A Predictive Nomogram for Predicting Improved Clinical Outcome Probability in Patients with COVID-19 in Zhejiang Province, China.

The aim of this research was to develop a quantitative method for clinicians to predict the probability of improved prognosis in patients with coronavirus disease 2019 (COVID-19). Data on 104 patients admitted to hospital with laboratory-confirmed COVID-19 infection from 10 January 2020 to 26 February 2020 were collected. Clinical information and laboratory findings were collected and compared between the outcomes of improved patients and non-improved patients. The least absolute shrinkage and selection operator (LASSO) logistics regression model and two-way stepwise strategy in the multivariate logistics regression model were used to select prognostic factors for predicting clinical outcomes in COVID-19 patients. The concordance index (C-index) was used to assess the discrimination of the model, and internal validation was performed through bootstrap resampling. A novel predictive nomogram was constructed by incorporating these features. Of the 104 patients included in the study (median age 55 years), 75 (72.1%) had improved short-term outcomes, while 29 (27.9%) showed no signs of improvement. There were numerous differences in clinical characteristics and laboratory findings between patients with improved outcomes and patients without improved outcomes. After a multi-step screening process, prognostic factors were selected and incorporated into the nomogram construction, including immunoglobulin A (IgA), C-reactive protein (CRP), creatine kinase (CK), acute physiology and chronic health evaluation II (APACHE II), and interaction between CK and APACHE II. The C-index of our model was 0.962 (95% confidence interval (CI), 0.931-0.993) and still reached a high value of 0.948 through bootstrapping validation. A predictive nomogram we further established showed close performance compared with the ideal model on the calibration plot and was clinically practical according to the decision curve and clinical impact curve. The nomogram we constructed is useful for clinicians to predict improved clinical outcome probability for each COVID-19 patient, which may facilitate personalized counselling and treatment.

Identification of Monocytes Associated with Severe COVID-19 in the PBMCs of Severely Infected patients Through Single-Cell Transcriptome Sequencing.

Understanding the immunological characteristics of monocytes-including the characteristics associated with fibrosis-in severe coronavirus disease 2019 (COVID-19) is crucial for understanding the pathogenic mechanism of the disease and preventing disease severity. In this study, we performed single-cell transcriptomic sequencing of peripheral blood samples collected from six healthy controls and 14 COVID-19 samples including severe, moderate, and convalescent samples from three severely/critically ill and four moderately ill patients. We found that the monocytes were strongly remodeled in the severely/critically ill patients with COVID-19, with an increased proportion of monocytes and seriously reduced diversity. In addition, we discovered two novel severe-disease-specific monocyte subsets: Mono 0 and Mono 5. These subsets expressed amphiregulin (AREG), epiregulin (EREG), and cytokine interleukin-18 (IL-18) gene, exhibited an enriched erythroblastic leukemia viral oncogene homolog (ErbB) signaling pathway, and appeared to exhibit pro-fibrogenic and pro-inflammation characteristics. We also found metabolic changes in Mono 0 and Mono 5, including increased glycolysis/gluconeogenesis and an increased hypoxia inducible factor-1 (HIF-1) signaling pathway. Notably, one pre-severe sample displayed a monocyte atlas similar to that of the severe/critical samples. In conclusion, our study discovered two novel severe-disease-specific monocyte subsets as potential predictors and therapeutic targets for severe COVID-19. Overall, this study provides potential predictors for severe disease and therapeutic targets for COVID-19 and thus provides a resource for further studies on COVID-19.

Delayed Clearance of Viral RNA in Sputum for Severity COVID-19 Patients with Initial High Viral Load.

