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the Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genoa, Genoa, Italy.Anesthesia and Intensive Care, San Martino Policlinico Hospital, IRCCS for Oncology and Neurosciences, Genoa, Italy.
the Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genoa, Genoa, Italy.Anesthesia and Intensive Care, San Martino Policlinico Hospital, IRCCS for Oncology and Neurosciences, Genoa, Italy.
Corresponding author: Sharon Einav, Intensive Care Unit of the Shaare Zedek Medical Medical Center and Hebrew University Faculty of Medicine, Samuel Byte 12, Jerusalem, 9103102, Israel.
Few reports have studied lung aeration and perfusion in normal lungs, COVID-19 and ARDS from other causes (NC-ARDS) using dual-energy computed tomography pulmonary angiograms (DE-CTPA).
Aims
To describe lung aeration and blood-volume distribution using DE-CTPAs of patients with NC-ARDS, COVID-19 and controls with a normal DE-CTPA (“healthy lungs”). We hypothesized that each of these conditions have unique ranges of aeration and pulmonary blood volumes.
Methods
This retrospective, single-center study of DE-CTPAs included patients with COVID-19, NC-ARDS (Berlin criteria) and controls. Patients with macroscopic pulmonary embolism were excluded. The outcomes studied were the (1) lung blood-volume in areas with different aeration levels (normal, ground glass opacities [GGO], consolidated lung) and (2) aeration/blood-volume ratios.
Results
Included were 20 patients with COVID-19 (10 mild, 10 moderate-severe), 6 with NC-ARDS and 12 healthy-controls. Lung aeration was lowest in patients with severe COVID-19 24%(IQR13%-31%) followed by those with NC-ARDS 40%(IQR21%-46%). Blood-volume in GGO was lowest in patients with COVID-19 [moderate-severe:-28.6(IQR-33.1–23.2); mild: -30.1(IQR-33.3–23.4)] and highest in normal aerated areas in NC-ARDS -37.4(IQR-52.5–30.2-) and moderate-severe COVID-19 -33.5(IQR-44.2–28.5). Median aeration/blood-volume ratio was lowest in severe COVID-19 but some values overlapped with those observed among patients with NC-ARDS.
Conclusion
Severe COVID-19 disease is associated with low total aerated lung volume and blood-volume in areas with GGO and overall aeration/blood volume ratios, and with high blood volume in normal lung areas. In this hypothesis-generating study, these findings were most pronounced in severe COVID disease. Larger studies are needed to confirm these preliminary findings.
], based on the fact that moderate-severe COVID-19 patients typically fulfill the Berlin Criteria for ARDS, yet controversy still surrounds use of the term ARDS in this context [
Attenuated accumulation of regulatory T cells and reduced production of interleukin 10 lead to the exacerbation of tissue injury in a mouse model of acute respiratory distress syndrome.
] and these manifest in lung tissue as a variety of thrombotic phenomena ranging from capillary micro thromboses to large pulmonary vessel occlusions [
]. Moreover, subsegmental pulmonary vascular enlargement has been described in computed tomography (CT) of COVID-19 patients even without macroscopic pulmonary thromboses [
]. Finally, a previous study comparing the CT scans of NC-ARDS and COVID-19 patients showed that COVID-19 lungs with similar compliance and weights yielded significantly lower PaO2/FiO2 despite higher lung gas volumes. The venous admixture was related to the amount of non-aerated tissue in NC-ARDS but not in COVID-19 and increased Positive end-expiratory pressure (PEEP) improved lung mechanics and decreased dead space probably due to recruitment in NC-ARDS but had no beneficial effect on COVID-19 [
Dual-energy computed tomography (DECT) demonstrates aeration as does conventional CT, differentiating between normal areas, those with ground glass opacities [GGO] and consolidations. However, DECT also allows to determine the blood-volume in the lung [
We aimed to quantify lung blood-volume in areas with different aeration (normal, GGO, consolidated) using DECT pulmonary angiograms (DE-CTPAs) in three cohorts of patients – NC-ARDS, COVID-19 and controls with healthy lungs. We also aimed to quantify the severity of aeration – blood volume mismatch. We hypothesized that overall lung regions receiving blood-volume would be similar in patients with NC-ARDS and controls with normal lungs but lower in patients with severe COVID-19. We also hypothesized that the aeration/blood-volume ratio is worse in patients with severe COVID-19 than in patients with NC-ARDS.
