Weakly-supervised lesion analysis with a CNN-based framework for COVID-19.

Objective.Lesions of COVID-19 can be clearly visualized using chest CT images, and hence provide valuable evidence for clinicians when making a diagnosis. However, due to the variety of COVID-19 lesions and the complexity of the manual delineation procedure, automatic analysis of lesions with unknown and diverse types from a CT image remains a challenging task. In this paper we propose a weakly-supervised framework for this task requiring only a series of normal and abnormal CT images without the need for annotations of the specific locations and types of lesions.Approach.A deep learning-based diagnosis branch is employed for classification of the CT image and then a lesion identification branch is leveraged to capture multiple types of lesions.Main Results.Our framework is verified on publicly available datasets and CT data collected from 13 patients of the First Affiliated Hospital of Shantou University Medical College, China. The results show that the proposed framework can achieve state-of-the-art diagnosis prediction, and the extracted lesion features are capable of distinguishing between lesions showing ground glass opacity and consolidation.Significance.The proposed approach integrates COVID-19 positive diagnosis and lesion analysis into a unified framework without extra pixel-wise supervision. Further exploration also demonstrates that this framework has the potential to discover lesion types that have not been reported and can potentially be generalized to lesion detection of other chest-based diseases.

2019冠状病毒病(COVID-19)诊疗浙江经验 Management of COVID-19: the Zhejiang experience

当前2019冠状病毒病（COVID-19）疫情仍处于胶着状态。浙江大学医学院附属第一医院是国家感染性疾病临床医学中心，浙江省COVID-19患者救治中心。疫情一线的专家集智攻关，以国家卫生健康委员会和国家中医药管理局发布的COVID-19诊治指南为依据，以抗病毒、抗休克、抗低氧血症、抗继发感染、维持水电解质和酸碱平衡、维持微生态平衡的“四抗二平衡”救治策略为核心，总结完善诊治方案，聚焦临床实践的一些具体问题，为COVID-19患者临床诊治提供借鉴。推荐以多学科协作诊治个性化治疗提高COVID-19患者救治质量。建议病原学检测、炎症指标监测和肺部影像学动态观察指导临床诊治。痰液的病毒核酸检测阳性率最高，约10%的急性期患者血液中检测到病毒核酸，50%的患者粪便中检测到病毒核酸，粪便中可分离出活病毒，须警惕粪便是否具有传染性；开展细胞因子等炎症指标监测有助于发现是否出现细胞因子风暴，判断是否需要人工肝血液净化治疗。通过以“四抗二平衡”为核心的综合治疗提高治愈率、降低病死率；早期抗病毒治疗能减少重症、危重症发生，前期使用阿比多尔联合洛匹那韦/利托那韦抗病毒显示出一定效果。休克和低氧血症多为细胞因子风暴所致，人工肝血液净化治疗能迅速清除炎症介质，阻断细胞因子风暴，对维持水电解质酸碱平衡也有很好的作用，可以提高危重型患者的疗效。重型病例疾病早期可适量、短程应用糖皮质激素。氧疗过程中，患者氧合指数小于200 mmHg时应及时转入重症医学科治疗；采用保守氧疗策略，不推荐常规进行无创通气；机械通气患者应严格执行集束化呼吸机相关性肺炎预防管理策略；氧合指数大于150 mmHg时，及早减、停镇静剂并撤机拔管。不推荐预防性使用抗菌药物，对于病程长，体温反复升高和血降钙素原水平升高的患者可酌情使用抗菌药物；要关注COVID-19患者继发真菌感染的诊治。COVID-19患者有肠道微生态紊乱，肠道乳酸杆菌、双歧杆菌等有益菌减少，推荐对所有患者进行营养和胃肠道功能评估，以营养支持和补充大剂量肠道微生态调节剂，纠正肠道微生态失衡，减少细菌移位和继发感染。COVID-19患者普遍存在焦虑和恐惧心理，应建立动态心理危机干预和处理。提倡中西医结合辨证施治；优化重型患者护理促进康复。严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染后病毒清除规律仍不明了，出院后仍须居家隔离2周，并定期随访。以上经验和建议在本中心实行，取得较好效果，但COVID-19是一种新的疾病，其诊治方案及策略仍有待进一步探索与完善。

Clinical efficacy of methylprednisolone and the combined use of lopinavir/ritonavir with arbidol in treatment of coronavirus disease 2019.

