Ventilatory ratio and mechanical power in prolonged mechanically ventilated COVID-19 patients versus respiratory failures of other etiologies.

BACKGROUND: Evidence suggests differences in ventilation efficiency and respiratory mechanics between early COVID-19 pneumonia and classical acute respiratory distress syndrome (ARDS), as measured by established ventilatory indexes, such as the ventilatory ratio (VR; a surrogate of the pulmonary dead-space fraction) or mechanical power (MP; affected, e.g., by changes in lung-thorax compliance). OBJECTIVES: The aim of this study was to evaluate VR and MP in the late stages of the disease when patients are ready to be liberated from the ventilator after recovering from COVID-19 pneumonia compared to respiratory failures of other etiologies. DESIGN: A retrospective observational cohort study of 249 prolonged mechanically ventilated, tracheotomized patients with and without COVID-19-related respiratory failure. METHODS: We analyzed each group's VR and MP distributions and trajectories [repeated-measures analysis of variance (ANOVA)] during weaning. Secondary outcomes included weaning failure rates between groups and the ability of VR and MP to predict weaning outcomes (using logistic regression models). RESULTS: The analysis compared 53 COVID-19 cases with a heterogeneous group of 196 non-COVID-19 subjects. VR and MP decreased across both groups during weaning. COVID-19 patients demonstrated higher values for both indexes throughout weaning: median VR 1.54 versus 1.27 (p < 0.01) and MP 26.0 versus 21.3 Joule/min (p < 0.01) at the start of weaning, and median VR 1.38 versus 1.24 (p < 0.01) and MP 24.2 versus 20.1 Joule/min (p < 0.01) at weaning completion. According to the multivariable analysis, VR was not independently associated with weaning outcomes, and the ability of MP to predict weaning failure or success varied with lung-thorax compliance, with COVID-19 patients demonstrating consistently higher dynamic compliance along with significantly fewer weaning failures (9% versus 30%, p < 0.01). CONCLUSION: COVID-19 patients differed considerably in ventilation efficiency and respiratory mechanics among prolonged ventilated individuals, demonstrating significantly higher VRs and MP. The differences in MP were linked with higher lung-thorax compliance in COVID-19 patients, possibly contributing to the lower rate of weaning failures observed.

Dead space ventilation-related indices: bedside tools to evaluate the ventilation and perfusion relationship in patients with acute respiratory distress syndrome.

Cumulative evidence has demonstrated that the ventilatory ratio closely correlates with mortality in acute respiratory distress syndrome (ARDS), and a primary feature in coronavirus disease 2019 (COVID-19)-ARDS is increased dead space that has been reported recently. Thus, new attention has been given to this group of dead space ventilation-related indices, such as physiological dead space fraction, ventilatory ratio, and end-tidal-to-arterial PCO2 ratio, which, albeit distinctive, are all global indices with which to assess the relationship between ventilation and perfusion. These parameters have already been applied to positive end expiratory pressure titration, prediction of responses to the prone position and the field of extracorporeal life support for patients suffering from ARDS. Dead space ventilation-related indices remain hampered by several deflects; notwithstanding, for this catastrophic syndrome, they may facilitate better stratifications and identifications of subphenotypes, thereby providing therapy tailored to individual needs.

Early decrease of ventilatory ratio after prone position ventilation may predict successful weaning in patients with acute respiratory distress syndrome: A retrospective cohort study.

Background: Previous studies usually identified patients who benefit the most from prone positioning by oxygenation improvement. However, inconsistent results have been reported. Physiologically, pulmonary dead space fraction may be more appropriate in evaluating the prone response. As an easily calculated bedside index, ventilatory ratio (VR) correlates well with pulmonary dead space fraction. Hence, we investigated whether the change in VR after prone positioning is associated with weaning outcomes at day 28 and to identify patients who will benefit the most from prone positioning. Materials and methods: This retrospective cohort study was performed in a group of mechanically ventilated, non-COVID ARDS patients who received prone positioning in the ICU at Zhongda hospital, Southeast University. The primary outcome was the rate of successful weaning patients at day 28. Arterial blood gas results and corresponding ventilatory parameters on five different time points around the first prone positioning were collected, retrospectively. VR responders were identified by Youden's index. Competing-risk regression models were used to identify the association between the VR change and liberation from mechanical ventilation at day 28. Results: One hundred and three ARDS patients receiving prone positioning were included, of whom 53 (51%) successfully weaned from the ventilator at day 28. VR responders were defined as patients showing a decrease in VR of greater than or equal to 0.037 from the baseline to within 4 h after prone. VR responders have significant longer ventilator-free days, higher successful weaning rates and lower mortality compared with non-responders at day 28. And a significant between-group difference exists in the respiratory mechanics improvement after prone (P < 0.05). A linear relationship was also found between VR change and compliance of the respiratory system (Crs) change after prone (r = 0.32, P = 0.025). In the multivariable competing-risk analysis, VR change (sHR 0.57; 95% CI, 0.35-0.92) was independently associated with liberation from mechanical ventilation at day 28. Conclusion: Ventilatory ratio decreased more significantly within 4 h after prone positioning in patients with successful weaning at day 28. VR change was independently associated with liberation from mechanical ventilation at day 28.