Materials and methods
Study design
This retrospective cohort comparison study was conducted in a single medical center in Jerusalem, Israel. The study was approved by the institutional ethics review board with waiver of informed consent due to its retrospective nature. The study is reported in accordance with "strengthening the reporting of observational studies in epidemiology" (STROBE) [
STROBE Initiative. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies.
American Thoracic Society, European Society of Intensive Care Medicine, and Society of Critical Care Medicine. 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.
]. During the first three pandemic surges, the hospital treated more than 1600 COVID-19 patients.
During 2020 the hospital radiology service performed 31811 CT scans. Of these 1420 were CT pulmonary angiographies (CTPAs) and about 90% of the CTPAs were performed with the dual energy technique. For the purpose of this study, all relevant DE-CTPAs of the chest were re-reviewed by a senior radiologist trained in cardiothoracic imaging, with 26 years of experience (NB) and expert radiologist with 10 years of experience (YF).
Data sources: Using the hospital administrative database we identified all patients that had undergone DE-CTPAs. Exams with marked respiratory motion artifacts were excluded.
Eligibility criteria
For patients with COVID-19 and controls we screened the files of all consecutive patients for those fulfilling criteria as follows:
For inclusion in the COVID-19 group the files of all patients referred from the COVID-19 ICUs and COVID-19 wards (1-March-2020 to 30-April-2021) were reviewed. Patients were only coded as COVID positive if they had a positive RT-PCR test. Inclusion criteria were similar, patients with known heart disease were excluded. Included patients were classified as either mild COVID-19 or moderate severe COVID-19 at the time of DECT based on National Institutes of Health classification [
For inclusion in the NC-ARDS group, we used a historical cohort of patients that underwent DE-CTPA. These patients all fulfilled ARDS criteria at the time of ICU admission [
] and had undergone studies to inform on left ventricular systolic function and cardiac valve disease. For the current study we re-examined the data and if heart disease was raised as an alternative option for the pulmonary findings the DE-CTPAs of these patients were further reviewed for signs of pulmonary fluid overload and excluded if such were found.
For inclusion in the control group, all the DE-CTPAs archived in the hospital picture archiving and communication system (PACS) between the dates 1-March-2019 to 30-June-2019 were reviewed. Patients were selected from the pre-pandemic period in order to exclude patients with asymtomatic/undiagnosed COVID-19. These images screened by two expert radiologists with 10 and 26 years of experience (YF and NB) and only studies with no evidence of parenchymal lung disease (i.e.“healthy” controls)were included.
Patients with pre-existing lung disease (e.g. emphysema) or an alternative pulmonary diagnosis were excluded. Patients with any evidence of central, segmental or subsegmental pulmonary embolism were excluded from all three groups in order to focus on blood-volume at the microvascular level.
Variables
The primary outcome was the distribution of the lung blood volume in areas with different aeration (normal, ground glass opacities [GGO], consolidated). The secondary outcome was the quantification of aeration/blood-volume ratio.
We prespecified DE-CTPA lung aeration classification in accordance with prior publications defining attenuation thresholds in COVID-19 patients (Supplement A.1). Aeration was assumed inversely proportional to CT attenuation expressed in Hounsfield Units (HU), as in previous studies in NC-ARDS [
]. Lung iodine content was estimated based on the difference in attenuation at the two energy levels; this parameter is proportional to the pulmonary blood volume and is a surrogate for lung perfusion [
]. Lung aeration/blood-volume ratio (as a surrogate for V/Q mismatch) was calculated by dividing lung aeration by lung blood-volume. See Supplement A.2 for further details.
