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An appraisal of respiratory system compliance in mechanically ventilated covid-19 patients

Abstract

Background

Heterogeneous respiratory system static compliance (CRS) values and levels of hypoxemia in patients with novel coronavirus disease (COVID-19) requiring mechanical ventilation have been reported in previous small-case series or studies conducted at a national level.

Methods

We designed a retrospective observational cohort study with rapid data gathering from the international COVID-19 Critical Care Consortium study to comprehensively describe CRS—calculated as: tidal volume/[airway plateau pressure-positive end-expiratory pressure (PEEP)]—and its association with ventilatory management and outcomes of COVID-19 patients on mechanical ventilation (MV), admitted to intensive care units (ICU) worldwide.

Results

We studied 745 patients from 22 countries, who required admission to the ICU and MV from January 14 to December 31, 2020, and presented at least one value of CRS within the first seven days of MV. Median (IQR) age was 62 (52–71), patients were predominantly males (68%) and from Europe/North and South America (88%). CRS, within 48 h from endotracheal intubation, was available in 649 patients and was neither associated with the duration from onset of symptoms to commencement of MV (p = 0.417) nor with PaO2/FiO2 (p = 0.100). Females presented lower CRS than males (95% CI of CRS difference between females-males: − 11.8 to − 7.4 mL/cmH2O p < 0.001), and although females presented higher body mass index (BMI), association of BMI with CRS was marginal (p = 0.139). Ventilatory management varied across CRS range, resulting in a significant association between CRS and driving pressure (estimated decrease − 0.31 cmH2O/L per mL/cmH20 of CRS, 95% CI − 0.48 to − 0.14, p < 0.001). Overall, 28-day ICU mortality, accounting for the competing risk of being discharged within the period, was 35.6% (SE 1.7). Cox proportional hazard analysis demonstrated that CRS (+ 10 mL/cm H2O) was only associated with being discharge from the ICU within 28 days (HR 1.14, 95% CI 1.02–1.28, p = 0.018).

Conclusions

This multicentre report provides a comprehensive account of CRS in COVID-19 patients on MV. CRS measured within 48 h from commencement of MV has marginal predictive value for 28-day mortality, but was associated with being discharged from ICU within the same period. Trial documentation: Available at https://www.covid-critical.com/study.

Trial registration: ACTRN12620000421932.

Background

Millions of people have been infected by SARS-CoV-2 worldwide, and many of those have been hospitalized for respiratory complications associated with coronavirus disease-2019 (COVID-19). Many of those COVID-19 hospitalised patients have received mechanical ventilation (MV), due to the development of acute hypoxemic respiratory failure and acute respiratory distress syndrome (ARDS) [1,2,3,4]. To date, several landmark studies [5,6,7,8] have improved our understanding of COVID-19 pulmonary pathophysiology, but pulmonary derangement in COVID-19 and appropriate ventilatory management remains incompletely characterized.

Earlier reports on the pulmonary pathophysiology of COVID-19 patients reported conflicting results and extreme heterogeneity in levels of pulmonary shunting, static respiratory system compliance (CRS), [9,10,11,12] and substantial heterogeneity in lung recruitability [13, 14]. Adding further to the controversy over CRS in COVID-19 patients, Grasselli and collaborators [7] have compared findings from an Italian repository of COVID-19 ARDS with previous ARDS cases of different etiologies. They found statistically significant higher CRS in patients with COVID-19 ARDS. In addition, they found that patients who presented with lower CRS and higher D-dimer values had the greatest mortality risk. In line with these figures, in a small-case series, Chiumello and collaborators found that COVID-19 patients presented higher CRS levels in comparison with patients with ARDS from other etiologies and matched levels of hypoxemia [12]. Regrettably, those previous reports did not provide any information on how CRS progressed beyond a punctual assessment during the period of MV. In contrast, in another landmark study by Ferrando et al. [6], CRS figures from a Spanish database were very similar to previously published cohorts of ARDS patients. The authors also found that intensive care unit (ICU) discharge and mortality were not influenced by the initial levels of CRS.

In a pandemic caused by a novel virus, access to international data is vital, because it may help account for differences in populations, access to medical care, equipment and critical variations in clinical managements among countries. Thus, analysis of international repositories improves the overall understanding of a novel disease and helps establishing best practices to enhance outcome. One example of how single-center or single-country studies can influence medical care early in a pandemic, before being contradicted by subsequent international findings is the issue of CRS. Indeed, as this parameter can be markedly impacted by fine variations in ventilatory management, extrapolations from mono-center or single-country studies may be challenging. In early January 2020, the COVID-19 Critical Care Consortium incorporating the ExtraCorporeal Membrane Oxygenation for 2019 novel Coronavirus Acute Respiratory Disease (COVID-19–CCC/ECMOCARD) group was founded to investigate patients presenting to ICUs worldwide.

Here, we present a comprehensive appraisal of CRS in mechanically ventilated COVID-19 patients enrolled into the COVID-19–CCC/ECMOCARD international study, in order to understand the dynamics of CRS during the first week of mechanical ventilation and its potential impact on patient outcomes.

Materials and methods

Study design and oversight

The COVID-19-CCC/ECMOCARD is an international, multicentre, cohort observational study ongoing in 351 hospitals across 53 countries. The full study protocol is available elsewhere [15]. To summarize, participating hospitals obtained local ethics committee approval and a waiver of informed consent was granted in all cases. ISARIC/SPRINT-SARI data collection began at admission to hospital, while data collection for the COVID-19–CCC observational study commenced at admission to the ICU. De-identified patient data were collected retrospectively and stored via the REDCap electronic data capture tool, hosted at the University of Oxford, United Kingdom or Monash University, Melbourne, Australia.

Study population

We reviewed data of all patients admitted to the ICU at a COVID-19–CCC collaborating site, from January 14 through September 30, 2020, with a clinically suspected or laboratory confirmed diagnosis of SARS-CoV-2 infection, through naso-pharyngeal swab for real-time PCR SARS-CoV-2 detection. Of note, suspicion of SARS-CoV-2 infection was based on symptoms and onset of infection and was confirmed by the clinician when COVID-19 infection was the most likely cause of the symptoms experienced. Patients excluded were those under the age of 15 years or admitted to an ICU for other reasons. We focused our analysis on patients on controlled MV and with a computed CRS value within 48 h of MV commencement.

Definitions and pulmonary mechanics computations

CRS was calculated as: tidal volume (mL)/[(airway plateau pressure-PEEP (cmH2O))]. Of note, we provided to data collectors a detailed data dictionary, with instructions on how to collect airway plateau pressure values, via an inspiratory pause of approximately 3 s. We computed CRS using the first measured tidal volume, airway plateau pressure and PEEP values, within 48 h of MV commencement. In the sub-population of patients on controlled MV, without ECMO support, we analysed key pulmonary variables, such as tidal volume, positive end expiratory pressure (PEEP), static driving pressure, inspiratory fraction of oxygen (FiO2), and gas exchange, recorded during routine clinical practice and only. Tidal volume was reported in mL/kg of predicted body weight (PBW) [16].

Data collection

After enrolment, data on demographics, comorbidities, clinical symptoms and laboratory results were collected by clinical and research staff of the participating ICUs in an electronic case report form [15]. Details of respiratory and hemodynamic support, physiological variables, and laboratory results were collected daily. Of note, the worst daily values were preferentially recorded. The duration of MV and ICU stay, and hospital mortality were recorded. Analysis of daily data was restricted to the first seven days from commencement of MV.

Statistical analyses

Descriptive statistics summarised demographics, clinical signs on ICU admission, ICU management and clinical outcomes for the overall study cohort and subjects with baseline compliance measured within the first 48 h of controlled MV. Statistics were reported as medians (interquartile range) for continuous variables and numbers (percentage) for categorical variables. Linear regression was applied to summarise associations between baseline compliance with body mass index (BMI) (including interaction between BMI and sex), days from symptom onset to MV commencement and PaO2/FiO2, adjusted for BMI. Linear mixed modelling was used to investigate trends in compliance over time and associations with key respiratory parameters during the first 7 days of controlled MV. Models assumed a linear effect for days and a random intercept per subject to account for repeated measures. Consistent with exploratory analyses, BMI was included as a fixed effect to adjust for potential confounding in the clinical characteristics and management of patients with different BMI. Hypothesis testing was applied to all fixed effects, assuming a 5% level of statistical significance. Results were summarised graphically with uncertainty in estimated trends represented by 95% prediction intervals. Expected patient outcomes including length of ICU stay, duration of MV and risk of ICU mortality versus discharge were examined using multi-state modelling [17]. Compared with exploratory analyses of clinical outcomes, the multistate model accounted for ICU discharge and death as competing events and allowed data from all patients to be included, regardless of study follow-up time. The model comprised of four states, to describe patients prior to commencement of MV (non MV), on mechanical ventilation (MV), ICU discharged (Discharge) and mortality (Death). States were presented as percentage and standard error (SE) in the text. Patients extubated before death or discharge were assumed to transition between MV an non-MV states. State transitions were modelled by Cox proportional hazards, with patients censored at last known follow-up, up to 28 days from ICU admission. Follow-up analysis considered Cox proportional hazard regression to examine associations between baseline compliance and competing risks of ICU mortality and discharge, following commencement of MV. Baseline compliance was included as a linear effect, with age, sex, BMI and comorbidities (hypertension, chronic cardiac disease, chronic kidney disease) as additional covariates and adjusted for recruiting centre. A shared frailty term (Gamma distributed) was included to account for residual variation between study sites. Analyses were conducted using R version 3.6.2 or higher (The R Foundation).

