The COVID-19 pandemic has resulted in significant acute morbidity and mortality worldwide. There is now a growing recognition of the longer-term sequelae of this infection, termed “long COVID”. However, little is known about this condition. Here, we describe a distinct phenotype seen in a subset of patients with long COVID who have reduced exercise tolerance as measured by the 6 min walk test. They are associated with significant exertional dyspnea, reduced health-related quality of life and poor functional status. However, surprisingly, they do not appear to have any major pulmonary function abnormalities or increased burden of neurologic, musculoskeletal or fatigue symptoms.

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Background: Mortality risk stratification is essential in lung transplantation (LTx) to allow listing, prioritization and mitigating strategies. In cystic fibrosis (CF) patients, predictors of post-LTx mortality are not established. Methods: For this systematic review and meta-analysis, seven databases were searched until January 3, 2018 to identify predictors of post-LTx mortality in CF. We excluded studies of multi-organ transplantation, re-transplantation and graft survival. For multiple studies assessing the same population during overlapping time-periods, the largest one was analyzed. Risk of bias was assessed with the Newcastle-Ottawa scale (NOS). Pooled hazard ratios were calculated using random-effects models. Results: Fifty-four studies were included in the systematic review and 11 studies in the meta-analyses (low-tomoderate bias risk, NOS score ≥ 5). Among 10 factors assessed in the meta-analysis, B. cepacia complex (BCC) (N = 1451, unadjusted HR = 2.35, 95%CI:1.80-3.06; I 2 = 20.4% and adjusted HR = 2.49, 95%CI:1.74-3.57; I 2 = 46.2%) and ascending chronological year of LTx (N = 4207, unadjusted HR = 0.98, 95%CI:0.97-0.98, I 2 = 4.8%) were predictors of post-LTx mortality. Male gender (N = 2903, adjusted HR = 1.12, 95%CI:1.0-1.26, I 2 = 0%) and age in adults (N = 3677, unadjusted HR = 0.99, 95%CI:0.97-1.00; I 2 = 64.1% and N = 2605, adjusted HR = 0.98, 95%CI:0.97-0.99; I 2 = 34.3%) had borderline significant associations with post-LTx mortality. P. aeruginosa colonization, forced expiratory volume in one second (FEV 1 ), pulmonary hypertension, body mass index (BMI), pancreatic insufficiency and CF-related diabetes (CFRD) were not predictors of mortality. Conclusions: BCC was associated with a higher post-LTx mortality whereas FEV 1 , pulmonary hypertension, BMI, CFRD and female gender were not associated with post-LTx mortality. These findings indicate that CF-specific risk estimates of post-LTx mortality should be considered.

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IntroductionThe evolution in pulmonary arterial hypertension (PAH) management has been summarized in three iterations of the European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines. No study has assessed whether changes in management, as reflected in the changing guidelines, has translated to improved long-term survival in PAH.MethodsMixed retrospective/prospective analysis of treatment naïve, incident PAH patients (n=392) diagnosed at three major centers in Canada from 2009–2021. Patients were divided into two groups based on their diagnosis date and in accordance with three ESC/ERS guideline iterations: 2009 and 2015. Overall survival was assessed based on date of diagnosis and initial treatment strategy (i.e. mono versus combination).ResultsIn Canada, there was a shift towards more aggressive upfront management with combination therapy after the publication of the 2015 guidelines (10.4% and 30.8% in 2009–2015 patients, and 36.0% and 57.4% in 2016–2021 patients, for baseline and 2-year follow-up respectively). A key factor associated with combination therapy after 2015 was higher pulmonary vascular resistance (p=0.009). The 1, 3 and 5 year survival rates in Canada were 89.2%, 75.6%. and 56.0%, respectively. Despite changes in management, there was no improvement in long-term survival before and after publication of the 2015 ESC/ERS guideline (p=0.53).ConclusionsThere was an increase in the use of initial and sequential combination therapy in Canada after publication of the 2015 ESC/ERS guidelines, which was not associated with improved long-term survival. These data highlight the continued difficulties of managing this aggressive pulmonary disease in an era without a cure.

Despite COVID-19’s significant morbidity and mortality, considering cost-effectiveness of pharmacologic treatment strategies for hospitalized patients remains critical to support healthcare resource decisions within budgetary constraints. As such, we calculated the cost-effectiveness of using remdesivir and dexamethasone for moderate to severe COVID-19 respiratory infections using the United States health care system as a representative model. A decision analytic model modelled a base case scenario of a 60-year-old patient admitted to hospital with COVID-19. Patients requiring oxygen were considered moderate severity, and patients with severe COVID-19 required intubation with intensive care. Strategies modelled included giving remdesivir to all patients, remdesivir in only moderate and only severe infections, dexamethasone to all patients, dexamethasone in severe infections, remdesivir in moderate/dexamethasone in severe infections, and best supportive care. Data for the model came from the published literature. The time horizon was 1 year; no discounting was performed due to the short duration. The perspective was of the payer in the United States health care system. Supportive care for moderate/severe COVID-19 cost $11,112.98 with 0.7155 quality adjusted life-year (QALY) obtained. Using dexamethasone for all patients was the most-cost effective with an incremental cost-effectiveness ratio of $980.84/QALY; all remdesivir strategies were more costly and less effective. Probabilistic sensitivity analyses showed dexamethasone for all patients was most cost-effective in 98.3% of scenarios. Dexamethasone for moderate-severe COVID-19 infections was the most cost-effective strategy and would have minimal budget impact. Based on current data, remdesivir is unlikely to be a cost-effective treatment for COVID-19.

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participated in developing the study and preparing the article. D.L. helped in collecting data and performing the analyses. K.H. developed the study, performed the main analyses, and wrote the final draft of the article.The data that support these analyses can be made available on reasonable request to the corresponding author (K.H.).