This study aims to comparatively analyze the therapeutic efficacy upon multiple medication plans over lopinavir/ritonavir (LPV/r), arbidol (ARB), and methylprednisolone on patients with coronavirus disease 2019 (COVID-19). Totally, 75 COVID-19 patients admitted to The First Affiliated Hospital, Zhejiang University School of Medicine from January 22, 2020 to February 29, 2020 were recruited and grouped based on whether or not LPV/r and ARB were jointly used and whether or not methylprednisolone was used. Indexes including body temperature, time for nucleic acid negative conversion, hospital stays, and laboratory indexes were examined and compared. For all patients, there were no significant differences in the change of body temperature, the time for negative conversion, and hospital stays whether LPV/r and ARB were jointly used or not. While for severe and critically severe patients, methylprednisolone noticeably reduced the time for negative conversion. Meanwhile, the clinical efficacy was superior on patients receiving methylprednisolone within 3 days upon admission, and the duration of hospital stays was much shorter when methylprednisolone was given at a total dose of 0-400 mg than a higher dose of >400 mg if all patients received a similar dose per day. Nonetheless, no significant changes across hepatic, renal, and myocardial function indexes were observed. LPV/r combined with ARB produced no noticeably better effect on COVID-19 patients relative to the single-agent treatment. Additionally, methylprednisolone was efficient in severe and critically severe cases, and superior efficacy could be realized upon its early, appropriate, and short-term application.

[CT imaging features of patients with different clinical types of COVID-19].

OBJECTIVE: To investigate the CT findings of patients with different clinical types of coronavirus disease 2019 (COVID-19). METHODS: A total of 67 patients diagnosed as COVID-19 by nucleic acid testing were collected and divided into 4 groups according to the clinical stages based on Diagnosis and treatment of novel coronavirus pneumonia (trial version 6). The CT imaging characteristics were analyzed among patients with different clinical types. RESULTS: Among 67 patients, 3(4.5%) were mild, 35 (52.2%) were moderate, 22 (32.8%) were severe, and 7(10.4%) were critical ill. No significant abnormality in chest CT imaging in mild patients. The 35 cases of moderate type included 3 (8.6%) single lesions, the 22 cases of severe cases included 1 (4.5%) single lesion and the rest cases were with multiple lesions. CT images of moderate patients were mainly manifested by solid plaque shadow and halo sign (18/35, 51.4%); while fibrous strip shadow with ground glass shadow was more frequent in severe cases (7/22, 31.8%). Consolidation shadow as the main lesion was observed in 7 cases, and all of them were severe or critical ill patients. CONCLUSIONS: CT images of patients with different clinical types of COVID-19 have characteristic manifestations, and solid shadow may predict severe and critical illness.

CT Quantification and Machine-learning Models for Assessment of Disease Severity and Prognosis of COVID-19 Patients.

