Prediction of potential severe coronavirus disease 2019 patients based on CT radiomics: A retrospective study.

PURPOSE: Coronavirus disease 2019 (COVID-19) is a recently declared worldwide pandemic. Triaging of patients into severe and non-severe could further help in targeted management. "Potential severe patients" is a category of patients who did not have severe symptoms at their initial diagnosis, but eventually progressed to be severe patients and are easily overlooked in the early stage. This work aimed to develop and evaluate a CT-based radiomics signature for the prediction of these potential severe COVID-19 patients. METHODS: One hundred fifty COVID-19 patients were enrolled and randomly divided into cross-validation and independent test sets. First, their clinical characteristics were screened using the univariate and multivariate logistic regression step by step. Then, radiomics features were extracted from the lesions on their chest CT images. Subsequently, the inter- and intra-class correlation coefficients (ICC) analysis, minimum-redundancy maximum-relevance (mRMR) selection, and the least absolute shrinkage and selection operator (LASSO) algorithm were used step by step for feature selection and construction of a radiomics signature. Finally, the screened clinical risk factors and constructed radiomics signature were combined for the combined model and Radiomics+Clinics nomogram construction. The predictive performance of the Radiomics and Combined models were evaluated and compared using receiver operating characteristic curve (ROC) analysis, Hosmer-Lemeshow test and Delong test. RESULTS: Clinical characteristics analysis resulted in the screening of five clinical risk factors. The combination of ICC, mRMR, and LASSO methods resulted in the selection of ten radiomics features, which made up of the radiomics signature. The differences in the radiomics signature between the potential severe and non-severe groups in cross-validation set and test sets were both p < 0.001. All Radiomics and Combined models showed a very good predictive performance with the accuracy and AUC of nearly or above 0.9. Additionally, we found no significant difference in the predictive performance between these two models. CONCLUSIONS: A CT-based radiomics signature for the prediction of potential severe COVID-19 patients was constructed and evaluated. Constructed Radiomics and Combined model showed good feasibility and accuracy. The Radiomics+Clinical nomogram, acted as a useful tool, may assist clinicians to better identify potential severe cases to target their management in the COVID-19 pandemic prevention and control.

RBD trimer mRNA vaccine elicits broad and protective immune responses against SARS-CoV-2 variants.

With the rapid emergence and spread of SARS-CoV-2 variants, development of vaccines with broad and potent protectivity has become a global priority. Here, we designed a lipid nanoparticle-encapsulated, nucleoside-unmodified mRNA (mRNA-LNP) vaccine encoding the trimerized receptor-binding domain (RBD trimer) and showed its robust capability in inducing broad and protective immune responses against wild-type and major variants of concern (VOCs) in the mouse model of SARS-CoV-2 infection. The protectivity was correlated with RBD-specific B cell responses especially the long-lived plasma B cells in bone marrow, strong ability in triggering BCR clustering, and downstream signaling. Monoclonal antibodies isolated from vaccinated animals demonstrated broad and potent neutralizing activity against VOCs tested. Structure analysis of one representative antibody identified a novel epitope with a high degree of conservation among different variants. Collectively, these results demonstrate that the RBD trimer mRNA vaccine serves as a promising vaccine candidate against SARS-CoV-2 variants and beyond.

Mix-and-Interpolate: A Training Strategy to Deal With Source-Biased Medical Data.

Till March 31st, 2021, the coronavirus disease 2019 (COVID-19) had reportedly infected more than 127 million people and caused over 2.5 million deaths worldwide. Timely diagnosis of COVID-19 is crucial for management of individual patients as well as containment of the highly contagious disease. Having realized the clinical value of non-contrast chest computed tomography (CT) for diagnosis of COVID-19, deep learning (DL) based automated methods have been proposed to aid the radiologists in reading the huge quantities of CT exams as a result of the pandemic. In this work, we address an overlooked problem for training deep convolutional neural networks for COVID-19 classification using real-world multi-source data, namely, the data source bias problem. The data source bias problem refers to the situation in which certain sources of data comprise only a single class of data, and training with such source-biased data may make the DL models learn to distinguish data sources instead of COVID-19. To overcome this problem, we propose MIx-aNd-Interpolate (MINI), a conceptually simple, easy-to-implement, efficient yet effective training strategy. The proposed MINI approach generates volumes of the absent class by combining the samples collected from different hospitals, which enlarges the sample space of the original source-biased dataset. Experimental results on a large collection of real patient data (1,221 COVID-19 and 1,520 negative CT images, and the latter consisting of 786 community acquired pneumonia and 734 non-pneumonia) from eight hospitals and health institutions show that: 1) MINI can improve COVID-19 classification performance upon the baseline (which does not deal with the source bias), and 2) MINI is superior to competing methods in terms of the extent of improvement.