Aim: To analyze the possible risk factors of delayed virus clearance in hospitalized patients with coronavirus disease 2019 (COVID-19). Methods: Retrospective analysis of patients with COVID-19 admitted to the isolation wards from our hospital from 19th Jan 2020 to 18th March 2020. We were collected patient's data including demographic, epidemiologic, and clinical information, as well as laboratory and radiologic findings. The possible confounding risk factors for prolonged viral RNA shedding of COVID-19 during hospitalization were explored by univariate analysis and any variables with a p value less than 0.05 after univariate analysis were included in a subsequent multivariate logistic regression model analysis. Results: The 104 patients included 30 mild patients and 74 severe or critically ill patients. The median duration of viral RNA positivity in sputum was 11 days, and the longest duration of viral RNA positivity was 49 days after admission. Multivariate analysis shown that the used with darunavir/cobicistat treatment (odds ratio [OR]: 4.25, 95% confidence interval [CI]: 1.25-14.42, p = 0.020), duration of fever (OR: 1.15, 95% CI: 1.03-1.30, p = 0.015) and time to radiological improvement (OR: 1.14, 95% CI: 1.01-1.30, p = 0.033) were associated with delayed clearance of SARS-CoV-2 in sputum from COVID-19 patients. Then adjusted in the multivariate binary logistic regression analysis model in severe COVID-19 and found that critical COVID-19 patients (OR: 13.25, 95% CI: 1.45-12.07, p = 0.022), lower virus cycle threshold (CT) values of RT-PCR (OR: 0.96, 95% CI: 0.93-0.99, p = 0.004) and used with darunavir/cobicistat treatment (OR: 8.44, 95% CI: 2.21-32.28, p = 0.022) were associated with delayed clearance of SARS-CoV-2 in sputum from COVID-19 patients. Conclude: Clearance of viral RNA in sputum was delayed in severe COVID-19 patients, especially with lower virus CT value. And antivirals with darunavir/cobicistat has little advantage in eliminating SARS-CoV-2.

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。

Predictors of COVID-19 Infection: A Prevalence Study of Hospitalized Patients.

AIM: To find the predictors of coronavirus disease 2019 (COVID-19) in hospitalized patients. METHODS: A prevalence study compared the characteristics of COVID-19 patients with non-COVID-19 patients from January 19, 2020, to February 18, 2020, during the COVID-19 outbreak. Laboratory test results and pulmonary chest imaging of confirmed COVID-19 and non-COVID-19 patients were collected by retrieving medical records in our center. RESULTS: 96 COVID-19 patients and 122 non-COVID-19 patients were enrolled in this study. COVID-19 patients were older (53 vs. 39; P < 0.001) and had higher body mass index (BMI) than non-COVID-19 group (24.21 ± 3.51 vs. 23.00 ± 3.27, P = 0.011); however, differences in gender were not observed between the two groups. Logistic regression analysis showed that exposure history (OR: 23.34, P < 0.001), rhinorrhea (odds radio (OR): 0.12, P = 0.006), alanine aminotransferase (ALT) (OR: 1.03, P = 0.049), lactate dehydrogenase (LDH) (OR: 1.01, P = 0.020), lymphocyte (OR: 0.27, P = 0.007), and bilateral involvement on chest CT imaging (OR: 23.01, P < 0.001) were independent risk factors for COVID-19. Moreover, bilateral involvement on chest CT imaging (AUC = 0.904, P < 0.001) had significantly higher AUC than others in predicting COVID-19. CONCLUSIONS: Exposure history, elevated ALT and LDH, absence of rhinorrhea, lymphopenia, and bilateral involvement on chest CT imaging provide robust evidence for the diagnosis of COVID-19, especially in resource-limited conditions where nucleic acid detection is not readily available.

Glycan Nanostructures of Human Coronaviruses.

Human coronaviruses present a substantial global disease burden, causing damage to populations' health, economy, and social well-being. Glycans are one of the main structural components of all microbes and organismic structures, including viruses-playing multiple essential roles in virus infection and immunity. Studying and understanding virus glycans at the nanoscale provide new insights into the diagnosis and treatment of viruses. Glycan nanostructures are considered potential targets for molecular diagnosis, antiviral therapeutics, and the development of vaccines. This review article describes glycan nanostructures (eg, glycoproteins and glycolipids) that exist in cells, subcellular structures, and microbes. We detail the structure, characterization, synthesis, and functions of virus glycans. Furthermore, we describe the glycan nanostructures of different human coronaviruses, such as human coronavirus 229E (HCoV-229E), human coronavirus OC43 (HCoV-OC43), severe acute respiratory syndrome-associated coronavirus (SARS-CoV), human coronavirus NL63 (HCoV-NL63), human coronavirus HKU1 (HCoV-HKU1), the Middle East respiratory syndrome-associated coronavirus (MERS-CoV), and how glycan nanotechnology can be useful to prevent and combat human coronaviruses infections, along with possibilities that are not yet explored.

