407 Phenotypic heterogeneity of COVID-19 pneumonia: clinical and phatophysiologic relevance of the vascular phenotype

Recent data support the existence of a distinctive ‘vascular’ phenotype with the involvement of both pulmonary parenchyma and its circulation in COVID-19 pneumonia. Its prompt identification is important for the accurate management of COVID-19 patients. The aim is to analyse the pro and contra of the different modalities to identify the ‘vascular’ phenotype. Chest computed tomography scan and angiogram may quantify both parenchyma and vascular damage, but the presence of thrombosis of pulmonary micro-circulation may be missed. Increased d-dimer concentration confirms a thrombotic state, but it cannot localize the thrombus. An elevation of troponin concentration nonspecifically reflects cardiac injury. Echocardiogram and electrocardiogram provide specific signs of right ventricular pressure overload. This is particularly relevant for the ‘vascular’ phenotype which does not necessarily represent the result of thromboembolic venous complications but, more frequently, it is the result of pulmonary microcirculation thrombosis in situ and needs immediate therapeutic action.

Mesenchymal Stromal Cells for the Treatment of Interstitial Lung Disease in Children: A Look from Pediatric and Pediatric Surgeon Viewpoints

Mesenchymal stromal cells (MSCs) have been proposed as a potential therapy to treat congenital and acquired lung diseases. Due to their tissue-regenerative, anti-fibrotic, and immunomodulatory properties, MSCs combined with other therapy or alone could be considered as a new approach for repair and regeneration of the lung during disease progression and/or after post- surgical injury. Children interstitial lung disease (chILD) represent highly heterogeneous rare respiratory diseases, with a wild range of age of onset and disease expression. The chILD is characterized by inflammatory and fibrotic changes of the pulmonary parenchyma, leading to gas exchange impairment and chronic respiratory failure associated with high morbidity and mortality. The therapeutic strategy is mainly based on the use of corticosteroids, hydroxychloroquine, azithromycin, and supportive care; however, the efficacy is variable, and their long-term use is associated with severe toxicity. The role of MSCs as treatment has been proposed in clinical and pre-clinical studies. In this narrative review, we report on the currently available on MSCs treatment as therapeutical strategy in chILD. The progress into the therapy of respiratory disease in children is mandatory to ameliorate the prognosis and to prevent the progression in adult age. Cell therapy may be a future therapy from both a pediatric and pediatric surgeon’s point of view.

Pancreatic Injury in Patients with SARS-Cov-2 (COVID-19) Infection: A Retrospective Analysis of CT Findings

Objective. To determine the association between COVID-19 infection and peripancreatic changes on CT as a sign of acute pancreatic injury. Methods. Retrospective analysis of CT examinations in patients with confirmed COVID-19 infection yielded 103 instances. An age- and gender-matched cohort of patients without COVID-19 was found. CT examinations were evaluated for peripancreatic stranding or edema, fluid collection, or necrosis, without any other explanation. Depicted pulmonary parenchyma was evaluated for possible COVID-19-related changes. Clinical and laboratory data were retrieved from the clinical database. Results. Peripancreatic fat stranding ( n = 8 ) or fluid collection ( n = 2 ) without any other cause was found in 10 (10%) patients. Abdominal complaints were reported in 4 (40%) patients. Elevated serum amylase or lipase levels were documented in 5 (50%) patients who also satisfied the diagnostic criteria for acute pancreatitis. From the study sample of 103 patients with COVID-19, pulmonary parenchyma was depicted in 102 (99%), and from these, 57 (55%) had an evidence of pulmonary changes compatible with COVID-19 pneumonia. This proportion was not significantly different between patients with and without peripancreatic changes ( p = 0.35 ). In the matched cohort, we found peripancreatic changes in 2 (2%, p = 0.033 ) patients. Patients with pancreatic injury and elevated amylase levels were more likely to require orotracheal intubation (35% vs. 12%, p = 0.021 ). Conclusions. We showed that the prevalence of peripancreatic stranding or fluid collection is higher in patients diagnosed with COVID-19 infection compared to an age- and gender-matched cohort. Patients with pancreatic injury and elevated amylase levels are more likely to require orotracheal intubation. Our findings corroborate the link between COVID-19 infection and pancreatic injury from the perspective of imaging.