Physiological response to prone positioning in intubated adults with COVID-19 acute respiratory distress syndrome: a retrospective study.

BACKGROUND: COVID-19 related acute respiratory distress syndrome (ARDS) has specific characteristics compared to ARDS in other populations. Proning is recommended by analogy with other forms of ARDS, but few data are available regarding its physiological effects in this population. This study aimed to assess the effects of proning on oxygenation parameters (PaO2/FiO2 and alveolo-arterial gradient (Aa-gradient)), blood gas analysis, ventilatory ratio (VR), respiratory system compliance (CRS) and estimated dead space fraction (VD/VT HB). We also looked for variables associated with treatment failure. METHODS: Retrospective monocentric study of intubated COVID-19 ARDS patients managed with an early intubation, low to moderate positive end-expiratory pressure and early proning strategy hospitalized from March 6 to April 30 2020. Blood gas analysis, PaO2/FiO2, Aa-gradient, VR, CRS and VD/VT HB were compared before and at the end of each proning session with paired t-tests or Wilcoxon tests (p < 0.05 considered as significant). Proportions were assessed using Fischer exact test or Chi square test. RESULTS: Forty-two patients were included for a total of 191 proning sessions, median duration of 16 (5-36) hours. Considering all sessions, PaO2/FiO2 increased (180 [148-210] vs 107 [90-129] mmHg, p < 0.001) and Aa-gradient decreased (127 [92-176] vs 275 [211-334] mmHg, p < 0.001) with proning. CRS (36.2 [30.0-41.8] vs 32.2 [27.5-40.9] ml/cmH2O, p = 0.003), VR (2.4 [2.0-2.9] vs 2.3 [1.9-2.8], p = 0.028) and VD/VT HB (0.72 [0.67-0.76] vs 0.71 [0.65-0.76], p = 0.022) slightly increased. Considering the first proning session, PaO2/FiO2 increased (186 [165-215] vs 104 [94-126] mmHg, p < 0.001) and Aa-gradient decreased (121 [89-160] vs 276 [238-321] mmHg, p < 0.001), while CRS, VR and VD/VT HB were unchanged. Similar variations were observed during the subsequent proning sessions. Among the patients who experienced treatment failure (defined as ICU death or need for extracorporeal membrane oxygenation), fewer expressed a positive response in terms of oxygenation (defined as increase of more than 20% in PaO2/FiO2) to the first proning (67 vs 97%, p = 0.020). CONCLUSION: Proning in COVID-19 ARDS intubated patients led to an increase in PaO2/FiO2 and a decrease in Aa-gradient if we consider all the sessions together, the first one or the 4 subsequent sessions independently. When considering all sessions, CRS increased and VR and VD/VT HB only slightly increased.

Vasculopathy and Increased Vascular Congestion in Fatal COVID-19 and Acute Respiratory Distress Syndrome.

