Quantitative Chest CT Analysis to Measure Short-Term Sequelae of COVID-19 Pneumonia: A Monocentric Prospective Study.

(1) Background: Quantitative CT analysis (QCT) has demonstrated promising results in the prognosis prediction of patients affected by COVID-19. We implemented QCT not only at diagnosis but also at short-term follow-up, pairing it with a clinical examination in search of a correlation between residual respiratory symptoms and abnormal QCT results. (2) Methods: In this prospective monocentric trial performed during the "first wave" of the Italian pandemic, i.e., from March to May 2020, we aimed to test the relationship between %deltaCL (variation of %CL-compromised lung volume) and variations of symptoms-dyspnea, cough and chest pain-at follow-up clinical assessment after hospitalization. (3) Results: 282 patients (95 females, 34%) with a median age of 60 years (IQR, 51-69) were included. We reported a correlation between changing lung abnormalities measured by QCT, and residual symptoms at short-term follow up after COVID-19 pneumonia. Independently from age, a low percentage of surviving patients (1-4%) may present residual respiratory symptoms at approximately two months after discharge. QCT was able to quantify the extent of residual lung damage underlying such symptoms, as the reduction of both %PAL (poorly aerated lung) and %CL volumes was correlated to their disappearance. (4) Conclusions QCT may be used as an objective metric for the measurement of COVID-19 sequelae.

Lung response to prone positioning in mechanically-ventilated patients with COVID-19.

BACKGROUND: Prone positioning improves survival in moderate-to-severe acute respiratory distress syndrome (ARDS) unrelated to the novel coronavirus disease (COVID-19). This benefit is probably mediated by a decrease in alveolar collapse and hyperinflation and a more homogeneous distribution of lung aeration, with fewer harms from mechanical ventilation. In this preliminary physiological study we aimed to verify whether prone positioning causes analogue changes in lung aeration in COVID-19. A positive result would support prone positioning even in this other population. METHODS: Fifteen mechanically-ventilated patients with COVID-19 underwent a lung computed tomography in the supine and prone position with a constant positive end-expiratory pressure (PEEP) within three days of endotracheal intubation. Using quantitative analysis, we measured the volume of the non-aerated, poorly-aerated, well-aerated, and over-aerated compartments and the gas-to-tissue ratio of the ten vertical levels of the lung. In addition, we expressed the heterogeneity of lung aeration with the standardized median absolute deviation of the ten vertical gas-to-tissue ratios, with lower values indicating less heterogeneity. RESULTS: By the time of the study, PEEP was 12 (10-14) cmH2O and the PaO2:FiO2 107 (84-173) mmHg in the supine position. With prone positioning, the volume of the non-aerated compartment decreased by 82 (26-147) ml, of the poorly-aerated compartment increased by 82 (53-174) ml, of the normally-aerated compartment did not significantly change, and of the over-aerated compartment decreased by 28 (11-186) ml. In eight (53%) patients, the volume of the over-aerated compartment decreased more than the volume of the non-aerated compartment. The gas-to-tissue ratio of the ten vertical levels of the lung decreased by 0.34 (0.25-0.49) ml/g per level in the supine position and by 0.03 (- 0.11 to 0.14) ml/g in the prone position (p < 0.001). The standardized median absolute deviation of the gas-to-tissue ratios of those ten levels decreased in all patients, from 0.55 (0.50-0.71) to 0.20 (0.14-0.27) (p < 0.001). CONCLUSIONS: In fifteen patients with COVID-19, prone positioning decreased alveolar collapse, hyperinflation, and homogenized lung aeration. A similar response has been observed in other ARDS, where prone positioning improves outcome. Therefore, our data provide a pathophysiological rationale to support prone positioning even in COVID-19.

Lung Response to a Higher Positive End-Expiratory Pressure in Mechanically Ventilated Patients With COVID-19.

