No abstract

Recent studies have reported that CRP levels are elevated in patients with COVID-19 and may correlate with severity of disease and disease progression. We conducted a retrospective cohort analysis of the medical records of 268 adult patients, who were admitted to one of the six cohorted COVID ICUs across Emory Healthcare System and had at least two CRP values within the first seven days of admission to study the temporal progression of CRP and its association with all-cause in-hospital mortality. The median CRP during hospitalization for the entire cohort was 130 mg/L (IQR 82–191 mg/L), and the median CRP on ICU admission was 169 (IQR 111–234). The hospitalization-wide median CRP was significantly higher amongst the patients who died, compared to those who survived [206 mg/L (157–288 mg/L) vs 114 mg/L (72–160 mg/L), p<0.001]. CRP levels increased in a linear fashion during the first week of hospitalization and peaked on day 5. Compared to patients who died, those who survived had lower peak CRP levels and earlier declines. CRP levels were significantly higher in patients who died compared to those who survived (p<0.001). Our findings support the utility of daily CRP values in hospitalized COVID-19 patients and provide early thresholds during hospitalization that may facilitate risk stratification and prognostication.

Background We aimed to assess the efficacy and safety of two neutralising monoclonal antibody therapies (sotrovimab [Vir Biotechnology and GlaxoSmithKline] and BRII-196 plus BRII-198 [Brii Biosciences]) for adults admitted to hospital for COVID-19 (hereafter referred to as hospitalised) with COVID-19. Methods In this multinational, double-blind, randomised, placebo-controlled, clinical trial (Therapeutics for Inpatients with COVID-19 [TICO]), adults (aged ≥18 years) hospitalised with COVID-19 at 43 hospitals in the USA, Denmark, Switzerland, and Poland were recruited. Patients were eligible if they had laboratory-confirmed SARS-CoV-2 infection and COVID-19 symptoms for up to 12 days. Using a web-based application, participants were randomly assigned (2:1:2:1), stratified by trial site pharmacy, to sotrovimab 500 mg, matching placebo for sotrovimab, BRII-196 1000 mg plus BRII-198 1000 mg, or matching placebo for BRII-196 plus BRII-198, in addition to standard of care. Each study product was administered as a single dose given intravenously over 60 min. The concurrent placebo groups were pooled for analyses. The primary outcome was time to sustained clinical recovery, defined as discharge from the hospital to home and remaining at home for 14 consecutive days, up to day 90 after randomisation. Interim futility analyses were based on two seven-category ordinal outcome scales on day 5 that measured pulmonary status and extrapulmonary complications of COVID-19. The safety outcome was a composite of death, serious adverse events, incident organ failure, and serious coinfection up to day 90 after randomisation. Efficacy and safety outcomes were assessed in the modified intention-to-treat population, defined as all patients randomly assigned to treatment who started the study infusion. This study is registered with ClinicalTrials.gov , NCT04501978 . Findings Between Dec 16, 2020, and March 1, 2021, 546 patients were enrolled and randomly assigned to sotrovimab (n=184), BRII-196 plus BRII-198 (n=183), or placebo (n=179), of whom 536 received part or all of their assigned study drug (sotrovimab n=182, BRII-196 plus BRII-198 n=176, or placebo n=178; median age of 60 years [IQR 50–72], 228 [43%] patients were female and 308 [57%] were male). At this point, enrolment was halted on the basis of the interim futility analysis. At day 5, neither the sotrovimab group nor the BRII-196 plus BRII-198 group had significantly higher odds of more favourable outcomes than the placebo group on either the pulmonary scale (adjusted odds ratio sotrovimab 1·07 [95% CI 0·74–1·56]; BRII-196 plus BRII-198 0·98 [95% CI 0·67–1·43]) or the pulmonary-plus complications scale (sotrovimab 1·08 [0·74–1·58]; BRII-196 plus BRII-198 1·00 [0·68–1·46]). By day 90, sustained clinical recovery was seen in 151 (85%) patients in the placebo group compared with 160 (88%) in the sotrovimab group (adjusted rate ratio 1·12 [95% CI 0·91–...

Perioperative stroke is an important source of morbidity and mortality, as reflected by significant increases in median surgical length of stay and all-cause 30-day mortality. The independent predictors of stroke that we have identified in this population are not readily modifiable and the majority of strokes occurred after postoperative day 1. Additional studies are required to identify potentially modifiable intraoperative or postoperative risk factors of perioperative stroke.

Routine use of preoperative metoprolol, but not atenolol, is associated with stroke after noncardiac surgery, even after adjusting for comorbidities. Intraoperative metoprolol but not esmolol or labetalol, is associated with increased risk of perioperative stroke. Drugs other than metoprolol should be considered during the perioperative period if β blockade is required.