Method of image acquisition and quantitative image analysis
All DE-CTPAs were conducted in a standardized manner, in maximal inspiration during breath-hold, on multidetector dual energy scanners (Siemens Healthcare, Forchheim, Germany). Tube voltage (kv) and milliamperes (mAs) were either 80/140kv; 238/92mAs, or 90/150Sn kv; 85/65 mAs or 100/140Sn kv; 71/66 mAs, depending on scanner model. Intravenous contrast material was administrated (60 ml of Omnipaque™ 350 at a rate of 3-4 ml/sec, using bolus triggering). High and low energy images were reconstructed at 1-mm slice thickness.
(Detailed CT acquisition and reconstruction techniques and injection protocols are given on Supplement A.2). For quantitative image analysis we used a postprocessing application developed in-house (RS) on Syngo.via Frontier platform (Siemens Healthcare, Erlangen, Germany) using MeVis.Lab (MeVis Medical Solutions AG, Heidelberg, Germany). Low and high energy images were used to segment lungs, using the region growing method to segment the entire lung applying a HU range from -50 to -1000. The lungs were classified to three regions: normal aerated lung (-949HU to -700HU), GGO (-699HU to -300 HU) and consolidated lung (– 299HU to –50 HU). For assessing lung blood-volume we then subtracted the low energy from the high energy for each voxel in both axial and coronal views, and the difference in HU values was recorded for each voxel. A large difference between the energy levels designates an area with higher iodine content and therefore more blood-volume. (Supplement A.2).
Bias: In order to minimize selection bias we assessed all referred cases for eligibility and included all cases that met predefined inclusion criteria despite the differences in cohort size and characteristics. Due to the small number of patients and the hypothesis-generating nature of the study no attempt was made to clinically match the patients in the study groups. Measurement bias was addressed by use of state-of-the-art devices, standard and recommended protocols and by using studies performed by specialized radiography technicians. The lists of consecutive cases were put together by a researcher blinded to patient outcomes (KC, OP). Clinical data was collected by researchers blinded to DE-CTPA results (HW, YH). Analyses were conducted by a physicist blinded to patient disease characteristics and outcomes (RS). All radiological data were reviewed independently and in duplicate by two expert radiologists, with 26 and 10 years of experience (NB, YF). For critically ill patients, to minimize lead and lag time biases, we selected the scan performed at greatest proximity to the severe acute respiratory deterioration if more than one DE-CTPA had been performed for a single patient.
Study size
Due to the exploratory nature of the study no preplanned sample size calculation was performed. However, the achieved sample size is similar to that of other studies on DECT in COVID-19 [
Collaborators of the GECOVID Group. Lung distribution of gas and blood volume in critically ill COVID-19 patients: a quantitative dual-energy computed tomography study.
For this proof of concept study only descriptive statistics were used with no adjustment for confounders. For categorical variables we presented counts, proportions and percentages. For continuous variables we presented averages with their standard deviations, medians, interquartile ranges and range). All estimates are given with their precision (95% confidence intervals) and category boundaries are provided for continuous variables in order to show overlaps. No cases were missing relevant DECT data and none were lost to follow-up.
Results
Overall, 38 patients were included - 6 NC-ARDS, 20 COVID-19 (10 mild, 10 moderate-severe) and 12 healthy controls. One of the NC-ARDS patients and 5 of the moderate –severe COVID-19 patients were intubated and ventilated. The full inclusion-exclusion process is detailed in Figure 1. The demographic characteristics and blood tests of the study participants are presented in Table 1 and Supplement B All but three of the patients with severe COVID-19 survived to hospital discharge.
