Risk Factors Associated with ICU Admission and Death in Patients Hospitalized with COVID-19 Differ Between Solid Organ Transplant and Non-Solid Organ Transplant Patients

Purpose: Despite the large numbers of reports on patient risk factors for poor clinical outcomes with COVID-19, little is known about how these risks may differ for solid organ transplant (SOT) recipients versus non-SOT (NSOT) patients. Method(s): We reviewed demographic and comorbid conditions in a cohort of SOT (n=129) and NSOT patients (n=708) admitted to our center for COVID-19 between December 2019 and February 2021. Patient characteristics were compared between groups using the t-test or chi-square test. Univariable and multivariable (stepwise reduced) logistic regression models were constructed for our outcomes of interest. Result(s): Patient age and sex were similar between SOT and NSOT cohorts. However, SOT patients were more likely to be of Hispanic ethnicity (64% v. 39%, p<0.001). Both SOT and NSOT had similar incidence of neurologic conditions (23% and 21%, p=0.476), but SOT patients were more likely to have comorbid conditions including diabetes mellitus, cardiovascular condition, or lung disease (all p<0.001). Several clinical factors were associated with ICU admission in NSOT patients, including patient age, diabetes, cardiac disease, neurologic disease, obesity, and hepatobiliary disease (all p < 0.05). In contrast, only cardiac disease was associated with ICU admission for SOT patients (p=0.010). Multivariable analysis of factors associated with increased mortality revealed that neurologic condition (OR 3.0, 95% CI 0.8-11.4) and lung disease (OR 3.5, 95% CI 0.7-18.2) were significant for SOT patients in a model including age, sex, and other comorbid conditions. In contrast, for NSOT patients, history of a neurologic condition (OR 2.3, 95% CI 1.3-4.0) and age >65 (OR 4.2, 95% CI 2.1-8.7) were significantly associated with death in a multivariate analysis. Conclusion(s): It has been previously unclear whether risk factors associated with poor outcomes in NSOT patients with COVID-19 will be similarly important in SOT recipients. Our analysis demonstrated different risk associations in contemporaneous patient cohorts at a single academic center. This observation suggests that SOT-specific approaches for risk stratification would be beneficial for patient evaluation and triage.

Impact of the COVID-19 pandemic on a tertiary care public hospital in Singapore: resources and economic costs.

BACKGROUND: The COVID-19 pandemic has prompted hospitals to respond with stringent measures. Accurate estimates of costs and resources used in outbreaks can guide evaluations of responses. We report on the financial expenditure associated with COVID-19, the bed-days used for COVID-19 patients and hospital services displaced due to COVID-19 in a Singapore tertiary hospital. METHODS: We conducted a retrospective cost analysis from January to December 2020 in the largest public hospital in Singapore. Costs were estimated from the hospital perspective. We examined financial expenditures made in direct response to COVID-19; hospital admissions data related to COVID-19 inpatients; and the number of outpatient and emergency department visits, non-emergency surgeries, inpatient days in 2020, compared with preceding years of 2018 and 2019. Bayesian time-series was used to estimate the magnitude of displaced services. RESULTS: USD $41.96 million was incurred in the hospital for COVID-19-related expenses. Facilities set-up and capital assets accounted for 51.6% of the expenditure; patient-care supplies comprised 35.1%. Of the 19,611 inpatients tested for COVID-19 in 2020, 727 (3.7%) had COVID-19. The total inpatient- and intensive care unit (ICU)-days for COVID-19 patients in 2020 were 8009 and 8 days, respectively. A decline in all hospital services was observed from February following a raised disease outbreak alert level; most services quickly resumed when the lockdown was lifted in June. CONCLUSION: COVID-19 led to an increase in healthcare expenses and a displacement in hospital services. Our findings are useful for informing economic evaluations of COVID-19 response and provide some information about the expected costs of future outbreaks.

Case study: Kidney transplant patient with COVID-19: impact of viral infection on background cell-free DNA in a donor-derived cell-free DNA rejection assay

Introduction: Donor-derived cell-free DNA (dd-cfDNA) assays are clinically validated to detect kidney transplant injury, reporting the donor fraction as a percentage of the total, or background, cfDNA. Various clinical factors can cause a significant increase in recipient cfDNA, contributing to higher background cfDNA and lower donor fraction, which may result in a false negative test result. Case Description: A 50+ year old woman with end-stage renal disease secondary to polycystic kidney disease presented with 4 days (d) of diffuse muscle pain at 11 months post-kidney transplant. In the emergency department she had a fever to 101°F, bilateral infiltrates on chest x-ray, and a positive COVID-19 (SARS-CoV-2) test. She remained febrile for 3d before developing acute respiratory distress requiring oxygen supplementation;her creatinine level was 3 mg/dL. Due to worsening of her respiratory status, she was intubated and started empirically on vancomycin, meropenem, and azithromycin;mycophenolate mofetil was discontinued. She rapidly progressed to septic shock requiring vasopressor therapy. Her renal function deteriorated, and she was started on continuous renal replacement therapy on hospital d7. She received leronlimab on hospital d7 and d14 and convalescent plasma on hospital d11. Tacrolimus was discontinued on hospital d10 and she continued prednisone at 5 mg/d. Dd-cfDNA testing to assess allograft injury and to rule out active rejection was performed. At hospital d20, her dd-cfDNA was 0.07% with an elevated background cfDNA of 28,569 arbitrary units (AU, ∼57X median value). At the second blood draw at hospital d25, her dd-cfDNA was 0.25% with a background cfDNA level reduced to 7,503 AU (∼15X median value). Discussion: In this case, infection with the SARS-CoV-2 virus was associated with a very elevated background cfDNA level, likely due to cellular apoptosis due to the immune process and/or tissue ischemia due to sepsis-associated hypoperfusion. Although this patient was not known to have active rejection of her allograft, the very high background levels complicate the interpretation of results, especially when donor fraction were reported.