Cytokine Signature Associated With Disease Severity in COVID-19.

Coronavirus disease 2019 (COVID-19) broke out and then became a global epidemic at the end of 2019. With the increasing number of deaths, early identification of disease severity and interpretation of pathogenesis are very important. Aiming to identify biomarkers for disease severity and progression of COVID-19, 75 COVID-19 patients, 34 healthy controls and 23 patients with pandemic influenza A(H1N1) were recruited in this study. Using liquid chip technology, 48 cytokines and chemokines were examined, among which 33 were significantly elevated in COVID-19 patients compared with healthy controls. HGF and IL-1ß were strongly associated with APACHE II score in the first week after disease onset. IP-10, HGF and IL-10 were correlated positively with virus titers. Cytokines were significantly correlated with creatinine, troponin I, international normalized ratio and procalcitonin within two weeks after disease onset. Univariate analyses were carried out, and 6 cytokines including G-CSF, HGF, IL-10, IL-18, M-CSF and SCGF-ß were found to be associated with the severity of COVID-19. 11 kinds of cytokines could predict the severity of COVID-19, among which IP-10 and M-CSF were excellent predictors for disease severity. In conclusion, the levels of cytokines in COVID-19 were significantly correlated with the severity of the disease in the early stage, and serum cytokines could be used as warning indicators of the severity and progression of COVID-19. Early stratification of disease and intervention to reduce hypercytokinaemia may improve the prognosis of COVID-19 patients.

Hock-a-loogie saliva as a diagnostic specimen for SARS-CoV-2 by a PCR-based assay: A diagnostic validity study.

To clarify the effect of different respiratory sample types on SARS-CoV-2 detection, we collected throat swabs, nasal swabs and hock-a-loogie saliva or sputum, and compared their detection rates and viral loads. The detection rates of sputum (95.65%, 22/23) and hock-a-loogie saliva (88.09%, 37/42) were significantly higher than those in throat swabs (41.54%, 27/65) and nasal swabs (72.31%, 47/65) (P < 0.001). The Ct Values of sputum, hock-a-loogie saliva and nasal swabs were significantly higher than that in throat swabs, whereas no significant difference was observed between sputum and saliva samples. Hock-a-loogie saliva are reliable sample types that can be used to detect SARS-CoV-2, and worthy of clinical promotion.

One-year follow-up of chest CT findings in patients after SARS-CoV-2 infection.

BACKGROUND: Knowledge about the 1-year outcome of COVID-19 is limited. The aim of this study was to follow-up and evaluate lung abnormalities on serial computed tomography (CT) scans in patients with COVID-19 after hospital discharge. METHODS: A prospective cohort study of patients with COVID-19 from the First Affiliated Hospital, Zhejiang University School of Medicine was conducted, with assessments of chest CT during hospitalization and at 2 weeks, 1 month, 3 months, 6 months, and 1 year after hospital discharge. Risk factors of residual CT opacities and the influence of residual CT abnormalities on pulmonary functions at 1 year were also evaluated. RESULTS: A total of 41 patients were followed in this study. Gradual recovery after hospital discharge was confirmed by the serial CT scores. Around 47% of the patients showed residual aberration on pulmonary CT with a median CT score of 0 (interquartile range (IQR) of 0-2) at 1 year after discharge, with ground-glass opacity (GGO) with reticular pattern as the major radiologic pattern. Patients with residual radiological abnormalities were older (p = 0.01), with higher rate in current smokers (p = 0.04), higher rate in hypertensives (p = 0.05), lower SaO2 (p = 0.004), and higher prevalence of secondary bacterial infections during acute phase (p = 0.02). Multiple logistic regression analyses indicated that age was a risk factor associated with residual radiological abnormalities (OR 1.08, 95% CI 1.01-1.15, p = 0.02). Pulmonary functions of total lung capacity (p = 0.008) and residual volume (p < 0.001) were reduced in patients with residual CT abnormalities and were negatively correlated with CT scores. CONCLUSION: During 1-year follow-up after discharge, COVID-19 survivors showed continuous improvement on chest CT. However, residual lesions could still be observed and correlated with lung volume parameters. The risk of developing residual CT opacities increases with age.

Thyroid Function Abnormalities in COVID-19 Patients.