Lung aeration – Total lung volumes and volumes of lung areas with different aeration (normal, ground glass opacities [GGO], consolidated) are presented in Supplement C. The proportion of aerated lung volume relative to total lung volume was highest in controls with a median value approximating 79% (IQR 68% to 85%). COVID-19 patients with mild disease had a slightly lower proportion of aerated lung volume relative to total lung volume with a median of 67% (IQR 40% to 71%). Most patients with NC-ARDS had even lower aerated lung volumes relative to total lung volume with a median approximating 40% (IQR 21% to 46%) and patients with moderate- severe COVID-19 patients had the lowest aerated lung volume relative to total lung volume with a median of 24% (IQR 13% to 31%). Patients with NC-ARDS and moderate- severe COVID-19 had considerable overlap in lung volumes. However, only minimal overlap was observed between normal values and the values for either NC-ARDS or moderate-severe COVID-19 (Figure 2)
Figure 2Violin plot showing the proportion of aerated lung volume relative to total lung volume in each patient group.
In normal patients (light gray) the ratio of aerated/total lung is high with the median value approximating 79% (IQR 68-85). In NC-ARDS patients (medium light gray) the ratio of aerated to total lung is lower, with a median approximating 40% (21-46). COVID patients with mild disease (dark gray) have a proportion of aerated/total lung volume slightly lower than normal with a median of 67% (40-71). COVID patients with moderate-severe disease (medium dark gray) have the lowest proportion of aerated/total lung volume - median 24% (13-31).
Lung blood-volume – In areas with normal aeration, lung blood-volume is increased in patients with NC- ARDS (-41.6 ± 17.6, median -37.4, IQR -52.5 to -30.2) and in patients with moderate-severe COVID-19 (-36.4 ± 13.3, median -33.5, IQR -44.2 to -28.5) when compared to normal controls (-31.2 ± 13.1, median -32, IQR -37.7 to -30.2) and patients with mild COVID-19 (-29.6 ± 12.9, median -26.2, IQR -38.2 to -19.5), although considerable overlap was observed between the groups.
In areas with GGO, lung blood-volume is increased in patients with NC-ARDS and normal controls [(-34.2 ± 12.1, median -32.8, IQR -45.8 to -21.3), (-33.9 ± 11.9, median -34.8, IQR -42.1 to -26.0)] and lower in patients with moderate-severe COVID-19 (-29.0 ± 9.0, median -28.6, IQR -33.1 to -23.6) and patients with mild COVID-19 (-28.6 ± 8.0, median -30.1, IQR -33.4 to -23.4). The blood-volume of consolidated lung was overall low in all groups (Figure 3A, B).
Figure 3Lung blood-volume in the different study populations, with separation of mild and moderate-severe COVID. The X axis demonstrates the division to three lung zones by aeration according to HU (normal, ground glass and consolidated). The Y axis demonstrates the blood-volume based on the difference (in HU) between the two energies. More negative values indicate larger blood-volume. (A) Shows lung blood-volumes with their 95% confidence intervals, demonstrating the overlap between the four study populations (B) shows lung blood-volumes per lung aeration in 50 HU steps. The size of the dot represents the percentage of each value per study population
In areas with GGO - patients with NC-ARDS have a higher blood-volume than do patients with both mild and moderate-severe COVID. In areas with normal aeration - patients with NC-ARDS have the highest blood-volume, followed by patients with severe COVID and both have a larger blood-volume compared to normal controls or patients with mild COVID disease. The blood-volume in consolidated lung in both NC-ARDS and COVID is overall low.
Multiplanar sagittal and coronal reconstructions of the typical pattern of aeration and blood-volume observed in patients in each group are presented in Figure 4A to F
Figure 4Simplified 3D example reconstructions of aeration and blood-volume in (A) normal lung – coronal view (B) normal lung –sagittal view (C) NC-ARDS lung – coronal view (D) NC-ARDS lung –sagittal view (E) COVID lung – coronal view (F) COVID lung –sagittal view.