Results

We studied 745 patients from 22 countries, who required admission to the ICU and MV from January 14 to December 31, 2020, and presented at least one value of CRS within the first seven days of MV. Among those, 597 (80%) had laboratory-confirmed diagnosis of SARS-CoV2 infection, while in 148 (20%), infection was clinically suspected. Enrolment rate, since January 2020, is reported in Fig. 1. CRS, within 48 h from endotracheal intubation, was available in 649 patients (Fig. 2). No association between CRS and days from onset of symptoms to commencement of MV was found (Fig. 3). Median CRS (IQR), within the first 48 h of mechanical ventilation, was 34.1 mL/cmH2O (26.4–44.0) and PaO2/FiO2 113.0 mmHg (84.0–161.3), without any linear association between these parameters. In particular, 16%, 46% and 38% of the patients presented with mild, moderate or severe hypoxemia, respectively (Fig. 4a). Female sex was associated with a significantly lower CRS than in males (95% CI of difference between genders: − 11.8 to − 7.4 mL/cmH2O p < 0.001) (Fig. 4b). Females also presented higher body mass index (BMI) (95% CI of difference between males and females: − 1.9 to − 5.5, p < 0.001), but as shown in Fig. 5, CRS and BMI were not linearly associated. Our model estimated that CRS was 37.57 cmH2O/mL (95% CI 36.5–38.6) upon commencement of MV (Fig. 6), with further worsening in the first seven days of MV (estimated decrease − 0.31 cmH2O/mL per day, 95% CI − 0.48 to − 0.14, p < 0.001). In addition, as detailed in Fig. 7, PaCO2, tidal volume, PEEP, driving pressure and FiO2 significantly varied across the range of CRS, and a significant association was found between inspiratory plateau pressure and CRS changes (Fig. 8).

Fig. 1
figure1

Patient enrolment rate from January 14 through December 31, 2020

Fig. 2
figure2

Patient population flow chart. The analysis of 1505 COVID-19 patients on mechanical ventilation identified 649 patients with static respiratory system compliance within 48 h from commencement of mechanical ventilation

Fig. 3
figure3

Linear regression analysis of days from onset of symptoms to commencement of mechanical ventilation and static respiratory system compliance, based on the first measurement obtained within 48 h from commencement of mechanical ventilation, adjusted for body mass index. Dark black horizontal bar depicts median value, and upper and lower horizontal light black bars show 90th and 10th percentile. Days of onset of symptoms to commencement of mechanical ventilation was not associated with static respiratory system compliance (estimate 0.92 mL/cmH2O, 95% CI − 0.31–0.31 p = 0.417)

Fig. 4
figure4

a Linear regression analysis of arterial partial pressure of oxygen (PaO2/FiO2) and respiratory system compliance (CRS), based on the first measurement obtained within 48 h from commencement of mechanical ventilation, with an interaction of gender and adjusted for body mass index (BMI). No statistically significant association was found between PaO2/FiO2 and CRS (estimate 0.49, 95% CI − 0.09–1.07 p = 0.100). Typical acute respiratory distress syndrome stratification groups [35] (severe, moderate and mild based on levels of hypoxemia) are highlighted in dark, medium and light grey, respectively. b Static respiratory system compliance (CRS) distribution by sex, based on the first measurement obtained within 48 h from commencement of mechanical ventilation. Dashed black lines depict median values for females and males

Fig. 5
figure5

Linear regression analysis of static respiratory system compliance, based on the first measurement obtained within 48 h from commencement of mechanical ventilation, and body mass index with an interaction for sex. Per each graph, fitted line of the model is depicted and the upper and lower lines display the 95% predictive interval. Dark grey dots depict female patients, while light grey dots males. Static respiratory system compliance did not vary according to the body mass index (estimate − 0.12 cmH2O/mL, 95%CI − 0.29 to − 0.04, p = 0.139), but was associated with female sex (estimate − 10.73 cmH2O/mL, 95%CI − 18.54 to − 2.92, p = 0.007)

Fig. 6
figure6

Static respiratory system compliance dynamics. Evolution of static respiratory system compliance over the first 7 days of mechanical ventilation, adjusted for body mass index. Under each day, the number of analysed patients is reported in parenthesis. Fitted line of the model is depicted, and the upper and lower lines display the 95% predictive interval. Respiratory system compliance varied during the first seven days of mechanical ventilation (estimate − 0.31 cmH2O/mL, 95%CI − 0.48 to 0.14, p < 0.001)

Fig. 7
figure7

Linear Mixed model analysis of respiratory system compliance vs. crucial pulmonary variables during the first 7 days of mechanical ventilation (grey-scale coded bar for day 1 through 7 is reported on the right section of each graph and in parenthesis is reported the number of analysed patients). Per each graph, fitted line of the model is depicted and the upper and lower lines display the 95% predictive interval. All analyses are adjusted for body mass index. Static compliance of respiratory system was found to be associated with PaCO2 (estimated decrease − 0.11 mmHg, 95% CI − 0.15 to − 0.06, p < 0.001), tidal volume (estimated increase 0.04 mL/Kg of predicted body weight per day, 95% CI 0.03–0.04, p < 0.001), PEEP (estimated increase − 0.03 cmH2O, 95% CI 0.02–0.04, p < 0.001), driving pressure (estimated decrease − 0.31 cmH2O/L, 95% CI − 0.48 to 0.14, p < 0.001) and FiO2 (estimated decrease − 0.15%, 95% CI − 0.23 to − 0.06, p < 0.001). While PaO2/FiO2, was not significantly associated with static compliance of respiratory system (estimated increase 0.29 mmHg, 95% CI − 0.03 to 0.61, p = 072) PaO2/FiO2, ratio between arterial partial pressure of oxygen and inspiratory fraction of oxygen; PaCO2 arterial partial pressure of carbon dioxide; PEEP, positive end-expiratory pressure

Fig. 8
figure8

Association of airway inspiratory plateau pressure with static respiratory system compliance. Linear Mixed model analysis of the association of respiratory system compliance with airway inspiratory plateau pressure during the first 7 days of mechanical ventilation (grey-scale coded bar for day 1 through 7 is reported on the right section of each graph and in parenthesis is reported the number of analysed patients). Fitted line of the model is depicted, and the upper and lower lines display the 95% predictive interval. Analysis is adjusted for body mass index. The model highlights significant association between respiratory system compliance and airway plateau pressure (estimated decrease − 0.22 cmH2O/L, 95% CI − 0.23 to − 0.21, p < 0.001), but based on the model prediction, airway plateau pressure remained predominantly below 30 cmH2O

Baseline characteristics upon ICU admission, applied interventions and outcomes, are summarized in Table 1. The most common interventions applied to the study population were use of antibiotics (96%), neuromuscular blocking agents (81%) and prone position (61%). The overall hospital mortality of the study population was 40%, and among those patients who died in the hospital or were discharged alive, the median (IQR) duration of MV was 11 days (6–18) and 14 days (8–23), respectively. Overall, 28-day ICU mortality, accounting for competing risks, was 35.6% (SE 1.7) and estimated 28-day mortality from commencement of MV was 37.1% (SE 1.7) (Fig. 9b). Cox proportional hazard analysis (Fig. 9c) demonstrated that age (hazard ratio 1.37, 95% CI 1.19–1.59, p < 0.001) and chronic cardiac diseases (HR 1.62, 95% CI 1.14–2.29, p < 0.001) were the only baseline factors associated with 28-day mortality risk. In addition, age (HR 0.77, 95% CI 0.66–0.83, p < 0.001), male sex (HR 0.59, 95% CI 0.44–0.79, p < 0.001), BMI (HR 0.86, 95% CI 0.79–0.95, p = 0.003) and CRS (+ 10 mL/cm H2O) (HR 1.14, 95% CI 1.02–1.28, p = 0.018) were associated with the chance of being discharge from the ICU within 28 days.