Purpose: The novel coronavirus COVID-19, has caused a worldwide pandemic, impairing several human organs and systems. Whether COVID-19 affects human thyroid function remains unknown. Methods: Eighty-four hospitalized COVID-19 patients in the First Affiliated Hospital, Zhejiang University School of Medicine (Hangzhou, China) were retrospectively enrolled in this study, among which 22 cases had complete records of thyroid hormones. In addition, 91 other patients with pneumonia and 807 healthy subjects were included as controls. Results: We found that levels of total triiodothyronine (TT3) and thyroid stimulating hormone (TSH) were lower in COVID-19 patients than healthy group (p < 0.001). Besides, TSH level in COVID-19 patients was obviously lower than non-COVID-19 patients (p < 0.001). Within the group of COVID-19, 61.9% (52/84) patients presented with thyroid function abnormalities and the proportion of thyroid dysfunction was higher in severe cases than mild/moderate cases (74.6 vs. 23.8%, p < 0.001). Patients with thyroid dysfunction tended to have longer viral nucleic acid cleaning time (14.1 ± 9.4 vs. 10.6 ± 8.3 days, p = 0.088). To note, thyroid dysfunction was also associated with decreased lymphocytes (p < 0.001) and increased CRP (p = 0.002). The correlation between TT3 and TSH level seemed to be positive rather than negative in the early stage, and gradually turned to be negatively related over time. Conclusion: Thyroid function abnormalities are common in COVID-19 patients, especially in severe cases. This might be partially explained by nonthyroidal illness syndrome.

The serum metabolome of COVID-19 patients is distinctive and predictive.

BACKGROUND: Metabolism is critical for sustaining life, immunity and infection, but its role in COVID-19 is not fully understood. METHODS: Seventy-nine COVID-19 patients, 78 healthy controls (HCs) and 30 COVID-19-like patients were recruited in a prospective cohort study. Samples were collected from COVID-19 patients with mild or severe symptoms on admission, patients who progressed from mild to severe symptoms, and patients who were followed from hospital admission to discharge. The metabolome was assayed using gas chromatography-mass spectrometry. RESULTS: Serum butyric acid, 2-hydroxybutyric acid, l-glutamic acid, l-phenylalanine, l-serine, l-lactic acid, and cholesterol were enriched in COVID-19 and COVID-19-like patients versus HCs. Notably, d-fructose and succinic acid were enriched, and citric acid and 2-palmitoyl-glycerol were depleted in COVID-19 patients compared to COVID-19-like patients and HCs, and these four metabolites were not differentially distributed in non-COVID-19 groups. COVID-19 patients had enriched 4-deoxythreonic acid and depleted 1,5-anhydroglucitol compared to HCs and enriched oxalic acid and depleted phosphoric acid compared to COVID-19-like patients. A combination of d-fructose, citric acid and 2-palmitoyl-glycerol distinguished COVID-19 patients from HCs and COVID-19-like patients, with an area under the curve (AUC) > 0.92 after validation. The combination of 2-hydroxy-3-methylbutyric acid, 3-hydroxybutyric acid, cholesterol, succinic acid, L-ornithine, oleic acid and palmitelaidic acid predicted patients who progressed from mild to severe COVID-19, with an AUC of 0.969. After discharge, nearly one-third of metabolites were recovered in COVID-19 patients. CONCLUSIONS: The serum metabolome of COVID-19 patients is distinctive and has important value in investigating pathogenesis, determining a diagnosis, predicting severe cases, and improving treatment.

Application value of artificial liver support system in the treatment of cytokine storm in patients with COVID-19.