Shades of red represent the blood-volume in aerated lung (dark red – larger blood-volume, orange smaller blood-volume). Shades of blue represent the blood-volume in non-aerated lung with ground glass opacities or consolidation (dark blue larger blood-volume, light blue to white – smaller blood-volume). In normal lung (figures A and B) aeration and blood-volume are overall homogenous as seen by the prevalence of red coloring. In NC-ARDS lung (figures C and D) aerated lung with a larger blood-volume is seen predominantly in the apex. Patchy distribution of partially aerated and non-aerated lung with a larger blood-volume is seen in the mid and lower left segments. In COVID lung (figures E and F) a very small amount of aerated lung with a larger blood-volume is seen mostly in the periphery and in anterior regions. The majority of the lungs are non-aerated and have a smaller blood-volume.
Aeration/blood-volume ratio - Median aeration/blood-volume ratio was lowest among patients with moderate-severe COVID-19 but the overall range of values overlapped with those observed among patients with NC-ARDS. The aeration/blood-volume ratio of patients with mild COVID-19 was lower than that of controls with normal lung and higher than that of patients with NC-ARDS or severe COVID-19, again with significant overlap (Figure 5). See Supplement D for further details.
Figure 5Violin plot showing the aeration/blood-volume ratio (a surrogate of ventilation perfusion mismatch) in each patient group. The X-axis represents a non- unit value of the ratio of lung Hounsfield unit (HU) value divided by the low and high-energy difference. There is inverse relation between lung aeration and HU value; lower HU value, indicates more aerated lung. The low and high-energy difference reflects the iodine content in the tissue; higher difference indicates higher blood volume. The right side of the X-axis represents higher ratio between lung aeration and blood volume.
In normal patients (light gray) aeration/blood-volume ratio is the lowest, followed by patients with mild COVID (dark gray). The median aeration/blood-volume ratio of patients with NC-ARDS (medium light gray) seems somewhat lower than that of patients with moderate-severe COVID (medium dark gray). Considerable overlap exists between the groups, possibly due to the small number of patients included. The ratio was calculated by dividing lung aeration (measured as Hounsfield Units) by lung blood-volume (measured as the difference between the HU measurements using the two energies).
The current study shows that in terms of aeration, patients with NC-ARDS and severe COVID-19 both have significantly lower volumes of aerated lung than normal patients. Despite overlap in aerated lung volumes, the median volume of aerated lung in patients with moderate- severe COVID-19 is smaller than in patients with NC-ARDS. In terms of blood-volume, abnormal lung areas (i.e. areas with GGO and consolidation) are less perfused among patients with mild and moderate-severe COVID-19 than among patients with NC-ARDS. This could be compatible with microvascular thromboses. Both patients with NC-ARDS and patients with moderate-severe COVID-19 had increased blood-volume in areas of normal lung. The median aeration/blood-volume ratio seems somewhat lower in patients with moderate-severe COVID-19 than in patients with NC-ARDS, with considerable overlap.
A previous study comparing COVID-19 patients with and without mechanical ventilation showed greater loss of aeration among mechanically ventilated patients [
Collaborators of the GECOVID Group. Lung distribution of gas and blood volume in critically ill COVID-19 patients: a quantitative dual-energy computed tomography study.
]. In our study the median volume of aerated lung in patients with moderate-severe COVID-19 was also smaller than that of patients with NC-ARDS. This is remarkable given that all of the patients with NC-ARDS were intubated due to respiratory failure shortly after DE-CTPAs. It would be reasonable to expect greater loss of aeration among patients with NC-ARDS pre-intubation than in mechanically ventilated COVID-19 patients with optimally recruited lungs.
Based on prior data suggesting that dead space plays a predominant role in COVID-19 [
], we hypothesized that blood-volume (i.e. perfusion) would be similar in normal controls and in NC-ARDS patients but moderate severe COVID-19 patients would have lower lung blood-volume and hence a higher aeration/blood-volume ratio. We found that consolidated lung areas seem to be similar in amount and in aeration/blood-volume ratio in patients with moderate to severe COVID-19 and in patients with NC-ARDS. The difference between these two diseases therefore seems attributable to areas of GGO and to areas of normal lung.
