ABSTRACT
BACKGROUND: Studies using fast-acting subcutaneous (SQ) insulin analogs in diabetic ketoacidosis (DKA) have demonstrated efficacy, safety, and cost-effectiveness, allowing treatment of mild-to-moderate (MTM)-severity DKA patients in non-intensive care unit (ICU) settings. However, emergency department (ED)-based studies are few, with limited exploration of impacts on operational metrics. METHODS: We implemented the SQuID (Subcutaneous Insulin in Diabetic Ketoacidosis) protocol for adults with MTM-severity DKA in an urban academic ED, collecting data from August 1, 2021, to February 28, 2022. We examined fidelity (frequency of required q2h glucose checks), safety (proportion of patients administered rescue dextrose for hypoglycemia), and ED length of stay (EDLOS) for the SQuID cohort compared to patients (non-ICU) treated with a traditional insulin infusion. We also examined ICU admission rate among MTM-severity DKA patients after introduction of SQuID to two historical control periods (pre-intervention and pre-COVID). We used Mann-Whitney U to test for differences in EDLOS distributions, bootstrapped (n = 1000) confidence intervals (CIs) for EDLOS median differences, and the two-sample z-test for differences in ICU admissions. RESULTS: We identified 177 MTM-severity DKA patients in the study period (78 SQuID, 99 traditional cohort) and 163 preintervention and 161 pre-COVID historical control patients. Fidelity to the SQuID pathway was good, with glucose checks exceeding the q2-h requirement. We found no difference in the proportion of rescue dextrose administration compared to the traditional pathway. We observed significant reductions in median EDLOS for the SQuID cohort compared to the traditional cohort during the study period (-3.0, 95% CI -8.5 to -1.4), the preintervention period (-1.4, 95% CI -3.1 to -0.1), and the pre-COVID control period (-3.6, 95% CI -7.5 to -1.8). CONCLUSIONS: In this single-center study at an academic ED, treatment of patients with MTM-severity DKA with a SQ insulin protocol was effective, demonstrated equivalent safety, and reduced ED length of stay.
ABSTRACT
COVID-19 caused by SARS-CoV-2 has become a global pandemic requiring the development of interventions for the prevention or treatment to curtail mortality and morbidity. No vaccine to boost mucosal immunity, or as a therapeutic, has yet been developed to SARS-CoV-2. In this study, we discover and characterize a cross-reactive human IgA monoclonal antibody, MAb362. MAb362 binds to both SARS-CoV and SARS-CoV-2 spike proteins and competitively blocks ACE2 receptor binding, by overlapping the ACE2 structural binding epitope. Furthermore, MAb362 IgA neutralizes both pseudotyped SARS-CoV and SARS-CoV-2 in 293 cells expressing ACE2. When converted to secretory IgA, MAb326 also neutralizes authentic SARS-CoV-2 virus while the IgG isotype shows no neutralization. Our results suggest that SARS-CoV-2 specific IgA antibodies, such as MAb362, may provide effective immunity against SARS-CoV-2 by inducing mucosal immunity within the respiratory system, a potentially critical feature of an effective vaccine.