Pathophysiology of COVID-19-associated acute respiratory distress syndrome
Authors: Ananthu Narayan, Prerna Garg, Umang Arora, Animesh Ray, Naveet Wig
Journal: The Lancet Respiratory Medicine (2020)

We congratulate Giacomo Grasselli and colleagues1Grasselli G Tonetti T Protti A et al.Pathophysiology of COVID-19-associated acute respiratory distress syndrome: a multicentre prospective observational study.Lancet Respir Med. 2020; 8: 1201-1208Summary Full Text Full Text PDF PubMed Scopus (478) Google Scholar on their work in comparing acute respiratory distress syndrome (ARDS) in COVID-19 with classical ARDS. They found that median compliance in COVID-19 ARDS was higher than in classical ARDS, even after stratified analysis. However, they finally concluded that this difference was not significant. There are multiple reasons why important differentiating information might have been lost in the analyses. The grouping is based on the dichotomisation (high vs low) of the two continuous variables: D-dimer levels and compliance. Dichotomisation is well known to lead to loss of information, with up to a third being lost,2Altman DG Royston P The cost of dichotomising continuous variables.BMJ. 2006; 3321080Crossref PubMed Google Scholar as well as increasing the risk of generating a false-positive hypothesis.3Austin PC Brunner LJ Inflation of the type I error rate when a continuous confounding variable is categorized in logistic regression analyses.Stat Med. 2004; 23: 1159-1178Crossref PubMed Scopus (166) Google Scholar Dichotomisation using the median value as a cutoff in unimodal data is unlikely to find populations that are significantly different from each other. A multivariate regression analysis with mortality as the primary outcome might have been better. While ventilatory ratio is a good surrogate marker for dead space in lungs, the Enghoff modification of the Bohr equation or the Harris-Benedict equation of energy expenditure are more accurate markers that could have been used in this study.4Beitler JR Thompson BT Matthay MA et al.Estimating dead-space fraction for secondary analyses of ARDS clinical trials.Crit Care Med. 2015; 43: 1026-1035Crossref PubMed Scopus (41) Google Scholar Additionally, since the estimation of lung weight on CT scan was done only on 20 patients (less than 7% of all 301 patients), it is unlikely to be representative of the entire population. Information on the distribution of baseline comorbidities such as hypertension, diabetes, and pre-existing lung disease has not been provided. Furthermore, even though a large proportion of the study population received therapy with steroids (128 [43%] patients) and anticoagulation (182 [60%] patients), their distribution among the groups is not known. Since these factors are known to affect mortality, these covariates need to be adjusted for in all mortality analyses. Finally, both the pro-inflammatory state in COVID-19 and the high body-mass index of the population (median 27·8, IQR 25·3–31·1) would predispose patients to cardiovascular mortality, which might behave as a confounder in the analysis on mortality. Thus, the cause of death (respiratory, cardiovascular, septic, or other) needs to be taken into account while drawing conclusions about mortality in relation to ARDS. We declare no competing interests. Pathophysiology of COVID-19-associated acute respiratory distress syndrome: a multicentre prospective observational studyPatients with COVID-19-associated ARDS have a form of injury that, in many aspects, is similar to that of those with ARDS unrelated to COVID-19. Notably, patients with COVID-19-related ARDS who have a reduction in respiratory system compliance together with increased D-dimer concentrations have high mortality rates. Full-Text PDF Pathophysiology of COVID-19-associated acute respiratory distress syndrome – Authors' replyLuigi Camporota and colleagues and Vasiliki Tsolaki and colleagues challenge our finding that suggests that patients with COVID-19 have a form of injury that is encompassed by the conceptual model of acute respiratory distress syndrome (ARDS). The argument used by Camporota and colleagues and Tsolaki and colleagues is that the median static compliance we observed in patients with COVID-19-associated ARDS (41 mL/cm H2O) was significantly higher compared with patients with classical ARDS. However, they miss the point that the distribution of compliance in patients with COVID-19 ARDS was wide and only 17 (6%) of 297 patients had compliance greater than the 95th percentile of the classical ARDS cohort. Full-Text PDF Pathophysiology of COVID-19-associated acute respiratory distress syndromeWe congratulate Giacomo Grasselli and colleagues for their important and informative work on the pathophysiology of COVID-19-associated acute respiratory distress syndrome (ARDS).1 In particular, we appreciate the clarity with which the data show that respiratory system compliance was significantly higher in COVID-19-associated ARDS compared with classical aetiology ARDS, despite the former having more severe hypoxaemia. Along this line, we note their result that "static compliance decreased as [the ratio of partial pressure of arterial oxygen to fractional concentration of oxygen in inspired air] decreased in patients with classical ARDS and in a pneumonia subset of patients with ARDS, while it remained unchanged in patients with COVID-19 ARDS". Full-Text PDF Pathophysiology of COVID-19-associated acute respiratory distress syndromeWe read with great interest Giacomo Grasselli and colleagues' study concerning the pathophysiology of COVID-19-associated acute respiratory distress syndrome (ARDS).1 The authors conclude that COVID-19 ARDS presents lung mechanics that largely match those of classical ARDS.1 However, we feel this conclusion is not supported by their findings. Full-Text PDF Pathophysiology of COVID-19-associated acute respiratory distress syndromeCompared with diseases from other coronaviruses (ie, severe acute respiratory syndrome and Middle East respiratory syndrome), COVID-19 has more adverse effects on the cardiovascular system, leading to a high incidence of cardiovascular events—most notably life-threatening pulmonary vessel injury and cardiac dysfunction, with and without severe myocardial injury.1 Small pulmonary vessel injuries and thrombosis associated with pulmonary blood flow alterations followed by right heart dilation and right ventricular failure have been found among the major causes of death related to COVID‑19. Full-Text PDF