Impact of COVID-19 in Solid Organ Transplant Recipients

Lara Danziger-Isakov; Emily A. Blumberg; Oriol Manuel; Martina Sester


American Journal of Transplantation. 2021;21(3):925-937. 

In This Article

Epidemiology and Outcomes

As the COVID-19 pandemic developed, the impact on transplant recipients began to emerge with reports initially from China, then Italy and Spain.[56–70] The prevalence of infection in SOT during the first wave of the pandemic varied geographically. In New York City, 22 (5.5%) of approximately 400 heart transplant recipients followed at a single center acquired COVID-19.[71] Similarly, 5% (66/1216) kidney transplant recipients in a French surveillance program were identified with COVID-19.[72] A study from 12 kidney transplant centers following 9845 patients reported 144 (1.5%) kidney transplant recipients hospitalized with COVID-19 over a 9-week period.[73] The largest and most comprehensive evaluation to date interrogated the UK transplant registry over a 4 months period from February to May 2020.[74] Positive testing for SARS-CoV-2 was identified in 3.8% (197/5184) of waitlisted patients and 1.3% (597/46789) of transplant recipients.

The average age of SOT recipients with COVID-19 ranged from 50 to 71 years and presented an average of 3–6 years posttransplant.[17,71,75–80] According to several reports, Blacks and Hispanics were disproportionately affected with US centers reporting 39–100% of SOT admissions with COVID-19 involving Black patients and one center noting that 15% of COVID-19 infected patients were Hispanic.[81–83] These differences were seen globally with 40% Hispanic and 25% Black in cases from the TANGO collaborative of centers in Spain, Italy, and the United States.[73] More extensive investigation is underway to address the underpinning causes of these differences which may be related not only to local penetrance of SARS-CoV-2 and prevention measures but also to significant concerns of systemic bias related to socioeconomic status and race.

The presentation of SOT recipients with COVID-19 appears similar to the general population. Fever (61–83%), cough (45–75%), and diarrhea (22–57%) were the most common symptoms reported.[14–16,71,75,79,80,83–88] Abnormalities in chest imaging occurred frequently; cohorts of SOT recipients in New York City reported abnormal chest radiographs in 96%–100%.[83,84] As testing availability increased and understanding of the spectrum of symptoms improved, the proportion of SOT recipients with abnormal initial chest radiographs decreased to 50–75%.[75,89] In the limited number of patients with initial chest CT, all were abnormal with half (4/8) showing infiltrates in more than 50% of the lung.[89]

Hospitalization, morbidity, and mortality from COVID-19 ranged broadly across populations and countries. Reported hospitalization rates ranged from 32 to 78% in most studies that included outpatients.[14–17] However, reporting bias certainly occurred, especially in large cohorts with voluntary reporting of cases and limited testing availability early in the pandemic for non-hospitalized patients. In recent international cohorts, 78–89% of identified patients were hospitalized which is higher than in the general public, although this also may reflect reporting or testing bias of differential health care utilization for transplant patients.[17,90] Once hospitalized, rates of transition to the intensive care unit ranged from 8.6% in the Netherlands to 18%–34% in other cohorts internationally.[15,17,33,79,84,91,92] Intubation and non-invasive ventilation ranged broadly from 8 to 60% in smaller cohorts;[78,79,83,93] however, the largest cohorts reported 30%–39% non-invasive ventilation or intubation.[17,84,92] Pre-existing comorbidities associated with disease, morbidity, and mortality in the general population have been frequently reported in SOT recipients with COVID-19, potentially impacting the high rates of hospitalization and severe disease. At least one comorbidity was recorded in 18 of 26 (69%) heart transplant recipients from Italy and in 443 of 482 (92%) SOT recipients in a large multi-national cohort.[17,94] Hypertension (9%–94%), diabetes mellitus (41%–69%), and chronic kidney disease (37–89%) were most common.[17,72,83,84,86,92,95]

Across all organ types, acute kidney injury (AKI) was reported in 20%–70% of hospitalized patients.[73,80,85,86,89,96] In comparison to non-transplant patients admitted for COVID-19, statistically significant increases in AKI during hospitalization were reported in SOT recipients (20% vs. 5%) with a trend to statistical significance in another SOT cohort being compared to critically ill non-transplant patients (37% vs. 27%).[86,96] Unusual complications observed in kidney and heart transplant recipients included encephalopathy, renal infarction, and the appearance of donor-specific antibodies.[97–101] Incidence of superinfection occurred at a higher rate in SOT recipients compared to controls (50% vs. 15.5%).[102]

Mortality ranged from 9 to 46% with most in the 18–30% range depending on the cohort and circumstances.[14,15,17,33,72,73,75,77–79,83–85,88,89,91,94,95,103,104] All-cause mortality during the study period of the UK registry reached 26% for SOT recipients and 10% for those on the waitlist, although local utilization decisions related to resource availability may have impacted these numbers.[74] The largest cohort to date including 482 SOT recipients from more than 50 transplant centers reported 20.5% mortality, and two compilations of cases found 18%–19% mortality overall.[17,87,88] In a UK database analyzing 10926 COVID-19 related deaths, SOT recipients had a hazard ratio of 3.53 [95% CI 2.77–4.49] for death as compared to the general population.[105] Mortality rates may be biased by hospitalization. In a small study among 35 SOT recipients that was restricted to hospitalized patients, morbidity and mortality was similarly high compared to hospitalized non-transplant patients (48% vs. 40%).[86] Intubation portended poor outcome with 40%–100% of ventilated patients dying in small cohorts.[71,92] Interestingly, according to a series of 26 pediatric SOT recipients, children did not suffer significant morbidity, with none requiring oxygen support and all recovering within 7 days, mirroring the less severe course described in immunocompetent pediatric patients.[106] Many studies have addressed risk factors for mortality with older age,[17,73,74,77,86,89,95,105] underlying cardiovascular or lung disease,[17,77,95] increased inflammatory markers[73,77,89] and lymphopenia[17,73] most commonly associated with increased mortality. Additional risk factors included obesity[17,95] and pre-existing frailty.[91] More recently, the presence of SARS-CoV-2 viral RNAemia was reported as increased risk for both disease severity and mortality in kidney transplant recipients, while viral load from swabs of the upper respiratory tract was not related to disease severity.[20] Differences in the intensity of immunosuppression did not appear to affect mortality[17,77] aside from a report in heart transplant recipients where discontinuation of immunosuppression was associated with mortality.[94]

Persistence of symptoms including fatigue and dyspnea for more than 60 days has been reported in a non-transplant population from northern Italy;[107] however, data on long-term patient and graft outcomes among transplant recipients are currently lacking.