OBJECTIVE: This study was to investigate the CT quantification of COVID-19 pneumonia and its impacts on the assessment of disease severity and the prediction of clinical outcomes in the management of COVID-19 patients. MATERIALS METHODS: Ninety-nine COVID-19 patients who were confirmed by positive nucleic acid test (NAT) of RT-PCR and hospitalized from January 19, 2020 to February 19, 2020 were collected for this retrospective study. All patients underwent arterial blood gas test, routine blood test, chest CT examination, and physical examination on admission. In addition, follow-up clinical data including the disease severity, clinical treatment, and clinical outcomes were collected for each patient. Lung volume, lesion volume, nonlesion lung volume (NLLV) (lung volume - lesion volume), and fraction of nonlesion lung volume (%NLLV) (nonlesion lung volume / lung volume) were quantified in CT images by using two U-Net models trained for segmentation of lung and COVID-19 lesions in CT images. Furthermore, we calculated 20 histogram textures for lesions volume and NLLV, respectively. To investigate the validity of CT quantification in the management of COVID-19, we built random forest (RF) models for the purpose of classification and regression to assess the disease severity (Moderate, Severe, and Critical) and to predict the need and length of ICU stay, the duration of oxygen inhalation, hospitalization, sputum NAT-positive, and patient prognosis. The performance of RF classifiers was evaluated using the area under the receiver operating characteristic curves (AUC) and that of RF regressors using the root-mean-square error. RESULTS: Patients were classified into three groups of disease severity: moderate (n = 25), severe (n = 47) and critical (n = 27), according to the clinical staging. Of which, a total of 32 patients, 1 (1/25) moderate, 6 (6/47) severe, and 25 critical (25/27), respectively, were admitted to ICU. The median values of ICU stay were 0, 0, and 12 days, the duration of oxygen inhalation 10, 15, and 28 days, the hospitalization 12, 16, and 28 days, and the sputum NAT-positive 8, 9, and 13 days, in three severity groups, respectively. The clinical outcomes were complete recovery (n = 3), partial recovery with residual pulmonary damage (n = 80), prolonged recovery (n = 15), and death (n = 1). The %NLLV in three severity groups were 92.18 ± 9.89%, 82.94 ± 16.49%, and 66.19 ± 24.15% with p value <0.05 among each two groups. The AUCs of RF classifiers using hybrid models were 0.927 and 0.929 in classification of moderate vs (severe + critical), and severe vs critical, respectively, which were significantly higher than either radiomics models or clinical models (p < 0.05). The root-mean-square errors of RF regressors were 0.88 weeks for prediction of duration of hospitalization (mean: 2.60 ± 1.01 weeks), 0.92 weeks for duration of oxygen inhalation (mean: 2.44 ± 1.08 weeks), 0.90 weeks for duration of sputum NAT-positive (mean: 1.59 ± 0.98 weeks), and 0.69 weeks for stay of ICU (mean: 1.32 ± 0.67 weeks), respectively. The AUCs for prediction of ICU treatment and prognosis (partial recovery vs prolonged recovery) were 0.945 and 0.960, respectively. CONCLUSION: CT quantification and machine-learning models show great potentials for assisting decision-making in the management of COVID-19 patients by assessing disease severity and predicting clinical outcomes.

First report of manic-like symptoms in a COVID-19 patient with no previous history of a psychiatric disorder.

BACKGROUND: In December 2019, the novel coronavirus (SARS-CoV-2) infection was first reported in Wuhan city, central China, which has spread rapidly. The common clinical features of patients with SARS-CoV-2 infection included fever, fatigue, and damage to the respiratory or digestive system. However, it is still unclear whether SARS-CoV-2 infection could cause damage to the central nervous system (CNS) inducing psychiatric symptoms. CASE REPORT: Herein, we present the first case of SARS-CoV-2 infection with manic-like symptoms and describe the diagnosis, clinical course, and treatment of the case, focusing on the identifications of SARS-CoV-2 in the specimen of cerebrospinal fluid (CSF). The patient developed manic-like symptoms when his vital signs recovered on illness day 17. After manic-like attack, the detection of SARS-CoV-2 specific IgG antibody in CSF was positive, while the reverse transcriptase-polymerase chain reaction (RT-PCR) on CSF for the SARS-CoV-2 was negative. The patient received Olanzapine for treatment and his mood problems concurrently improved as indicated by scores of Young Manic Rating Scale (YMRS). LIMITATION: This is a single case report only, and the RT-PCR test for SARS-CoV-2 in CSF was not performed simultaneously when SARS-CoV-2 was positive in samples of sputum and stool. CONCLUSION: This first case of COVID-19 patient with manic-like symptoms highlights the importance of evaluation of mental health status and may contribute to our understanding of potential risk of CNS impairments by SARS-CoV-2 infection.

Coronavirus disease 2019 (COVID-19): chest CT characteristics benefit to early disease recognition and patient classification-a single center experience.

