Daily Respiratory Research Analysis

BACKGROUND: Preventing and treating post-acute sequelae of COVID-19 infection (PASC), commonly known as Long COVID, has become a public health priority. This study tests whether Paxlovid treatment in the acute phase of COVID-19 could help prevent the onset of PASC. METHODS AND FINDINGS: We used electronic health records from the National Clinical Cohort Collaborative to define a cohort of 445,738 patients who had COVID-19 since April 1, 2022, and were eligible for Paxlovid treatment due to risk for progression to severe COVID-19. We used the target trial emulation framework to estimate the effect of Paxlovid treatment on PASC incidence. We emulated a series of six sequential trials: one for each day of a 5-day treatment grace period. For each sequential trial, the treatment group was defined as patients prescribed Paxlovid on the trial start day, and the control group was defined as all patients meeting eligibility criteria who remained untreated on the trial start day. We pooled individual record-level data from the sequential trials for analysis. The follow-up period was 180 days. The primary outcome was overall PASC incidence measured using a computable phenotype. Secondary outcomes were incident cognitive, fatigue, and respiratory symptoms in the post-acute period. We controlled for a wide range of demographic and medical history covariates. Compared to the control group, Paxlovid treatment did not have a significant effect on overall PASC incidence or incident respiratory symptoms. It had a small protective effect against cognitive (relative risk [RR] 0.91; 95% CI [0.84, 0.98]; p = 0.019) and fatigue (RR 0.94; 95% CI [0.90, 0.98]; p = 0.002) symptoms. Finally, we estimated Paxlovid's effect on overall PASC incidence across strata of age, COVID-19 vaccination status, and Charlson Comorbidity Index (CCI) prior to COVID-19. We found small protective effects among patients aged 65 years or more (RR 0.92; 95% CI [0.88, 0.97]; p < 0.001; absolute risk difference [ARD] -0.43%; number needed to treat [NNT] 233) and with a CCI of 3 or 4 (RR 0.83; 95% CI [0.75, 0.92]; p < 0.001; ARD -1.30%; NNT 76). This study's main limitation is that the causal interpretation relies on the assumption that we controlled for all confounding variables. CONCLUSIONS: Although some prior observational studies suggested that Paxlovid held promise as a PASC preventive, this study-with a large, nationally sampled cohort; a contemporary study period; and causal inference methodology-found that Paxlovid treatment during acute COVID-19 had no effect on subsequent PASC incidence. Stratified analyses suggest that Paxlovid may have a small protective effect among higher-risk patients, but the NNT is high. In conclusion, we see Paxlovid as unlikely to become a definitive solution for PASC prevention.

BACKGROUND: Nirsevimab, a novel monoclonal antibody with a long half-life, has received European Union approval to prevent lower respiratory tract infections (LRTIs) caused by respiratory syncytial virus (RSV) during the first season of exposure. It was implemented in Catalonia (Spain) in the 2023-2024 season. Our main objective was to analyse the impact of the nirsevimab on LRTIs presenting to the Emergency Department (ED) in Catalonia (Spain) by comparing presentations to those at five sites in the United Kingdom (UK) and Rome (Italy). METHODS: In this multi-national retrospective analysis of emergency department attendances and admissions, we retrospectively collected information for all diagnoses, respiratory diagnoses excluding bronchiolitis, and bronchiolitis, for different age groups from 68 hospitals in Catalonia (Spain), one hospital in Rome (Italy), and four hospitals in the UK (Bristol, Leicester, Glasgow, and Edinburgh), from May 1st, 2018, to April 30th 2024. Applying a generalised linear model (GLM) in Poisson regression, we obtained the risk ratio (RR) and 95% confidence intervals (CI) of bronchiolitis in 2023-2024 season compared to the mean of all previous seasons. We analysed data in annual bins, from May 1st to April 30th, excluding 2020-21 as a COVID year, for a total of 5 years of data. FINDINGS: Data was available for 1,574,392 ED attendances (96,028 for bronchiolitis) and 255,689 hospital admissions (27,691 for bronchiolitis). In the 2023-2024 season, in Catalonia there was a reduction in the RR for bronchiolitis hospital admissions in the youngest infants aged <6 months (0.52, 95% CI: 0.48-0.55). There was also a reduction in Catalonia in the RR for hospital attendances for bronchiolitis in nirsevimab eligible age groups (0-11 months), with a RR of 0.56 (95% CI: 0.54-0.58) for infants <6 m and 0.93 (95% CI: 0.89-0.97) for infants 6-11 m. None of the other sites or age groups showed a significant reduction in the RR for attendances or admissions for the 2023-2024 season compared to previous years. INTERPRETATION: Nirsevimab had a clear impact in reducing attendances and admissions for infants with bronchiolitis aged <6 months in Catalonia. However, the impact on older infants was less clear. FUNDING: None.