Relationship Between Serum Severe Acute Respiratory Syndrome Coronavirus 2 Nucleic Acid and Organ Damage in Coronavirus 2019 Patients: A Cohort Study.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide and has the ability to damage multiple organs. However, information on serum SARS-CoV-2 nucleic acid (RNAemia) in patients affected by coronavirus disease 2019 (COVID-19) is limited. METHODS: Patients who were admitted to Zhongnan Hospital of Wuhan University with laboratory-confirmed COVID-19 were tested for SARS-COV-2 RNA in serum from 28 January 2020 to 9 February 2020. Demographic data, laboratory and radiological findings, comorbidities, and outcomes data were collected and analyzed. RESULTS: Eighty-five patients were included in the analysis. The viral load of throat swabs was significantly higher than of serum samples. The highest detection of SARS-CoV-2 RNA in serum samples was between 11 and 15 days after symptom onset. Analysis to compare patients with and without RNAemia provided evidence that computed tomography and some laboratory biomarkers (total protein, blood urea nitrogen, lactate dehydrogenase, hypersensitive troponin I, and D-dimer) were abnormal and that the extent of these abnormalities was generally higher in patients with RNAemia than in patients without RNAemia. Organ damage (respiratory failure, cardiac damage, renal damage, and coagulopathy) was more common in patients with RNAemia than in patients without RNAemia. Patients with vs without RNAemia had shorter durations from serum testing SARS-CoV-2 RNA. The mortality rate was higher among patients with vs without RNAemia. CONCLUSIONS: In this study, we provide evidence to support that SARS-CoV-2 may have an important role in multiple organ damage. Our evidence suggests that RNAemia has a significant association with higher risk of in-hospital mortality.

Artificial intelligence-based approaches for COVID-19 patient management.

During the highly infectious pandemic of coronavirus disease 2019 (COVID-19), artificial intelligence (AI) has provided support in addressing challenges and accelerating achievements in controlling this public health crisis. It has been applied in fields varying from outbreak forecasting to patient management and drug/vaccine development. In this paper, we specifically review the current status of AI-based approaches for patient management. Limitations and challenges still exist, and further needs are highlighted.

Radiomics analysis of chest CT to predict the overall survival for the severe patients of COVID-19 pneumonia.

Personalized assessment and treatment of severe patients with COVID-19 pneumonia have greatly affected the prognosis and survival of these patients. This study aimed to develop the radiomics models as the potential biomarkers to estimate the overall survival (OS) for the COVID-19 severe patients. A total of 74 COVID-19 severe patients were enrolled in this study, and 30 of them died during the follow-up period. First, the clinical risk factors of the patients were analyzed. Then, two radiomics signatures were constructed based on two segmented volumes of interest of whole lung area and lesion area. Two combination models were built depend on whether the clinic risk factors were used and/or whether two radiomics signatures were combined. Kaplan-Meier analysis were performed for validating two radiomics signatures and C-index was used to evaluated the predictive performance of all radiomics signatures and combination models. Finally, a radiomics nomogram combining radiomics signatures with clinical risk factors was developed for predicting personalized OS, and then assessed with respect to the calibration curve. Three clinical risk factors were found, included age, malignancy and highest temperature that influence OS. Both two radiomics signatures could effectively stratify the risk of OS in COVID-19 severe patients. The predictive performance of the combination model with two radiomics signatures was better than that only one radiomics signature was used, and became better when three clinical risk factors were interpolated. Calibration curves showed good agreement in both 15 d survival and 30 d survival between the estimation with the constructed nomogram and actual observation. Both two constructed radiomics signatures can act as the potential biomarkers for risk stratification of OS in COVID-19 severe patients. The radiomics+clinical nomogram generated might serve as a potential tool to guide personalized treatment and care for these patients.

