ABSTRACT
Background Increased mortality rates among coronavirus disease 2019 (COVID-19) positive patients admitted to intensive care units (ICUs) highlight a compelling need to establish predictive criteria for ICU admissions. The aim of our study was to identify criteria for recognizing patients with COVID-19 at elevated risk for ICU admission. Methods We identified patients who tested positive for COVID-19 and were hospitalized between March and May 2020. Patients' data were manually abstracted through review of electronic medical records. An ICU admission prediction model was derived from a random sample of half the patients using multivariable logistic regression. The model was validated with the remaining half of the patients using c-statistic. Results We identified 1,094 patients; 204 (18.6%) were admitted to the ICU. Correlates of ICU admission were age, body mass index (BMI), quick Sequential Organ Failure Assessment (qSOFA) score, arterial oxygen saturation to fraction of inspired oxygen ratio, platelet count, and white blood cell count. The c-statistic in the derivation subset (0.798, 95% confidence interval [CI]: 0.748, 0.848) and the validation subset (0.764, 95% CI: 0.706, 0.822) showed excellent comparability. At 22% predicted probability for ICU admission, the derivation subset estimated sensitivity was 0.721, (95% CI: 0.637, 0.804) and specificity was 0.763, (95% CI: 0.722, 0.804). Our pilot predictive model identified the combination of age, BMI, qSOFA score, and oxygenation status as significant predictors for ICU admission. Conclusion ICU admission among patients with COVID-19 can be predicted by age, BMI, level of hypoxia, and severity of illness.
ABSTRACT
Protein kinase C (PKC) targets cardiac troponin I (cTnI) S43/45 for phosphorylation in addition to other residues. During heart failure, cTnI S43/45 phosphorylation is elevated, and yet there is ongoing debate about its functional role due, in part, to the emergence of complex phenotypes in animal models. The individual functional influences of phosphorylated S43 and S45 also are not yet known. The present study utilizes viral gene transfer of cTnI with phosphomimetic S43D and/or S45D substitutions to evaluate their individual and combined influences on function in intact adult cardiac myocytes. Partial replacement (≤40%) with either cTnIS43D or cTnIS45D reduced the amplitude of contraction, and cTnIS45D slowed contraction and relaxation rates, while there were no significant changes in function with cTnIS43/45D. More extensive replacement (≥70%) with cTnIS43D, cTnIS45D, and cTnIS43/45D each reduced the amplitude of contraction. Additional experiments also showed cTnIS45D reduced myofilament Ca(2+) sensitivity of tension. At the same time, shortening rates returned toward control values with cTnIS45D and the later stages of relaxation also became accelerated in myocytes expressing cTnIS43D and/or S45D. Further studies demonstrated this behavior coincided with adaptive changes in myofilament protein phosphorylation. Taken together, the results observed in myocytes expressing cTnIS43D and/or S45D suggest these 2 residues reduce function via independent mechanism(s). The changes in function associated with the onset of adaptive myofilament signaling suggest the sarcomere is capable of fine tuning PKC-mediated cTnIS43/45 phosphorylation and contractile performance. This modulatory behavior also provides insight into divergent phenotypes reported in animal models with cTnI S43/45 phosphomimetic substitutions.
