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

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.