our center (Institutional Review Board-approved database, HHC-2020-0124). Table 1 provides case summaries of the study population. Ten patients were alive at the end of the study period and 6 (38%) expired. The average age was 63 ± 10 years old with an average 12 ± 8 years of graft life. Twelve patients (75%) were hospitalized; 2 (13%) required intensive care, and expired from respiratory failure. Immunosuppression changes varied based on severity of illness, ranging from no changes to dose reductions and medication discontinuation. COVID-19 specific treatment was variable wherein 6 patients received azithromycin, 4 hydroxychloroquine, 3 high-dose corticosteroids, 2 convalescent plasma, and 1 tocilizumab. No patients in this cohort received remdesivir. Interestingly, 3 of our deceased patients received no COVID-specific treatment whatsoever. More interestingly, SOT recipients with COVID-19–related mortality were more likely to have a history of a stroke (67% versus 10%; P = 0.04), be admitted from a skilled nursing facility (50% versus 0%; P = 0.04), and have a “do not resuscitate” (DNR) order (67% versus 0%; P = 0.008).

TABLE 1. - Case summaries of inpatient and outpatient COVID-19 cases are described, including demographics, indication for testing, immunosuppression information, treatment, and outcomes
Outpatient cases
Case Gender/age (y) Race or ethnicity Organ/time interval (y) BMI Major comorbidities Indication for testing Immunosuppression at testing Immunosuppression changes Treatment
1 58 White Kidney/7.8 21 GN, breast cancer, HLD Cough, “cold like symptoms” Sirolimus (trough 6.7 ng/mL), prednisone 5 mg None Supportive care
2 81 Other Kidney/14.4 45 HTN, SCC Fever, chills, night sweats, rhinorrhea, cough, body aches Tacrolimus (trough 5.7 ng/mL), MMF 1000 mg TDD, prednisone 2.5 mg None Supportive care
3 47 White Kidney/24.3 22 HTN, HLD, multiple myloma Fever, cough, sore throat, body aches Prednisone 5 mg None Supportive care
4 44 Hispanic Kidney/0.4 35 HTN, DM, asthma, sleep apnea Fever, SOB, body aches Tacrolimus (trough 7.6 ng/mL), MMF 1000 mg TDD Reduced MMF to 500 mg TDD Azithromycin
Inpatient cases
Case Age (y) Race or ethnicity Organ/time interval (y) From SNF/DNR on file BMI Major comorbidities Indication for testing IS at testing IS changes Treatment beyond supportive care Complications Outcome
5 64 African American Kidney/5.6 No/No 28 HTN, HLD, DM, CHF Cough, SOB Tacrolimus (trough 6 ng/mL), MMF 1000 mg TDD, prednisone 5 mg MMF held None Empiric ceftriaxone/doxycycline for CAP (cx negative) Discharged after 6 d
6 56 White Kidney/14.2 No/No 37 IgA nephropathy, colon cancer, HTN Cough, SOB, diarrhea, loss of taste/smell Tacrolimus (trough 13 ng/mL), prednisone 5 mg Tacrolimus dose reduced HCQ Empiric ceftriaxone/doxycycline for CAP (cx negative) Discharged after 2 d
7 71 White Liver/19.4 No/No 32 HTN, DM, CHF, seizures, Parkinson’s Fever, SOB, cough, confusion Tacrolimus (trough 3 ng/mL) None HCQ, azithromycin Encephalopathy, CKD, started HD during admission Discharged after 15 d
8 76 Hispanic Liver/16 No/No 31 DM, CHF, PTLD Recently discharged from SNF, syncope Tacrolimus (trough 3 ng/mL) None None Encephalopathy, empiric ceftriaxone for sepsis (cx negative) Discharged after 11 d
9 56 White Kidney/ 23.4 No/No 26 MI, seizure, stroke Fever, weakness, poor oral intake None (failed allograft) - None Severe depression Discharged after 13 d
10 55 Hispanic Kidney/ 5.3 No/No 22 HTN, psoriasis Fever, cough, SOB Tacrolimus (trough 5 ng/mL), MMF 2000 mg TDD, prednisone 5 mg MMF held Azithromycin, convalescent plasma Empiric vancomycin/cefepime (cx negative) Discharged after 8 d
11 68 Hispanic Kidney/ 12.8 Yes/Yes 29 DM, atrial fibrillation, stroke, seizure, vascular dementia Fever, cough, fall Tacrolimus (trough 3 ng/mL), MMF 1000 mg TDD, prednisone 5 mg None None Presented after fall at SNF, admitted CMO due to DNR/DNI/do not hospitalize order Deceased after 1 d
12 61 Hispanic Kidney/ 4.5 No/No 35 DM, HTN, sleep apnea Fever, cough, diarrhea, weakness, confusion Tacrolimus (trough 9.6 ng/mL), MMF 2000 mg TDD, prednisone 5 mg MMF dose reduced to 500 mg TDD, tacrolimus trough target reduced to 2-5 ng/mL HCQ, high dose hydrocortisone Superimposed pseudomonas pneumonia treated with cefepime, encephalopathy, severe ARDS Deceased after 31 d
13 75 White Kidney/ 19.8 Yes/Yes 29 HTN, DM, CHF, SAH, RA, Crohn’s disease, dementia Unknown—tested at SNF before admission Sirolimus (trough >20 ng/mL), prednisone 7.5 mg Sirolimus held None Became unresponsive d 2, stroke suspected, DNR/DNI transitioned to CMO Deceased after 2 d
14 66 White Kidney/1.6 Yes/Yes 19 HTN, HLD, Parkinson’s Crohn’s, PE, CVA, osteoporosis SOB, scratchy throat, COVID+ roommate at SNF Belatacept 5 mg/kg monthly, MPA 1440 mg TDD MPA held None SBO with no surgical option, DNR/DNI transitioned to CMO Deceased after 4 d
15 56 African American Heart and Kidney/ 0.2 No/No 17 HTN, HLD, DM, Non-hodgkin’s lymphoma, asplenia, stroke Routine screen preop for tracheostomy Tacrolimus (trough 7 ng/mL), prednisone 5 mg Reduced tacrolimus goal trough HCQ, azithromycin, high dose hydrocortisone Intubated x1 mo before COVID-19+, tested for screening before tracheostomy, numerous comorbid infections (BK, MRSA, VRE, Klebsiella/ Morganella, rotavirus), CVVH/HD, PEA arrest Deceased after 67 d
16 70 White Kidney/ 22.4 No/Yes 29 HTN, atrial fibrillation Fever, cough, SOB, hypoxia None (failed allograft) - Azithromycin, tocilizumab, convalescent plasma, high dose methylprednisolone Hyperactive delirium, DNR/DNI so not transferred to ICU Deceased after 1 d
ARDS, acute respiratory distress syndrome; BMI, body mass index; CAP, community acquired pneumonia; CHF, congestive heart failure; CKD, chronic kidney disease; CMO, comfort measures only; CVA, cerebrovascular accident; CVVH, continuous venovenous hemofiltration; Cx, culture; DM, diabetes mellitus; DNI, do not intubate; DNR, do not resuscitate; GN, glomerulonephritis; HCQ, hydroxychloroquine; HD, hemodialysis; HLD, hyperlipidemia; HTN, hypertension; IS, immunosuppression; MI, myocardial infarction; MMF, Mycophenolate mofetil; MPA, mycophenolic acid; PE, pulmonary embolism; PTLD, posttransplant lymphoproliferative disease; RA, rheumatoid arthritis; SBO, small bowel obstruction; SCC, squamous cell carcinoma; SOB, shortness of breath; SAH, subarachnoid hemorrhage; SNF, skilled nursing facility; TDD, total daily dose.

