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: High flow nasal cannula oxygen (HFNC) has a firm evidence base in the management of hypoxaemic respiratory failure. It has been shown to reduce mortality and increase ventilator free days when compared with use of standard oxygen or continuous positive airway pressure (CPAP), and it has been shown to reduce intubation rates in patients with a P: F ratio of <200mmHg.1 However, provisional data from the use of HFNC in COVID-19 suggest no significant reduction in intubation rates and no mortality benefit over conventional oxygen therapy or CPAP.2 These contradictory findings complicate our understanding of any potential role for HFNC in COVID-19. In our organisation, all patients with COVID-19 who remained hypoxic despite standard oxygen therapy were initially managed with HFNC and only if they failed this modality were then trialled on CPAP or intubated for invasive mechanical ventilation. HFNC was provided on our physician led Respiratory Support Unit (RSU) with daily critical care input. Our approach differs to that employed in the most recent multicentre randomised controlled trial of respiratory support in COVID-19 and therefore offers the opportunity to understand how HFNC may be of benefit in patients with COVID-19. Objectives: To explore the potential role and safety for HFNC in COVID-19. Methods: Retrospective analysis of all patients with COVID-19 admitted to a single NHS acute Trust between March 2020 and February 2021, who required escalation of respiratory support to HFNC with or without subsequent CPAP or intubation. Data collected included patient demographics, comorbidities, respiratory support requirements, ceiling of treatment and outcomes. Logistic regression analysis was used to compare mortality rates for patients who did or did not receive HFNC. Results: One hundred and forty-seven patients met inclusion criteria of whom fifty-five (37%) were managed solely on the Respiratory Support Unit (RSU). Nineteen patients (13%) had HFNC as their ceiling of care, of whom nine died. Of those patients deemed appropriate for full escalation, fifty-four (37%) received only HFNC and thirty-two (22%) subsequently required intubation after a trial of HFNC. The relative risk of mortality for patients who received HFNC prior to intubation compared to those who were intubated without HFNC was 0.48 (95% CI 0.26-0.89). There were no safety concerns associated with HFNC. Conclusion: Our data suggests that HFNC may offer survival benefit in those with care limitations in organ support, as demonstrated by our survival rate of 53% in this patient cohort. HFNC is generally well tolerated and is associated with fewer adverse events than other forms of non-invasive respiratory support. HFNC can be employed as a safe tool for assessing patients' respiratory support requirements and monitoring trajectory in RSUs, sparing ICU capacity in healthcare systems under strain. Furthermore, it is associated with a favourable mortality profile in those who subsequently require intubation (34% mortality), particularly when compared with the UK national average for mortality in COVID-19 ventilated patients (50%). HFNC may therefore still have a role in the management of patients with COVID-19 with acute hypoxaemic respiratory failure and this warrants further examination.
ABSTRACT
Aims and ObjectivesAn increased incidence of pulmonary thrombosis (PT) and right ventricular (RV) dysfunction is reported in COVID-19. The clinical significance is not fully understood and there are few large, multicentre studies. The National Covid-19 Chest Imaging Database (NCCID) was analysed for prevalence of PT in COVID-19 patients;we hypothesised associations between macroscopic PT, severity of parenchymal disease, evidence of RV dysfunction on CT and mortality.MethodsNCCID is a multicentre UK-wide centralised database comprised of radiological images from hospitalised COVID-19 patients. 391 thoracic contrast CT scans from 14 centres across England and Wales performed between 2nd March 2020 – 10th September 2020 underwent automated post-processing software (IMBIO LLC.) to determine RV:LV diameter ratio. Scans were manually reported for PT and quantitatively scored for arterial obstruction and severity of parenchymal involvement using CT- Severity Scoring (CT-SS)[1]. Imaging metrics were analysed for association with PT and 30 day mortality.ResultsAutomated RV:LV analysis was successful in 90% (351/391) of scans. Mean age: 64, 53% (186/351) male. Mortality data was available for 325 patients: 22 died within 30 days of scan (6.7% (22/325)).Macroscopic PT was present in 16% (56/351). Median Qanadli score was 6% (IQR 3%-17.5%), indicating low burden arterial obstruction. PT was not associated with mortality (p=0.18).RV:LV >1 on CT was observed in 59% (206/351) (mean RV:LV 1.08). RV:LV was significantly higher in the presence of PT (mean RVLV 1.17 vs 1.06 p=0.011, χ2(2) = 6.499). RV:LV was not predictive of mortality (AUC 0.467, CI 0.358–0.576).CT-SS significantly predicted mortality (AUC 0.787, p=<0.0005, CI 0.693–0.881). However there was no correlation between severity of parenchymal involvement and RV:LV (r 0.82, p=0.123), nor presence of PT (χ2(2) 2.305, p=0.129).ConclusionsRV dilatation and PT were prevalent in this multicentre cohort of COVID-19 patients, but were not associated with mortality or parenchymal disease severity. PT is frequently low burden and, in contrast to PT outside the context of COVID-19, RV:LV >1 is not discriminatory for prognosis.ReferenceYang R., et al. Chest CT severity score: an imaging tool for assessing severe COVID-19. Radiology: Cardiothoracic Imaging 2020;2(2):e200047. doi: 10.1148/ryct.2020200047
ABSTRACT
Introductions and Objectives BTS guidelines advise that patients with a clinico-radiological diagnosis of COVID-19 undergo follow-up based on severity of disease: either Group 1 (required ICU/HDU admission or significant respiratory support), or Group 2 (any other admitted patients). The BTS guidelines themselves address concerns that delivering this follow-up might prove difficult due to disrupted working patterns and large caseloads. To address these concerns, we established a post-COVID-19 Pre-Follow Up Multi- Disciplinary Team (pre-FU-MDT). We have reviewed its impact on COVID-19 follow-up streams. Methods To capture all relevant patients we cross-referenced a list of all RT-PCR swabs sent for symptomatic purposes against those who had a recent CXR. The CXR reports, coded in real time, were used to establish a list of patients who had CXRs consistent with or indeterminate for COVID- 19 pneumonia. The database was screened by a specialist respiratory nurse who assigned follow-up streams based on level of respiratory support required and CXR report. All Group 1, Group 2 and Indeterminate cases were discussed at MDT, which consisted of a consultant respiratory physician and a thoracic radiologist. Cases were discussed with discharge summaries, results and imaging. Follow-up streams were reallocated as necessary. Time for MDT was re-allocated from services reduced during the pandemic. Results Of 1532 'symptomatic' swabs, there were 495 patients with a potential clinico-radiological diagnosis of COVID-19 pneumonia discussed at the Pre-FU-MDT. We performed a subgroup analysis on 392 consecutive cases (Table 1). The pre-FU-MDT changed the follow-up pathway in 21% of non-indeterminate cases (23/108). Follow up was ceased in 5% (17/108). Patients with indeterminate CXRs represented the largest cohort. The pre-FU-MDT ceased follow-up in 57% (150/261) and the remaining 43% (111/261) were stratified to Group 1, Group 2 or other appropriate non- COVID follow up. Conclusions A Pre-FU-MDT has significant clinical impact. By redistributing clinicians' time, an efficient mechanism has been created to reduce unnecessary CXRs and clinic appointments, and focus on those most likely to require follow-up. Review of our follow-up outcomes is ongoing and the results will be available at the time of the BTS meeting.