COVID-19 Pneumonia with Migratory Pattern in Agammaglobulinemic Patients: A Report of Two Cases and Review of Literature.

X-linked agammaglobulinemia (XLA) is a primary immunodeficiency characterized by marked reduction in serum immunoglobulins and early-onset infections. Coronavirus Disease-2019 (COVID-19) pneumonia in immunocompromised patients presents clinical and radiological peculiarities which have not yet been completely understood. Very few cases of agammaglobulinemic patients with COVID-19 have been reported since the beginning of the pandemic in February 2020. We report two cases of migrant COVID-19 pneumonia in XLA patients.

Multi-center validation of an artificial intelligence system for detection of COVID-19 on chest radiographs in symptomatic patients.

OBJECTIVES: While chest radiograph (CXR) is the first-line imaging investigation in patients with respiratory symptoms, differentiating COVID-19 from other respiratory infections on CXR remains challenging. We developed and validated an AI system for COVID-19 detection on presenting CXR. METHODS: A deep learning model (RadGenX), trained on 168,850 CXRs, was validated on a large international test set of presenting CXRs of symptomatic patients from 9 study sites (US, Italy, and Hong Kong SAR) and 2 public datasets from the US and Europe. Performance was measured by area under the receiver operator characteristic curve (AUC). Bootstrapped simulations were performed to assess performance across a range of potential COVID-19 disease prevalence values (3.33 to 33.3%). Comparison against international radiologists was performed on an independent test set of 852 cases. RESULTS: RadGenX achieved an AUC of 0.89 on 4-fold cross-validation and an AUC of 0.79 (95%CI 0.78-0.80) on an independent test cohort of 5,894 patients. Delong's test showed statistical differences in model performance across patients from different regions (p < 0.01), disease severity (p < 0.001), gender (p < 0.001), and age (p = 0.03). Prevalence simulations showed the negative predictive value increases from 86.1% at 33.3% prevalence, to greater than 98.5% at any prevalence below 4.5%. Compared with radiologists, McNemar's test showed the model has higher sensitivity (p < 0.001) but lower specificity (p < 0.001). CONCLUSION: An AI model that predicts COVID-19 infection on CXR in symptomatic patients was validated on a large international cohort providing valuable context on testing and performance expectations for AI systems that perform COVID-19 prediction on CXR. KEY POINTS: • An AI model developed using CXRs to detect COVID-19 was validated in a large multi-center cohort of 5,894 patients from 9 prospectively recruited sites and 2 public datasets. • Differences in AI model performance were seen across region, disease severity, gender, and age. • Prevalence simulations on the international test set demonstrate the model's NPV is greater than 98.5% at any prevalence below 4.5%.

Breath-holding physiology, radiological severity and adverse outcomes in COVID-19 patients: A prospective validation study.

BACKGROUND AND OBJECTIVE: COVID-19 remains a major cause of respiratory failure, and means to identify future deterioration is needed. We recently developed a prediction score based on breath-holding manoeuvres (desaturation and maximal duration) to predict incident adverse COVID-19 outcomes. Here we prospectively validated our breath-holding prediction score in COVID-19 patients, and assessed associations with radiological scores of pulmonary involvement. METHODS: Hospitalized COVID-19 patients (N = 110, three recruitment centres) performed breath-holds at admission to provide a prediction score (Messineo et al.) based on mean desaturation (20-s breath-holds) and maximal breath-hold duration, plus baseline saturation, body mass index and cardiovascular disease. Odds ratios for incident adverse outcomes (composite of bi-level ventilatory support, ICU admission and death) were described for patients with versus without elevated scores (>0). Regression examined associations with chest x-ray (Brixia score) and computed tomography (CT; 3D-software quantification). Additional comparisons were made with the previously-validated '4C-score'. RESULTS: Elevated prediction score was associated with adverse COVID-19 outcomes (N = 12/110), OR[95%CI] = 4.54[1.17-17.83], p = 0.030 (positive predictive value = 9/48, negative predictive value = 59/62). Results were diminished with removal of mean desaturation from the prediction score (OR = 3.30[0.93-11.72]). The prediction score rose linearly with Brixia score (ß[95%CI] = 0.13[0.02-0.23], p = 0.026, N = 103) and CT-based quantification (ß = 1.02[0.39-1.65], p = 0.002, N = 45). Mean desaturation was also associated with both radiological assessment. Elevated 4C-scores (≥high-risk category) had a weaker association with adverse outcomes (OR = 2.44[0.62-9.56]). CONCLUSION: An elevated breath-holding prediction score is associated with almost five-fold increased adverse COVID-19 outcome risk, and with pulmonary deficits observed in chest imaging. Breath-holding may identify COVID-19 patients at risk of future respiratory failure.