BACKGROUND: Perioperative oxygen administration has been proposed as a strategy to reduce postoperative complications. However, uncertainty exists as to which strategies are the most clinically effective. OBJECTIVES: To provide an overview on the effectiveness of perioperative oxygen therapy and formulate recommendations to inform clinical decision-making and research. METHODS: We followed the Preferred Reporting Items for Overviews of Reviews guidelines. We searched key databases for systematic reviews (from inception to September 2021) and randomised controlled trials (from April 2018 to March 2022) comparing perioperative oxygen strategies. Reviews with the most comprehensive coverage of literature were chosen as anchoring reviews. We assessed risk of bias for each anchoring review using the Risk of Bias in Systematic Reviews tool. We updated meta-analyses from anchoring reviews with data from recent randomised controlled trials and conducted subgroup analyses and meta-regression. We assessed the certainty of evidence using grading of recommendations assessment, development and evaluation framework and conducted trial sequential analysis. We used grading of recommendations assessment, development and evaluation informative statements to communicate our findings. Our advisory panel reviewed mapping of studies and interpretation of evidence. RESULTS: We identified 59 systematic reviews and selected 5 anchoring reviews. A high fraction of inspired oxygen may result in a slight reduction in surgical site infection compared with a low fraction of inspired oxygen (risk ratio 0.91, 95% confidence interval 0.78 to 1.05; risk difference 1.2% lower, 2.9% lower to 0.7% higher, low-certainty evidence). This effect may be modified by type of surgery, oxygen delivery method or study quality. The evidence suggests that a high fraction of inspired oxygen results in a large increase in the incidence of atelectasis (risk ratio 1.47, 95% confidence interval 1.20 to 1.79; risk difference 6.5% higher, 2.8% higher to 10.9% higher, low-certainty evidence) and may increase postoperative pulmonary complications slightly (risk ratio 1.06, 0.77 to 1.46; risk difference 1.1% higher, 4.1% lower to 8.2% higher) but the evidence is very uncertain. A high fraction of inspired oxygen may result in little to no difference in mortality, nausea and vomiting, and length of hospital stay. Postoperative high-flow nasal oxygen may reduce the need to escalate respiratory support compared with conventional oxygen therapy (risk ratio 0.61, 0.41 to 0.91; risk difference 7.8% lower, 11.7% lower to 1.8% lower) but the evidence is very uncertain. High-flow nasal oxygen may result in little to no difference in mortality and reintubation rate. Compared with conventional oxygen therapy, postoperative non-invasive ventilation may decrease postoperative pulmonary complications (risk ratio 0.62, 0.44 to 0.87; risk difference 12.2% lower, 18% lower to 4.2% lower) and probably results in a slight reduction in the incidence of acute respiratory distress syndrome (risk ratio 0.70, 0.53 to 0.93; risk difference 1.2% lower, 1.9% lower to 0.3% lower). Non-invasive ventilation results in little to no difference in mortality, pneumonia or reintubation rate. Grading of recommendations assessment, development and evaluation certainty in evidence was low for most outcomes. Trial sequential analysis revealed further studies are required to provide conclusive evidence on the effectiveness of perioperative oxygen therapy. CONCLUSIONS: There is no clear evidence that either a high or a low fraction of inspired oxygen improves outcomes in surgical patients. Existing evidence is insufficient for recommending routine use of non-invasive ventilation or high-flow nasal oxygen. FUTURE WORK: Future randomised controlled trials should stratify participants by type of surgery, anaesthesia technique and documented risk factors for postoperative complications, such as body mass index. STUDY REGISTRATION: This study is registered as PROSPERO CRD42021272361. FUNDING: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR132987) and is published in full in