Rationale: The leading cause of death in coronavirus disease 2019 (COVID-19) is severe pneumonia, with many patients developing acute respiratory distress syndrome (ARDS) and diffuse alveolar damage (DAD). Whether DAD in fatal COVID-19 is distinct from other causes of DAD remains unknown. Objective: To compare lung parenchymal and vascular alterations between patients with fatal COVID-19 pneumonia and other DAD-causing etiologies using a multidimensional approach. Methods: This autopsy cohort consisted of consecutive patients with COVID-19 pneumonia (n = 20) and with respiratory failure and histologic DAD (n = 21; non-COVID-19 viral and nonviral etiologies). Premortem chest computed tomography (CT) scans were evaluated for vascular changes. Postmortem lung tissues were compared using histopathological and computational analyses. Machine-learning-derived morphometric analysis of the microvasculature was performed, with a random forest classifier quantifying vascular congestion (CVasc) in different microscopic compartments. Respiratory mechanics and gas-exchange parameters were evaluated longitudinally in patients with ARDS. Measurements and Main Results: In premortem CT, patients with COVID-19 showed more dilated vasculature when all lung segments were evaluated (P = 0.001) compared with controls with DAD. Histopathology revealed vasculopathic changes, including hemangiomatosis-like changes (P = 0.043), thromboemboli (P = 0.0038), pulmonary infarcts (P = 0.047), and perivascular inflammation (P < 0.001). Generalized estimating equations revealed significant regional differences in the lung microarchitecture among all DAD-causing entities. COVID-19 showed a larger overall CVasc range (P = 0.002). Alveolar-septal congestion was associated with a significantly shorter time to death from symptom onset (P = 0.03), length of hospital stay (P = 0.02), and increased ventilatory ratio [an estimate for pulmonary dead space fraction (Vd); p = 0.043] in all cases of ARDS. Conclusions: Severe COVID-19 pneumonia is characterized by significant vasculopathy and aberrant alveolar-septal congestion. Our findings also highlight the role that vascular alterations may play in Vd and clinical outcomes in ARDS in general.

Early prolonged prone position in noninvasively ventilated patients with SARS-CoV-2-related moderate-to-severe hypoxemic respiratory failure: clinical outcomes and mechanisms for treatment response in the PRO-NIV study.

BACKGROUND: Whether prone position (PP) improves clinical outcomes in COVID-19 pneumonia treated with noninvasive ventilation (NIV) is unknown. We evaluated the effect of early PP on 28-day NIV failure, intubation and death in noninvasively ventilated patients with moderate-to-severe acute hypoxemic respiratory failure due to COVID-19 pneumonia and explored physiological mechanisms underlying treatment response. METHODS: In this controlled non-randomized trial, 81 consecutive prospectively enrolled patients with COVID-19 pneumonia and moderate-to-severe (paO2/FiO2 ratio < 200) acute hypoxemic respiratory failure treated with early PP + NIV during Dec 2020-May 2021were compared with 162 consecutive patients with COVID-19 pneumonia matched for age, mortality risk, severity of illness and paO2/FiO2 ratio at admission, treated with conventional (supine) NIV during Apr 2020-Dec 2020 at HUMANITAS Gradenigo Subintensive Care Unit, after propensity score adjustment for multiple baseline and treatment-related variables to limit confounding. Lung ultrasonography (LUS) was performed at baseline and at day 5. Ventilatory parameters, physiological dead space indices (DSIs) and circulating inflammatory and procoagulative biomarkers were monitored during the initial 7 days. RESULTS: In the intention-to-treat analysis. NIV failure occurred in 14 (17%) of PP patients versus 70 (43%) of controls [HR = 0.32, 95% CI 0.21-0.50; p < 0.0001]; intubation in 8 (11%) of PP patients versus 44 (30%) of controls [HR = 0.31, 95% CI 0.18-0.55; p = 0.0012], death in 10 (12%) of PP patients versus 59 (36%) of controls [HR = 0.27, 95% CI 0.17-0.44; p < 0.0001]. The effect remained significant within different categories of severity of hypoxemia (paO2/FiO2 < 100 or paO2/FiO2 100-199 at admission). Adverse events were rare and evenly distributed. Compared with controls, PP therapy was associated with improved oxygenation and DSIs, reduced global LUS severity indices largely through enhanced reaeration of dorso-lateral lung regions, and an earlier decline in inflammatory markers and D-dimer. In multivariate analysis, day 1 CO2 response outperformed O2 response as a predictor of LUS changes, NIV failure, intubation and death. CONCLUSION: Early prolonged PP is safe and is associated with lower NIV failure, intubation and death rates in noninvasively ventilated patients with COVID-19-related moderate-to-severe hypoxemic respiratory failure. Early dead space reduction and reaeration of dorso-lateral lung regions predicted clinical outcomes in our study population. CLINICAL TRIAL REGISTRATION: ISRCTN23016116 . Retrospectively registered on May 1, 2021.

Clinical characteristics, respiratory management, and determinants of oxygenation in COVID-19 ARDS: A prospective cohort study.

