Strategies to safely rule out pulmonary embolism in COVID-19 outpatients: a multicenter retrospective study.

OBJECTIVES: The objective was to define a safe strategy to exclude pulmonary embolism (PE) in COVID-19 outpatients, without performing CT pulmonary angiogram (CTPA). METHODS: COVID-19 outpatients from 15 university hospitals who underwent a CTPA were retrospectively evaluated. D-Dimers, variables of the revised Geneva and Wells scores, as well as laboratory findings and clinical characteristics related to COVID-19 pneumonia, were collected. CTPA reports were reviewed for the presence of PE and the extent of COVID-19 disease. PE rule-out strategies were based solely on D-Dimer tests using different thresholds, the revised Geneva and Wells scores, and a COVID-19 PE prediction model built on our dataset were compared. The area under the receiver operating characteristics curve (AUC), failure rate, and efficiency were calculated. RESULTS: In total, 1369 patients were included of whom 124 were PE positive (9.1%). Failure rate and efficiency of D-Dimer > 500 µg/l were 0.9% (95%CI, 0.2-4.8%) and 10.1% (8.5-11.9%), respectively, increasing to 1.0% (0.2-5.3%) and 16.4% (14.4-18.7%), respectively, for an age-adjusted D-Dimer level. D-dimer > 1000 µg/l led to an unacceptable failure rate to 8.1% (4.4-14.5%). The best performances of the revised Geneva and Wells scores were obtained using the age-adjusted D-Dimer level. They had the same failure rate of 1.0% (0.2-5.3%) for efficiency of 16.8% (14.7-19.1%), and 16.9% (14.8-19.2%) respectively. The developed COVID-19 PE prediction model had an AUC of 0.609 (0.594-0.623) with an efficiency of 20.5% (18.4-22.8%) when its failure was set to 0.8%. CONCLUSIONS: The strategy to safely exclude PE in COVID-19 outpatients should not differ from that used in non-COVID-19 patients. The added value of the COVID-19 PE prediction model is minor. KEY POINTS: • D-dimer level remains the most important predictor of pulmonary embolism in COVID-19 patients. • The AUCs of the revised Geneva and Wells scores using an age-adjusted D-dimer threshold were 0.587 (95%CI, 0.572 to 0.603) and 0.588 (95%CI, 0.572 to 0.603). • The AUC of COVID-19-specific strategy to rule out pulmonary embolism ranged from 0.513 (95%CI: 0.503 to 0.522) to 0.609 (95%CI: 0.594 to 0.623).

What level of D-dimers can safely exclude pulmonary embolism in COVID-19 patients presenting to the emergency department?

OBJECTIVES: To identify which level of D-dimer would allow the safe exclusion of pulmonary embolism (PE) in COVID-19 patients presenting to the emergency department (ED). METHODS: This retrospective study was conducted on the COVID database of Assistance Publique - Hôpitaux de Paris (AP-HP). COVID-19 patients who presented at the ED of AP-HP hospitals between March 1 and May 15, 2020, and had CTPA following D-dimer dosage within 48h of presentation were included. The D-dimer sensitivity, specificity, and positive and negative predictive values were calculated for different D-dimer thresholds, as well as the false-negative and failure rates, and the number of CTPAs potentially avoided. RESULTS: A total of 781 patients (mean age 62.0 years, 53.8% men) with positive RT-PCR for SARS-Cov-2 were included and 60 of them (7.7%) had CTPA-confirmed PE. Their median D-dimer level was significantly higher than that of patients without PE (4,013 vs 1,198 ng·mL-1, p < 0.001). Using 500 ng·mL-1, or an age-adjusted cut-off for patients > 50 years, the sensitivity and the NPV were above 90%. With these thresholds, 17.1% and 31.5% of CTPAs could have been avoided, respectively. Four of the 178 patients who had a D-dimer below the age-adjusted cutoff had PE, leading to an acceptable failure rate of 2.2%. Using higher D-dimer cut-offs could have avoided more CTPAs, but would have lowered the sensitivity and increased the failure rate. CONCLUSION: The same D-Dimer thresholds as those validated in non-COVID outpatients should be used to safely rule out PE. KEY POINTS: • The median D-dimer level was significantly higher in COVID-19 patients with PE as compared to those without PE (4,013 ng·mL-1 vs 1,198 ng·mL-1 respectively, p < 0.001). • Using 500 ng·mL-1, or an age-adjusted D-dimer cut-off to exclude pulmonary embolism, the sensitivity and negative predictive value were above 90%. • Higher cut-offs would lead to a reduction in the sensitivity below 85% and an increase in the failure rate, especially for patients under 50 years.

Deep learning for lung disease segmentation on CT: Which reconstruction kernel should be used?