Every cloud has a silver lining: COVID-19 chest-CT screening prevents unnecessary cardiac surgery.

BACKGROUND: Unenhanced chest CT can identify incidental findings (IFs) leading to management strategy change. We report our institutional experience with routine chest-CT as preoperative screening tool during the COVID-19 pandemic, focusing on the impact of IFs. METHODS: All patients scheduled for cardiac surgery from May 1st to December 31st 2020, underwent preoperative unenhanced chest-CT according to COVID-19 pandemic institutional protocol. We have analyzed IFs incidence, reported consequent operative changes, and identified IFs clinical determinants. RESULTS: Out of 447, 278 patients were included. IFs rate was 7.2% (20/278): a solid mass (11/20, 55%), lymphoproliferative disease (1/20, 5%), SARS-CoV-2 pneumonia (2/20, 10%), pulmonary artery chronic thromboembolism (1/20, 5%), anomalous vessel anatomy (2/20, 10%), voluminous hiatal hernia (1/20, 5%), mitral annulus calcification (1/20, 5%), and porcelain aorta (1/20, 5%) were reported. Based on IFs, 4 patients (20%-4/278, 1.4%) were not operated, 8 (40%-8/278, 2.9%) underwent a procedure different from the one originally planned one, and 8 (40%-8/278, 2.9%) needed additional preoperative investigations before undergoing the planned surgery. At univariate regression, coronary artery disease, atrial fibrillation, and history of cancer were significantly more often present in patients presenting with significant IFs. History of malignancy was identified as the only independent determinant of significant IFs at chest-CT (OR=4.27 IQR: [1.14-14.58], P=0.0227). CONCLUSIONS: Unenhanced chest-CT as a preoperative screening tool in cardiac surgery led to incidental detection of significant clinical findings, which justified even procedures cancellation. Malignancy history is a determinant for CT incidental findings and could support a tailored screening approach for high-risk patients.

One-year pulmonary impairment after severe COVID-19: a prospective, multicenter follow-up study.

BACKGROUND: Long-term pulmonary sequelae following hospitalization for SARS-CoV-2 pneumonia is largely unclear. The aim of this study was to identify and characterise pulmonary sequelae caused by SARS-CoV-2 pneumonia at 12-month from discharge. METHODS: In this multicentre, prospective, observational study, patients hospitalised for SARS-CoV-2 pneumonia and without prior diagnosis of structural lung diseases were stratified by maximum ventilatory support ("oxygen only", "continuous positive airway pressure (CPAP)" and "invasive mechanical ventilation (IMV)") and followed up at 12 months from discharge. Pulmonary function tests and diffusion capacity for carbon monoxide (DLCO), 6 min walking test, high resolution CT (HRCT) scan, and modified Medical Research Council (mMRC) dyspnea scale were collected. RESULTS: Out of 287 patients hospitalized with SARS-CoV-2 pneumonia and followed up at 1 year, DLCO impairment, mainly of mild entity and improved with respect to the 6-month follow-up, was observed more frequently in the "oxygen only" and "IMV" group (53% and 49% of patients, respectively), compared to 29% in the "CPAP" group. Abnormalities at chest HRCT were found in 46%, 65% and 80% of cases in the "oxygen only", "CPAP" and "IMV" group, respectively. Non-fibrotic interstitial lung abnormalities, in particular reticulations and ground-glass attenuation, were the main finding, while honeycombing was found only in 1% of cases. Older patients and those requiring IMV were at higher risk of developing radiological pulmonary sequelae. Dyspnea evaluated through mMRC scale was reported by 35% of patients with no differences between groups, compared to 29% at 6-month follow-up. CONCLUSION: DLCO alteration and non-fibrotic interstitial lung abnormalities are common after 1 year from hospitalization due to SARS-CoV-2 pneumonia, particularly in older patients requiring higher ventilatory support. Studies with longer follow-ups are needed.

Chest X-ray versus chest computed tomography for outcome prediction in hospitalized patients with COVID-19.