PURPOSE: To identify determinants of oxygenation over time in patients with COVID-19 acute respiratory distress syndrome (ARDS); and to analyze their characteristics according to Berlin definition categories. MATERIALS AND METHODS: Prospective cohort study including consecutive mechanically ventilated patients admitted between 3/20/2020-10/31/2020 with ARDS. Epidemiological and clinical data on admission; outcomes; ventilation, respiratory mechanics and oxygenation variables were registered on days 1, 3 and 7 for the entire population and for ARDS categories. RESULTS: 1525 patients aged 61 ± 13, 69% male, met ARDS criteria; most frequent comorbidities were obesity, hypertension, diabetes and respiratory disease. On admission, 331(21%), 849(56%) and 345(23%) patients had mild, moderate and severe ARDS; all received lung-protective ventilation (mean tidal volumes between 6.3 and 6.7 mL/kg PBW) and intermediate PEEP levels (10-11 cmH2O). PaO2/FiO2, plateau pressure, static compliance, driving pressure, ventilation ratio, pH and D-dimer >2 mg/L remained significantly different among the ARDS categories over time. In-hospital mortality was, respectively, 55%, 58% and 70% (p < 0.000). Independent predictors of changes of PaO2/FiO2 over time were BMI; preexistent respiratory disease; D-dimer >2 mg/L; day 1-PEEP, and day 1-ventilatory ratio. CONCLUSION: Hypoxemia in patients with COVID-19-related ARDS is associated with comorbidities, deadspace and activated coagulation markers, and disease severity-reflected by the PEEP level required.

Mortality and Pulmonary Embolism in Acute Respiratory Distress Syndrome From COVID-19 vs. Non-COVID-19.

Purpose: There may be a difference in respiratory mechanics, inflammatory markers, and pulmonary emboli in COVID-19 associated ARDS vs. ARDS from other etiologies. Our purpose was to determine differences in respiratory mechanics, inflammatory markers, and incidence of pulmonary embolism in patients with and without COVID-19 associated ARDS admitted in the same period and treated with a similar ventilation strategy. Methods: A cohort study of COVID-19 associated ARDS and non COVID-19 patients in a Saudi Arabian center between June 1 and 15, 2020. We measured respiratory mechanics (ventilatory ratio (VR), recruitability index (RI), markers of inflammation, and computed tomography pulmonary angiograms. Results: Forty-two patients with COVID-19 and 43 non-COVID patients with ARDS comprised the cohort. The incidence of "recruitable" patients using the recruitment/inflation ratio was slightly lower in COVID-19 patients (62 vs. 86%; p = 0.01). Fifteen COVID-19 ARDS patients (35.7%) developed a pulmonary embolism as compared to 4 (9.3%) in other ARDS patients (p = 0.003). In COVID-19 patients, a D-Dimer ≥ 5.0 mcg/ml had a 73% (95% CI 45-92%) sensitivity and 89% (95% CI 71-98%) specificity for predicting pulmonary embolism. Crude 60-day mortality was higher in COVID-19 patients (35 vs. 15%; p = 0.039) but three multivariate analysis showed that independent predictors of 60-day mortality included the ventilatory ratio (OR 3.67, 95% CI 1.61-8.35), PaO2/FIO2 ratio (OR 0.93; 95% CI 0.87-0.99), IL-6 (OR 1.02, 95% CI 1.00-1.03), and D-dimer (OR 7.26, 95% CI 1.11-47.30) but not COVID-19 infection. Conclusion: COVID-19 patients were slightly less recruitable and had a higher incidence of pulmonary embolism than those with ARDS from other etiologies. A high D-dimer was predictive of pulmonary embolism in COVID-19 patients. COVID-19 infection was not an independent predictor of 60-day mortality in the presence of ARDS.

Inhaled pulmonary vasodilators are not associated with improved gas exchange in mechanically ventilated patients with COVID-19: A retrospective cohort study.

