Pathophysiology of COVID-19-associated acute respiratory distress syndrome: a multicentre prospective observational study

Abstract

Background Patients with COVID-19 can develop acute respiratory distress syndrome (ARDS), which is associated with high mortality. The aim of this study was to examine the functional and morphological features of COVID-19-associated ARDS and to compare these with the characteristics of ARDS unrelated to COVID-19. Methods This prospective observational study was done at seven hospitals in Italy. We enrolled consecutive, mechanically ventilated patients with laboratory-confirmed COVID-19 and who met Berlin criteria for ARDS, who were admitted to the intensive care unit (ICU) between March 9 and March 22, 2020. All patients were sedated, paralysed, and ventilated in volume-control mode with standard ICU ventilators. Static respiratory system compliance, the ratio of partial pressure of arterial oxygen to fractional concentration of oxygen in inspired air, ventilatory ratio (a surrogate of dead space), and D-dimer concentrations were measured within 24 h of ICU admission. Lung CT scans and CT angiograms were done when clinically indicated. A dataset for ARDS unrelated to COVID-19 was created from previous ARDS studies. Survival to day 28 was assessed. Findings Between March 9 and March 22, 2020, 301 patients with COVID-19 met the Berlin criteria for ARDS at participating hospitals. Median static compliance was 41 mL/cm H 2 O (33–52), which was 28% higher than in the cohort of patients with ARDS unrelated to COVID-19 (32 mL/cm H 2 O [25–43]; p<0·0001). 17 (6%) of 297 patients with COVID-19-associated ARDS had compliances greater than the 95th percentile of the classical ARDS cohort. Total lung weight did not differ between the two cohorts. CT pulmonary angiograms (obtained in 23 [8%] patients with COVID-19-related ARDS) showed that 15 (94%) of 16 patients with D-dimer concentrations greater than the median had bilateral areas of hypoperfusion, consistent with thromboembolic disease. Patients with D-dimer concentrations equal to or less than the median had ventilatory ratios lower than those of patients with D-dimer concentrations greater than the median (1·66 [1·32–1·95] vs 1·90 [1·50–2·33]; p=0·0001). Patients with static compliance equal to or less than the median and D-dimer concentrations greater than the median had markedly increased 28-day mortality compared with other patient subgroups (40 [56%] of 71 with high D-dimers and low compliance vs 18 [27%] of 67 with low D-dimers and high compliance, 13 [22%] of 60 with low D-dimers and low compliance, and 22 [35%] of 63 with high D-dimers and high compliance, all p=0·0001). Interpretation Patients 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-dim...

Physiological and quantitative CT-scan characterization of COVID-19 and typical ARDS: a matched cohort study

“…This observation strongly suggests that the major component of the venous admixture in COVID-19-ARDS is ventilationperfusion mismatch, rather than true right-to-left shunt. The important role of V A /Q mismatch in COVID-19-ARDS is consistent with (but not entirely explained by) the reported high incidence of micro and macro thrombosis in this disease [11,14,30,31] and with the importance of markers of immune-thrombosis (e.g., d-dimers) in the outcome of COVID-19-ARDS [8]. Lung gas volume measured in the 10 equally spaced lung segments along the sterno-vertebral axis (level 1 = closest to the sternum, level 10 = closest to the vertebra).…”

“…Differently from typical ARDS, where the decrease of PaO 2 /FiO 2 ratio is associated with a decrease in Crs, in our COVID-19-ARDS population PaO 2 /FiO 2 ratio and Crs were unrelated. This has also been found in a recent larger study comparing typical ARDS with COVID-19-ARDS [8]. This contrasts with the decision taken in Berlin to exclude Crs from the ARDS definition as unnecessary, as it added no prognostic value to the PaO 2 /FiO 2 ratio alone [10].…”

“…The conditions of measurement are also important. Most studies, such as the largest one yet published on COVID-19 pathophysiology [8], report Crs values measured under the prevailing "clinical conditions". In all cohorts of our COVID-19-ARDS, PaO 2 /FiO 2 -matched-ARDS and Compliance-matched-ARDS populations, all measurements were performed at a standard PEEP of 5 cmH 2 O.…”

“…We have reported [2,3] that severe hypoxemia with relatively well-preserved respiratory system compliance (Crs) measured under standard conditions is characteristic of COVID-19-ARDS, and it differs from ARDS of other causes (typical ARDS), while others did not recognize consistent differences [4][5][6][7]. However, the increased frequency of higher Crs in COVID-19-ARDS was noted by some of the same authors [4,5], and a significantly higher Crs associated with severe hypoxemia was recently documented [8]. The heterogeneous nature of ARDS allows that-at the population level-there may be wide overlap between COVID-19-ARDS and typical ARDS, and these observations continue to drive a debate [6,9].…”

Management reorganization of a Radiology ward during the Covid-19 pandemic in a University Hospital structured inpavilions.

“…This illness presents with symptoms such as fever, malaise, dry cough, dyspnoea, diarrhea, skin rashes, conjunctivitis and respiratory distress, with a more severe clinical course in elderly patients with comorbidities, causing respiratory failure due to diffuse alveolar damage, multi organ failure, shock and possibly death [5][6][7]. Patients who suffer from COVID-19-associated ARDS who have both a reduction in respiratory system compliance and an increased D-dimer concentrations are subject to higher mortality rates [8].…”