ABSTRACT
Background: Neutrophil serine proteases (NSPs) are involved in the pathogenesis of COVID19 and are increased in severe and fatal infection. We investigated whether treatment with Brensocatib, an inhibitor of dipeptidyl peptidase-1, an enzyme responsible for the activation of NSPs, would improve outcomes in hospitalized patients with COVID19. Method(s): In a randomized, double-blind, placebo-controlled trial, 406 hospitalized patients with COVID19 with at least one risk factor for severe disease were randomized 1:1 to once-daily Brensocatib 25mg (n=192) or placebo (n=214) for 28 days. Primary outcome was the 7-point World Health Organisation Clinical Status scale at day 29. Secondary outcomes included time to clinical improvement, national early warning score, new oxygen and ventilation use, neutrophil elastase activity in blood and mortality. Finding(s): Brensocatib treatment was associated with worse clinical status at day 29 (adjusted odds ratio 0 72, 95%CI 0 57-0 92) compared to placebo. The adjusted hazard ratio (aHR) for time to clinical improvement was 0 87 (95%CI 0 76-1 00) and time to hospital discharge was 0 98 (95%CI 0 84-1 13). During the 28-day follow-up period, 23 (11%) and 29 (15%) patients died in the placebo and Brensocatib treated groups respectively). Oxygen and new ventilation use were greater in the Brensocatib treated patients. Neutrophil elastase activity in blood was significantly reduced in the Brensocatib group from baseline to day 29. Prespecified subgroup analyses of the primary outcome supported the primary results.
ABSTRACT
Introduction Plain chest radiograph (CXR) is the most common imaging modality used to evaluate respiratory symptoms. CXR severity scoring has been shown to be an independent predictor of need for hospital admission and intubation and mechanical ventilation (I&MV) in COVID19 patients, but its role in predicting mortality is yet to be explored. Aim We evaluated the predictive value and prognostic utility of CXRs in adult patients with COVID 19 infections. Methods A retrospective analysis of 200 consecutive patients between March 2020 to May 2020 admitted to our tertiary centre with confirmed COVID 19 infection was conducted. Lung fields on CXRs were divided into 6 zones: Right and left upper, mid and lower zones. Mild changes were defined as unilateral changes zones 1-3;moderate changes were: Bilateral changes zones 2-3;severe changes: Changes zones 4-6. CXRs were reviewed and scored independently by 2 reporters: Thoracic radiologist and acute medical physician who were blinded to baseline patient characteristics and outcomes. Results 200 patients (median age: 79 (IQR 63-86) years) were included, 108 of which were females and 92 males. 61 (30.5%) died and 139 (69.5%) were discharged. During admission, 19 (9.5%) were admitted to ITU, 2 (1%) to the Non-invasive ventilation (NIV) unit and 179 (89.5%) to COVID Medical wards. Of the 61 patients (median age: 82 (IQR 73-89) years;27 (44.3%) male, 34 (55.7%) female) who died: 3 (4.9%) were admitted to ITU, 1 (1.6%) to NIV unit and 57 (93.4%) to COVID medical wards;45 (73.8%) received oxygen up to 15L, 1 (1.6%) received nasal high flow oxygen, 2 (3.3%) received CPAP and 3 (4.9%) received I&MV. CXR changes on admission were not an independent predictor of mortality;no CXR changes (p=0.099), Mild CXR changes (p=0.416), Moderate CXR changes (p=0.283), Severe CXR changes (p=0.994). Severe CXR changes was an independent predictor of I&MV (OR 2.298;95% CI 1.156-4.566;p=0.018). Conclusion We conclude that a CXR severity score is an effective tool to predict risk for hospital admission and the need for I&MV. Further larger studies will help validate this score by following up repeat CXRs to determine disease trajectory.
ABSTRACT
IntroductionPlain chest radiograph (CXR) is the most common imaging modality used to evaluate respiratory symptoms. CXR severity scoring has been shown to be an independent predictor of need for hospital admission and intubation and mechanical ventilation (I&MV) in COVID19 patients, but its role in predicting mortality is yet to be explored.AimWe evaluated the predictive value and prognostic utility of CXRs in adult patients with COVID 19 infections.MethodsA retrospective analysis of 200 consecutive patients between March 2020 to May 2020 admitted to our tertiary centre with confirmed COVID 19 infection was conducted. Lung fields on CXRs were divided into 6 zones: right and left upper, mid and lower zones. Mild changes were defined as unilateral changes zones 1–3;moderate changes were: bilateral changes zones 2–3;severe changes: changes zones 4–6. CXRs were reviewed and scored independently by 2 reporters: thoracic radiologist and acute medical physician who were blinded to baseline patient characteristics and outcomes.Results200 patients (median age: 79 (IQR 63–86) years) were included, 108 of which were females and 92 males. 61 (30.5%) died and 139 (69.5%) were discharged. During admission, 19 (9.5%) were admitted to ITU, 2 (1%) to the Non-invasive ventilation (NIV) unit and 179 (89.5%) to COVID Medical wards. Of the 61 patients (median age: 82 (IQR 73–89) years;27 (44.3%) male, 34 (55.7%) female) who died: 3 (4.9%) were admitted to ITU, 1 (1.6%) to NIV unit and 57 (93.4%) to COVID medical wards;45 (73.8%) received oxygen up to 15L, 1 (1.6%) received nasal high flow oxygen, 2 (3.3%) received CPAP and 3 (4.9%) received I&MV. CXR changes on admission were not an independent predictor of mortality;no CXR changes (p=0.099), Mild CXR changes (p=0.416), Moderate CXR changes (p=0.283), Severe CXR changes (p=0.994). Severe CXR changes was an independent predictor of I&MV (OR 2.298;95% CI 1.156–4.566;p=0.018).ConclusionWe conclude that a CXR severity score is an effective tool to predict risk for hospital admission and the need for I&MV. Further larger studies will help validate this score by following up repeat CXRs to determine disease trajectory.