Evaluation of Clinical Predictors for Major Outcomes in Patients Hospitalized With COVID-19: The Potential Role of the Rothman Index.

Introduction The Rothman Index (RI, PeraHealth, Inc. Charlotte, NC, USA) is a predictive model intended to provide continuous monitoring of a patient's clinical status. There is limited data to support its use in the risk stratification of patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We hypothesized that low admission RI scores would correlate with higher rates of adverse outcomes in patients hospitalized for coronavirus disease 2019 (COVID-19). Methods Medical records of adult patients admitted to a single 1,200-bed tertiary academic center were retrospectively reviewed for demographic data, baseline characteristics, RI scores, admission to intensive care unit (ICU), need for mechanical ventilation, and inpatient mortality. Statistical analyses were performed using STATA statistical software, version 17 (Stata Corp LLC, College Station, TX, USA). Continuous variables were analyzed using the Mann-Whitney test, and categorical variables were analyzed using Fisher's exact test. Both univariate and multivariate analyses were performed. A p-value <0.05 was considered statistically significant. Results Median admission RI score for the entire cohort was 63.0 (IQR 45.0 - 77.1). The cohort was divided by admission RI into a low-risk group (RI ≥70; n=70) and a high-risk group (RI <70; n=107). Compared to patients with low-risk RI, patients with high-risk RI had higher mortality (95.2%, 95% CI: 85.8 - 105 vs 4.8%, 95% CI: -5 - 14.2, p < 0.01), were more likely to require ICU admission (90.2%, 95% CI: 81.9 - 98.5 vs 9.8%, 95% CI: 1.5 - 18.1, p < 0.01) and mechanical ventilation (89.7%, 95% CI: 78.3 - 101 vs 10.3%, 95% CI: -1 - 21.7, p < 0.01), and had a longer median hospital length of stay (12 days, 95% CI: 9 - 14 vs 5 days, 95% CI: 4 - 7, p < 0.01). Conclusions High-risk RI was associated with increased admission to the ICU, mechanical ventilation, and mortality. These results suggest that it may be used as a tool to aid provider judgment in the setting of COVID-19.

Evaluation of Clinical Predictors for Major Outcomes in Patients Hospitalized With COVID-19: The Potential Role of the Rothman Index

Introduction The Rothman Index (RI, PeraHealth, Inc. Charlotte, NC, USA) is a predictive model intended to provide continuous monitoring of a patient's clinical status. There is limited data to support its use in the risk stratification of patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We hypothesized that low admission RI scores would correlate with higher rates of adverse outcomes in patients hospitalized for coronavirus disease 2019 (COVID-19). Methods Medical records of adult patients admitted to a single 1,200-bed tertiary academic center were retrospectively reviewed for demographic data, baseline characteristics, RI scores, admission to intensive care unit (ICU), need for mechanical ventilation, and inpatient mortality. Statistical analyses were performed using STATA statistical software, version 17 (Stata Corp LLC, College Station, TX, USA). Continuous variables were analyzed using the Mann-Whitney test, and categorical variables were analyzed using Fisher’s exact test. Both univariate and multivariate analyses were performed. A p-value <0.05 was considered statistically significant. Results Median admission RI score for the entire cohort was 63.0 (IQR 45.0 - 77.1). The cohort was divided by admission RI into a low-risk group (RI ≥70;n=70) and a high-risk group (RI <70;n=107). Compared to patients with low-risk RI, patients with high-risk RI had higher mortality (95.2%, 95% CI: 85.8 - 105 vs 4.8%, 95% CI: -5 - 14.2, p < 0.01), were more likely to require ICU admission (90.2%, 95% CI: 81.9 - 98.5 vs 9.8%, 95% CI: 1.5 - 18.1, p < 0.01) and mechanical ventilation (89.7%, 95% CI: 78.3 - 101 vs 10.3%, 95% CI: -1 - 21.7, p < 0.01), and had a longer median hospital length of stay (12 days, 95% CI: 9 - 14 vs 5 days, 95% CI: 4 - 7, p < 0.01). Conclusions High-risk RI was associated with increased admission to the ICU, mechanical ventilation, and mortality. These results suggest that it may be used as a tool to aid provider judgment in the setting of COVID-19.

Correlation of alpha-1 antitrypsin levels and exosome associated neutrophil elastase endothelial injury in subjects with SARS-CoV2 infection.

BACKGROUND: Severe acute respiratory syndrome caused by a novel coronavirus 2 (SARS-CoV-2) has infected more than 18 million people worldwide. The activation of endothelial cells is a hallmark of signs of SARS-CoV-2 infection that includes altered integrity of vessel barrier and endothelial inflammation. OBJECTIVES: Pulmonary endothelial activation is suggested to be related to the profound neutrophil elastase (NE) activity, which is necessary for sterilization of phagocytosed bacterial pathogens. However, unopposed activity of NE increases alveolocapillary permeability and extracellular matrix degradation. The uncontrolled protease activity of NE during the inflammatory phase of lung diseases might be due to the resistance of exosome associated NE to inhibition by alpha-1 antitrypsin. METHOD: 31 subjects with a diagnosis of SARS-CoV2 infection were recruited in the disease group and samples from 30 voluntaries matched for age and sex were also collected for control. RESULTS: We measured the plasma levels of exosome-associated NE in SARS-CoV-2 patients which, were positively correlated with sign of endothelial damage in those patients as determined by plasma levels of LDH. Notably, we also found strong correlation with plasma levels of alpha-1 antitrypsin and exosome-associated NE in SARS-CoV-2 patients. Using macrovascular endothelial cells, we also observed that purified NE activity is inhibited by purified alpha-1 antitrypsin while, NE associated with exosomes are resistant to inhibition and show less sensitivity to alpha-1 antitrypsin inhibitory activity, in vitro. CONCLUSIONS: Our results point out the role of exosome-associated NE in exacerbation of endothelial injury in SARS-CoV-2 infection. We have demonstrated that exosome-associated NE could be served as a new potential therapeutic target of severe systemic manifestations of SARS-CoV-2 infection.

Severe COVID-19 After Recent Heart Transplantation Complicated by Allograft Dysfunction.

A 50-year-old male presented with atrial flutter 25 days after heart and kidney transplantation. Rejection was excluded, but he developed severe COVID-19 infection with cardiac allograft dysfunction. Despite continued corticosteroid and tacrolimus therapy, he remained aviremic. Respiratory and myocardial functions recovered after a week of mechanical ventilation. The cardiomyopathy was stress induced. (Level of Difficulty: Advanced.).