Certainly, our study presents an elderly SOT population with long graft life, many of whom resided in a nursing facility before presentation. One of the most thought-provoking findings in our cohort is the role that DNR orders have played in medical decision-making for patients during the COVID-19 pandemic. A number of groups around the world have grappled with similar decision-making aspects of their DNR orders as they relate to COVID-19 and the resourceful allocation of limited resources—ventilators, healthcare workers, and personal protective equipment.1-3 While some groups advocate shifting from patient-centered care toward community-centered care,1 this has led to making difficult ethical decisions regarding resuscitation and access to intensive care unit services for DNR COVID-19 patients. This study gives credence to the notion that in healthcare, where limited resources dictate many of our decisions, certain populations – such as the elderly SOT recipient—may be at a disadvantage because of their resource-intensive care.

Our study confirms the vulnerability of the SOT recipient infected with SARS-CoV-2 and insinuates an interplay between age and frailty as compounding risks for survival from COVID-19 and the role that DNR orders have played in medical decision-making for patients during the COVID-19 pandemic. As the pandemic continues to unfold, the heterogeneity in outcomes in SARS-CoV-2-infected SOT recipients support the need for further studies given their potential disadvantage because of their resource-intensive care in a resource-depleted era.

REFERENCES

1. Shamieh O, Richardson K, Abdel-Razeq H, et al. COVID-19-Impact on DNR orders in the largest cancer center in Jordan. J Pain Symptom Manage. 2020;60:e87–e89.
2. Dyer C. Covid-19: Campaigner calls for national guidance to stop DNR orders being made without discussion with patients and families. BMJ. 2020;369:m1856
3. Adams C. Goals of care in a pandemic: our experience and recommendations. J Pain Symptom Manage. 2020;60:e15–e17.
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