BACKGROUND: The current outbreak of coronavirus disease 2019 (COVID-19), epi-centered in Wuhan, Hubei Province of the China, has become a global health emergency. Several studies from China have recently provided the evidence of epidemiological, clinical, laboratory, and outcomes of COVID-19 patients. Investigation on the role of chest CT in patient screening and management course in a large cohort remains paucity. METHODS: This was a retrospective observational study based on the data collected between January 19 and 2020 to February 15, 2020. A clinic workflow using chest CT and RT-PCR assay to screen suspected patient was reviewed. Clinical data were evaluated and patients were classified to mild, common, severe and critical group. Chest CT characteristics of each patient were evaluated and a CT scoring system was applied to grade the lung involvement. RESULTS: Of 98 enrolled patients, 1, 29, 51 and 17 were clinically classified into mild, common, severe and critical group, respectively. Eighty-three patients (84.7%) demonstrated ground-glass opacity (GGO), 76 patients (77.5%) demonstrated consolidation and 18 patients (18.4%) demonstrated crazy-paving pattern on chest CT. Based on the CT scoring, 2, 35, 55 and 6 patients were categorized to grade 0, grade 1, grade 2 and grade 3, respectively, which significantly consistent with clinical classification (kappa =0.638, P﹤0.05). Twenty-nine patients admitted from fever clinic, with an average interval of 1.2 days (range, 0-4 days) between CT examination and onset of symptom. Three of these patients had negative initial RT-PCR result while abnormalities displayed on the initial chest CT. CONCLUSIONS: Peripheral lung distributed GGO and consolidation, without subpleural sparing, are the most common manifestations on chest CT of COVID-19. Abnormalities on chest CT can occur in an early stage of COVID-19, even when RT-PCR assay negative, which may help to early recognition and rapid diagnosis of this disease.

Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January-March 2020: retrospective cohort study.

OBJECTIVE: To evaluate viral loads at different stages of disease progression in patients infected with the 2019 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the first four months of the epidemic in Zhejiang province, China. DESIGN: Retrospective cohort study. SETTING: A designated hospital for patients with covid-19 in Zhejiang province, China. PARTICIPANTS: 96 consecutively admitted patients with laboratory confirmed SARS-CoV-2 infection: 22 with mild disease and 74 with severe disease. Data were collected from 19 January 2020 to 20 March 2020. MAIN OUTCOME MEASURES: Ribonucleic acid (RNA) viral load measured in respiratory, stool, serum, and urine samples. Cycle threshold values, a measure of nucleic acid concentration, were plotted onto the standard curve constructed on the basis of the standard product. Epidemiological, clinical, and laboratory characteristics and treatment and outcomes data were obtained through data collection forms from electronic medical records, and the relation between clinical data and disease severity was analysed. RESULTS: 3497 respiratory, stool, serum, and urine samples were collected from patients after admission and evaluated for SARS-CoV-2 RNA viral load. Infection was confirmed in all patients by testing sputum and saliva samples. RNA was detected in the stool of 55 (59%) patients and in the serum of 39 (41%) patients. The urine sample from one patient was positive for SARS-CoV-2. The median duration of virus in stool (22 days, interquartile range 17-31 days) was significantly longer than in respiratory (18 days, 13-29 days; P=0.02) and serum samples (16 days, 11-21 days; P<0.001). The median duration of virus in the respiratory samples of patients with severe disease (21 days, 14-30 days) was significantly longer than in patients with mild disease (14 days, 10-21 days; P=0.04). In the mild group, the viral loads peaked in respiratory samples in the second week from disease onset, whereas viral load continued to be high during the third week in the severe group. Virus duration was longer in patients older than 60 years and in male patients. CONCLUSION: The duration of SARS-CoV-2 is significantly longer in stool samples than in respiratory and serum samples, highlighting the need to strengthen the management of stool samples in the prevention and control of the epidemic, and the virus persists longer with higher load and peaks later in the respiratory tissue of patients with severe disease.

Lack of Vertical Transmission of Severe Acute Respiratory Syndrome Coronavirus 2, China.

A woman with coronavirus disease in her 35th week of pregnancy delivered an infant by cesarean section in a negative-pressure operating room. The infant was negative for severe acute respiratory coronavirus 2. This case suggests that mother-to-child transmission is unlikely for this virus.