Table 1 Only patients with the following characteristics were included in this analysis: (1) on controlled mechanical ventilation; (2) airway plateau pressure, tidal volume and positive-end-expiratory pressure recorded within 48 h from commencement of mechanical ventilation
Fig. 9
figure9

Multistate modelling and Cox regression analysis outcomes for patient with static compliance recorded within 48 h of commencing mechanical ventilation. a Multistate model structure for estimating expected outcomes up to 28 days from admission to intensive care unit (ICU). Modelled health states include not on invasive mechanical ventilation (non-MV), on mechanical ventilation (MV), ICU discharge and death. Patients start in the non-MV state if not mechanically ventilated upon or prior to ICU admission, or in the MV state otherwise. b Predicted probabilities of occupying health states up to 28 days from ICU admission. c Results of Cox proportional hazards modelling for risk of death and ICU discharge from commencement of mechanical ventilation. Covariates comprise age, body mass index (BMI), selected comorbidities (hypertension, chronic cardiac disease, chronic kidney disease) and baseline static compliance. Parameter estimates are presented as estimated hazard ratios with 95% confidence intervals (CI). Further details on factors significantly associated with assessed outcomes are available in the results section

Discussion

This large observational report from intensive care units throughout the world found that initial static respiratory system compliance was only associated with hazard of being discharged from the ICU within 28 days. The duration from onset of symptoms to commencement of MV did not influence CRS, and interestingly lower CRS was found in female patients. In the evaluated population, neuromuscular blocking agents and prone position were commonly applied and ventilatory management across CRS levels varied in terms of tidal volume, PEEP and FiO2, throughout the first 7 days of MV.

In comparison with previous reports on ARDS patients without COVID-19 [18], we similarly found that the majority of patients exhibited moderate hypoxemia, even when presented higher CRS. We also noted a larger range of CRS in line with previous studies [7, 8], but in contrast with values from a larger COVID-19 ARDS series from Spain [6]. Considering that we focused our analysis on static compliance of the respiratory system, without partitioning into the pulmonary and chest wall components [19, 20], it is interesting that CRS was not associated with BMI, suggesting that patients with higher BMI potentially presented also with higher lung compliance. Irrespective, we found lower CRS in female patients, who also presented higher BMIs. To the best of our knowledge, no studies have systematically investigated the effects of gender/BMI on COVID-19 severity; thus, whether obesity might be a crucial risk factor for ICU admission and mechanical ventilation, specifically in female patients, and its effects on lung compliance should be further explored. We also found that throughout the range of CRS values, plateau pressure was within what is typically presumed as lung protective ranges [21], but this resulted in potentially harmful driving pressures, specifically for patients with the lowest CRS values. As many of these patients were obese, this raises the question of whether these modest pressures might have increased the risk of pulmonary derecruitment, or in patients with normal BMI, the resulting driving pressure might have been related to pulmonary overdistention. These factors could have contributed to sustained hypoxemia and impaired lung function throughout the study period. In such circumstances, it is questionable whether MV guided by oesophageal pressure monitoring may have some benefits [22], but more research is needed to corroborate such reasoning.

Phenotypic subsets of COVID-19-associated ARDS have been proposed [9, 13, 23,24,25]. Recent study has also explored whether CRS—related phenotype patterns existed among patients with ARDS before the COVID-19 pandemic [26]. Various investigators [7, 27], who did not find significant CRS variability among COVID-19 patients requiring MV, questioned the overall clinical value of CRS in the COVID-19 population. In a very small case series, Gattinoni et al [9] found an initial CRS of 50 mL/cmH2O, but high levels of shunt fraction that could have explained the resulting severe hypoxemia. In subsequent study, Chiumello and collaborators found higher CRS in patient with COVID-19 ARDS and ARDS caused by other injuries, while matching for similar levels of PaO2/FiO2 [12]. Interestingly, these findings were in line with computed tomography studies results, corroborating higher proportion of normally aerated tissue in COVID-19 ARDS. In similar reports, heterogeneous pathophysiology among patients with different levels of pulmonary compliance has been implied [10, 25]. As corroborated by landmark post-mortem studies [28] and clinical studies [7, 29], SARS-CoV-2 heterogeneously affects pulmonary ventilation and perfusion. Hence, it could be argued that the use of CRS as key pathophysiological parameter to predict clinical evolution might be over simplistic and in-depth characterization of pulmonary pathophysiology should be recommended for COVID-19 patients, specifically when obese. Interestingly, our report is the first that specifically focused on the dynamics of CRS, rather than only baseline CRS. We found that CRS was not related to the duration from the onset of symptoms to commencement of MV, emphasising the need for inclusive data on mechanisms of lung injury in not ventilated COVID-19 patients [30]. The median CRS value found in our population was 34.1 mL/cmH2O, similar to findings by Ferrando et al. [6], not dissimilar to findings by Bellani et al. on patients with non-COVID-19 ARDS [31], but lower than figures recently reported by Grasselli [7] and Grieco [32] in COVID-19 patients. In addition, we found a further decrease in CRS during the first week of MV. This could have been related to the specific ventilatory management in our reported population, but such discrepancy further highlights the need of a comprehensive appraisal of pulmonary and chest wall mechanics in COVID-19 patients [20].

One of the most striking results was the continued use of high PEEP over the first seven days of MV, even in patients with high compliance. This seems counterintuitive, given that current recommendations in ARDS suggest decreasing PEEP, especially in the face of high compliance. As hypoxemia persisted even with high PEEP and high compliance, our results add to the hypothesis that maintaining high PEEP may worsen gas exchange from lung overdistension, resulting in increased dead space and intrapulmonary shunting. Other authors have speculated that using high levels of PEEP in COVID-19 patients with low recruitability may be detrimental, and that lowering PEEP may improve gas exchange and limit ventilator-induced lung injury [33]. Our results in this large cohort of patients from multiple global areas support this theory. Finally, we found that patients required two weeks of MV, and 28-day mortality in the overall population was 35.6%, with hospital mortality up to 40%. These figures are in line with mortality rates reported by Grasselli [7] in the subgroups characterized by low D-dimer, and mortality in severe-moderate COVID-19 ARDS, as corroborated by Ferrando [6]. Nevertheless, we found that CRS was only associated with the discharge from ICU within 28 days. Thus, the marginal clinical value of CRS as a predictor of mortality in COVID-19 patients calls for urgent identification of valuable markers that could inclusively describe pulmonary derangement and guide personalized treatment.

Strengths and limitations

Collaborations between international data collection efforts have the ability to answer many questions related to COVID 19 and to pave the way for future novel diseases to achieve rapid and global data access to help guide best practice. The international COVID-19 Critical Care Consortium study [15], in collaboration with the ISARIC/SPRINT-SARI networks [34], provides inferences not limited by ventilatory management specific to small patient cohort or single-country studies. In addition, in comparison with previous studies, we provided more granular data to inclusively appraise the dynamics of CRS in COVID-19 patients on MV and to study its association with laboratory, and clinical features. A few limitations of our observational study should also be emphasized. First, we centred our analysis on COVID-19 patients, without comparisons against previous repositories of patients with ARDS from different aetiologies. Yet, we provided a wide-ranging discussion of the characteristics of our population in the context of previous analyses in ARDS patients. Second, inferences on pulmonary perfusion disorders in our population can only be speculative, since D-dimer was only available in a small subset of patients (Table 1). Third, as reported by the enrolment rate (Fig. 1 Supplemental Digital Content), patients were mostly enrolled in the early phase of the pandemic, hence extrapolations from our findings should take into account potential biases related to overwhelmed critical care services. Fourthly, it is important to emphasise that we centred our analysis on CRS, but due to the complex respiratory pathophysiology in COVID-19 patients and the high percentage of patients with increased BMI, the use of oesophageal pressure monitoring to fully describe lung and chest wall compliances is advisable and should be prioritised in future investigations. Fifth, the majority of patients were admitted in centers located in North America, Europe and South America. Although these findings are in line with the global distribution of COVID-19 cases, extrapolations of our findings in other regions should be applied cautiously.

Conclusions

Our comprehensive appraisal of COVID-19 patients on MV from a large international observational study implies that expected CRS within 48 h from commencement of MV is not influenced by the duration from onset of symptoms to commencement of MV, but after intubation, a further decrease in CRS might be expected during the first week of ventilation. In addition, baseline CRS is associated with the chance of being discharged from the ICU within 28 days, but it is not a predictive marker of 28-day mortality. Based on potential inferences from our findings, future studies that could provide an in-depth characterization of lungs and chest wall compliance in COVID-19 patients will be critical to guide best practice in ventilatory management.

Availability of data materials

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Abbreviations

ARDS:

Acute respiratory distress syndrome

COVID-19:

Coronavirus disease-2019

COVID-19–CCC/ECMOCARD:

COVID-19 Critical Care Consortium incorporating the ExtraCorporeal Membrane Oxygenation for 2019 novel Coronavirus Acute Respiratory Disease

FiO2 :

Inspiratory fraction of oxygen

ICU:

Intensive care unit

IQR:

Interquartile range

MV:

Mechanical ventilation

PBW:

Predicted body weight

PEEP:

Positive end expiratory pressure

C RS :

Static respiratory system compliance

References

  1. 1.