Changes in pulmonary microcirculation after COVID-19

The endothelium is a tissue most vulnerable to the SARS-CoV-2 virus. Systemic endothelial dysfunction leads to the development of endothelitis which causes the main manifestations of the disease and systemic disturbance of microcirculation in various organs. Pulmonary microcirculatory damage, the most striking clinical manifestation, was the reason to perform SPECT to detect microcirculation disorders.Aim. To assess microcirculatory changes in the lungs of patients who had no previous respiratory diseases and had a COVID-19 infection at different times from the onset of the disease.Methods. SPECT data were analyzed in 136 patients who had a proven coronavirus infection of varying severity from May 2020 to June 2021.Results. All patients showed changes in microcirculation in the lungs in the post-COVID period. The severity of microcirculation disorders had a significant correlation (rs = 0.76; p = 0.01) with the degree of damage to the pulmonary parenchyma and an average correlation (rs = 0.48; p = 0.05) with the timing of the post-COVID period and the degree of residual lesions on CT (rs = 0.49; p = 0.01). The examined patients with persistent clinical complaints had pulmonary microcirculatory lesions, which may indicate the development of vasculitis, at all stages of the post-COVID period. Despite regression of the lesions confirmed by CT in 3 to 6 months after the acute COVID-19 infection, specialists from Russian and other countries report that 30–36% of patients develop pulmonary fibrosis. Similar changes were identified in 19.1% of the examined patients in our study.Conclusion. Microcirculation disorders are detected in all patients in the post-COVID period, irrespective of the severity according to CT. Progressive decrease in microcirculation in the lower parts of the lungs, local zones of hypoperfusion with the critically low accumulation of radiopharmaceuticals, persistent areas of compaction of the lung tissue (so-called “ground glass”), reticular changes, and the development of traction bronchiectasis, a decrease in the diffusion capacity of the lungs and alveolar volume may indicate fibrotic lesions with subsequent development of virus-associated interstitial lung disease.

Differences in Dynamics of Lung Computed Tomography Patterns between Survivors and Deceased Adult Patients with COVID-19

This study’s aim was to investigate CT (computed tomography) pattern dynamics differences within surviving and deceased adult patients with COVID-19, revealing new prognostic factors and reproducing already known data with our patients’ cohort: 635 hospitalized patients (55.3% of them were men, 44.7%—women), of which 87.3% had a positive result of RT-PCR (reverse transcription-polymerase chain reaction) at admission. The number of deaths was 53 people (69.8% of them were men and 30.2% were women). In total, more than 1500 CT examinations were performed on patients, using a GE Optima CT 660 computed tomography (General Electric Healthcare, USA). The study was performed at hospital admission, the frequency of repetitive scans further varied based on clinical need. The interpretation of the imaging data was carried out by 11 radiologists with filling in individual registration cards that take into account the scale of the lesion, the location, contours, and shape of the foci, the dominating types of changes, as well as the presence of additional findings and the dynamics of the process—a total of 45 parameters. Statistical analysis was performed using the software packages SPSS Statistics version 23.0 (IBM, Armonk, NY, USA) and R software version 3.3.2. For comparisons in pattern dynamics across hospitalization we used repeated measures general linear model with outcome and disease phase as factors. The crazy paving pattern, which is more common and has a greater contribution to the overall CT picture in different phases of the disease in deceased patients, has isolated prognostic significance and is probably a reflection of faster dynamics of the process with a long phase of progression of pulmonary parenchyma damage with an identical trend of changes in the scale of the lesion (as recovered) in this group of patients. Already known data on typical pulmonological CT manifestations of infection, frequency of occurrence, and the prognostic significance of the scale of the lesion were reproduced, new differences in the dynamics of the process between recovered and deceased adult patients were also found that may have prognostic significance and can be reflected in clinical practice.