PURPOSE: The purpose of this study was to determine whether a single reconstruction kernel or both high and low frequency kernels should be used for training deep learning models for the segmentation of diffuse lung disease on chest computed tomography (CT). MATERIALS AND METHODS: Two annotated datasets of COVID-19 pneumonia (323,960 slices) and interstitial lung disease (ILD) (4,284 slices) were used. Annotated CT images were used to train a U-Net architecture to segment disease. All CT slices were reconstructed using both a lung kernel (LK) and a mediastinal kernel (MK). Three different trainings, resulting in three different models were compared for each disease: training on LK only, MK only or LK+MK images. Dice similarity scores (DSC) were compared using the Wilcoxon signed-rank test. RESULTS: Models only trained on LK images performed better on LK images than on MK images (median DSC = 0.62 [interquartile range (IQR): 0.54, 0.69] vs. 0.60 [IQR: 0.50, 0.70], P < 0.001 for COVID-19 and median DSC = 0.62 [IQR: 0.56, 0.69] vs. 0.50 [IQR 0.43, 0.57], P < 0.001 for ILD). Similarly, models only trained on MK images performed better on MK images (median DSC = 0.62 [IQR: 0.53, 0.68] vs. 0.54 [IQR: 0.47, 0.63], P < 0.001 for COVID-19 and 0.69 [IQR: 0.61, 0.73] vs. 0.63 [IQR: 0.53, 0.70], P < 0.001 for ILD). Models trained on both kernels performed better or similarly than those trained on only one kernel. For COVID-19, median DSC was 0.67 (IQR: =0.59, 0.73) when applied on LK images and 0.67 (IQR: 0.60, 0.74) when applied on MK images (P < 0.001 for both). For ILD, median DSC was 0.69 (IQR: 0.63, 0.73) when applied on LK images (P = 0.006) and 0.68 (IQR: 0.62, 0.72) when applied on MK images (P > 0.99). CONCLUSION: Reconstruction kernels impact the performance of deep learning-based models for lung disease segmentation. Training on both LK and MK images improves the performance.

Computed tomography after severe COVID-19 pneumonia: findings at 6†months and beyond.

Parenchymal bands and ground-glass opacities consistent with a pattern of late organising pneumonia are frequently observed 6 months after ICU admission for #COVID19, whereas fibrotic changes of limited extent are only observed in about 1/3 of patients https://bit.ly/2UGOsbr.

Pre-test probability for SARS-Cov-2-related infection score: The PARIS score.

INTRODUCTION: In numerous countries, large population testing is impossible due to the limited availability of RT-PCR kits and CT-scans. This study aimed to determine a pre-test probability score for SARS-CoV-2 infection. METHODS: This multicenter retrospective study (4 University Hospitals) included patients with clinical suspicion of SARS-CoV-2 infection. Demographic characteristics, clinical symptoms, and results of blood tests (complete white blood cell count, serum electrolytes and CRP) were collected. A pre-test probability score was derived from univariate analyses of clinical and biological variables between patients and controls, followed by multivariate binary logistic analysis to determine the independent variables associated with SARS-CoV-2 infection. RESULTS: 605 patients were included between March 10th and April 30th, 2020 (200 patients for the training cohort, 405 consecutive patients for the validation cohort). In the multivariate analysis, lymphocyte (<1.3 G/L), eosinophil (<0.06 G/L), basophil (<0.04 G/L) and neutrophil counts (<5 G/L) were associated with high probability of SARS-CoV-2 infection but no clinical variable was statistically significant. The score had a good performance in the validation cohort (AUC = 0.918 (CI: [0.891-0.946]; STD = 0.014) with a Positive Predictive Value of high-probability score of 93% (95%CI: [0.89-0.96]). Furthermore, a low-probability score excluded SARS-CoV-2 infection with a Negative Predictive Value of 98% (95%CI: [0.93-0.99]). The performance of the score was stable even during the last period of the study (15-30th April) with more controls than infected patients. CONCLUSIONS: The PARIS score has a good performance to categorize the pre-test probability of SARS-CoV-2 infection based on complete white blood cell count. It could help clinicians adapt testing and for rapid triage of patients before test results.

Study of Thoracic CT in COVID-19: The STOIC Project.

Background There are conflicting data regarding the diagnostic performance of chest CT for COVID-19 pneumonia. Disease extent at CT has been reported to influence prognosis. Purpose To create a large publicly available data set and assess the diagnostic and prognostic value of CT in COVID-19 pneumonia. Materials and Methods This multicenter, observational, retrospective cohort study involved 20 French university hospitals. Eligible patients presented at the emergency departments of the hospitals involved between March 1 and April 30th, 2020, and underwent both thoracic CT and reverse transcription-polymerase chain reaction (RT-PCR) testing for suspected COVID-19 pneumonia. CT images were read blinded to initial reports, RT-PCR, demographic characteristics, clinical symptoms, and outcome. Readers classified CT scans as either positive or negative for COVID-19 based on criteria published by the French Society of Radiology. Multivariable logistic regression was used to develop a model predicting severe outcome (intubation or death) at 1-month follow-up in patients positive for both RT-PCR and CT, using clinical and radiologic features. Results Among 10 930 patients screened for eligibility, 10 735 (median age, 65 years; interquartile range, 51-77 years; 6147 men) were included and 6448 (60%) had a positive RT-PCR result. With RT-PCR as reference, the sensitivity and specificity of CT were 80.2% (95% CI: 79.3, 81.2) and 79.7% (95% CI: 78.5, 80.9), respectively, with strong agreement between junior and senior radiologists (Gwet AC1 coefficient, 0.79). Of all the variables analyzed, the extent of pneumonia at CT (odds ratio, 3.25; 95% CI: 2.71, 3.89) was the best predictor of severe outcome at 1 month. A score based solely on clinical variables predicted a severe outcome with an area under the curve of 0.64 (95% CI: 0.62, 0.66), improving to 0.69 (95% CI: 0.6, 0.71) when it also included the extent of pneumonia and coronary calcium score at CT. Conclusion Using predefined criteria, CT reading is not influenced by reader's experience and helps predict the outcome at 1 month. ClinicalTrials.gov identifier: NCT04355507 Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Rubin in this issue.