    Grasselli G, Zangrillo A, Zanella A, Antonelli M, Cabrini L, Castelli A, et al. Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the lombardy region, Italy. JAMA J Am Med Assoc. 2020;323:1574–81.

    CAS  Article  Google Scholar 

  2. 2.

    Guan W, Ni Z, Hu Y, Liang W, Ou C, He J, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382:1708–20.

    CAS  Article  Google Scholar 

  3. 3.

    Richardson S, Hirsch JS, Narasimhan M, Crawford JM, McGinn T, Davidson KW, et al. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area. JAMA J Am Med Assoc. 2020;323:E1-8.

    Article  Google Scholar 

  4. 4.

    Karagiannidis C, Mostert C, Hentschker C, Voshaar T, Malzahn J, Schillinger G, et al. Case characteristics, resource use, and outcomes of 10 021 patients with COVID-19 admitted to 920 German hospitals: an observational study. Lancet Respir Med [Internet]. Elsevier; 2020 [cited 2020 Aug 6];0. Available from: https://linkinghub.elsevier.com/retrieve/pii/S2213260020303167.

  5. 5.

    Gibson PG, Qin L, Puah SH. COVID-19 acute respiratory distress syndrome (ARDS): clinical features and differences from typical pre-COVID-19 ARDS. Med J Aust. 2020;2020:54-56.e1.

    Article  Google Scholar 

  6. 6.

    Ferrando C, Suarez-Sipmann F, Mellado-Artigas R, Hernández M, Gea A, Arruti E, et al. Clinical features, ventilatory management, and outcome of ARDS caused by COVID-19 are similar to other causes of ARDS. Intensive Care Med [Internet]. Springer; 2020 [cited 2020 Aug 13];1–12. Available from: https://doi.org/10.1007/s00134-020-06192-2.

  7. 7.

    Sacco F, Tonetti MT, Pizzilli G, Ranieri VM, di Radiologia Monteduro DF, Zompatori M, et al. Pathophysiology of COVID-19-associated acute respiratory distress syndrome: a multicentre prospective observational study. 2020; Available from: www.thelancet.com/respiratory.

  8. 8.

    Gattinoni L, Coppola S, Cressoni M, Busana M, Rossi S, Chiumello D. COVID-19 does not lead to a “Typical” acute respiratory distress syndrome. Am J Respir Crit Care Med. 2020;201:1299–300.

    CAS  Article  Google Scholar 

  9. 9.

    Gattinoni L, Coppola S, Cressoni M, Busana M, Chiumello D. Covid-19 does not lead to a “Typical” acute respiratory distress syndrome. Am J Respir Crit Care Med. 2020;2020:201.

    Google Scholar 

  10. 10.

    Gattinoni L, Chiumello D, Rossi S. COVID-19 pneumonia: ARDS or not? [Internet]. Crit. Care. BioMed Central Ltd.; 2020 [cited 2020 Jun 6]. p. 154. Available from: https://doi.org/10.1186/s13054-020-02880-z

  11. 11.

    Schenck EJ, Hoffman K, Goyal P, Choi J, Torres L, Rajwani K, et al. Respiratory mechanics and gas exchange in COVID-19 associated respiratory failure. American Thoracic Society; 2020.

    Google Scholar 

  12. 12.

    Chiumello D, Busana M, Coppola S, Romitti F, Formenti P, Bonifazi M, et al. Physiological and quantitative CT-scan characterization of COVID-19 and typical ARDS: a matched cohort study. Intensive Care Med [Internet]. Springer Science and Business Media Deutschland GmbH; 2020 [cited 2020 Nov 18];1–10. Available from: https://doi.org/https://doi.org/10.1007/s00134-020-06281-2

  13. 13.

    Beloncle FM, Pavlovsky B, Desprez C, Fage N, Olivier PY, Asfar P, et al. Recruitability and effect of PEEP in SARS-Cov-2-associated acute respiratory distress syndrome. Ann Intensive Care. Springer; 2020;10.

  14. 14.

    Pan C, Chen L, Lu C, Zhang W, Xia JA, Sklar MC, et al. Lung Recruitability in SARS-CoV-2 Associated Acute Respiratory Distress Syndrome: A Single-center, Observational Study. Am J Respir Crit Care Med. NLM (Medline); 2020;201.

  15. 15.

    ECMOCARD [Internet]. [cited 2020 Jun 2]. Available from: https://www.elso.org/COVID19/ECMOCARD.aspx.

  16. 16.

    Network ARDS, Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, et al. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. N Engl J Med [Internet]. 2000;342:1301–8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/10793162.

  17. 17.

    Hazard D, Kaier K, Von Cube M, Grodd M, Bugiera L, Lambert J, et al. Joint analysis of duration of ventilation, length of intensive care, and mortality of COVID-19 patients: A multistate approach. BMC Med Res Methodol [Internet]. BioMed Central; 2020 [cited 2020 Oct 13];20:206. Available from: https://doi.org/10.1186/s12874-020-01082-z.

  18. 18.

    Bellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban A, et al. Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries. JAMA. 2016;315:788–800.

    CAS  Article  Google Scholar 

  19. 19.

    Pelosi P, Caironi P, Gattinoni L. Pulmonary and extrapulmonary forms of acute respiratory distress syndrome. Semin Respir Crit Care Med. 2001;22:259–68.

    CAS  Article  Google Scholar 

  20. 20.

    Chiumello D, Carlesso E, Cadringher P, Caironi P, Valenza F, Polli F, et al. Lung stress and strain during mechanical ventilation for acute respiratory distress syndrome. Am J Respir Crit Care Med. 2008;178:346–55.

    Article  Google Scholar 

  21. 21.

    Fan E, Del Sorbo L, Goligher EC, Hodgson CL, Munshi L, Walkey AJ, et al. An official American Thoracic Society/European Society of intensive care medicine/society of critical care medicine clinical practice guideline: Mechanical ventilation in adult patients with acute respiratory distress syndrome. Am J Respir Crit Care Med [Internet]. American Thoracic Society; 2017 [cited 2020 Oct 12];195:1253–63. Available from: https://pubmed.ncbi.nlm.nih.gov/28459336/.

  22. 22.

    Talmor D, Sarge T, Malhotra A, O’Donnell CR, Ritz R, Lisbon A, et al. Mechanical ventilation guided by esophageal pressure in acute lung injury. N Engl J Med. 2008;359:2095–104.

    CAS  Article  Google Scholar 

  23. 23.

    Marini JJ, Gattinoni L. Management of COVID-19 respiratory distress. JAMA J Am Med Assoc. 2020;323:2329–30.

    Article  Google Scholar 

  24. 24.

    Li X, Ma X. Acute respiratory failure in COVID-19: is it “typical” ARDS? Crit. Care. NLM (Medline); 2020. p. 198.

  25. 25.

    Gattinoni L, Chiumello D, Caironi P, Busana M, Romitti F, Brazzi L, et al. COVID-19 pneumonia: different respiratory treatments for different phenotypes? Intensive Care Med. Springer; 2020. p. 1.

  26. 26.

    Panwar R, Madotto F, Laffey JG, Van Haren FMP. Compliance Phenotypes in Early ARDS Before the COVID-19 Pandemic. Am J Respir Crit Care Med [Internet]. American Thoracic Society; 2020 [cited 2020 Oct 12]; Available from: https://pubmed.ncbi.nlm.nih.gov/32805143/.

  27. 27.

    Pan C, Chen L, Lu C, Zhang W, Xia JA, Sklar MC, et al. Lung recruitability in COVID-19–associated acute respiratory distress syndrome: A single-center observational study [Internet]. Am. J. Respir. Crit. Care Med. American Thoracic Society; 2020 [cited 2020 Aug 13]. p. 1294–7. Available from: https://doi.org/10.1164/rccm.202003-0527LE.

  28. 28.

    Ackermann M, Verleden SE, Kuehnel M, Haverich A, Welte T, Laenger F, et al. Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19. N Engl J Med [Internet]. Massachusetts Medical Society; 2020 [cited 2020 Jun 2];NEJMoa2015432. Available from: https://doi.org/10.1056/NEJMoa2015432.

  29. 29.

    Lang M, Som A, Mendoza DP, Flores EJ, Reid N, Carey D, et al. Hypoxaemia related to COVID-19: vascular and perfusion abnormalities on dual-energy CT. Lancet Infect. Dis. Lancet Publishing Group; 2020.

  30. 30.

    Cruces P, Retamal J, Hurtado DE, Erranz B, Iturrieta P, González C, et al. A physiological approach to understand the role of respiratory effort in the progression of lung injury in SARS-CoV-2 infection [Internet]. Crit. Care. BioMed Central Ltd; 2020 [cited 2021 Feb 7]. p. 494. Available from: https://doi.org/10.1186/s13054-020-03197-7.

  31. 31.

    Bellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban A, et al. Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries. JAMA [Internet]. 2016;315:788. Available from: internal-pdf://0.0.13.130/Epidemiology, Patterns of Care, and Mortality for.webarchive

  32. 32.

    Grieco DL, Bongiovanni F, Chen L, Menga LS, Cutuli SL, Pintaudi G, et al. Respiratory physiology of COVID-19-induced respiratory failure compared to ARDS of other etiologies. Crit Care [Internet]. NLM (Medline); 2020 [cited 2020 Oct 12];24:529. Available from: https://pubmed.ncbi.nlm.nih.gov/32859264/.

  33. 33.

    Roesthuis L, van den Berg M, van der Hoeven H. Advanced respiratory monitoring in COVID-19 patients: use less PEEP! Crit Care. Springer Science and Business Media LLC; 2020;24.

  34. 34.

    COVID-19 Clinical Research Resources · ISARIC [Internet]. [cited 2020 Oct 12]. Available from: https://isaric.tghn.org/covid-19-clinical-research-resources/.

  35. 35.

    Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, et al. Acute Respiratory Distress Syndrome. JAMA [Internet]. 2012;307:2526–33. Available from: https://doi.org/10.1001/jama.2012.5669.

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Acknowledgements

We fully acknowledge statistical guidance by Adrian Barnett, Head Statistician of the COVID-19 Critical Care Consortium. We recognize the crucial importance of the ISARIC and SPRINT-SARI networks for the development and expansion of the COVID-19 Critical Care Consortium. We thank the generous support we received from ELSO and ECMOnet. We owe Li Wenliang, MD from the Wuhan Central Hospital an eternal debt of gratitude for reminding the world that doctors should never be censored during a pandemic. Finally, we acknowledge all members of the COVID-19 Critical Care Consortium and various collaborators.