The purpose of this study was to compare the prognostic value of chest X-ray (CXR) and chest computed tomography (CT) in a group of hospitalized patients with COVID-19. For this study, we retrospectively selected a cohort of 106 hospitalized patients with COVID-19 who underwent both CXR and chest CT at admission. For each patient, the pulmonary involvement was ranked by applying the Brixia score for CXR and the percentage of well-aerated lung (WAL) for CT. The Brixia score was assigned at admission (A-Brixia score) and during hospitalization. During hospitalization, only the highest score (H-Brixia score) was considered. At admission, the percentage of WAL (A-CT%WAL) was quantified using a dedicated software. On logistic regression analyses, H-Brixia score was the most effective radiological marker for predicting in-hospital mortality and invasive mechanical ventilation. Additionally, A-CT%WAL did not provide substantial advantages in the risk stratification of hospitalized patients with COVID-19 compared to A-Brixia score.

Early prediction of in-hospital death of COVID-19 patients: a machine-learning model based on age, blood analyses, and chest x-ray score.

An early-warning model to predict in-hospital mortality on admission of COVID-19 patients at an emergency department (ED) was developed and validated using a machine-learning model. In total, 2782 patients were enrolled between March 2020 and December 2020, including 2106 patients (first wave) and 676 patients (second wave) in the COVID-19 outbreak in Italy. The first-wave patients were divided into two groups with 1474 patients used to train the model, and 632 to validate it. The 676 patients in the second wave were used to test the model. Age, 17 blood analytes, and Brescia chest X-ray score were the variables processed using a random forests classification algorithm to build and validate the model. Receiver operating characteristic (ROC) analysis was used to assess the model performances. A web-based death-risk calculator was implemented and integrated within the Laboratory Information System of the hospital. The final score was constructed by age (the most powerful predictor), blood analytes (the strongest predictors were lactate dehydrogenase, D-dimer, neutrophil/lymphocyte ratio, C-reactive protein, lymphocyte %, ferritin std, and monocyte %), and Brescia chest X-ray score (https://bdbiomed.shinyapps.io/covid19score/). The areas under the ROC curve obtained for the three groups (training, validating, and testing) were 0.98, 0.83, and 0.78, respectively. The model predicts in-hospital mortality on the basis of data that can be obtained in a short time, directly at the ED on admission. It functions as a web-based calculator, providing a risk score which is easy to interpret. It can be used in the triage process to support the decision on patient allocation.

Impact of the COVID-19 pandemic on the selection of chest imaging modalities and reporting systems: a survey of Italian radiologists.

PURPOSE: Chest imaging modalities play a key role for the management of patient with coronavirus disease (COVID-19). Unfortunately, there is no consensus on the optimal chest imaging approach in the evaluation of patients with COVID-19 pneumonia, and radiology departments tend to use different approaches. Thus, the main objective of this survey was to assess how chest imaging modalities have been used during the different phases of the first COVID-19 wave in Italy, and which diagnostic technique and reporting system would have been preferred based on the experience gained during the pandemic. MATERIAL AND METHODS: The questionnaire of the survey consisted of 26 questions. The link to participate in the survey was sent to all members of the Italian Society of Medical and Interventional Radiology (SIRM). RESULTS: The survey gathered responses from 716 SIRM members. The most notable result was that the most used and preferred chest imaging modality to assess/exclude/monitor COVID-19 pneumonia during the different phases of the first COVID-19 wave was computed tomography (51.8% to 77.1% of participants). Additionally, while the narrative report was the most used reporting system (55.6% of respondents), one-third of participants would have preferred to utilize structured reporting systems. CONCLUSION: This survey shows that the participants' responses did not properly align with the imaging guidelines for managing COVID-19 that have been made by several scientific, including SIRM. Therefore, there is a need for continuing education to keep radiologists up to date and aware of the advantages and limitations of the chest imaging modalities and reporting systems.

BS-Net: Learning COVID-19 pneumonia severity on a large chest X-ray dataset.

In this work we design an end-to-end deep learning architecture for predicting, on Chest X-rays images (CXR), a multi-regional score conveying the degree of lung compromise in COVID-19 patients. Such semi-quantitative scoring system, namely Brixia score, is applied in serial monitoring of such patients, showing significant prognostic value, in one of the hospitals that experienced one of the highest pandemic peaks in Italy. To solve such a challenging visual task, we adopt a weakly supervised learning strategy structured to handle different tasks (segmentation, spatial alignment, and score estimation) trained with a "from-the-part-to-the-whole" procedure involving different datasets. In particular, we exploit a clinical dataset of almost 5,000 CXR annotated images collected in the same hospital. Our BS-Net demonstrates self-attentive behavior and a high degree of accuracy in all processing stages. Through inter-rater agreement tests and a gold standard comparison, we show that our solution outperforms single human annotators in rating accuracy and consistency, thus supporting the possibility of using this tool in contexts of computer-assisted monitoring. Highly resolved (super-pixel level) explainability maps are also generated, with an original technique, to visually help the understanding of the network activity on the lung areas. We also consider other scores proposed in literature and provide a comparison with a recently proposed non-specific approach. We eventually test the performance robustness of our model on an assorted public COVID-19 dataset, for which we also provide Brixia score annotations, observing good direct generalization and fine-tuning capabilities that highlight the portability of BS-Net in other clinical settings. The CXR dataset along with the source code and the trained model are publicly released for research purposes.