Determining extent of COVID-19 pneumonia on CT based on biological variables.

INTRODUCTION: Covid-19 pneumonia CT extent correlates well with outcome including mortality. However, CT is not widely available in many countries. This study aimed to explore the relationship between Covid-19 pneumonia CT extent and blood tests variations. The objective was to determine for the biological variables correlating with disease severity the cut-off values showing the best performance to predict the parenchymal extent of the pneumonia. METHODS: Bivariate correlations were calculated between biological variables and grade of disease extent on CT. Receiving Operating Characteristic curve analysis determined the best cutoffs for the strongest correlated biological variables. The performance of these variables to predict mild (<10%) or severe pneumonia (>50% of parenchyma involved) was evaluated. RESULTS: Correlations between biological variables and disease extent was evaluated in 168 patients included in this study. LDH, lymphocyte count and CRP showed the strongest correlations (with 0.67, -0.41 and 0.52 correlation coefficient, respectively). Patients were split into a training and a validation cohort according to their centers. If one variable was above/below the following cut-offs, LDH>380, CRP>80 or lymphocyte count <0.8G/L, severe pneumonia extent on CT was detected with 100% sensitivity. Values above/below all three thresholds were denoted in 73% of patients with severe pneumonia extent. The combination of LDH<220 and CRP<22 was associated with mild pneumonia extent (<10%) with specificity of 100%. DISCUSSION: LDH showed the strongest correlation with the extent of Covid-19 pneumonia on CT. Combined with CRP±lymphocyte count, it helps predicting parenchymal extent of the pneumonia when CT scan is not available.

AI-driven quantification, staging and outcome prediction of COVID-19 pneumonia.

Coronavirus disease 2019 (COVID-19) emerged in 2019 and disseminated around the world rapidly. Computed tomography (CT) imaging has been proven to be an important tool for screening, disease quantification and staging. The latter is of extreme importance for organizational anticipation (availability of intensive care unit beds, patient management planning) as well as to accelerate drug development through rapid, reproducible and quantified assessment of treatment response. Even if currently there are no specific guidelines for the staging of the patients, CT together with some clinical and biological biomarkers are used. In this study, we collected a multi-center cohort and we investigated the use of medical imaging and artificial intelligence for disease quantification, staging and outcome prediction. Our approach relies on automatic deep learning-based disease quantification using an ensemble of architectures, and a data-driven consensus for the staging and outcome prediction of the patients fusing imaging biomarkers with clinical and biological attributes. Highly promising results on multiple external/independent evaluation cohorts as well as comparisons with expert human readers demonstrate the potentials of our approach.

COVID-19 pneumonia: Diagnostic and prognostic role of CT based on a retrospective analysis of 214 consecutive patients from Paris, France.

OBJECTIVES: To evaluate the diagnostic and prognostic performance of CT in patients referred for COVID19 suspicion to a French university hospital, depending on symptoms and date of onset. METHODS: From March 1st to March 28th, 214 patients having both chest CT scan and reverse transcriptase polymerase chain reaction (RT- PCT) within 24 h were retrospectively evaluated. Sensitivity, specificity, negative and positive predictive values of first and expert readings were calculated together with inter reader agreement, with results of RT-PCR as standard of reference and according to symptoms and onset date. Patient characteristics and disease extent on CT were correlated to short-term outcome (death or intubation at 3 weeks follow-up). RESULTS: Of the 214 patients (119 men, mean age 59 ±â€¯19 years), 129 had at least one positive RT-PCR result. Sensitivity, specificity, negative and positive predictive values were 79 % (95 % CI: 71-86 %), 84 %(74-91 %), 72 %(63-81 %) and 88 % (81-93 %) for initial CT reading and 81 %(74-88 %), 91 % (82-96 %), 76 % (67-84 %) and 93 % (87-97 %), for expert reading, with strong inter-reader agreement (kappa index: 0.89). Considering the 123 patients with symptoms for more than 5 days, the corresponding figures were 90 %, 78 %, 80 % and 89 % for initial reading and 93 %, 88 %, 86 % and 94 % for the expert. Disease extent exceeded 25 % for 68 % and 26 % of severe and non-severe patients, respectively (p < 0.001). CONCLUSION: CT sensitivity increased after 5 days of symptoms. A disease extent > 25 % was associated with poorer outcome.