Contributors

Prefix/First name/Last name Site name
Tala Al-Dabbous Al Adan Hospital
Dr Huda Alfoudri
Dr Mohammed Shamsah
Dr Subbarao Elapavaluru
Ashley Berg
Christina Horn
Allegheny General Hospital
Dr Stephan Schroll Barmherzige Bruder Regansburg
Dr Jorge Velazco
Wanda Fikes
Ludmyla Ploskanych
Baylor Scott & White Health—Temple
Dr Dan Meyer
Maysoon Shalabi-McGuire
Trent Witt
Ashley Ehlers
Baylor University Medical Centre, Dallas
Dr Lorenzo Grazioli Bergamo Hospital
Dr E. Wilson Grandin
Jose Nunez
Tiago Reyes
Beth Israel Deaconess Medical Centre
Dr Mark Joseph
Dr Brook Mitchell
Martha Tenzer
Carilion Clinic
Dr Ryuzo Abe
Yosuke Hayashi
Chiba University Graduate School of Medicine
Dr Hwa Jin Cho
Dr In Seok Jeong
Chonnam National University Hospital
Dr Nicolas Brozzi
Dr Jaime Hernandez-Montfort
Cleveland Clinic—Florida
Omar Mehkri
Stuart Houltham
Cleveland Clinic—Ohio
Dr Jerónimo Graf
Rodrigo Perez
Clinica Alemana De Santiago
Dr Roderigo Diaz
Camila Delgado
Joyce González
Maria Soledad Sanchez
Clinica Las Condez
Dr Diego Fernando Bautista Rincón
Melissa Bustamante Duque
Dr Angela Maria Marulanda Yanten
Clinica Valle de Lilli
Dr Dan Brodie Columbia University Medical Centre
Dr Desy Rusmawatiningtyas Dr Sardjito Hospital (Paediatrics)
Gabrielle Ragazzo Emory University Healthcare System
Dr Azhari Taufik
Dr Margaretha Gunawan
Dr Vera Irawany
Muhammad Rayhan
Dr Elizabeth Yasmin Wardoyo
Fatmawati Hospital
Dr Mauro Panigada
Dr Chiara Martinet
Dr Sebastiano Colombo
Dr Giacomo Grasselli
Dr Michela Leone
Dr Alberto Zanella
Fondazione IRCCS Policlinico of Milan (Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico)
Prof Massimo Antonelli
Dr Simone Carelli
Domenico L. Grieco
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Motohiro Asaki Fujieda Municipal General Hospital
Dr Kota Hoshino Fukuoka University
Dr Leonardo Salazar
Laura Duarte
Fundación Cardiovascular de Colombia
Dr Joseph McCaffrey
Allison Bone
Geelong Hospital
Dr David Thomson
Dr Christel Arnold-Day
Jerome Cupido
Zainap Fanie
Dr Malcom Miller
Dr Lisa Seymore
Dawid van Straaten
Groote Schuur Hospital
Dr Ibrahim Hassan
Dr Ali Ait Hssain
Jeffrey Aliudin
Al-Reem Alqahtani
Khoulod Mohamed
Ahmed Mohamed
Darwin Tan
Joy Villanueva
Ahmed Zaqout
Hamad General Hospital—Weill Cornell Medical College in Qatar
Dr Ethan Kurtzman
Arben Ademi
Ana Dobrita
Khadija El Aoudi
Juliet Segura
Hartford HealthCare
Dr Gezy Giwangkancana Hasan Sadikin Hospital (Adult)
Dr Shinichiro Ohshimo Hiroshima University
Dr Koji Hoshino
Saito Hitoshi
Dr Yuka Uchinami
Hokkaido University Hospital
Dr Javier Osatnik Hospital Alemán
Dr Anne Joosten Hospital Civil Marie Curie
Dr Antoni Torres
Ana Motos
Dr Minlan Yang
Hospital Clinic, Barcelona
Carlos Luna Hospital de Clínicas
Francisco Arancibia Hospital del Tórax
Virginie Williams
Alexandre Noel
Hospital du Sacre Coeur (Universite de Montreal)
Dr Nestor Luque Hospital Emergencia Ate Vitarte
Dr Trieu Huynh Trung
Sophie Yacoub
Hospital for Tropical Diseases
Marina Fantini Hospital Mater Dei
Dr Ruth Noemi Jorge García
Dr Enrique Chicote Alvarez
Hospital Nuestra Señora de Gracia
Dr Anna Greti
Oscar Lomeli
Hospital Puerta de Hierro
Dr Adrian Ceccato Hospital Universitari Sagrat Cor
Dr Angel Sanchez Hospital Universitario Sant Joan d’Alacant
Dr Ana Loza Vazquez Hospital Universitario Virgen de Valme
Dr Ferran Roche-Campo Hospital Verge de la Cinta de Tortosa
Dr Divina Tuazon
Dr Toni Duculan
Houston Methodist Hospital
Hiroaki Shimizu Kakogawa Acute Care Medical Center, Hyogo
Marcelo Amato
Luciana Cassimiro
Flavio Pola
Francis Ribeiro
Guilherme Fonseca
INCOR (Universidade de São Paulo)
Dr Heidi Dalton
Dr Mehul Desai
Dr Erik Osborn
Hala Deeb
INOVA Fairfax Hospital
Dr Antonio Arcadipane
Claudia Bianco
Raffaele Cuffaro
Gennaro Martucci
Giovanna Occhipinti
Matteo Rossetti
Chiara Vitiello
ISMETT
Dr Sung-Min Cho
Kate Calligy
Dr Glenn Whitman
Johns Hopkins
Dr Hiroaki Shimizu
Dr Naoki Moriyama
Kakogawa Acute Care Medical Center
Dr Jae-Burm Kim Keimyung University Dong San Hospital
Dr Nobuya Kitamura
Takashi Shimazui
Kimitsu Chuo Hospital
Dr Abdullah Al-Hudaib
Dr Alyaa Elhazmi
King Faisal Specialist Hospital and Research Center
Dr Johannes Gebauer Klinikum Passau
Dr Toshiki Yokoyama Kouritu Tousei Hospital
Dr Abdulrahman Al-Fares
Esam Alamad
Fatma Alawadhi
Kalthoum Alawadi
Dr Sarah Buabbas
Al-Amiri and Jaber Al-Ahmed Hospitals, Kuwait Extracorporeal Life Support Program
Dr Hiro Tanaka Kyoto Medical Centre
Dr Satoru Hashimoto
Masaki Yamazaki
Kyoto Prefectural University of Medicine
Tak-Hyuck Oh Kyung Pook National University Chilgok Hospital
Dr Mark Epler
Dr Cathleen Forney
Jared Feister
Katherine Grobengieser
Louise Kruse
Joelle Williamson
Lancaster General Health
Dr Eric Gnall
Dr Mara Caroline
Sasha Golden
Colleen Karaj
Sherry McDermott
Lynn Sher
Dr Timothy Shapiro
Lisa Thome
Mark Vanderland
Mary Welch
Lankenau Institute of Medical Research (Main Line Health)
Prof Luca Brazzi Le Molinette Hospital (Ospedale Molinette Torino)
Dr Tawnya Ogston Legacy Emanuel Medical Center
Dr Dave Nagpal
Karlee Fischer
London Health Sciences Centre
Dr Roberto Lorusso
Maria de Piero
Maastricht University Medical Centre
Prof Mariano Esperatti Mar del Plata Medical Foundation Private Community Hospital
Dr Diarmuid O’Briain Maroondah Hospital
Dr Edmund G. Carton Mater Misericordiae University Hospital
Ayan Sen
Amanda Palacios
Deborah Rainey
Mayo Clinic College of Medicine
Cassandra Seefeldt
Dr Lucia Durham
Dr Octavio Falcucci
Amanda Emmrich
Jennifer Guy
Carling Johns
Emily Neumann
Medical College of Wisconsin (Froedtert Hospital)
Dr Nina Buchtele
Dr Michael Schwameis
Medical University of Vienna
Dr Stephanie-Susanne Stecher
Delila Singh
Dr Michaela Barnikel
Lukas Arenz
Medical Department II, LMU Hospital Munich
Dr Akram Zaaqoq
Lan Anh Galloway
Caitlin Merley
MedStar Washington Hospital Centre
Dr Marc Csete
Luisa Quesada
Isabela Saba
Mount Sinai Medical Centre
Dr Daisuke Kasugai
Hiroaki Hiraiwa
Taku Tanaka
Nagoya University Hospital
Dr Eva Marwali
Yoel Purnama
Dr Santi Rahayu Dewayanti
Dr Ardiyan
Dr Debby Siagian
National Cardiovascular Center Harapan Kita
Yih-Sharng Chen National Taiwan University Hospital
Prof John Laffey
Dr Bairbre McNicholas
Dr David Cosgrave
Galway University Hospitals
Marlice VanDyk
Sarah MacDonald
Netcare Unitas ECMO Centre
Dr Ian Seppelt Nepean Hospital
Dr Indrek Ratsep
Lauri Enneveer
Kristo Erikson
Dr Getter Oigus
Andra-Maris Post
Piret Sillaots
North Estonia Medical Centre
Frank Manetta Northwell Health
Mamoru Komats Obihiro-Kosei General Hospital
Dr S. Veena Satyapriya
Dr Amar Bhatt
Marco Echeverria
Juan Fiorda
Alicia Gonzalez
Dr Nahush A. Mokadam
Johnny McKeown
Joshua Pasek
Haixia Shi
Alberto Uribe
Ohio State University Medical Centre
Dr Rita Moreno Oklahoma Heart Institute
Bishoy Zakhary
Hannah Johnson
Nolan Pow
Oregon Health and Science University Hospital (OHSU)
Dr Marco Cavana
Dr Alberto Cucino
Ospedale di Arco (Trento hospital)
Prof Giuseppe Foti
Dr Marco Giani
Dr Vincenzo Russotto
Ospedale San Gerardo
Prof Davide Chiumello
Valentina Castagna
Silvia Coppola
Ospedale San Paolo
Dr Andrea Dell’Amore Padua University Hospital (Policlinico of Padova)
Dr Hoi-Ping Shum Pamela Youde Nethersole Eastern Hospital
Dr Alain Vuysteke Papworth Hospitals NHS Foundation Trust
Dr Asad Usman
Andrew Acker
Blake Mergler
Nicolas Rizer
Federico Sertic
Benjamin Smood
Alexandra Sperry
Dr Madhu Subramanian
Penn Medicine (Hospital of the University of Pennsylvania)
Dr Erlina Burhan
Dr Navy Lolong
Dr Ernita Akmal
Prof Menaldi Rasmin
Bhat Naivedh
Dr Faya Sitompu
Persahabatan General Hospital
Dr Peter Barrett
Julia Daugherty
Dr David Dean
Piedmont Atlanta Hospital
Dr Antonio Loforte Policlinico di S. Orsola, Università di Bologna
Dr Irfan Khan
Olivia DeSantis
Dr Mohammed Abraar Quraishi
Presbyterian Hospital Services, Albuquerque
Dr Gavin Salt Prince of Wales
Dr Dominic So
Darshana Kandamby
Princess Margaret Hospital
Dr Jose M. Mandei
Hans Natanael
Prof Dr R. D. Kandou General Hospital—Paediatric
Eka YudhaLantang
Anastasia Lantang
Prof Dr R. D. Kandou General Hospital—Adult
Anna Jung
Dr Terese Hammond
Providence Saint John's Health Centre
George Ng
Dr Wing Yiu Ng
Queen Elizabeth Hospital, Hong Kong
Dr Pauline Yeung Queen Mary Hospital
Dr Shingo Adachi Rinku general medical center (and Senshu trauma and critical care center)
Dr Pablo Blanco
Ana Prieto
Jesús Sánchez
Rio Hortega University Hospital
Dr Meghan Nicholson Rochester General Hospital
Dr Michael Farquharson Royal Adelaide Hospital
Dr Warwick Butt
Alyssa Serratore
Carmel Delzoppo
Royal Children’s Hospital
Dr Pierre Janin
Elizabeth Yarad
Royal North Shore Hospital
Dr Richard Totaro
Jennifer Coles
Royal Prince Alfred Hospital
Robert Balk
Samuel Fox
James Hays
Esha Kapania
Pavel Mishin
Andy Vissing
Garrett Yantosh
Rush University, Chicago
Saptadi Yuliarto
Dr Kohar Hari Santoso
Dr Susanthy Djajalaksana
Saiful Anwar Malang Hospital (Brawijaya University) (Paediatrics)
Dr Arie Zainul Fatoni Saiful Anwar Malang Hospital (Brawijaya University) (Adult)
Dr Masahiro Fukuda Saiseikai Senri Hospital
Prof Keibun Liu Saiseikai Utsunomiya Hospital
Prof Paolo Pelosi
Dr Denise Battaglini
San Martino Hospital
Dr Juan Fernando Masa Jiménez San Pedro de Alcantara Hospital
Dr Sérgio Gaião
Dr Roberto Roncon-Albuquerque
São João Hospital Centre, Porto
Jessica Buchner Sentara Norfolk General Hospital
Dr Young-Jae Cho
Dr Sang Min Lee
Seoul National University Hospital
Dr Su Hwan Lee Severance Hospital
Dr Tatsuya Kawasaki Shizuoka Children's Hospital
Dr Pranya Sakiyalak
Prompak Nitayavardhana
Siriraj Hospital
Dr Tamara Seitz Sozialmedizinisches Zentrum Süd—Kaiser-Franz-Josef-Spital
Rakesh Arora
David Kent
St Boniface Hospital (University of Mannitoba)
Dr Swapnil Parwar
Andrew Cheng
Jennene Miller
St George Hospital
Daniel Marino
Jillian E Deacon
St. Christopher's Hospital for Children
Dr Shigeki Fujitani
Dr Naoki Shimizu
St Marianna Medical University hospital
Dr Jai Madhok
Dr Clark Owyang
Stanford University Hospital
Dr Hergen Buscher
Claire Reynolds
St Vincent’s Hospital
Dr Olavi Maasikas
Dr Aleksandr Beljantsev
Vladislav Mihnovits
Tartu University Hospital
Dr Takako Akimoto
Mariko Aizawa
Dr Kanako Horibe
Ryota Onodera
Teine Keijinkai Hospital
Prof Carol Hodgson
Meredith Young
The Alfred Hospital
Timothy Smith
Cheryl Bartone
The Christ Hospital
Dr Timothy George The Heart Hospital Baylor Plano, Plano
Dr Kiran Shekar
Niki McGuinness
Lacey Irvine
The Prince Charles Hospital
Brigid Flynn
Abigail Houchin
The University of Kansas Medical Centre
Dr Keiki Shimizu
Jun Hamaguchi
Tokyo Metropolitan Medical Center
Leslie Lussier
Grace Kersker
Dr John Adam Reich
Tufts Medical Centre (and Floating Hospital for Children)
Dr Gösta Lotz Universitätsklinikum Frankfurt (University Hospital Frankfurt)(Uniklinik)
Dr Maximilian Malfertheiner
Esther Dreier
Dr Lars Maier
Universitätsklinikum Regensburg (Klinik für Innere Medizin II)
Dr Neurinda Permata Kusumastuti University Airlangga Hospital (Paediatric)
Dr Colin McCloskey
Dr Al-Awwab Dabaliz
Dr Tarek B Elshazly
Josiah Smith
University Hospital Cleveland Medical Centre (UH Cleveland hospital)
Dr Konstanty S. Szuldrzynski
Dr Piotr Bielański
University Hospital in Krakow
Dr Yusuff Hakeem University Hospitals of Leicester NHS Trust (Glenfield Hospital)
Dr Keith Wille
Rebecca Holt
University of Alabama at Birmingham Hospital (UAB)
Dr Ken Kuljit S. Parhar
Dr Kirsten M. Fiest
Cassidy Codan
Anmol Shahid
University of Calgary (Peter Lougheed Centre, Foothills Medical Centre, South Health Campus and Rockyview General Hospital)
Dr Mohamed Fayed
Dr Timothy Evans
Rebekah Garcia
Ashley Gutierrez
Hiroaki Shimizu
University of California, San Francisco-Fresno Clinical Research Centre
Dr Tae Song
Rebecca Rose
University of Chicago
Dr Suzanne Bennett
Denise Richardson
University of Cincinnati Medical Centre
Dr Giles Peek
Dalia Lopez-Colon
University of Florida
Dr Lovkesh Arora
Kristina Rappapport
Kristina Rudolph
Zita Sibenaller
Lori Stout
Alicia Walter
University of Iowa
Dr Daniel Herr
Nazli Vedadi
University of Maryland—Baltimore
Dr Lace Sindt
Cale Ewald
Julie Hoffman
Sean Rajnic
Shaun Thompson
University of Nebraska Medical Centre
Dr Ryan Kennedy University of Oklahoma Health Sciences Centre (OU)
Dr Matthew Griffee
Dr Anna Ciullo
Yuri Kida
University of Utah Hospital
Dr Ricard Ferrer Roca
Cynthia Alegre
Dr Sofia Contreras
Dr JordI Riera
Vall d'Hebron University Hospital, Barcelona
Dr Christy Kay
Irene Fischer
Elizabeth Renner
Washington University in St. Louis/Barnes Jewish Hospital
Dr Hayato Taniguci Yokohama City University Medical Center
Gabriella Abbate
Halah Hassan
Dr Silver Heinsar
Varun A Karnik
Dr Katrina Ki
Hollier F. O'Neill
Dr Nchafatso Obonyo
Dr Leticia Pretti Pimenta
Janice D. Reid
Dr Kei Sato
Dr Kiran Shekar
Aapeli Vuorinen
Dr Karin S. Wildi
Emily S. Wood
Dr Stephanie Yerkovich
COVID-19 Critical Care Consortium