Lombardy, Northern Italy: COVID-19 second wave less severe and deadly than the first? A preliminary investigation.

BACKGROUND: The much-heralded second wave of coronavirus disease (COVID-19) has arrived in Italy. Right now, one of the main questions about COVID-19 is whether the second wave is less severe and deadly than the first wave. In order to answer this challenging question, we decided to evaluate the chest X-ray (CXR) severity of COVID-19 pneumonia, the mechanical ventilation (MV) use, the patient outcome, and certain clinical/laboratory data during the second wave and compare them with those of the first wave. METHODS: During the two COVID-19 waves two independent groups of hospitalised patients were selected. The first group consisted of the first 100 COVID-19 patients admitted to our hospital during the first wave. The second group consisted of another 100 consecutive COVID-19 patients admitted to our hospital during the second wave. We enlisted only Caucasian male patients over the age of fifty for whom the final outcome was available. For each patient, the CXR severity of COVID-19 pneumonia, the MV use, the patient outcome, comorbidities, corticosteroid use, and C-reactive protein (CRP) levels were considered. Nonparametric statistical tests were used to compare the data obtained from the two waves. RESULTS: The CXR severity of COVID-19 pneumonia, the in-hospital mortality, and CRP levels were significantly higher in the first wave than in the second wave (p ≤ .041). Although not statistically significant, the frequency of MV use was higher in the first wave. CONCLUSIONS: This preliminary investigation seems to confirm that the COVID-19 second wave is less severe and deadly than the first wave.

Which role for chest x-ray score in predicting the outcome in COVID-19 pneumonia?

OBJECTIVE: We aim to demonstrate that a chest X-ray (CXR) scoring system for COVID-19 patients correlates with patient outcome and has a prognostic value. METHODS: This retrospective study included CXRs of COVID-19 patients that reported the Brixia score, a semi-quantitative scoring system rating lung involvement from 0 to 18. The highest (H) and lowest (L) values were registered along with scores on admission (A) and end of hospitalization (E). The Brixia score was correlated with the outcome (death or discharge). RESULTS: A total of 953 patients met inclusion criteria. In total, 677/953 were discharged and 276/953 died during hospitalization. A total of 524/953 had one CXR and 429/953 had more than one CXR. H-score was significantly higher in deceased (median, 12; IQR 9-14) compared to that in discharged patients (median, 8; IQR 5-11) (p < 0.0001). In 429/953 patients with multiple CXR, A-score, L-score, and E-score were higher in deceased than in discharged patients (A-score 9 vs 8; p = 0.039; L-score 7 vs 5; p < 0.0003; E-score 12 vs 7; p < 0.0001). In the entire cohort, logistic regression showed a significant predictive value for age (p < 0.0001, OR 1.13), H-score (p < 0.0001, OR 1.25), and gender (p = 0.01, male OR 1.67). AUC was 0.863. In patients with ≥ 2 CXR, A-, L-, and E-scores correlated significantly with the outcome. Cox proportional hazards regression indicated age (p < 0.0001, HR 4.17), H-score (< 9, HR 0.36, p = 0.0012), and worsening of H-score vs A score > 3 (HR 1.57, p = 0.0227) as associated with worse outcome. CONCLUSIONS: The Brixia score correlates strongly with disease severity and outcome; it may support the clinical decision-making, particularly in patients with moderate-to-severe signs and symptoms. The Brixia score should be incorporated in a prognostic model, which would be desirable, particularly in resource-constraint scenarios. KEY POINTS: • To demonstrate the importance of the Brixia score in assessing and monitoring COVID-19 lung involvement. • The Brixia score strongly correlates with patient outcome and can be easily implemented in the routine reporting of CXR.

Chest X-ray severity index as a predictor of in-hospital mortality in coronavirus disease 2019: A study of 302 patients from Italy.