PURPOSE: Measure the effect of inhaled pulmonary vasodilators on gas exchange in mechanically ventilated patients with COVID-19. METHODS: A retrospective observational cohort study at three New York University Hospitals was performed including eighty-four mechanically ventilated SARS Cov-2 nasopharyngeal PCR positive patients, sixty nine treated with inhaled nitric oxide (iNO) and fifteen with inhaled epoprostenol (iEPO). The primary outcomes were change in PAO2:FIO2 ratio, oxygenation Index (OI), and ventilatory ratio (VR) after initiation of inhaled pulmonary vasodilators. RESULTS: There was no significant change in PAO2:FIO2ratio after initiation of iNO (mean - 4.1, 95% CI -17.3-9.0, P = 0.54) or iEPO (mean - 3.4, 95% CI -19.7-12.9, P = 0.66), in OI after initiation of iNO (mean 2.1, 95% CI-0.04-4.2, P = 0.054) or iEPO (mean - 3.4, 95% CI -19.7-12.9, P = 0.75), or in VR after initiation of iNO (mean 0.17, 95% CI -0.03-0.36, P = 0.25) or iEPO (mean 0.33, 95% CI -0.0847-0.74, P = 0.11). PAO2:FIO2, OI and VR did not significantly change over a five day period starting the day prior to drug initiation in patients who received either iNO or iEPO assessed with a fixed effects model. CONCLUSION: Inhaled pulmonary vasodilators were not associated with significant improvement in gas exchange in mechanically ventilated patients with COVID-19.

The evolution of the ventilatory ratio is a prognostic factor in mechanically ventilated COVID-19 ARDS patients.

BACKGROUND: Mortality due to COVID-19 is high, especially in patients requiring mechanical ventilation. The purpose of the study is to investigate associations between mortality and variables measured during the first three days of mechanical ventilation in patients with COVID-19 intubated at ICU admission. METHODS: Multicenter, observational, cohort study includes consecutive patients with COVID-19 admitted to 44 Spanish ICUs between February 25 and July 31, 2020, who required intubation at ICU admission and mechanical ventilation for more than three days. We collected demographic and clinical data prior to admission; information about clinical evolution at days 1 and 3 of mechanical ventilation; and outcomes. RESULTS: Of the 2,095 patients with COVID-19 admitted to the ICU, 1,118 (53.3%) were intubated at day 1 and remained under mechanical ventilation at day three. From days 1 to 3, PaO2/FiO2 increased from 115.6 [80.0-171.2] to 180.0 [135.4-227.9] mmHg and the ventilatory ratio from 1.73 [1.33-2.25] to 1.96 [1.61-2.40]. In-hospital mortality was 38.7%. A higher increase between ICU admission and day 3 in the ventilatory ratio (OR 1.04 [CI 1.01-1.07], p = 0.030) and creatinine levels (OR 1.05 [CI 1.01-1.09], p = 0.005) and a lower increase in platelet counts (OR 0.96 [CI 0.93-1.00], p = 0.037) were independently associated with a higher risk of death. No association between mortality and the PaO2/FiO2 variation was observed (OR 0.99 [CI 0.95 to 1.02], p = 0.47). CONCLUSIONS: Higher ventilatory ratio and its increase at day 3 is associated with mortality in patients with COVID-19 receiving mechanical ventilation at ICU admission. No association was found in the PaO2/FiO2 variation.

Survival of COVID-19 Patients With Respiratory Failure is Related to Temporal Changes in Gas Exchange and Mechanical Ventilation.

Background: Respiratory failure due to coronavirus disease of 2019 (COVID-19) often presents with worsening gas exchange over a period of days. Once patients require mechanical ventilation (MV), the temporal change in gas exchange and its relation to clinical outcome is poorly described. We investigated whether gas exchange over the first 5 days of MV is associated with mortality and ventilator-free days at 28 days in COVID-19. Methods: In a cohort of 294 COVID-19 patients, we used data during the first 5 days of MV to calculate 4 daily respiratory scores: PaO2/FiO2 (P/F), oxygenation index (OI), ventilatory ratio (VR), and Murray lung injury score. The association between these scores at early (days 1-3) and late (days 4-5) time points with mortality was evaluated using logistic regression, adjusted for demographics. Correlation with ventilator-free days was assessed (Spearman rank-order coefficients). Results: Overall mortality was 47.6%. Nonsurvivors were older (P < .0001), more male (P = .029), with more preexisting cardiopulmonary disease compared to survivors. Mean PaO2 and PaCO2 were similar during this timeframe. However, by days 4 to 5 values for all airway pressures and FiO2 had diverged, trending lower in survivors and higher in nonsurvivors. The most substantial between-group difference was the temporal change in OI, improving 15% in survivors and worsening 11% in nonsurvivors (P < .05). The adjusted mortality OR was significant for age (1.819, P = .001), OI at days 4 to 5 (2.26, P = .002), and OI percent change (1.90, P = .02). The number of ventilator-free days correlated significantly with late VR (-0.166, P < .05), early and late OI (-0.216, P < .01; -0.278, P < .01, respectively) and early and late P/F (0.158, P < .05; 0.283, P < .01, respectively). Conclusion: Nonsurvivors of COVID-19 needed increasing intensity of MV to sustain gas exchange over the first 5 days, unlike survivors. Temporal change OI, reflecting both PaO2 and the intensity of MV, is a potential marker of outcome in respiratory failure due to COVID-19.