BACKGROUND: International guidelines suggest using a higher (> 10 cm H2O) positive end-expiratory pressure (PEEP) in patients with moderate-to-severe ARDS due to COVID-19. However, even if oxygenation generally improves with a higher PEEP, compliance, and Paco2 frequently do not, as if recruitment was small. RESEARCH QUESTION: Is the potential for lung recruitment small in patients with early ARDS due to COVID-19? STUDY DESIGN AND METHODS: Forty patients with ARDS due to COVID-19 were studied in the supine position within 3 days of endotracheal intubation. They all underwent a PEEP trial, in which oxygenation, compliance, and Paco2 were measured with 5, 10, and 15 cm H2O of PEEP, and all other ventilatory settings unchanged. Twenty underwent a whole-lung static CT scan at 5 and 45 cm H2O, and the other 20 at 5 and 15 cm H2O of airway pressure. Recruitment and hyperinflation were defined as a decrease in the volume of the non-aerated (density above -100 HU) and an increase in the volume of the over-aerated (density below -900 HU) lung compartments, respectively. RESULTS: From 5 to 15 cm H2O, oxygenation improved in 36 (90%) patients but compliance only in 11 (28%) and Paco2 only in 14 (35%). From 5 to 45 cm H2O, recruitment was 351 (161-462) mL and hyperinflation 465 (220-681) mL. From 5 to 15 cm H2O, recruitment was 168 (110-202) mL and hyperinflation 121 (63-270) mL. Hyperinflation variably developed in all patients and exceeded recruitment in more than half of them. INTERPRETATION: Patients with early ARDS due to COVID-19, ventilated in the supine position, present with a large potential for lung recruitment. Even so, their compliance and Paco2 do not generally improve with a higher PEEP, possibly because of hyperinflation.

Environmental triggers for connective tissue disease: the case of COVID-19 associated with dermatomyositis-specific autoantibodies.

PURPOSE OF REVIEW: The aim of the present review is to analyze the link between autoimmune diseases and environmental factors, in particular severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19) as it shares numerous features with the interstitial lung disease associated with connective tissue diseases positive for rare autoantibodies directed at highly specific autoantigens (i.e., MDA5 and RIG1) among the intracellular sensors of SARS-CoV-2 in the innate response against viruses. RECENT FINDINGS: As shown in recent publications and in our original data, specific autoantibodies may be functionally relevant to COVID-19 infection. We evaluated sera from 35 hospitalized patients with COVID-19 to identify antinuclear antibodies and autoantibodies directed against specific antigenic targets, and we identified anti-nuclear antibodies (ANA) in 20/35 of patients with COVID-19 (57%), in patients with need for supplemental oxygen (90% vs. 20% in ANA-negative cases; P < 0.0001). In 7/35 COVID-19 sera, we detected anti-MJ/NXP2 (n = 3), anti-RIG1 (n = 2), anti-Scl-70/TOPO1 (n = 1), and anti-MDA5 (n = 1), overall associated with a significantly worse pulmonary involvement at lung computerized tomography scans. Eleven (31%) patients were positive for antibodies against the E2/E3 subunits of mitochondrial pyruvate dehydrogenase complex. SUMMARY: Viral infections such as COVID-19 are associated with ANA and autoantibodies directed toward antiviral signaling antigens in particular in patients with worse pulmonary involvement.

Compromised Lung Volume and Hemostatic Abnormalities in COVID-19 Pneumonia: Results from an Observational Study on 510 Consecutive Patients.

