Evolution of Care and Outcomes Across Surges in Hospitalized Patients with Coronavirus Disease 2019.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has unfolded in distinct surges. Understanding how surges differ may reveal important insights into the evolution of the pandemic and improve patient care. METHODS: We leveraged the Michigan Medicine COVID-19 Cohort, a prospective observational study at an academic tertiary medical center that systematically enrolled 2309 consecutive patients hospitalized for COVID-19, comprising 5 distinct surges. RESULTS: As the pandemic evolved, patients hospitalized for COVID-19 tended to have a lower burden of comorbidities and a lower inflammatory burden as measured by admission levels of C-reactive protein, ferritin, lactate dehydrogenase, and D-dimer. Use of hydroxychloroquine and azithromycin decreased substantially after Surge 1, while use of corticosteroids and remdesivir markedly increased (P < .001 for all). In-hospital mortality significantly decreased from 18.3% in Surge 1 to 5.3% in Surge 5 (P < .001). The need for mechanical ventilation significantly decreased from 42.5% in Surge 1 to 7.0% in Surge 5 (P < .001), while the need for renal replacement therapy decreased from 14.4% in Surge 1 to 2.3% in Surge 5 (P < .001). Differences in patient characteristics, treatments, and inflammatory markers accounted only partially for the differences in outcomes between surges. CONCLUSIONS: The COVID-19 pandemic has evolved significantly with respect to hospitalized patient populations and therapeutic approaches, and clinical outcomes have substantially improved. Hospitalization after the first surge was independently associated with improved outcomes, even after controlling for relevant clinical covariates.

Biomarker Trends, Incidence, and Outcomes of Immune Checkpoint Inhibitor-Induced Myocarditis.

Background: Myocarditis is a dreaded and unpredictable complication of immune checkpoint inhibitors (ICI). We sought to determine whether routinely measured biomarkers could be helpful in monitoring for ICI myocarditis. Objectives: The authors examined biomarker trends of patients on ICI and their association with the incidence of ICI myocarditis and outcomes. Methods: We conducted an observational cohort study of adults who received at least one dose of ICI at Michigan Medicine between June 2014 and December 2021 and underwent systematic serial testing for aspartate aminotransferase (AST) and alanine aminotransferase (ALT), creatine phosphokinase (CPK), and lactate dehydrogenase during ICI therapy. Results: Among 2,606 patients (mean age 64 ± 13 years; 60.7% men), 27 (1.0%) were diagnosed with ICI myocarditis. At diagnosis, patients with myocarditis had an elevated high-sensitivity troponin T (100%), ALT (88.9%), AST (85.2%), CPK (88.9%), and lactate dehydrogenase (92.6%). Findings were confirmed in an independent cohort of 30 patients with biopsy-confirmed ICI myocarditis. A total of 95% of patients with ICI myocarditis had elevations in at least 3 biomarkers compared with 5% of patients without myocarditis. Among the noncardiac biomarkers, only CPK was associated (per 100% increase) with the development of myocarditis (HR: 1.83; 95% CI: 1.59-2.10) and all-cause mortality (HR: 1.10; 95% CI: 1.01-1.20) in multivariable analysis. Elevations in CPK had a sensitivity of 99% and specificity of 23% for identifying myocarditis. Conclusions: ICI myocarditis is associated with changes in AST, ALT, and CPK. An increase in noncardiac biomarkers during ICI treatment, notably CPK, should prompt further evaluation for ICI myocarditis.