Factors associated with greater severity of COVID-19 disease among solid transplant recipients

1. For solid organ transplant recipients with symptomatic COVID-19, factors associated with increased requirement of supplemental oxygen include older age, greater number of comorbid conditions, higher tacrolimus levels, lower lymphocyte count, being a lung transplant recipient, and being on prednisone.

2. Protective factors for requirement of supplemental oxygen include being a liver transplant recipient and being on azathioprine, whereas no association was found with COVID-19 vaccine status.

Evidence Rating Level: 2 (Good)

Study Rundown: Patients who have received organ transplants are reported to have a two to five times increased mortality rate from COVID-19. This greater mortality could be from comorbid conditions, taking immunosuppressive medications for life, or both. Despite this, initial trials that assessed the efficacy of COVID-19 treatments and vaccines excluded transplant recipients. Therefore, this current study aimed to identify factors associated with disease severity amongst COVID-19 patients who had received organ transplants. This was a multi-centre prospective cohort study including organ transplant recipients with symptomatic COVID-19 in 2020 and 2021, from 9 centres across Canada. The primary outcome was the requirement for supplemental oxygen, as a proxy for severity of disease, which was a decision amenable to provider subjectivity. Overall, the results showed that older age, number of comorbidities, and immunosuppression (higher tacrolimus levels, lower lymphocyte count, being on prednisone) were associated with needing supplemental oxygen. Individuals with lung transplants had the highest mortality rate compared to kidney, heart, liver, and kidney-pancreas transplants. As well, vaccination against SARS-CoV-2 was not associated with differences in requiring oxygen supplementation, while being a liver transplant recipient or being on azathioprine was a protective factor.

Click here to read the study in CMAJ

Relevant Reading: Coronavirus Disease 2019 in Solid Organ Transplant: A Multicenter Cohort Study

In depth [prospective cohort]: The study population consisted of 509 solid organ transplant recipients, both inpatient and outpatient, with symptomatic PCR-confirmed COVID-19. Data was collected for 90 days post-diagnosis. 16.1%, 10.4%, and 0.6% received 1, 2, and 3 vaccine doses respectively. As well, 59.3% of patients had a reduction of their immunosuppression: 0.0132% of those patients experienced acute rejection, and 0.0193% of those not having an immunosuppression reduction also experiencing acute rejection. In total, 54.2% of patients were admitted to hospital, and 37.3% required supplemental oxygen. The results showed a number of factors associated with requirement for supplemental oxygen, including older age (odds ratio 1.04, 95% CI 1.02-1.07), number of comorbidities (OR 1.63, 95% CI 1.30-2.04), higher level of tacrolimus (OR 1.20, 95% CI 1.09-1.31), and lower lymphocyte count (OR 1.02, 95% CI 1.0003-1.032). Due to missing laboratory parameters for some patients, a separate multivariable analysis was run excluding those parameters, which also found an association with lung transplant (OR 2.83, 95% CI 1.42-5.65) and prednisone use (OR 2.36, 95% CI 1.13-4.93). Being a liver transplant recipient (OR 0.41, 95% CI 0.15-1.19) and being on azathioprine (OR 0.27, 95% CI 0.09-0.83) were found to be protective factors for requiring supplemental oxygen. For vaccinated individuals, the proportion of those requiring oxygen were 37.2%, 42.3%, 37.7%, and 0% respectively for 0, 1, 2, and 3 doses. This did not result in a statistically significant difference between those requiring and not requiring oxygen (p = 0.9, 0.6, 0.95, and 0.2 respectively). The requirement of oxygen was also associated with longer hospital stay, with a median of 14 days, (interquartile range 7-27 days), compared to a median of 6 days in those not requiring oxygen (IQR 3-11.75 days, p < 0.001). Additionally, 18.5% of patients were admitted to ICU, 14.9% required mechanical ventilation, 11.2% passed away within 28 days of diagnosis, and 0.0413% passed away between 29 and 90 days of diagnosis. For individuals who were vaccinated, the 90-day all-cause mortality was 11.5%, 7.6%, and 0% for those with 1, 2, and 3 doses respectively. With regards to treatment, 71.6% were treated with dexamethasone, 35.8% with remdesivir, and 17.9% with tocilizumab, with remdesivir being associated with the highest 90-day survival (p = 0.04). Overall, this study demonstrated that age, comorbidities, and level of immunosuppression were associated with increased severity of COVID-19 disease amongst solid organ transplant recipients, especially lung transplant recipients.

Image: PD

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