OBJECTIVE: To explore the application value of artificial liver support system in the clinical treatment of coronavirus disease 2019 (COVID-19) patients with cytokine storm. METHODS: Six cases of severe or critically severe COVID-19 patients treated in The First Affiliated Hospital, College of Medicine, Zhejiang University from January 22 to February 4, 2020 were recruited, and all of them received artificial liver support treatment. Statistical analysis was carried out on the change of cytokines (TNF-α, IL-10, IL-6, IFN-γ, IL-2, IL-4), inflammation-related indicators (white blood cell, neutrophil, lymphocyte, C-reactive protein and procalcitonin), immune-related indicators (B lymphocyte percentage, natural killer cell percentage, CD3+CD4+CD8 T cell percentage), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the 6 patients before and after treatment, and the proportions of patients with abnormal indicators were analyzed as well. In addition, computed tomography (CT) was used to observe the absorption of pulmonary lesions before and after the artificial liver support treatment. RESULTS: The levels of cytokines (IL-6 and IL-10) were effectively reduced in the 6 patients after treatment with the artificial liver support system. Meanwhile, the proportions of patients with abnormal TNF-α, IL-10, IL-6 and IFN-γ were all decreased (p < 0.05). The levels of inflammation-related indicators including white blood cell, C-reactive protein and procalcitonin, and the proportions of patients with these abnormal indicators were both significantly reduced (p < 0.05). The level of neutrophil was not effectively reduced before and after the treatment, but the proportion was significantly reduced (p < 0.05). However, the abnormality of lymphocyte in the patients was not improved. There was no significant difference in immune-related indicators, AST and ALT before and after the treatment (p > 0.05). CT imaging showed that the artificial liver support treatment contributed to absorption of pulmonary lesions. CONCLUSIONS: The artificial liver support system had a great clinical effect in the treatment of cytokine storm and inflammation in COVID-19 patients, and it could promote the absorption of infected lesions.

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.

Evaluation of the safety and efficacy of using human menstrual blood-derived mesenchymal stromal cells in treating severe and critically ill COVID-19 patients: An exploratory clinical trial.

The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in December 2019 and has subsequently spread worldwide. Currently, there is no effective method to cure COVID-19. Mesenchymal stromal cells (MSCs) may be able to effectively treat COVID-19, especially for severe and critical patients. Menstrual blood-derived MSCs have recently received much attention due to their superior proliferation ability and their lack of ethical problems. Forty-four patients were enrolled from January to April 2020 in a multicenter, open-label, nonrandomized, parallel-controlled exploratory trial. Twenty-six patients received allogeneic, menstrual blood-derived MSC therapy, and concomitant medications (experimental group), and 18 patients received only concomitant medications (control group). The experimental group was treated with three infusions totaling 9 × 107 MSCs, one infusion every other day. Primary and secondary endpoints related to safety and efficacy were assessed at various time points during the 1-month period following MSC infusion. Safety was measured using the frequency of treatment-related adverse events (AEs). Patients in the MSC group showed significantly lower mortality (7.69% died in the experimental group vs 33.33% in the control group; P = .048). There was a significant improvement in dyspnea while undergoing MSC infusion on days 1, 3, and 5. Additionally, SpO2 was significantly improved following MSC infusion, and chest imaging results were improved in the experimental group in the first month after MSC infusion. The incidence of most AEs did not differ between the groups. MSC-based therapy may serve as a promising alternative method for treating severe and critical COVID-19.

The Artificial-Liver Blood-Purification System Can Effectively Improve Hypercytokinemia for COVID-19.

Since the December 2019 outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, the infection has spread locally and globally resulting in a pandemic. As the numbers of confirmed diagnoses and deaths continue to rise, COVID-19 has become the focus of international public health. COVID-19 is highly contagious, and there is no effective treatment yet. New treatment strategies are urgently needed to improve the treatment success rate of severe and critically ill patients. Increasing evidence has shown that a cytokine storm plays an important role in the progression of COVID-19. The artificial-liver blood-purification system (ALS) is expected to improve the outcome of the cytokine storm. In the present study, the levels of cytokines were detected in 12 COVID-19 patients pre- and post-ALS with promising results. The present study shows promising evidence that ALS can block the cytokine storm, rapidly remove the inflammatory mediators, and hopefully, suppress the progression of the disease, thereby providing a new strategy for the clinical treatment of COVID-19.

Safety of protease inhibitors and Arbidol for SARS-CoV-2 pneumonia in Zhejiang Province, China.

The aim of this study was to evaluate the safety of an antiviral regimen of protease inhibitors combined with Arbidol (umifenovir) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia patients. The genomic sequence of SARS-CoV-2 is highly homologous to that of SARS-CoV (Zhou et al., 2020). Previously published basic and clinical research on anti-SARS-CoV treatment found that lopinavir/ritonavir (LPV/r) could improve the prognosis of SARS patients (Chan et al., 2003; Chu et al., 2004). Darunavir (DRV) is another protease inhibitor that blocks the binding of SARS-CoV-2 to human angiotensin-converting enzyme 2 (Omotuyi et al., 2020). The broad-spectrum antiviral drug Arbidol (umifenovir) also shows in vitro anti-SARS-CoV activity (Khamitov et al., 2008).