BACKGROUND: Hemostatic abnormalities have been described in COVID-19, and pulmonary microthrombosis was consistently found at autopsy with concomitant severe lung damage. METHODS: This is a retrospective observational cross-sectional study including consecutive patients with COVID-19 pneumonia who underwent unenhanced chest CT upon admittance at the emergency room (ER) in one large academic hospital. QCT was used for the calculation of compromised lung volume (%CL). Clinical data were retrieved from patients' files. Laboratory data were obtained upon presentation at the ER. AIM: The aim of this study was to evaluate the correlation between hemostatic abnormalities and lung involvement in patients affected by COVID-19 pneumonia as described using computer-aided quantitative evaluation of chest CT (quantitative CT (QCT)). RESULTS: A total of 510 consecutive patients (68% males), aged 67 years in median, diagnosed with COVID-19 pneumonia, who underwent unenhanced CT scan upon admission to the ER, were included. In all, 115 patients had %CL > 23%; compared to those with %CL < 23%, they showed higher levels of D-dimer, fibrinogen, and CRP, greater platelet count, and longer PT ratio. Via multivariate regression analysis, BMI ≥ 30 kg/m2, D-dimer levels > 500 ng/mL, CRP > 5.0 ng/mL and PT ratio > 1.2 were found to be independent predictors of a %CL > 23% (adjusted odds ratios (95% confidence intervals): 2.1 (1.1-4.0), 3.1 (1.6-5.8), 2.4 (1.3-4.5), and 3.4 (1.4-8.5), respectively). CONCLUSIONS: Hemostatic abnormalities in patients affected by COVID-19 correlate with the severity of lung injury as measured by %CL. Our results underline the pathogenetic role of hemostasis in COVID-19 pneumonia beyond the presence of clinically evident thromboembolic complications.

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

BACKGROUND: Patients with COVID-19 can develop acute respiratory distress syndrome (ARDS), which is associated with high mortality. The aim of this study was to examine the functional and morphological features of COVID-19-associated ARDS and to compare these with the characteristics of ARDS unrelated to COVID-19. METHODS: This prospective observational study was done at seven hospitals in Italy. We enrolled consecutive, mechanically ventilated patients with laboratory-confirmed COVID-19 and who met Berlin criteria for ARDS, who were admitted to the intensive care unit (ICU) between March 9 and March 22, 2020. All patients were sedated, paralysed, and ventilated in volume-control mode with standard ICU ventilators. Static respiratory system compliance, the ratio of partial pressure of arterial oxygen to fractional concentration of oxygen in inspired air, ventilatory ratio (a surrogate of dead space), and D-dimer concentrations were measured within 24 h of ICU admission. Lung CT scans and CT angiograms were done when clinically indicated. A dataset for ARDS unrelated to COVID-19 was created from previous ARDS studies. Survival to day 28 was assessed. FINDINGS: Between March 9 and March 22, 2020, 301 patients with COVID-19 met the Berlin criteria for ARDS at participating hospitals. Median static compliance was 41 mL/cm H2O (33-52), which was 28% higher than in the cohort of patients with ARDS unrelated to COVID-19 (32 mL/cm H2O [25-43]; p<0·0001). 17 (6%) of 297 patients with COVID-19-associated ARDS had compliances greater than the 95th percentile of the classical ARDS cohort. Total lung weight did not differ between the two cohorts. CT pulmonary angiograms (obtained in 23 [8%] patients with COVID-19-related ARDS) showed that 15 (94%) of 16 patients with D-dimer concentrations greater than the median had bilateral areas of hypoperfusion, consistent with thromboembolic disease. Patients with D-dimer concentrations equal to or less than the median had ventilatory ratios lower than those of patients with D-dimer concentrations greater than the median (1·66 [1·32-1·95] vs 1·90 [1·50-2·33]; p=0·0001). Patients with static compliance equal to or less than the median and D-dimer concentrations greater than the median had markedly increased 28-day mortality compared with other patient subgroups (40 [56%] of 71 with high D-dimers and low compliance vs 18 [27%] of 67 with low D-dimers and high compliance, 13 [22%] of 60 with low D-dimers and low compliance, and 22 [35%] of 63 with high D-dimers and high compliance, all p=0·0001). INTERPRETATION: Patients with COVID-19-associated ARDS have a form of injury that, in many aspects, is similar to that of those with ARDS unrelated to COVID-19. Notably, patients with COVID-19-related ARDS who have a reduction in respiratory system compliance together with increased D-dimer concentrations have high mortality rates. FUNDING: None.

Risk factors for myocardial injury and death in patients with COVID-19: insights from a cohort study with chest computed tomography.

