Pathophysiology of COVID-19-associated acute respiratory distress syndrome
Authors: Michael Dandel
Journal: The Lancet Respiratory Medicine (2020)

Compared 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.1Gupta A Madhavan MV Sehgal K et al.Extrapulmonary manifestations of COVID-19.Nat Med. 2020; 26: 1017-1032Crossref PubMed Scopus (1965) Google Scholar 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‑19.1Gupta A Madhavan MV Sehgal K et al.Extrapulmonary manifestations of COVID-19.Nat Med. 2020; 26: 1017-1032Crossref PubMed Scopus (1965) Google Scholar In The Lancet Respiratory Medicine, Giacomo Grasselli and colleagues2Grasselli 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 showed that COVID-19-associated pulmonary injury with acute respiratory distress syndrome (ARDS) is characterised by decreased pulmonary compliance and increased lung weight. Of particular importance is the observation that, when pulmonary damage occurred together with high D-dimer concentrations, mortality increased: 28-day mortality was twice as high in the high D-dimers–low compliance patient group (40 [56%] of 71 patients) compared with the low D-dimers−high compliance group (18 [27%] of 67 patients). CT also revealed filling defects or occlusions of the pulmonary vasculature that were more prominent in patients with high D-dimer concentrations (15 [94%] of 16 patients with elevated D-dimer concentrations had bilateral, diffuse areas of hypoperfusion, consistent with the presence of thrombi or emboli). These observations strongly indicate that pulmonary vascular thrombosis can be the main cause of COVID-19-related death. In this regard, it would be particularly important to have information on pulmonary arterial pressure and right-sided heart anatomy and function because, due to the direct alterations and damages of the pulmonary circulation, the pathophysiological role of the heart–lung interactions will become mainly involved in the development and progression of life-threatening right ventricular dysfunction. Echocardiography has revealed elevated pulmonary arterial pressure in nearly 70% of patients with COVID-19.3García-Cruz E Manzur-Sandoval D Rascón-Sabido R et al.Critical care ultrasonography during COVID-19 pandemic: the ORACLE protocol.Echocardiography. 2020; (published online Aug 29.)https://doi.org/10.1111/echo.14837Crossref PubMed Scopus (38) Google Scholar In one study, right ventricular dilation was present in 31% of hospitalised patients and on multivariate analysis, right ventricular dilation was the only variable associated with mortality.4Argulian E Sud K Vogel B et al.Right ventricular dilation in hospitalized patients with COVID-19 infection.JACC Cardiovasc Imaging. 2020; (published online May 15.)https://doi.org/10.1016/j.jcmg.2020.05.010Crossref Scopus (159) Google Scholar In heart-transplanted patients with COVID-19 who needed mechanical ventilation, the high mortality (up to 87%) appeared mainly associated with increased pulmonary arterial pressure and right ventricular dysfunction, whereas no patient showed left ventricular dysfunction.5Rivinius R Kaya Z Schramm R et al.COVID-19 among heart transplant recipients in Germany: a multicenter survey.Clin Res Cardiol. 2020; (published online Aug 11.)https://doi.org/10.1007/s00392-020-01722-wCrossref Scopus (62) Google Scholar Putting together all the information regarding D-dimers, respiratory system compliance, pulmonary hypoperfusion, pulmonary arterial pressure, and right-sided heart dilation and dysfunction leads to the conclusion that these aspects, and particularly the often neglected right ventricular, need more attention. Hand-held laptop-based echocardiography devices, which can be sufficient for assessment of right-sided heart alterations and dysfunction, could substantially improve the management of patients with symptomatic COVID-19 to reduce the particularly high mortality rates. I declare no competing interests. Pathophysiology of COVID-19-associated acute respiratory distress syndromeWe congratulate Giacomo Grasselli and colleagues1 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. 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 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 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 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