Patients with mild and moderate-severe COVID-19 seem to have lower blood-volume in areas of GGO and higher blood-volume in normal lung than do patients with NC-ARDS. This could support the hypothesis put forward by Gattinnoni et al. regarding the presence of two COVID-19 phenotypes [
]. In L-type COVID-19, lung compliance is preserved whereas lung perfusion decreases (increased V/Q ratio). We found the highest aeration/blood volume ratio in areas of GGO in patients with mild COVID-19. This suggests that a reduction in perfusion with resultant dead-space predominates in patients with mild COVID-19 (type L). In H-type COVID-19, lung compliance is reduced and shunt increases. Areas of GGO may have low blood volume due to vascular involvement in the disease process. Consolidated lung areas have a high shunt fraction unless compensated by hypoxic vasoconstriction or mechanical constriction of blood vessels. As these areas increase in moderate severe COVID-19, perfusion may be redirected to areas of normal lung. Since perfusion to areas with GGO is worse in H-type COVID-19 than it probably is in patients with NC-ARDS, more blood is redirected to normal lung areas in these patients than in NC-ARDS. In other words, as areas of normal aeration are reduced and perfusion to areas with GGO worsens, blood is redirected to the diminishing residual areas with normal aeration.
Patients with NC-ARDS and moderate-severe COVID-19 both had increased blood-volume to areas of normal lung while patients with mild COVID-19 had no increase in blood-volume. The effects of nitric oxide can be ruled out as the elimination half time of this drug is seconds while transfer times to DE-CTPA were much longer.
We hypothesized that the aeration/blood-volume ratio would be highest in severe COVID-19 patients. Prior authors have suggested that COVID-19 patients have less effective blood flow redistribution and/or lower lung recruitment potential [
]. It seems that lung aeration/ blood-volume is only part of the problem. The aeration/blood-volume ratio was only slightly lower in patients with severe COVID-19 when compared to patients with NC-ARDS since blood-volume increases in areas of normal lung. However overall aeration was much lower. The main issue in severe COVID-19 patients may therefore be the small volume of normal lung that remains.
Prior studies have used DECT to characterize lung findings in COVID-19 patients. One study quantified vasculopathy measuring global lung iodine content in three planes. Perfusion was averaged across the lung as a whole, without separation of areas with different aeration [
]. Another study examined aeration/perfusion using two planar cuts of the lung. Perfusion was assessed using pulmonary blood volume maps and aeration was assessed using a custom-made script made in Matlab for three-material decomposition in COVID-19 patients with and without mechanical ventilation [
Collaborators of the GECOVID Group. Lung distribution of gas and blood volume in critically ill COVID-19 patients: a quantitative dual-energy computed tomography study.
]. Contrary to these findings, Arru et al, used artificial intelligence to estimate quantitative perfusion in 74 patients noted similar values in areas with GGO and in areas of normal lung. However, similar to our findings, they noted that patients with worse disease (as determined by CT severity scores and clinical outcomes) also had lower iodine content [
]. None of these studies excluded patients with macroscopic pulmonary embolism, thus their assessments of perfusion may have been confounded by proximal arterial obstruction.
We assessed regional lung blood-volume distribution with DE-CTPAs. We studied both patients with severe COVID-19 and patients with NC-ARDS. We also classified patients with COVID-19 as either mild or moderate severe based on NIH recommendations to make our findings more translatable for clinical use at the bedside. Our study, conducted using an in-house algorithm for data analysis, quantified the HU-difference per voxel as a surrogate of perfusion covering the entire lung volume in a three-dimensional manner and separating the lung into three areas with different aeration.
