COVID-19 in solid organ transplant recipients: Dynamics of disease progression and inflammatory markers in ICU and non-ICU admitted patients.

BACKGROUND: COVID-19 infection varies in severity from minimal symptoms to critical illness associated with a hyperinflammatory response. Data on disease progression in immunosuppressed solid organ transplant (SOT) recipients are limited. METHODS: We examined the electronic medical records of all SOT recipients with COVID-19 from 12 Massachusetts hospitals between February 1, and May 6, 2020. We analyzed the demographics, clinical parameters, course, and outcomes of illness in these patients. RESULTS: Of 52 COVID-19-positive SOT patients, 77% were hospitalized and 35% required ICU admission. Sixty-nine percent of hospitalized patients had immunosuppression reduced, 6% developed suspected rejection. Co-infections occurred in 45% in ICU vs 5% in non-ICU patients (P = .037). A biphasic pattern of evolution of laboratory tests was observed. In the first 5 days of illness, inflammatory markers were moderately increased. Subsequently, WBC, CRP, ferritin, and D Dimer increased with increasing stay in the ICU, and lymphocyte counts were similar. Five patients (16%) died. CONCLUSIONS: Our data indicate that SOT is associated with high rate of hospitalization, ICU admission, and death from COVID-19 compared to data in the general population of patients with COVID-19. Despite reduction in immunosuppression, suspected rejection was rare. The clinical course and trend of laboratory biomarkers is biphasic with a later, pronounced peak in inflammatory markers seen in those admitted to an ICU. CRP is a useful marker to monitor disease progression in SOT.

Clinical Predictors of Neurotoxicity After Chimeric Antigen Receptor T-Cell Therapy.

Importance: Chimeric antigen receptor (CAR) T-cell therapy for relapsed or refractory hematologic malignant neoplasm causes severe neurologic adverse events ranging from encephalopathy and aphasia to cerebral edema and death. The cause of neurotoxicity is incompletely understood, and its unpredictability is a reason for prolonged hospitalization after CAR T-cell infusion. Objective: To identify clinical and laboratory parameters predictive of neurotoxicity and to develop a prognostic score associated with its risk. Design, Setting, and Participants: This single-center diagnostic/prognostic accuracy study was conducted at Brigham and Women's Hospital/Dana Farber Cancer Institute from April 2015 to February 2020. A consecutive sample of all patients undergoing CAR T-cell therapy with axicabtagene ciloleucel for relapsed or refractory lymphoma were assessed for inclusion (n = 213). Patients who had previously received CAR T cells or who were treated for mantle cell lymphoma were excluded (n = 9). Patients were followed up for a minimum of 30 days from the date of CAR T-cell infusion. Main Outcomes and Measures: The primary outcomes were measures of performance (accuracy, sensitivity, specificity, area under the curve) of a diagnostic tool to predict the occurrence of CAR-associated neurotoxicity, as graded by the Common Terminology Criteria for Adverse Events criteria. Results: Two hundred four patients (127 men [62.2%]; mean [SD] age, 60.0 [12.1] years) were included in the analysis, of which 126 (61.8%) comprised a derivation cohort and 78 (38.2%), an internal validation cohort. Seventy-three patients (57.9%) in the derivation cohort and 45 patients (57.7%) in the validation cohort experienced neurotoxicity. Clinical and laboratory values obtained early in admission were used to develop a multivariable score that can predict the subsequent development of neurotoxicity; when tested on an internal validation cohort, this score had an area under the curve of 74%, an accuracy of 77%, a sensitivity of 82%, and a specificity of 70% (positive:negative likelihood ratio, 2.71:0.26). Conclusions and Relevance: The score developed in this study may help predict which patients are likely to experience CAR T-cell-associated neurotoxicity. The score can be used for triaging and resource allocation and may allow a large proportion of patients to be discharged from the hospital early.

Characteristics and Outcomes of Latinx Patients With COVID-19 in Comparison With Other Ethnic and Racial Groups.

BACKGROUND: There is a limited understanding of the impact of coronavirus disease 2019 (COVID-19) on the Latinx population. We hypothesized that Latinx patients would be more likely to be hospitalized and admitted to the intensive care unit (ICU) than White patients. METHODS: We analyzed all patients with COVID-19 in 12 Massachusetts hospitals between February 1 and April 14, 2020. We examined the association between race, ethnicity, age, reported comorbidities, and hospitalization and ICU admission using multivariable regression. RESULTS: Of 5190 COVID-19 patients, 29% were hospitalized; 33% required the ICU, and 4.3% died. Forty-six percent of patients were White, 25% Latinx, 14% African American, and 3% Asian American. Ethnicity and race were significantly associated with hospitalization. More Latinx and African American patients in the younger age groups were hospitalized than whites. Latinxs and African Americans disproportionally required the ICU, with 39% of hospitalized Latinx patients requiring the ICU compared with 33% of African Americans, 24% of Asian Americans, and 30% of Whites (P < .007). Within each ethnic and racial group, age and male gender were independently predictive of hospitalization. Previously reported preexisting comorbidities contributed to the need for hospitalization in all racial and ethnic groups (P < .05). However, the observed disparities were less likely related to reported comorbidities, with Latinx and African American patients being admitted at twice the rate of Whites, regardless of such comorbidities. CONCLUSIONS: Latinx and African American patients with COVID-19 have higher rates of hospitalization and ICU admission than White patients. The etiologies of such disparities are likely multifactorial and cannot be explained only by reported comorbidities.