Risk factors and clinical features of deterioration in COVID-19 patients in Zhejiang, China: a single-centre, retrospective study.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection swept through Wuhan and spread across China and overseas beginning in December 2019. To identify predictors associated with disease progression, we evaluated clinical risk factors for exacerbation of SARS-CoV-2 infection. METHODS: A retrospective analysis was used for PCR-confirmed COVID-19 (coronavirus disease 2019)-diagnosed hospitalized cases between January 19, 2020, and February 19, 2020, in Zhejiang, China. We systematically analysed the clinical characteristics of the patients and predictors of clinical deterioration. RESULTS: One hundred patients with COVID-19, with a median age of 54 years, were included. Among them, 49 patients (49%) had severe and critical disease. Age ([36-58] vs [51-70], P = 0.0001); sex (49% vs 77.6%, P = 0.0031); Body Mass Index (BMI) ([21.53-25.51] vs [23.28-27.01], P = 0.0339); hypertension (17.6% vs 57.1%, P < 0.0001); IL-6 ([6.42-30.46] vs [16.2-81.71], P = 0.0001); IL-10 ([2.16-5.82] vs [4.35-9.63], P < 0.0001); T lymphocyte count ([305-1178] vs [167.5-440], P = 0.0001); B lymphocyte count ([91-213] vs [54.5-163.5], P = 0.0001); white blood cell count ([3.9-7.6] vs [5.5-13.6], P = 0.0002); D2 dimer ([172-836] vs [408-953], P = 0.005), PCT ([0.03-0.07] vs [0.04-0.15], P = 0.0039); CRP ([3.8-27.9] vs [17.3-58.9], P < 0.0001); AST ([16, 29] vs [18, 42], P = 0.0484); artificial liver therapy (2% vs 16.3%, P = 0.0148); and glucocorticoid therapy (64.7% vs 98%, P < 0.0001) were associated with the severity of the disease. Age and weight were independent risk factors for disease severity. CONCLUSION: Deterioration among COVID-19-infected patients occurred rapidly after hospital admission. In our cohort, we found that multiple factors were associated with the severity of COVID19. Early detection and monitoring of these indicators may reduce the progression of the disease. Removing these factors may halt the progression of the disease. In addition, Oxygen support, early treatment with low doses of glucocorticoids and artificial liver therapy, when necessary, may help reduce mortality in critically ill patients.

Factors Associated With Prolonged Viral RNA Shedding in Patients with Coronavirus Disease 2019 (COVID-19).

BACKGROUND: An outbreak of coronavirus disease 2019 (COVID-19) is becoming a public health emergency. Data are limited on the duration and host factors related to viral shedding. METHODS: In this retrospective study, risk factors associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA shedding were evaluated in a cohort of 113 symptomatic patients from 2 hospitals outside Wuhan. RESULTS: The median (interquartile range) duration of SARS-CoV-2 RNA detection was 17 (13-22) days as measured from illness onset. When comparing patients with early (<15 days) and late (≥15 days after illness onset) viral RNA clearance, prolonged SARS-CoV-2 RNA shedding was associated with male sex (P = .009), old age (P = .033), concomitant hypertension (P = .009), delayed admission to hospital after illness onset (P = .001), severe illness at admission (P = .049), invasive mechanical ventilation (P = .006), and corticosteroid treatment (P = .025). Patients with longer SARS-CoV-2 RNA shedding duration had slower recovery of body temperature (P < .001) and focal absorption on radiograph images (P < .001) than patients with early SARS-CoV-2 RNA clearance. Male sex (OR, 3.24; 95% CI, 1.31-8.02), delayed hospital admission (OR, 1.30; 95% CI, 1.10-1.54), and invasive mechanical ventilation (OR, 9.88; 95% CI, 1.11-88.02) were independent risk factors for prolonged SARS-CoV-2 RNA shedding. CONCLUSIONS: Male sex, delayed admission to hospital after illness onset, and invasive mechanical ventilation were associated with prolonged SARS-CoV-2 RNA shedding. Hospital admission and general treatments should be started as soon as possible in symptomatic COVID-19 patients, especially male patients.