Collaborators

Prefix/First name/Last name Site name
Dr Emma Hartley Aberdeen Royal Infirmary (Foresterhill Health Campus)
Bastian Lubis Adam Malik Hospital
Takanari Ikeyama Aichi Childrens Health and Medical Center
Balu Bhaskar American Hospital
Dr Jae-Seung Jung Anam Korea University Hospital
Sandra Rossi Marta
Fabio Guarracino
Azienda Ospedaliero Universitaria Parma
Prof Fabio Guarracino Azienda Ospedaliero Universitaria Pisana
Stacey Gerle Banner University Medical Centre
Emily Coxon Baptist Health Louisville
Dr Bruno Claro Barts Hospital
Dr. Gonzo Gonzalez-Stawinski Baylor All Saints Medical Centre, Forth Worth
Daniel Loverde Billings Clinic
Dr Vieri Parrini Borgo San Lorenzo Hospital
Dr Diarmuid O’Briain
Stephanie Hunter
Box Hill Hospital
Dr Angela McBride Brighton and Sussex Medical School
Kathryn Negaard
Dr Phillip Mason
Brooke Army Medical Centre
Dr Angela Ratsch Bundaberg Hospital
Dr Mahesh Ramanan
Julia Affleck
Caboolture Hospital
Ahmad Abdelaziz Cairo University Hospital
Dr Sumeet Rai
Josie Russell-Brown
Mary Nourse
Canberra Hospital
Juan David Uribe Cardio VID
Dr Adriano Peris Careggi Hospital
Mark Sanders Cedar Park Regional Medical Center
Dominic Emerson Cedars-Sinai Medical Centre
Muhammad Kamal Cengkareng Hospital
Prof Pedro Povoa Centro Hospitalar de Lisboa
Dr Roland Francis Charite-Univerrsitatsmedizi n Berlin
Ali Cherif Charles Nicolle University Hospital
Dr Sunimol Joseph Children’s Health Ireland (CHI) at Crumlin
Dr Matteo Di Nardo Children’s Hospital Bambino Gesù
Micheal Heard Children's Healthcare of Atlanta-Egleston Hospital
Kimberly Kyle Children's Hospital
Ray A Blackwell Christiana Care Health System's Centre for Heart and Vascular Health
Dr Michael Piagnerelli
Dr Patrick Biston
CHU de Charleroi
Hye Won Jeong Chungbuk National University Hospital
Reanna Smith Cincinnati Children's
Yogi Prawira Cipto Mangunkusumo Hospital
Dr Giorgia Montrucchio
Dr Gabriele Sales
Città della Salute e della Scienza Hospital—Turin, Italy
Nadeem Rahman
Vivek Kakar
Cleveland Clinic, Abu Dhabi
Dr Michael Piagnerelli
Dr Josefa Valenzuela Sarrazin
Clinica Las Condes
Dr Arturo Huerta Garcia Clínica Sagrada Família
Dr Bart Meyns Collaborative Centre Department Cardiac Surgery, UZ Leuven
Marsha Moreno Dignity Health Medical Group-Dominican
Rajat Walia Dignity Health St. Joseph's Hospital and Medical Center (SJHMC)
Dr Annette Schweda Donaustauf hospital
Cenk Kirakli Dr. Suat Seren Chest Diseases and Surgery Practice and Training Centre
Estefania Giraldo Fundación Clinica Shaio (Shaio Clinic)
Dr Wojtek Karolak Gdansk Medical University
Dr Martin Balik General University Hospital
Elizabeth Pocock George Washington University Hospital
Evan Gajkowski Giesinger Medical Centre
Dr James Winearls
Mandy Tallott
Gold Coast University Hospital
Kanamoto Masafumi Gunma University Graduate School of Medicine
Dr Nicholas Barrett Guy's and St Thomas NHS Foundation Trust Hospital
Yoshihiro Takeyama Hakodate City Hospital
Sunghoon Park Hallym University Sacred Heart Hospital
Faizan Amin Hamilton General Hospital
Dr Erina Fina Hasan Sadikin Hospital
Dr Serhii Sudakevych Heart Institute Ministry of Health of Ukraine
Dr Angela Ratsch Hervey Bay Hospital
Patrícia Schwarz
Ana Carolina Mardini
Hospital de Clínicas de Porto Alegre
Ary Serpa Neto Hospital Israelita Albert Einstein
Dr Andrea Villoldo Hospital Privado de Comunidad
Alexandre Siciliano Colafranceschi Hospital Pro Cardíaco
Dr Alejandro Ubeda Iglesias Hospital Punta de Europa
Lívia Maria Garcia Melro
Giovana Fioravante Romualdo
Hospital Samaritano Paulista
Diego Gaia Hospital Santa Catarina
Helmgton Souza Hospital Santa Marta
Dr Diego Bastos Hospital Cura D’ars Fortaleza
Filomena Galas Hospital Sirio Libanes
Dr Rafael Máñez Mendiluce Hospital Universitario de Bellvitge
Alejandra Sosa Hospital Universitario Esperanza (Universidad Francisco Marroquin)
Dr Ignacio Martinez Hospital Universitario Lucus Augusti
Hiroshi Kurosawa Hyogo Prefectural Kobe Children's Hospital
Juan Salgado Indiana University Health
Dr Beate Hugi-Mayr Inselspital University Hospital
Eric Charbonneau Institut Universitaire de Cardiologie et de Pneumologie de Quebec—Universite Laval
Vitor Salvatore Barzilai Instituto de Cardiologia do Distrito Federal—ICDF
Veronica Monteiro Instituto de Medicina Integral Prof. Fernando Figueira (IMIP)
Rodrigo Ribeiro de Souza Instituto Goiano de Diagnostico Cardiovascular (IGDC)
Michael Harper INTEGRIS Baptist Medical Center
Hiroyuki Suzuki Japan Red Cross Maebashi Hospital
Celina Adams John C Lincoln Medical Centre
Dr Jorge Brieva John Hunter Hospital
George Nyale Kenyatta National Hospital (KNH)
Jihan Fatani
Dr Faisal Saleem Eltatar
King Abdullah Medical City Specialist Hospital
Dr. Husam Baeissa King Abdullah Medical Complex
Ayman AL Masri King Salman Hospital NWAF
Yee Hui Mok KK Women's and Children's Hospital
Masahiro Yamane KKR Medical Center
Hanna Jung Kyung Pook National University Hospital
Dr Matthew Brain
Sarah Mineall
Launceston General Hospital
Rhonda Bakken M Health Fairview
Dr Tim Felton Manchester University NHS Foundation Trust—Wythenshawe
Lorenzo Berra Massachusetts General Hospital
Gordan Samoukoviv
Dr Josie Campisi
McGill University Health Centre
Bobby Shah Medanta Hospital
Arpan Chakraborty Medica Super speciality Hospital
Monika Cardona Medical University of South Carolina
Harsh Jain Mercy Hospital of Buffalo
Dr Asami Ito Mie University Hospital
Brahim Housni Mohammed VI University hospital
Sennen Low National Centre for Infectious Diseases
Dr. Koji Iihara National Cerebral and Cardiovascular Center
Joselito Chavez National Kidney and Transplant Institute
Dr Kollengode Ramanathan National University Hospital, Singapore
Gustavo Zabert National University of Comahue
Krubin Naidoo Nelson Mandela Children's Hospital
Singo Ichiba Nippon Medical School Hospital
Randy McGregor Northwestern Medicine
Teka Siebenaler Norton Children's Hospital
Hannah Flynn Novant Health (NH) Presbyterian Medical Centre
Julia Garcia-Diaz
Catherine Harmon
Ochsner Clinic Foundation
Kristi Lofton Ochsner LSA Health Shreveport
Toshiyuki Aokage Okayama University Hospital
Kazuaki Shigemitsu Osaka City General Hospital
Dr Andrea Moscatelli Ospedale Gaslini
Dr Giuseppe Fiorentino Ospedali dei Colli
Dr Matthias Baumgaertel Paracelsus Medical University Nuremberg
Serge Eddy Mba Parirenyatwa General Hospital
Jana Assy Pediatric and Neonatal Cardiac intensive care at the American University
Holly Roush Penn State Heath S. Hershey Medical Centre
Kay A Sichting Peyton Manning Children's Hospital
Dr Francesco Alessandri Policlinico Umberto, Sapienza University of Rome
Debra Burns Presbyterian Hospital, New York/Weill Cornell Medical Centre
Ahmed Rabie Prince Mohammed bin Abdulaziz Hospital
Carl P. Garabedian Providence Sacred Heart Children's Hospital
Dr Jonathan Millar
Dr Malcolm Sim
Queen Elizabeth II University Hospital
Dr Adrian Mattke Queensland Children’s Hospital
Dr Danny McAuley Queens University of Belfast
Jawad Tadili Rabat university hospital
Dr Tim Frenzel Radboud University Medical Centre
Aaron Blandino Ortiz Ramón y Cajal University Hospital
Jackie Stone Rapha Medical Centre
Dr Alexis Tabah
Megan Ratcliffe
Maree Duroux
Redcliffe Hospital
Dr Antony Attokaran Rockhampton Hospital
Dr Brij Patel Royal Brompton &Harefield NHS Foundation Trust
Derek Gunning Royal Columbian Hospital
Dr Kenneth Baillie Royal Infirmary Edinburgh
Dr Pia Watson Sahlgrenska University Hospital
Kenji Tamai Saiseikai Yokohamashi Tobu Hospital
Dr Gede Ketut Sajinadiyasa
Dr Dyah Kanyawati
Sanglah General Hospital
Marcello Salgado Santa Casa de Misericordia de Juiz de Fora
Assad Sassine Santa Casa de Misericórdia de Vitoria
Dr Bhirowo Yudo Sardjito Hospital
Scott McCaul Scripps Memorial Hospital La Jolla
Bongjin Lee Seoul National University Children's Hospital
Yoshiaki Iwashita Shimane University Hospital
Laveena munshi Sinai Health Systems (Mount Sinai Hospital)
Dr Neurinda Permata Kusumastuti Soetomo General Hospital (FK UNAIR)
Dr Nicole Van Belle St. Antonius Hospital
Ignacio Martin-Loeches St James’s University Hospital
Dr Hergen Buscher St Vincent’s Hospital, Sydney
Surya Oto Wijaya Sulianti Saroso Hospital
Dr Lenny Ivatt Swansea Hospital
Chia Yew Woon Tan Tock Seng Hospital
Hyun Mi Kang The Catholic University of Seoul St Mary Hospital
Erskine James The Medical Centre Navicent Health
Nawar Al-Rawas Thomas Jefferson University Hospital
Tomoyuki Endo Tohoku Medical and Pharmaceutical University
Dr Yudai Iwasaki Tohoku University
Dr Eddy Fan
Kathleen Exconde
Toronto General Hospital
Kenny Chan King-Chung Tuen Mun Hospital
Dr Vadim Gudzenko UCLA Medical Centre (Ronald Regan)
Dr Beate Hugi-Mayr Universitätsspital Bern, Universitätsklinik für Herz- und Gefässchirurgie
Dr Fabio Taccone Universite Libre de Bruxelles
Dr Fajar Perdhana University Airlangga Hospital (Adult)
Yoan Lamarche University de Montreal (Montreal Heart Institute)
Dr Joao Miguel Ribeiro University Hospital CHLN
Dr Nikola Bradic University Hospital Dubrava
Dr Klaartje Van den Bossche University Hospital Leuven
Gurmeet Singh University of Aberta (Mazankowski Heart Institute)
Dr Gerdy Debeuckelaere University of Antwerp
Dr Henry T. Stelfox University of Calgary and Alberta Health Services
Cassia Yi University of California at San Diego
Jennifer Elia University of California, Irvine
Shu Fang University of Hong Kong
Thomas Tribble University of Kentucky Medical Center
Shyam Shankar University of Missouri
Dr Paolo Navalesi University of Padova
Raj Padmanabhan University of Pittsburgh Medical Centre
Bill Hallinan University of Rochester Medical Centre (UR Medicine)
Luca Paoletti University of South Carolina
Yolanda Leyva University of Texas Medical Branch
Tatuma Fykuda University of the Ryukus
Jillian Koch University of Wisconsin & American Family Children's Hospital
Amy Hackman UT Southwestern
Lisa Janowaik UTHealth (University of Texas)
Jennifer Osofsky Vassar Brothers Medical Center (VBMC)
A/Prof Katia Donadello Verona Integrated University Hospital
Josh Fine WellSpan Health—York Hospital
Dr Benjamin Davidson Westmead Hospital
Andres Oswaldo Razo Vazquez Yale New Haven Hospital

