ABSTRACT
BackgroundSARS-CoV-2 viral entry may disrupt angiotensin II (Ang II) homeostasis in part via ACE2 downregulation, potentially contributing to COVID-19 induced lung injury. Preclinical models of viral pneumonias that utilize ACE2 demonstrate Ang II type 1 receptor (AT1R) blockade mitigates lung injury, though observational COVID-19 data addressing the effect of AT1R blockade remain mixed. MethodsMulticenter, blinded, placebo-controlled randomized trial of losartan (50 mg PO twice daily for 10 days) versus placebo. Hospitalized patients with COVID-19 and a respiratory sequential organ failure assessment score of at least 1 and not already taking a renin-angiotensin-aldosterone system (RAAS) inhibitor were eligible. The primary outcome was the imputed partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) ratio at 7 days. Secondary outcomes included ordinal COVID-19 severity, oxygen, ventilator, and vasopressor-free days, and mortality. Losartan pharmacokinetics (PK) and RAAS components [Ang II, angiotensin-(1-7) (Ang-(1-7)), ACE, ACE2] were measured in a subgroup of participants. FindingsFrom April 2020 - February 2021, 205 participants were randomized, 101 to losartan and 104 to placebo. Compared to placebo, losartan did not significantly affect PaO2/FiO2 ratio at 7 days [difference of -24.8 (95% -55.6 to 6.1; p=0.12)]. Losartan did not improve any secondary clinical outcome, but worsened vasopressor-free days. PK data were consistent with appropriate steady-state concentrations, but we observed no significant effect of losartan on RAAS components. InterpretationInitiation of orally administered losartan to hospitalized patients with COVID-19 and acute lung injury does not improve PaO2 / FiO2 ratio at 7 days. These data may have implications for ongoing clinical trials. Trial RegistrationLosartan for Patients With COVID-19 Requiring Hospitalization (NCT04312009), https://clinicaltrials.gov/ct2/show/NCT04312009
ABSTRACT
OBJECTIVE: Vital sign trends are used in clinical practice to assess treatment response and aid in disposition, yet quantitative data to support this practice are lacking. This study aimed to determine the prognostic value of vital sign normalization. METHODS: Secondary analysis of a prospective cohort of adult emergency department (ED) patients admitted a single urban tertiary care hospital. A random sample of 182 days was chosen, and a manual review of all admissions was undertaken. Persistent tachycardia or tachypnea was defined as failure to decrease to a normal value in the ED. Elevated upon admission was defined as an abnormal value at the last set of vital signs documented. The primary outcome was in-hospital mortality. RESULTS: 4,878 patients were enrolled and 4.5 (±3.8) sets of vital signs were checked per patient. 1,770 patients were tachycardic and 1,499 were tachypneic. Among tachycardic patients, 941 (53%) were persistently tachycardic and 1,074 (61%) were tachycardic upon admission. Among tachypneic patients 639 (42%) were persistently tachypneic and 768 (51%) were tachypneic upon admission. Mortality was higher in patients persistently tachycardic (5.7% vs. 3.1%, P=0.008) or tachycardic upon admission (5.5% vs. 3.0%, P=0.014). Similar results were found in tachypneic patients (8.3% vs. 4.5%, P=0.003; 7.8% vs. 4.4%, P=0.006). CONCLUSION: Persistent tachycardia and tachypnea are associated with an increased risk of mortality in ED patients admitted to the hospital. Further study is necessary to determine if improved recognition or earlier interventions can affect outcomes.
