Outcomes among Transplant Recipients Hospitalized Due to COVID-19

Due to chronic immunosuppression as well as the presence of numerous comorbidities, the risk of developing severe COVID-19 may be high in kidney transplant recipients. Researchers in the United States, Italy, and Spain conducted a retrospective cohort study to examine the clinical outcomes among kidney transplant recipients to identify predictors of poor clinical outcomes. Results of the study were reported in the American Journal of Transplantation [2020;20(11):3140-3148].

The study was led by Paolo Cravedi, MD, PhD, division of nephrology, department of medicine, Icahn School of Medicine at Mount Sinai, New York, New York. The cohort included 144 kidney transplant recipients who were hospitalized due to COVID-19 at 12 transplant centers in North America and Europe. The 12 centers were participating in the TANGO International Transplant Consortium. All kidney transplant recipients ≥18 years of age with a functioning allograft who were admitted to a hospital between March 2 and May 15, 2020, were included.

Of the 144 patients, 66% (n=95) were male, median age was 62 years; 40% were Hispanic, 31% were White, and 25% were Black. The most common comorbidity was hypertension (95%), followed by diabetes (52%), obesity (49%), heart disease (28%), and lung disease (19%). Twenty-eight percent of the cohort had a prior or current history of smoking, 15% had a history of cancer, 17% (n=24) were receiving angiotensin II receptor antagonists at the time of diagnosis, and 14% (n=20) were taking angiotensin-converting enzyme (ACE) inhibitors.

The time to COVID-19 diagnosis following transplant ranged from <1 year to 31 years (median 5 years); 16% of the patients in the study cohort were diagnosed during the first year post-transplant. Causes of original kidney disease were diabetes (30%), glomerular disease (17%), hypertension (14%), and polycystic disease (9%). Seventy-eight percent of the cohort had undergone deceased-donor kidney transplant and 62% received induction therapy with T cell depletion at the time of transplant. Maintenance immunosuppression regimens included tacrolimus (91%), antimetabolite (mycophenolate) (77%), mTOR inhibitor (7.5%), and steroids (86%).

On admission, the most common symptoms were fever and dyspnea (67%), followed by myalgia (53%), and diarrhea (38%). Median follow-up was 52 days following the diagnosis of the first COVID-19 patient. During follow-up, 51% of the cohort (n=74) developed acute kidney injury, 29% (n=42) required mechanical ventilation, and 46 patients died, totaling 32% mortality. Of the patients who entered the intensive care unit, 51% (n=22) died. Median time from onset of illness (prior to admission) to discharge was 22 days; the median time to death was 15 days. Three patients were treated with extracorporeal membrane oxygenation; none of the three survived.

There was no difference in mortality across the 12 transplant centers. Patients who died were older than survivors (66 vs 60 years of age; P<.001); 71% of the patients >60 years of age were among those who died. There were no significant differences in outcomes between recipients of organs from living or deceased donors or between patients with <1 year since transplant compared with those with longer time since transplant. Among the patients who died, the time from onset of symptoms to admission was slightly shorter. There were no significant differences between survivors and nonsurvivors in race, comorbidities, induction therapy with depleting agents, maintenance immunosuppression, or therapy with renin angiotensin system inhibitors.

At admission, the respiratory rate was significantly higher in nonsurvivors compared with survivors, and diarrhea was less frequent in nonsurvivors (23.9% vs 44.9%). There were no significant differences between the two groups in other clinical characteristics at presentation.

Major laboratory markers were tracked from illness onset. Lymphopenia was present in 42% of patients. Baseline lymphocyte count was significantly higher in survivors compared with nonsurvivors (1.2 vs 0.7; P=.004), as was estimated glomerular filtration rate (eGFR; 53 vs 38 mL/min/1.73 m²). There were no significant differences between the groups in white blood cell, hemoglobin, platelet, alanine aminotransferase, and creatine phosphokinase levels. Nonsurvivors had higher aspartate transaminase (30 vs 24 U/L) and lactic acid dehydrogenase (LDH; 406 vs 296 U/L; P<.001) levels.

In 68% of the cases, mycophenolate (MMF/MPA) or everolimus was reduced or discontinued; calcineurin inhibitor was discontinued in 23% of the cohort (n=32). There was no significant association between immunosuppression withdrawal and mortality. Most patients received hydroxychloroquine (71%) and antibiotics (74%) and a smaller subset of patients received tocilizumab (13%) or antivirals (14%). With the exception of a slightly greater use of antibiotics in nonsurvivors, there was no significant difference in mortality among different treatments of COVID-19.

In univariable analysis, the odds of in-hospital mortality was higher in older patients and patients with higher respiratory rates, LDH, interleukin 6 (IL-6), and procalcitonin levels. In patients with diarrhea or higher eGFR levels, mortality risk was lower. Those variables were used for multivariable logistic regression models. In addition to age, there were associations between higher respiratory rate, lower eGFR, and higher IL-6 at admission and increased odds of death.

The researchers cited some limitations to the study, including differences in approaches and access to medications for the treatment of COVID-19, focusing on a homogenous cohort of hospitalized kidney transplant recipients, and the small sample size and retrospective design of the study.

“In conclusion, kidney transplant recipients should be closely monitored as they appear to have a high mortality and acute kidney injury rate. Investigation of the best strategy of immunosuppression adjustment on COVID-19 will be needed,” the researchers said.

Takeaway Points

1. Researchers in the TANGO International Transplant Consortium conducted a retrospective cohort study to examine the clinical outcomes of a cohort of 144 kidney transplant recipients who were hospitalized due to COVID-19 at 12 transplant centers in North America and Europe.
2. During a median follow-up of 52 days, 52% of the patients developed acute kidney injury, 29% required intubation, and 32% died.
3. The patients who died were older, and had lower lymphocyte counts and glomerular filtration rate levels compared with survivors.