Funding

University of Queensland; Wesley Medical Research; The Prince Charles Hospital Foundation; Fisher & Paykel; The Health Research Board of Ireland; Biomedicine international training research programme for excellent clinician-scientists; European Union’s research and innovation programme (Horizon 2020); la Caixa Foundation. Finally, Carol Hodgson is funded by a National Health and Medical Research Council Grant. Sally Schrapnel is funded by the Australian Research Council Centre of Excellence for Engineered Quantum Systems (Project number CE170100009).

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GLB conceived the study, participated in its design and coordination and helped to draft the manuscript; JYS conceived the study, participated in its design and coordination and helped to draft the manuscript drafted the manuscript; HD participated in the design of the study and helped to draft the manuscript; NW performed the statistical analysis and helped to draft the manuscript; SS participated in the coordination of the study, performed the statistical analysis and helped to draft the manuscript; JPF participated in the design of the study and helped to draft the manuscript; BL performed the statistical analysis and helped to draft the manuscript; SH participated in the coordination of the study performed the statistical analysis and helped to draft the manuscript; AV performed the statistical analysis and helped to draft the manuscript; GB performed the statistical analysis and helped to draft the manuscript; JEM participated in the design of the study and helped to draft the manuscript; SF participated in the design and coordination of the study and helped to draft the manuscript; MP participated in the coordination of the study helped to draft the manuscript; JL participated in the coordination of the study helped to draft the manuscript; DB participated in the coordination of the study helped to draft the manuscript; EF participated in the coordination of the study helped to draft the manuscript; AT participated in the coordination of the study helped to draft the manuscript; DC participated in the coordination of the study helped to draft the manuscript; AC participated in the design of the study and helped to draft the manuscript; AE participated in collection of data and helped to draft the manuscript; CH participated in coordination and collection of data and helped to draft the manuscript; SI participated in collection of data and helped to draft the manuscript; CL participated in coordination and collection of data and helped to draft the manuscript; SM participated in coordination and collection of data and helped to draft the manuscript; AN participated in coordination and collection of data and helped to draft the manuscript; PY participated in coordination and collection of data and helped to draft the manuscript; MO participated in coordination and collection of data and helped to draft the manuscript; AP participated in coordination and collection of data and helped to draft the manuscript; HTT participated in collection of data and helped to draft the manuscript; JFF conceived the study, participated in its design and coordination and helped to draft the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Gianluigi Li Bassi.

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Ethics approval and consent to participate

Participating hospitals obtained local ethics committee approval, and a waiver of informed consent was granted in all cases.

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Not applicable.

Statistical analysis

Nicole White; Sally Shrapnel; Benoit Liquet; Samuel Hinton; Aapeli Vuorinem; Gareth Booth.

Competing interests

GLB and JF received research funds, through their affiliated institution from Fisher & Paykel. All remaining authors do not have any conflict of interest related to this report.

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Li Bassi, G., Suen, J.Y., Dalton, H.J. et al. An appraisal of respiratory system compliance in mechanically ventilated covid-19 patients. Crit Care 25, 199 (2021). https://doi.org/10.1186/s13054-021-03518-4

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Keywords

  • Mechanical ventilation
  • Compliance
  • ARDS
  • COVID-19
  • SARS-CoV-2