Histogenetic morphotypes of rats respiratory system at the stages of early and late fetogenesis

Aim. Morphological analysis of the deployment of histogenetic information of pulmonary parenchyma at the stages of late embryogenesis and fetogenesis in laboratory rats within the limits of the norm of reaction with verification according to morphometric criteria of individual morphotypes.Materials and methods. Comparative morphological study of histogenesis of endodermal derivatives of the lungs of rats at critical periods of intrauterine development – late embryogenesis (day 14 of gestation), and late fetogenesis (day 20 of gestation) was performed using morphometric identification of plane parameters and a complex of plane form factors of epithelial structures of the lung. Morphometric studies were carried out in the Morphometer program on semi-thin sections of the rat lung.Results. Two critical stages of histogenesis of entodermal beginnings of fetal lungs are described – pseudoglandular and canalicular. The options of discordance of individual development within the response norm are justified. The lungs of the fetus at the pseudoglandular stage and the canalicular stage show significant fluctuations in the plane values of the pulmonary parenchyma, the presence in different individuals of variants of the plane values of entodermal derivatives, which indicated individual morphotypes of the development of the rat lung. At the pseudoglandular stage, in fetus with type I, called “compact”, the total area of the tubular system and the total perimeter are significantly inferior (p<0.001) to the same indicators of the lung II morphotype, designated as “air”. The values of one tubule (the outer perimeter, its area, the dimensions of the X-projection and Y-projection, the length of the epithelial tubes) in type I, on the contrary, are significantly larger than in type II (p<0.01). Among form factors, reliable differences have elongation (FE), squareness (FQ) and equivalent radius (FR) (p<0.01), less significant compactness (FF) and roundness (FC) (p<0.05). The discordance of development is established by a number of reliable values at the stage of late fetogenesis: the area of the tubule (p<0.01), the area of the epithelium of the preacinar department (p<0.001), the value of the outer perimeter of the tubule, the length and, to a lesser extent, the width of the tubule (p<0.05) significantly exceed such type II indicators. In this regard, the dimensions of X- and Y-projections for type I are also increased (p<0.05).Conclusion. As a result of morphological studies, the development of entodermal derivatives of pulmonary parenchyma at the pseudoglandular stage (day 14 of gestation) and the canalicular stage (day 20 of gestation) in rat fetus was verified; morphometric criteria for assessing the histogenesis of entodermal parenchyma units at critical stages of development have been introduced; comparative analysis of morphometric indices of different individuals in gestation dynamics; individual variants of two morphotypes are objectified – “compact-I” and “air-II” in the process of histogenesis of the fetal lungs.

Spectral Detector CT-Derived Pulmonary Perfusion Maps And Pulmonary Parenchyma Characteristics For The Semiautomated Classification of Pulmonary Hypertension

Objectives: To evaluate the usefulness of spectral detector CT (SDCT)-derived pulmonary perfusion maps and pulmonary parenchyma characteristics for the semiautomated classification of pulmonary hypertension (PH).Methods: A total of 162 consecutive patients with right heart catheter (RHC)-proven PH of different etiologies as defined by the Nice classification who underwent CT pulmonary angiography (CTPA) on SDCT and 20 patients with an invasive rule-out of PH were included in this retrospective study. Semiautomatic lung segmentation into normal and malperfused areas based on iodine content as well as automatic, virtual noncontrast-based emphysema quantification were performed. Corresponding volumes, histogram features and the ID SkewnessPerfDef-Emphysema-Index (O-index) accounting for the ratio of ID distribution in malperfused lung areas and the proportion of emphysematous lung parenchyma were computed and compared between groups.Results: Patients with PH showed a significantly greater extent of malperfused lung areas as well as stronger and more homogenous perfusion defects. In Nice class 3 and 4 patients, ID skewness revealed a significantly more homogenous ID distribution in perfusion defects than in all other subgroups. The b-index allowed for further subclassification of subgroups 3 and 4 (p < 0.001), identifying patients with chronic thromboembolic PH (CTEPH, subgroup 4) with high accuracy (AUC: 0.92, 95%-CI, 0.85-0.99).Conclusion: Abnormal pulmonary perfusion in PH can be detected and quantified by semiautomated SDCT-based pulmonary perfusion maps. ID skewness in malperfused lung areas, and the j-index allow for a classification of PH subgroups, identifying Nice class 3 and 4 patients with high accuracy, independent of reader expertise.

