ABSTRACT
Introduction: Currently patients with COVID-19 related acute respiratory failure (ARF) may receive respiratory support with conventional oxygen therapy, high-flow nasal oxygen (HFNO) or continuous positive airway pressure (CPAP). A proportion of patients will subsequently require invasive ventilation. However, there is insufficient evidence on the relative effectiveness of different modes of noninvasive respiratory support (NIRS). In the absence of robust evidence to guide clinical decisions, there is likely significant variation in their use in UK practice. The RECOVERY-RS trial sought to address this knowledge gap, aiming to identify the most effective method of non-invasive respiratory support in COVID-19. This survey, conducted whilst RECOVERY-RS was in progress, sought to characterise the current use of NIRS in COVID-19 patients across the UK. Methods: An anonymous, online survey (10 questions) was distributed via national networks and professional societies. Healthcare professionals involved in managing COVID-19 patients were invited to participate with responses collected over two months from September to October 2020. Results: Of 145 respondents, the majority were critical care (60%) or respiratory (27%) clinicians. Prior to the COVID-19 pandemic, most reported having commonly used HFNO (89%) or CPAP (70%) for infection-related ARF. A small minority (3% HFNO vs 9% CPAP) reported no previous experience of their use. In COVID-19 patients suitable for intubation and ventilation, 92% of respondents had used CPAP and 61% HFNO to bridge to or prevent intubation. Conversely, 5% reported they would never use CPAP and 8% would never use HFNO as a bridge to intubation. 68% of clinicians chose CPAP as their personal preferred method of NIRS vs 26% HFNO when treating COVID-19 patients. In patients not suitable for invasive ventilation, CPAP was also more frequently used than HFNO (92% vs 61%). 37% worked in trusts enrolled in the RECOVERY-RS trial and the majority (59%) felt that RECOVERY-RS was an important study, addressing a key unanswered research question. Conclusion: This survey identified that a variety of methods of NIRS are being used for COVID-19 patients in the UK. CPAP predominates as both a ceiling of care treatment and as a bridge to intubation. This appears to represent a change in practice compared to the management of infection-related ARF prior to the COVID-19 pandemic, despite a lack of evidence at that time to suggest superior efficacy of CPAP. The heterogeneous survey results support the need for evidence of the most effective NIRS in COVID-19 in order to deliver optimal and standardised treatment.
ABSTRACT
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.