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Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease 2019 (COVID-19) pandemic that has resulted in millions of deaths and a major strain on health systems worldwide. Medical treatments for COVID-19 (anticoagulants, corticosteroids, anti-inflammatory drugs, oxygenation therapy and ventilation) and vaccination have improved patient outcomes. The majority of patients will recover spontaneously or after acute-phase management, but clinicians are now faced with long-term complications of COVID-19 including a large variety of symptoms, defined as “post-acute COVID-19 syndrome”. Most studies have focused on patients hospitalised for severe COVID-19, but acute COVID-19 syndrome is not restricted to these patients and exists in outpatients. Given the diversity of symptoms and the high prevalence of persistent symptoms, the management of these patients requires a multidisciplinary team approach, which will result in the consumption of large amounts of health resources in the coming months. In this review, we discuss the presentation, prevalence, pathophysiology and evolution of respiratory complications and other organ-related injuries associated with post-acute COVID-19 syndrome.

Pulmonary arterial hypertension (PAH) is characterized by a progressive accumulation of pulmonary artery smooth muscle cells (PA-SMCs) in pulmonary arterioles leading to the narrowing of the lumen, right heart failure, and death. Although most studies have supported the notion of a role for IL-6/glycoprotein 130 (gp130) signaling in PAH, it remains unclear how this signaling pathway determines the progression of the disease. Here, we identify ectopic upregulation of membrane-bound IL-6 receptor (IL6R) on PA-SMCs in PAH patients and in rodent models of pulmonary hypertension (PH) and demonstrate its key role for PA-SMC accumulation in vitro and in vivo. Using Sm22a-Cre Il6rfl/fl, which lack Il6r in SM22A-expressing cells, we found that these animals are protected against chronic hypoxia-induced PH with reduced PA-SMC accumulation, revealing the potent pro-survival potential of membrane-bound IL6R. Moreover, we determine that treatment with IL6R-specific antagonist reverses experimental PH in two rat models. This therapeutic strategy holds promise for future clinical studies in PAH.

IntroductionContemporary risk assessment tools categorise patients with pulmonary arterial hypertension (PAH) as low, intermediate, or high-risk. A minority of patients achieve low-risk status with most remaining intermediate-risk. Our aim was to validate a 4-strata risk assessment approach categorising patients as low, intermediate-low, intermediate-high, or high risk, as proposed by the COMPERA Registry investigators.MethodsWe evaluated incident patients from the French PAH Registry and applied a 4-strata risk method at baseline and at first reassessment. We applied refined cut-points for 3 variables: World Health Organization functional class, 6-minute walk distance, and N-terminal pro-brain natriuretic peptide. We used Kaplan-Meier survival analyses and Cox proportional hazards regression to assess survival according to a 3-strata and 4-strata risk approach.ResultsAt baseline (n=2879), the 4-strata approach identified 4 distinct risk groups and performed better than a 3-strata method for predicting mortality. The 4-strata model discrimination was higher than the 3-strata method when applied during follow-up and refined risk categories among subgroups with idiopathic PAH, connective tissue disease-associated PAH, congenital heart disease, and portopulmonary hypertension. Using the 4-strata approach, 53% of patients changed risk category from baseline compared to 39% of patients when applying the 3-strata approach. Those who achieved or maintained a low-risk status had the best survival, whereas there were more nuanced differences in survival for patients who were intermediate-low and intermediate-high.ConclusionsThe 4-strata risk assessment method refined risk prediction, especially within the intermediate risk category of patients, performed better at predicting survival and was more sensitive to change than the 3-strata approach.

BackgroundViral respiratory infections are the main causes of asthma exacerbation. The susceptibility of asthmatics to develop an exacerbation when they present with severe pneumonia due to SARS-CoV-2 infection is unknown. The objective of this study was to investigate the characteristics and outcomes of asthmatic patients with COVID-19 pneumonia who required hospitalisation during the spring 2020 outbreak in Paris, France.MethodsA prospective cohort follow-up was carried out from March 15 to April 15, 2020 in Bicêtre Hospital, University Paris-Saclay, France. All hospitalised patients with a SARS-CoV-2 infection who reported a history of asthma were included.ResultsAmong 768 hospitalised patients, 37 (4.8%) reported a history of asthma, which had been previously confirmed by a pulmonologist in 85% of cases. Patients were mainly female (70%), non-smokers (85%), with a median age of 54 years (interquartile range, IQR 42–67). None of them presented with an asthma exacerbation. Twenty-two (59%) had major comorbidities and 31 (84%) had a body mass index ≥25 kg·m−2. The most common comorbidities were obesity (36%), hypertension (27%) and diabetes (19%). All patients had a confirmed diagnosis of COVID-19 pneumonia on computed tomography of the chest. Eosinopenia was a typical biologic feature with a median count of 0/mm3 (IQR 0–0). Eleven patients (30%) were admitted in intensive care unit with three death (8.1%) occurring in the context of comorbidities.ConclusionAsthmatics were not overrepresented among patients with severe pneumonia due to SARS-CoV-2 infection who required hospitalisation. Worst outcomes were observed mainly in patients with major comorbidities.

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Pleural effusion is a frequent side-effect of dasatinib, a second-generation tyrosine kinase inhibitor used in the treatment of chronic myelogenous leukaemia. However, the underlying mechanisms remain unknown. We hypothesised that dasatinib alters endothelial integrity, resulting in increased pulmonary vascular endothelial permeability and pleural effusion.To test this, we established the first animal model of dasatinib-related pleural effusion, by treating rats with a daily regimen of high doses of dasatinib (10 mg·kg·day for 8 weeks).Pleural ultrasonography revealed that rats chronically treated with dasatinib developed pleural effusion after 5 weeks. Consistent with these observations, dasatinib led to a rapid and reversible increase in paracellular permeability of human pulmonary endothelial cell monolayers as reflected by increased macromolecule passage, loss of vascular endothelial cadherin and zonula occludens-1 from cell-cell junctions, and the development of actin stress fibres. These results were replicated using human umbilical vein endothelial cells and confirmed by decreased endothelial resistance. Interestingly, we demonstrated that this increased endothelial permeability is a reactive oxygen species (ROS)-dependent mechanism and using a cotreatment with an antioxidant agent,-acetylcysteine.This study shows that dasatinib alters pulmonary endothelial permeability in a ROS-dependent manner and leading to pleural effusion.

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