Microvascular fluid flow in ex vivo and engineered lungs

In recent years, it has become common to experiment with ex vivo perfused lungs for organ transplantation, and to attempt regenerative pulmonary engineering using decellularized lung matrices. However, our understanding of the physiology of ex vivo organ perfusion is imperfect: it is not currently well understood how decreasing microvascular barrier affects the perfusion of pulmonary parenchyma. Additionally, protocols for lung perfusion and organ culture fluid-handling are far from standardized, with widespread variation on both basic methods and on ideally controlled parameters. To address both of these deficits, a robust, non-invasive, and mechanistic model is needed which is able to predict microvascular resistance and permeability in perfused lungs while providing insight into capillary recruitment. Although validated mathematical models exist for fluid flow in native pulmonary tissue, previous models generally assume minimal intravascular leak from artery to vein and do not assess capillary bed recruitment. Such models are difficult to apply to both ex vivo lung perfusions, in which edema can develop over time and microvessels can become blocked, and to decellularized ex vivo organomimetic cultures, in which microvascular recruitment is variable and arterially-perfused fluid enters into the alveolar space. Here, we develop a mathematical model of pulmonary microvascular fluid flow which is applicable in both instances, and we apply our model to data from native, decellularized, and regenerating lungs under ex vivo perfusion. The results provide substantial insight into microvascular pressure-flow mechanics, while producing previously unknown output values for tissue-specific capillary-alveolar hydraulic conductivity, microvascular recruitment, and total organ barrier resistance.

Interstitial Lung Disease at High Resolution CT after SARS-CoV-2-Related Acute Respiratory Distress Syndrome according to Pulmonary Segmental Anatomy

Background: The purpose of this study was to evaluate High-Resolution CT (HRCT) findings in SARS-CoV-2-related ARDS survivors treated with prolonged low-dose methylprednisolone after hospital discharge. Methods: A total of 44 consecutive patients (M: 32, F: 12, average age: 64), hospitalised in our department from April to September 2020 for SARS-CoV-2-related ARDS, who had a postdischarge CT scan, were enrolled into this retrospective study. We reviewed the electronic medical charts to collect laboratory, clinical, and demographic data. The CT findings were evaluated and classified according to lung segmental distribution. The imaging findings were correlated with spirometry results and included ground glass opacities (GGOs), consolidations, reticulations, bronchiectasis/bronchiolectasis, linear bands, and loss of pulmonary volume. Results: Alterations in the pulmonary parenchyma were observed in 97.7% of patients at HRCT (median time lapse between ARDS diagnosis and HRCT: 2.8 months, range 0.9 to 6.7). The most common findings were linear bands (84%), followed by GGOs (75%), reticulations (34%), bronchiolectasis (32%), consolidations (30%), bronchiectasis (30%) and volume loss (25%). They had a symmetric distribution, and both lower lobes were the most affected areas. Conclusions: A reticular pattern with a posterior distribution was observed 3 months after discharge from severe COVID-19 pneumonia, and this differs from previously described postCOVID-19 fibrotic-like changes. We hypothesized that the systematic use of prolonged low-dose of corticosteroid could be the main reason of this different CT scan appearance.

Clinical, Radiological And Laboratory Predictors Of Postcovid Interstitial Pulmonary Disease

The Fergana Valley model was used to study the risk of postcovid interstitial lung disease in patients who have had COVID-19 associated pneumonia with 50% or more of the pulmonary parenchyma affected. Predictors of the formation of postcovid pulmonary fibrosis were determined and a risk assessment scale was developed. It was found that the use of ultrasound scanners in the early postcovid period is informative and is not inferior in terms of predicting fibrosis by serial MSCT.