OBJECTIVES: This study aimed to assess the usefulness of a new chest X-ray scoring system - the Brixia score - to predict the risk of in-hospital mortality in hospitalized patients with coronavirus disease 2019 (COVID-19). METHODS: Between March 4, 2020 and March 24, 2020, all CXR reports including the Brixia score were retrieved. We enrolled only hospitalized Caucasian patients with COVID-19 for whom the final outcome was available. For each patient, age, sex, underlying comorbidities, immunosuppressive therapies, and the CXR report containing the highest score were considered for analysis. These independent variables were analyzed using a multivariable logistic regression model to extract the predictive factors for in-hospital mortality. RESULTS: 302 Caucasian patients who were hospitalized for COVID-19 were enrolled. In the multivariable logistic regression model, only Brixia score, patient age, and conditions that induced immunosuppression were the significant predictive factors for in-hospital mortality. According to receiver operating characteristic curve analyses, the optimal cutoff values for Brixia score and patient age were 8 points and 71 years, respectively. Three different models that included the Brixia score showed excellent predictive power. CONCLUSIONS: Patients with a high Brixia score and at least one other predictive factor had the highest risk of in-hospital death.

COVID-19 outbreak in Italy: experimental chest X-ray scoring system for quantifying and monitoring disease progression.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a new virus recently isolated from humans. SARS-CoV-2 was discovered to be the pathogen responsible for a cluster of pneumonia cases associated with severe respiratory disease that occurred in December 2019 in China. This novel pulmonary infection, formally called Coronavirus Disease 2019 (COVID-19), has spread rapidly in China and beyond. On 8 March 2020, the number of Italians with SARS-CoV-2 infection was 7375 with a 48% hospitalization rate. At present, chest-computed tomography imaging is considered the most effective method for the detection of lung abnormalities in early-stage disease and quantitative assessment of severity and progression of COVID-19 pneumonia. Although chest X-ray (CXR) is considered not sensitive for the detection of pulmonary involvement in the early stage of the disease, we believe that, in the current emergency setting, CXR can be a useful diagnostic tool for monitoring the rapid progression of lung abnormalities in infected patients, particularly in intensive care units. In this short communication, we present our experimental CXR scoring system that we are applying to hospitalized patients with COVID-19 pneumonia to quantify and monitor the severity and progression of this new infectious disease. We also present the results of our preliminary validation study on a sample of 100 hospitalized patients with SARS-CoV-2 infection for whom the final outcome (recovery or death) was available.

Radiographic severity index in COVID-19 pneumonia: relationship to age and sex in 783 Italian patients.

PURPOSE: To improve the risk stratification of patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an experimental chest X-ray (CXR) scoring system for quantifying lung abnormalities was introduced in our Diagnostic Imaging Department. The purpose of this study was to retrospectively evaluate correlations between the CXR score and the age or sex of Italian patients infected with SARS-CoV-2. MATERIALS AND METHODS: Between March 4, 2020, and March 18, 2020, all CXR reports containing the new scoring system were retrieved. Only hospitalized patients with SARS-CoV-2 infection were enrolled. For each patient, age, sex, and the CXR report containing the highest score were considered for the analysis. Patients were also divided into seven groups according to age. Nonparametric statistical tests were used to examine the relationship between the severity of lung disease and the age or sex. RESULTS: 783 Italian patients (532 males and 251 females) with SARS-CoV-2 infection were enrolled. The CXR score was significantly higher in males than in females only in groups aged 50 to 79 years. A significant correlation was observed between the CXR score and age in both males and females. Males aged 50 years or older and females aged 80 years or older with coronavirus disease 2019 showed the highest CXR score (median ≥ 8). CONCLUSIONS: Males aged 50 years or older and females aged 80 years or older showed the highest risk of developing severe lung disease. Our results may help to identify the highest-risk patients and those who require specific treatment strategies.

COVID-19 Pneumonia: Three Thoracic Complications in the Same Patient

The most dreaded thoracic complications in patients with coronavirus disease 2019 (COVID-19) are acute pulmonary embolism and pulmonary fibrosis. Both the complications are associated with an increased risk of morbidity and mortality. While acute pulmonary embolism is not a rare finding in patients with COVID-19 pneumonia, the prevalence of pulmonary fibrosis remains unclear. Spontaneous pneumothorax is another possible complication in COVID-19 pneumonia, although its observation is rather uncommon. Herein, we present interesting computed tomography images of the first case of COVID-19 pneumonia that initially developed acute pulmonary embolism and subsequently showed progression toward pulmonary fibrosis and spontaneous pneumothorax.