AIMS: Whether pulmonary artery (PA) dimension and coronary artery calcium (CAC) score, as assessed by chest computed tomography (CT), are associated with myocardial injury in patients with coronavirus disease 2019 (COVID-19) is not known. The aim of this study was to explore the risk factors for myocardial injury and death and to investigate whether myocardial injury has an independent association with all-cause mortality in patients with COVID-19. METHODS AND RESULTS: This is a single-centre cohort study including consecutive patients with laboratory-confirmed COVID-19 undergoing chest CT on admission. Myocardial injury was defined as high-sensitivity troponin I >20 ng/L on admission. A total of 332 patients with a median follow-up of 12 days were included. There were 68 (20.5%) deaths; 123 (37%) patients had myocardial injury. PA diameter was higher in patients with myocardial injury compared with patients without myocardial injury [29.0 (25th-75th percentile, 27-32) mm vs. 27.7 (25-30) mm, P < 0.001). PA diameter was independently associated with an increased risk of myocardial injury [adjusted odds ratio 1.10, 95% confidence interval (CI) 1.02-1.19, P = 0.01] and death [adjusted hazard ratio (HR) 1.09, 95% CI 1.02-1.17, P = 0.01]. Compared with patients without myocardial injury, patients with myocardial injury had a lower prevalence of a CAC score of zero (25% vs. 55%, P < 0.001); however, the CAC score did not emerge as a predictor of myocardial injury by multivariable logistic regression. Myocardial injury was independently associated with an increased risk of death by multivariable Cox regression (adjusted HR 2.25, 95% CI 1.27-3.96, P = 0.005). Older age, lower estimated glomerular filtration rate, and lower PaO2/FiO2 ratio on admission were other independent predictors for both myocardial injury and death. CONCLUSIONS: An increased PA diameter, as assessed by chest CT, is an independent risk factor for myocardial injury and mortality in patients with COVID-19. Myocardial injury is independently associated with an approximately two-fold increased risk of death.

Quantitative chest CT analysis in COVID-19 to predict the need for oxygenation support and intubation.

OBJECTIVE: Lombardy (Italy) was the epicentre of the COVID-19 pandemic in March 2020. The healthcare system suffered from a shortage of ICU beds and oxygenation support devices. In our Institution, most patients received chest CT at admission, only interpreted visually. Given the proven value of quantitative CT analysis (QCT) in the setting of ARDS, we tested QCT as an outcome predictor for COVID-19. METHODS: We performed a single-centre retrospective study on COVID-19 patients hospitalised from January 25, 2020, to April 28, 2020, who received CT at admission prompted by respiratory symptoms such as dyspnea or desaturation. QCT was performed using a semi-automated method (3D Slicer). Lungs were divided by Hounsfield unit intervals. Compromised lung (%CL) volume was the sum of poorly and non-aerated volumes (- 500, 100 HU). We collected patient's clinical data including oxygenation support throughout hospitalisation. RESULTS: Two hundred twenty-two patients (163 males, median age 66, IQR 54-6) were included; 75% received oxygenation support (20% intubation rate). Compromised lung volume was the most accurate outcome predictor (logistic regression, p < 0.001). %CL values in the 6-23% range increased risk of oxygenation support; values above 23% were at risk for intubation. %CL showed a negative correlation with PaO2/FiO2 ratio (p < 0.001) and was a risk factor for in-hospital mortality (p < 0.001). CONCLUSIONS: QCT provides new metrics of COVID-19. The compromised lung volume is accurate in predicting the need for oxygenation support and intubation and is a significant risk factor for in-hospital death. QCT may serve as a tool for the triaging process of COVID-19. KEY POINTS: • Quantitative computer-aided analysis of chest CT (QCT) provides new metrics of COVID-19. • The compromised lung volume measured in the - 500, 100 HU interval predicts oxygenation support and intubation and is a risk factor for in-hospital death. • Compromised lung values in the 6-23% range prompt oxygenation therapy; values above 23% increase the need for intubation.