Clinical Characteristics and Outcomes of COVID-19 in Solid Organ Transplant Recipients

A Cohort Study

Zohra S. Chaudhry; Jonathan D. Williams; Amit Vahia; Raef Fadel; Tommy Parraga Acosta; Rohini Prashar; Pritika Shrivastava; Nadeen Khoury; Julio Pinto Corrales; Celeste Williams; Shunji Nagai; Marwan Abouljoud; Milagros Samaniego-Picota; Odaliz Abreu-Lanfranco; Ramon del Busto; Mayur S. Ramesh; Anita Patel; George J. Alangaden

Disclosures

American Journal of Transplantation. 2020;20(11):3051-3060. 

In This Article

Results

We enrolled 47 SOT recipients (cases) and 100 consecutive hospitalized nontransplant COVID-19-positive patient (controls). All patients were followed for a median duration of 35 (IQR 20–36) days or until death.

The clinical characteristics of 47 SOT recipients (38 kidneys and 9 nonkidney organs) were compared to 100 controls. Twelve of 47 SOT recipients managed as outpatients were subsequently excluded from the outcome analyses to avoid potential selection bias.

Clinical Characteristics

The demographics, presence of coexisting conditions, clinical symptoms, laboratory findings, and severity of illness on presentation are shown in Table 1 and Table 2. We initially compared SOT recipients with COVID-19 that were hospitalized vs those who were managed as outpatients (Table 1). Overall 89% of all SOT recipients had undergone transplantation >1 year. Characteristics were comparable across all key demographics and coexisting conditions. Cough, fever, and shortness of breath were the most common presenting symptoms. Overall 55% of SOT recipients had diarrhea as a presenting symptom. Hospitalized SOT recipients were more likely to complain of shortness of breath compared to outpatients (68% vs 33%, P = .04). Hospitalized SOT recipients were more likely to have a lower median absolute lymphocyte counts (ALC) (0.5 vs 1.6 x 10−9 per liter, P = .02) and abnormal chest imaging (83% vs 25%, P = .0005). Overall, on presentation 28%, 66%, and 6% of SOT recipients were stratified as having mild, moderate, and severe disease, respectively, utilizing the HFH COVID-19 severity score. Hospitalized SOT recipients presented with a higher degree of illness severity, based on median qSOFA score (1 vs 0, P = .06), median NEWS score (6.5 vs 2, P = .0009), and HFH COVID-19 severity score.

Hospitalized SOT recipients and nontransplant patients with COVID-19 (Table 2) had similar demographics. SOT recipients had a higher proportion of chronic kidney disease (89% vs 57%, P = .0007), hypertension (94% vs 72%, P = .006), and diabetes mellitus (66% vs 33%, P = .0007) compared with nontransplant controls. SOT recipients were more likely to present with diarrhea (54% vs 17%, P ≤ 0.0001) and had lower median ALC (0.5 vs 0.8 x 10−9 per liter, P = .006) and lower median hemoglobin (11.9 vs 13.3 mg/dL, P = .04) compared to controls. SOT recipients presented with greater severity of illness as compared to controls (mean qSOFA 1.1 vs 0.7, P = .02). Using HFH COVID-19 severity score, the severity of illness among hospitalized transplant and nontransplant patients was comparable.

Additional subgroup analysis among kidney transplant recipients and recipients of other organs showed that demographics, clinical parameters, severity of illness at presentation, and outcomes were similar. (Table S1).

Management

Laboratory parameters including serum CRP, D-dimer, ferritin, LDH, procalcitonin, and abnormal chest radiography were comparable in hospitalized SOT recipients and nontransplant controls (Table 2).

Immunosuppression was reduced in 70% of all SOT recipients, more often in hospitalized patients than outpatients (Table 1). Withdrawal or dose reduction occurred in 84%, 15%, 3%, and 2% of patients receiving antimetabolite, CNIs, mammalian target of rapamycin (mTOR) inhibitors, and belatacept, respectively. Antiviral therapy with HCQ and adjunctive therapies with corticosteroids or tocilizumab was comparable (Table 2).

Outcomes

Overall mortality was 17% (8/47), in our transplant cohort, 23% (8/35) among those hospitalized and 58% (7/12) requiring mechanical ventilation. The primary composite outcome of ICU admission, mechanical ventilation, or death was comparable between hospitalized SOT recipients and nontransplant patients (Table 3). Overall, mortality between these 2 groups was comparable (23% vs 25% odds ratio [OR] 0.88 confidence interval [CI] [0.36–2.21] P = .8). Beyond the first week of hospitalization, fewer deaths occurred in the transplant cohort compared to the controls (Figure 1). Increasing HFH COVID-19 severity score was associated with greater risk of mortality, with no deaths among patients with mild disease (Figure S1).

Figure 1.

Survival curves in hospitalized transplant recipients and nontransplant controls [Color figure can be viewed at wileyonlinelibrary.com]

Secondary outcome analysis showed both groups had similar median duration of mechanical ventilation, degree of ARDS, LOS, and readmissions. However, AKI (47% vs 43%, OR 2.24 CI [1.02–4.95] P = .05) and AKI requiring renal replacement therapy (20% vs 4%, OR 6.0 CI [1.64–21.98] P = .007) were more frequent in SOT recipients.

Univariate analysis of all hospitalized patients showed age >60 years, higher qSOFA, NEWS, HFH COVID-19 severity score, and ferritin >500 ng/mL were associated with mortality (Table S2). In all hospitalized patients and SOT recipients, ICU stay was significantly associated with death. Multivariate modeling was performed adjusting for age, coexisting conditions, transplant status, and HFH COVID-19 severity score. It showed that age >60 years, and HFH COVID-19 severity score were significantly associated with both the primary composite outcome and mortality (Table 4). Transplant status itself was not associated with mortality in univariate (OR 0.9 CI [0.36–2.2] P = .8) or multivariate analysis (OR 1.11 CI [0.37–3.31] P = .85).

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