Our findings may have several therapeutic implications. First, GGO areas have low perfusion which might stem from microthrombi. This raises questions regarding therapeutic anticoagulation. High doses of heparin/low molecular weight heparin are beneficial in non-critical hospitalized COVID-19 patients [
]. The blood flow directed to normal lung areas and lung areas with GGO is higher than that directed to consolidated lung. In these circumstances, raising PEEP may fail to improve oxygenation; the blood flow will not increase in a parallel manner in the lung recruited in consolidated areas whereas in normal lung areas and areas with GGO applying a higher PEEP would only increase lung stress and dead space.
This hypothesis-driving study has several limitations. It is a single center and retrospective study and although efforts were made to decrease bias (e.g. blinding, duplicate readings, use of accepted classifications), our findings may not be generalizable. Only patients referred to DE-CTPAs who were also sufficiently stable to be transferred were included. This undoubtedly created selection bias, as evidenced by the inclusion only of pre-intubation rather than immediately post-intubation NC-ARDS patients. We did not match patient characteristics and present no data on lung mechanics. Although we excluded patients with emboli, it is possible that we were not able to visualize distal small peripheral emboli in severely diseased lung or with mild breathing artifacts. Pressures were not standardized during maximal inspiratory hold. Only a small number of cases fulfilled the rigorous inclusion/exclusion criteria we employed to ensure focus on microcirculation. This precludes matching and performance of statistical comparisons. Point estimates are of little value with such a small number of cases. We therefore used data visualization to drive this preliminary hypothesis. Less rigorous exclusion criteria (e.g. pulmonary embolism, alternative explanations for respiratory failure) would have increased our cohort size at the price of confounding. Our greatest study limitation is lack of standardization of lung pressures. We adjusted for this limitation by separation of lung areas by tissue density characteristics but this is not ideal.
In conclusion, this hypothesis driving DE-CTPA study describes blood-volume in lungs with different aeration not only in COVID-19 patients but also in patients with NC-ARDS and normal controls. Our findings suggest that the degree of reduction in aerated lung volume and blood-volume in lung with ground glass opacities and the balance between the two may determine the severity of COVID-19. In the future, a multicenter study with a larger sample size should be conducted to verify our findings, perhaps even derivation and validation datasets could be used to determine cutoff values for patient phenotypes.
Funding
The authors received no funding for this work
Contribution to the field
Coronavirus Disease 2019 (COVID-19) lung disease often meets the clinical criteria of acute respiratory distress syndrome (ARDS) but studies suggest that COVID-19 patients have less recruitable lung and different pattern of blood distribution. There are limited reports comparing lung aeration and perfusion in patients with COVID-19 versus NC-ARDS from other causes and healthy subjects.
We have developed in-house a technique for assessing lung aeration and blood-volume and aeration/blood-volume ratio using dual-energy computed tomography. In this feasibility study we describe the technique and our findings in lung areas with different aeration (normal, ground-glass-opacities [GGO], consolidated) among acute COVID-19 patients, NC-ARDS patients and healthy controls. Lung aeration is lowest in severe COVID-19 patients followed by those with NC- ARDS. Blood-volume in areas with GGO is lowest in patients with COVID-19 and highest in normal lung areas in patients with NC-ARDS and moderate-severe COVID-19. Median aeration/blood-volume ratio is lowest among patients with severe COVID-19, but the overall range of values overlap with those observed among NC-ARDS patients. We suggest that the degree of reduction of aerated lung volume and the distribution of blood-volume in lung with GGO and the balance between the two are associated with the severity of COVID-19.
Acknowledgements
The authors thank Dr. Henri Shapiro for his help in editing the manuscript.
Attenuated accumulation of regulatory T cells and reduced production of interleukin 10 lead to the exacerbation of tissue injury in a mouse model of acute respiratory distress syndrome.
STROBE Initiative. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies.
American Thoracic Society, European Society of Intensive Care Medicine, and Society of Critical Care Medicine. 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.
Collaborators of the GECOVID Group. Lung distribution of gas and blood volume in critically ill COVID-19 patients: a quantitative dual-energy computed tomography study.
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