Dead space estimates may not be independently associated with 28-day mortality in COVID-19 ARDS.

BACKGROUND: Estimates for dead space ventilation have been shown to be independently associated with an increased risk of mortality in the acute respiratory distress syndrome and small case series of COVID-19-related ARDS. METHODS: Secondary analysis from the PRoVENT-COVID study. The PRoVENT-COVID is a national, multicenter, retrospective observational study done at 22 intensive care units in the Netherlands. Consecutive patients aged at least 18 years were eligible for participation if they had received invasive ventilation for COVID-19 at a participating ICU during the first month of the national outbreak in the Netherlands. The aim was to quantify the dynamics and determine the prognostic value of surrogate markers of wasted ventilation in patients with COVID-19-related ARDS. RESULTS: A total of 927 consecutive patients admitted with COVID-19-related ARDS were included in this study. Estimations of wasted ventilation such as the estimated dead space fraction (by Harris-Benedict and direct method) and ventilatory ratio were significantly higher in non-survivors than survivors at baseline and during the following days of mechanical ventilation (p < 0.001). The end-tidal-to-arterial PCO2 ratio was lower in non-survivors than in survivors (p < 0.001). As ARDS severity increased, mortality increased with successive tertiles of dead space fraction by Harris-Benedict and by direct estimation, and with an increase in the VR. The same trend was observed with decreased levels in the tertiles for the end-tidal-to-arterial PCO2 ratio. After adjustment for a base risk model that included chronic comorbidities and ventilation- and oxygenation-parameters, none of the dead space estimates measured at the start of ventilation or the following days were significantly associated with 28-day mortality. CONCLUSIONS: There is significant impairment of ventilation in the early course of COVID-19-related ARDS but quantification of this impairment does not add prognostic information when added to a baseline risk model. TRIAL REGISTRATION: ISRCTN04346342. Registered 15 April 2020. Retrospectively registered.

Respiratory mechanics and gas exchanges in the early course of COVID-19 ARDS: a hypothesis-generating study.

RATIONALE: COVID-19 ARDS could differ from typical forms of the syndrome. OBJECTIVE: Pulmonary microvascular injury and thrombosis are increasingly reported as constitutive features of COVID-19 respiratory failure. Our aim was to study pulmonary mechanics and gas exchanges in COVID-2019 ARDS patients studied early after initiating protective invasive mechanical ventilation, seeking after corresponding pathophysiological and biological characteristics. METHODS: Between March 22 and March 30, 2020 respiratory mechanics, gas exchanges, circulating endothelial cells (CEC) as markers of endothelial damage, and D-dimers were studied in 22 moderate-to-severe COVID-19 ARDS patients, 1 [1-4] day after intubation (median [IQR]). MEASUREMENTS AND MAIN RESULTS: Thirteen moderate and 9 severe COVID-19 ARDS patients were studied after initiation of high PEEP protective mechanical ventilation. We observed moderately decreased respiratory system compliance: 39.5 [33.1-44.7] mL/cmH2O and end-expiratory lung volume: 2100 [1721-2434] mL. Gas exchanges were characterized by hypercapnia 55 [44-62] mmHg, high physiological dead-space (VD/VT): 75 [69-85.5] % and ventilatory ratio (VR): 2.9 [2.2-3.4]. VD/VT and VR were significantly correlated: r2 = 0.24, p = 0.014. No pulmonary embolism was suspected at the time of measurements. CECs and D-dimers were elevated as compared to normal values: 24 [12-46] cells per mL and 1483 [999-2217] ng/mL, respectively. CONCLUSIONS: We observed early in the course of COVID-19 ARDS high VD/VT in association with biological markers of endothelial damage and thrombosis. High VD/VT can be explained by high PEEP settings and added instrumental dead space, with a possible associated role of COVID-19-triggered pulmonary microvascular endothelial damage and microthrombotic process.