Conventional oxygen therapy versus CPAP as a ceiling of care in ward-based patients with COVID-19: a multi-centre cohort evaluation

S52 Figure 1Kaplan-Meier curve comparing overall survival in the two treatment groups (conventional oxygen therapy vs continuous positive airway pressure therapy). The null hypothesis of no survival difference is evaluated with a log-rank test (p = 0.92)[Figure omitted. See PDF]DiscussionThis is, as far as we are aware, the first study comparing conventional oxygen therapy with CPAP in cohorts unaffected by physician selection. No survival difference was found between using oxygen alone or CPAP to treat patients with severe COVID-19 who were nIMV. A high patient-initiated discontinuation rate for CPAP suggests a significant treatment burden. Further reflection is warranted on the continued widespread use of CPAP in this patient group.Please refer to page A189 for declarations of interest related to this abstract.

Incidence of candidaemia in prolonged venovenous extracorporeal membrane oxygenation.

This single-centre retrospective study reports the dynamics of the incidence of candida bloodstream infection (CBSI) in 145 patients receiving venovenous extracorporeal membrane oxygenation (ECMO) for respiratory support between January 2014 and December 2018. The incidence rate and odds ratio (OR) of CBSI were calculated, stratified by week of ECMO exposure. Weekly incidence increased throughout the ECMO run, with an increasing trend in OR (P=0.005), and a window of continued risk after decannulation was observed. Of the 13 patients who developed CBSI, five (38%) received empirical micafungin treatment before positive culture due to clinical suspicion. There is a need for prospective studies aiming to improve ECMO diagnostic stewardship practices and discourage unnecessary antifungal prophylaxis or empiric management.

Conventional oxygen therapy versus CPAP as a ceiling of care in ward-based patients with COVID-19: a multi-centre cohort evaluation.

BACKGROUND: Continuous positive airway pressure (CPAP) therapy is commonly used for respiratory failure due to severe COVID-19 pneumonitis, including in patients deemed not likely to benefit from invasive mechanical ventilation (nIMV). Little evidence exists demonstrating superiority over conventional oxygen therapy, whilst ward-level delivery of CPAP presents practical challenges. We sought to compare clinical outcomes of oxygen therapy versus CPAP therapy in patients with COVID-19 who were nIMV. METHODS: This retrospective multi-centre cohort evaluation included patients diagnosed with COVID-19 who were nIMV, had a treatment escalation plan of ward-level care and clinical frailty scale ≤ 6. Recruitment occurred during the first two waves of the UK COVID-19 pandemic in 2020; from 1st March to May 31st, and from 1st September to 31st December. Patients given CPAP were compared to patients receiving oxygen therapy that required FiO2 ≥0.4 for more than 12 hours at hospitals not providing ward-level CPAP. Logistic regression modelling was performed to compare 30-day mortality between treatment groups, accounting for important confounders and within-hospital clustering. FINDINGS: Seven hospitals provided data for 479 patients during the UK COVID-19 pandemic in 2020. Overall 30-day mortality was 75.6% in the oxygen group (186/246 patients) and 77.7% in the CPAP group (181/233 patients). A lack of evidence for a treatment effect persisted in the adjusted model (adjusted odds ratio 0.84 95% CI 0.57-1.23, p=0.37). 49.8% of patients receiving CPAP-therapy (118/237) chose to discontinue it. INTERPRETATION: No survival difference was found between using oxygen alone or CPAP to treat patients with severe COVID-19 who were nIMV. A high patient-initiated discontinuation rate for CPAP suggests a significant treatment burden. Further reflection is warranted on the current treatment guidance and widespread application of CPAP in this setting. FUNDING: L Pearmain is supported by the MRC (MR/R00191X/1). TW Felton is supported by the NIHR Manchester Biomedical Research Centre.

Persistence of neutrophil abnormalities inCOVID-19 convalescence

Background/AimsPatients infected with severe acute respiratory syndrome coronavirus2 (SARS-CoV-2) may develop acute respiratory inflammation, due toan exaggerated immune response and some develop chroniccomplications. Neutrophils play a major role in the pathology ofinflammatory diseases and have been shown to contribute to lung andvascular damage in COVID-19. Our aim was to establish a relationshipbetween neutrophil phenotype and disease severity and to determinewhether neutrophil abnormalities persist in convalescent patients.MethodsPeripheral blood samples were obtained from acute COVID-19patients (n = 74), follow-up (FU) patients discharged following inpatientadmission (n = 56), a median of 87 days after discharge, and healthycontrols (HCs, n = 22). Patients were stratified by disease severitybased on inspired oxygen (FiO2) and admission to intensive care (ICU).Neutrophils were isolated from whole blood by negative selection forphenotyping and functional analysis. PBMC Isolation Tubes were usedto quantify and phenotype low density neutrophils (LDNs) within thePBMC fraction. For quantification of reactive oxygen species (ROS)production, isolated neutrophils were incubated with a ROS reactivedye, DHR-123 and stimulated with PMA. All samples were stained andfixed prior to analysis by flow cytometry.ResultsThere was a marked increase in neutrophils expressing the activationand degranulation markers, CD64 (P < 0.0001) and CD63 (P < 0.0001)and a reduction in neutrophils expressing the maturity markers, CD10(P < 0.0005) and CD101 (P < 0.0005) in patients with acute COVID-19compared to HCs. Increased frequency of neutrophils expressingCD64 (P < 0.005), CD63 (P < 0.01) and expressing decreased CD101(P < 0.0001) were also detected in FU patients compared to HCs.Notably, 42.3 4.4% of neutrophils were CD101lo in FU patients, compared to 29.0 3.7% in acute patients and 9.6 4.1% in HCs.These changes were most apparent in FU patients recovering fromsevere COVID-19 compared to mild or moderate disease. Thefrequency of LDNs in PBMCs from acute patients was significantlyhigher than HCs (P < 0.0001), and correlated with disease severity.Similarly, the frequency of LDNs in FU patients was significantly higherthan in HCs (P < 0.0005). We found a trend towards higher basal ROSproduction in acute and FU patients, but a blunted response to PMAstimulated ROS production in neutrophils from acute patients versusHCs (P < 0.0001). Impaired ROS production persisted in FU patientscompared to HCs (P < 0.01).ConclusionCirculating neutrophils in acute COVID-19 have an altered phenotypeand comprise immature and activated cells. This altered phenotypepersisted in convalescence and may contribute to the persistence ofsymptoms and an increased susceptibility to subsequent infections.Future work will aim to investigate the functional implications of thesefindings.