Temporal changes of quantitative CT findings from 102 patients with COVID-19 in Wuhan, China: A longitudinal study.

BACKGROUND: Computed tomography (CT) imaging combined with artificial intelligence is important in the diagnosis and prognosis of lung diseases. OBJECTIVE: This study aimed to investigate temporal changes of quantitative CT findings in patients with COVID-19 in three clinic types, including moderate, severe, and non-survivors, and to predict severe cases in the early stage from the results. METHODS: One hundred and two patients with confirmed COVID-19 were included in this study. Based on the time interval between onset of symptoms and the CT scan, four stages were defined in this study: Stage-1 (0 ∼7 days); Stage-2 (8 ∼ 14 days); Stage-3 (15 ∼ 21days); Stage-4 (> 21 days). Eight parameters, the infection volume and percentage of the whole lung in four different Hounsfield (HU) ranges, ((-, -750), [-750, -300), [-300, 50) and [50, +)), were calculated and compared between different groups. RESULTS: The infection volume and percentage of four HU ranges peaked in Stage-2. The highest proportion of HU [-750, 50) was found in the infected regions in non-survivors among three groups. CONCLUSIONS: The findings indicate rapid deterioration in the first week since the onset of symptoms in non-survivors. Higher proportion of HU [-750, 50) in the lesion area might be a potential bio-marker for poor prognosis in patients with COVID-19.

AI-assisted CT imaging analysis for COVID-19 screening: Building and deploying a medical AI system.

The sudden outbreak of novel coronavirus 2019 (COVID-19) increased the diagnostic burden of radiologists. In the time of an epidemic crisis, we hope artificial intelligence (AI) to reduce physician workload in regions with the outbreak, and improve the diagnosis accuracy for physicians before they could acquire enough experience with the new disease. In this paper, we present our experience in building and deploying an AI system that automatically analyzes CT images and provides the probability of infection to rapidly detect COVID-19 pneumonia. The proposed system which consists of classification and segmentation will save about 30%-40% of the detection time for physicians and promote the performance of COVID-19 detection. Specifically, working in an interdisciplinary team of over 30 people with medical and/or AI background, geographically distributed in Beijing and Wuhan, we are able to overcome a series of challenges (e.g. data discrepancy, testing time-effectiveness of model, data security, etc.) in this particular situation and deploy the system in four weeks. In addition, since the proposed AI system provides the priority of each CT image with probability of infection, the physicians can confirm and segregate the infected patients in time. Using 1,136 training cases (723 positives for COVID-19) from five hospitals, we are able to achieve a sensitivity of 0.974 and specificity of 0.922 on the test dataset, which included a variety of pulmonary diseases.

Efficient and Effective Training of COVID-19 Classification Networks With Self-Supervised Dual-Track Learning to Rank.

Coronavirus Disease 2019 (COVID-19) has rapidly spread worldwide since first reported. Timely diagnosis of COVID-19 is crucial both for disease control and patient care. Non-contrast thoracic computed tomography (CT) has been identified as an effective tool for the diagnosis, yet the disease outbreak has placed tremendous pressure on radiologists for reading the exams and may potentially lead to fatigue-related mis-diagnosis. Reliable automatic classification algorithms can be really helpful; however, they usually require a considerable number of COVID-19 cases for training, which is difficult to acquire in a timely manner. Meanwhile, how to effectively utilize the existing archive of non-COVID-19 data (the negative samples) in the presence of severe class imbalance is another challenge. In addition, the sudden disease outbreak necessitates fast algorithm development. In this work, we propose a novel approach for effective and efficient training of COVID-19 classification networks using a small number of COVID-19 CT exams and an archive of negative samples. Concretely, a novel self-supervised learning method is proposed to extract features from the COVID-19 and negative samples. Then, two kinds of soft-labels ('difficulty' and 'diversity') are generated for the negative samples by computing the earth mover's distances between the features of the negative and COVID-19 samples, from which data 'values' of the negative samples can be assessed. A pre-set number of negative samples are selected accordingly and fed to the neural network for training. Experimental results show that our approach can achieve superior performance using about half of the negative samples, substantially reducing model training time.