Aims:Coronavirus disease 2019 caused by SARS-CoV-2 has rapidly evolved into a sweeping pandemic. While its major manifestation is in the respiratory tract, the general extent of organ involvement as well as microscopic changes in the lungs remain insufficiently characterised. Autopsies are essential to elucidate COVID-19-associated organ alterations.Methods: This study reports autopsy findings of 21 COVID-19 patients hospitalised at the University Hospital Basel and at the Cantonal Hospital Baselland, Switzerland. An in-corpore technique was performed to ensure optimal staff safety. Results:The primary cause of death was respiratory failure with exudative diffuse alveolar damage with massive capillary congestion often accompanied by microthrombi despite anticoagulation. Ten cases showed superimposed bronchopneumonia. Further findings included pulmonary embolisms (n=4), alveolar haemorrhage (n=3) and vasculitis (n=1). Pathologies in other organ systems were predominantly attributable to shock; three patients showed signs of generalised thrombotic microangiopathy. Six patients were diagnosed with senile cardiac amyloidosis upon autopsy. Most patients suffered from one or more comorbidities (hypertension, obesity, cardiovascular diseases, diabetes mellitus). Additionally, there was an overall predominance of males and individuals with blood group A (81% and 65%, respectively). All relevant histological slides are linked as open-source scans in supplementary files. Conclusions:This study provides an overview of post-mortem findings in COVID-19 cases, implying that hypertensive, elderly, obese, male individuals with severe cardiovascular comorbidities as well as those with blood group A may have a lower threshold of tolerance for COVID-19. This provides a pathophysiological explanation for higher mortality rates amongst these patients.

BackgroundAppropriate interpretation of pulmonary function tests (PFTs) involves the classification of observed values as within/outside the normal range based on a reference population of healthy individuals, integrating knowledge of physiologic determinants of test results into functional classifications, and integrating patterns with other clinical data to estimate prognosis. In 2005, the American Thoracic Society and the European Respiratory Society jointly adopted technical standards for the interpretation of PFTs. We aimed to update the 2005 recommendations and incorporate evidence from recent literature to establish new standard for PFT interpretation.MethodsThis technical standards document was developed by an international joint task force, appointed by the European Respiratory Society and the American Thoracic Society with multidisciplinary expertise in conducting and interpreting pulmonary function tests, and developing international standards. A comprehensive literature review was conducted, and published evidence was reviewed.ResultsRecommendations for the choice of reference equations and limits of normal of the healthy population to identify individuals with unusually low or high results, respectively are discussed. Interpretation strategies for bronchodilator responsiveness testing, limits of natural changes over time and severity are also updated. Interpretation of measurements made by spirometry, lung volumes and gas transfer are described as they relate to underlying pathophysiology with updated classification protocols of common impairments.ConclusionsPFTs interpretation must be complemented with clinical expertise and consider the inherent biological variability of the test and the uncertainty of the test result to ensure appropriate interpretation of an individual's lung function measurements.

This international task force report updates general considerations for bronchial challenge testing and the performance of the methacholine challenge test. There are notable changes from prior recommendations in order to accommodate newer delivery devices. Rather than basing the test result upon a methacholine concentration (provocative concentration (PC) causing a 20% fall in forced expiratory volume in 1 s (FEV)), the new recommendations base the result upon the delivered dose of methacholine causing a 20% fall in FEV (provocative dose (PD)). This end-point allows comparable results from different devices or protocols, thus any suitable nebuliser or dosimeter may be used, so long as the delivery characteristics are known. Inhalation may be by tidal breathing using a breath-actuated or continuous nebuliser for 1 min (or more), or by a dosimeter with a suitable breath count. Tests requiring maximal inhalations to total lung capacity are not recommended because the bronchoprotective effect of a deep breath reduces the sensitivity of the test.

Recently, this international task force reported the general considerations for bronchial challenge testing and the performance of the methacholine challenge test, a “direct” airway challenge test. Here, the task force provides an updated description of the pathophysiology and the methods to conduct indirect challenge tests. Because indirect challenge tests trigger airway narrowing through the activation of endogenous pathways that are involved in asthma, indirect challenge tests tend to be specific for asthma and reveal much about the biology of asthma, but may be less sensitive than direct tests for the detection of airway hyperresponsiveness. We provide recommendations for the conduct and interpretation of hyperpnoea challenge tests such as dry air exercise challenge and eucapnic voluntary hyperpnoea that provide a single strong stimulus for airway narrowing. This technical standard expands the recommendations to additional indirect tests such as hypertonic saline, mannitol and adenosine challenge that are incremental tests, but still retain characteristics of other indirect challenges. Assessment of airway hyperresponsiveness, with direct and indirect tests, are valuable tools to understand and to monitor airway function and to characterise the underlying asthma phenotype to guide therapy. The tests should be interpreted within the context of the clinical features of asthma.