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1.
Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences ; 49(2):147-157, 2020.
Article in Chinese | EuropePMC | ID: covidwho-1772475

ABSTRACT

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。

2.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325228

ABSTRACT

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is mostly causes lung damages, but also lead to gastroenterology injury. SARS-CoV-2 - associated acute pancreatitis has been reported, however, clearance of SARS-CoV-2 and the pancreatitis was not clear. Case presentation: A 62 year old diabetic female patient suffer from coronavirus diseases (COVID-19) and detection of SARS-CoV-2 turned negative on day 11 and day 12 in sputum. Two days latter, the patient was diagnosed with acute pancreatitis. Through the support treatment, the patient got better and discharged from our hospital 18 days later. Conclusions: : Our case provided an initial view of SARS-CoV-2 infection with acute pancreatitis and the acute pancreatitis may occur in COVID-19 patients with clearance of SARS-CoV-2 in lung.

3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324643

ABSTRACT

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 liver therapy, when necessary, may help reduce mortality in critically ill patients.

4.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324326

ABSTRACT

We found that the real time reverse transcription-polymerase chain reaction (RT-PCR) detection of viral RNA from sputum or nasopharyngeal swab has a relatively low positive rate in the early stage to determine COVID-19 (named by the World Health Organization). The manifestations of computed tomography (CT) imaging of COVID-19 had their own characteristics, which are different from other types of viral pneumonia, such as Influenza-A viral pneumonia. Therefore, clinical doctors call for another early diagnostic criteria for this new type of pneumonia as soon as possible.This study aimed to establish an early screening model to distinguish COVID-19 pneumonia from Influenza-A viral pneumonia and healthy cases with pulmonary CT images using deep learning techniques. The candidate infection regions were first segmented out using a 3-dimensional deep learning model from pulmonary CT image set. These separated images were then categorized into COVID-19, Influenza-A viral pneumonia and irrelevant to infection groups, together with the corresponding confidence scores using a location-attention classification model. Finally the infection type and total confidence score of this CT case were calculated with Noisy-or Bayesian function.The experiments result of benchmark dataset showed that the overall accuracy was 86.7 % from the perspective of CT cases as a whole.The deep learning models established in this study were effective for the early screening of COVID-19 patients and demonstrated to be a promising supplementary diagnostic method for frontline clinical doctors.

5.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315365

ABSTRACT

Objective: The novel coronavirus pneumonia (COVID-19) has spread rapidly across the globe with the movement of people. How to diagnose COVID-19 quickly and accurately is a concern for all. We retrospectively assessed the clinical characteristics of patients with COVID-19 detected by outpatient screening in areas outside Wuhan, China, to guide early screening outside the epidemic area, to isolate and treat COVID-19-positive patients, and to control the spread of this virus in the region. Results: : Among the 213 patients treated in the fever clinic of our hospital, 41 tested positive for novel coronavirus (2019-nCoV) and 172 were negative. Among the positive patients, 13 (31.7%) of the patients had been to Wuhan, while 28 (68.3%) had not been to Wuhan. There were 4 cases of clustering occurrence. The main symptoms exhibited by COVID-19-positive patients were fever (87.8%), cough (68.3%), and expectoration (34.1%). The C-reactive protein (CRP) levels were increased in 35 (85.3%) positive patients;the hydroxybutyrate dehydrogenase in the myocardial zymogram was increased in 22 positive patients (53.6%) and 38 negative patients (22.1%);computed tomography (CT) findings revealed lung lesions in all 41 positive patients (100%). Conclusion: We classified the patient population and analyzed the data to understand the early clinical performance of COVID-19. Our research illustrate that screening for COVID-19 outside Wuhan should focus on early symptoms such as fever and cough, in combination with lung CT findings, epidemiological history, and sputum pathogen detection to determine whether patients need further isolation.

6.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-308288

ABSTRACT

Background: The coronavirus disease 2019 (COVID-19) causing a cluster of respiratory infections in Wuhan, China, is identified in December 2019. The main symptoms are defined as fever, cough, shortness of breath, with early symptom of sputum, acute respiratory distress syndrome (ARDS), and the final lung injury and pulmonary fibrosis. Currently, there is no effective method to cure it. Mesenchymal stem cell (MSC) therapy is an immediate need for treating COVID-19 especially severe patients at present. Methods: : We describe the two confirmed case of COVID-19 severe patients in Hangzhou, China to explore the role of menstrual blood-derived MSC in the treatment of SARS-CoV-2 infection. Furthermore, we mimic disease model of pulmonary fibrosis in mice to assess the role of MSC. Then, a co-culture system to investigate the underlying mechanism between MSC and pulmonary-associated cells by a series of Physiological, biochemical, bioinformatics analysis. Results: : MSC transplantation increases the immune indicators (including lymphocytes) and decreases inflammatory indicators (such as IL-6, IL-10, TNF, and IFN). More importantly, the two patients alleviated symptom and discharged after 3 weeks’ treatment with MSC. Additionally, MSCs exhibit an anti-inflammatory role through suppressing some inflammatory factors (RANTES, GM-CSF, MIG-1g, MCP-5, Eotaxin), which is anastomotic to current clinical study using MSC to treat COVID-19. Conclusions: : This is the first report using menstrual blood-derived MSC in treating COVID-19 patients. From our clinical results, we hold one idea that MSCs reduced inflammatory effect to defend cytokine storm. The underlying mechanism is probably that MSCs inhibit epithelia cell apoptosis and reduce the secretion of inflammatory factors to prevent myofibroblasts activity. MSC provides an alternative method for treating COVID-19 particularly some patients with ARDS or subsequent pulmonary fibrosis. Trial registration: This clinical trial was submitted to and approved by the Ethics Committee of the First Affiliated Hospital, Collage of Medicine, Zhejiang University. MSC administration in patient with COVID-19 was conducted in a single center and open-label clinical trial (ChiCTR2000029606).

7.
Can J Infect Dis Med Microbiol ; 2021: 6213450, 2021.
Article in English | MEDLINE | ID: covidwho-1476877

ABSTRACT

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.

8.
Int J Nanomedicine ; 16: 4813-4830, 2021.
Article in English | MEDLINE | ID: covidwho-1406766

ABSTRACT

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.


Subject(s)
Betacoronavirus/chemistry , Nanostructures/analysis , Nanostructures/chemistry , Polysaccharides/analysis , Polysaccharides/chemistry , Humans
9.
Front Immunol ; 12: 681516, 2021.
Article in English | MEDLINE | ID: covidwho-1399136

ABSTRACT

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.


Subject(s)
COVID-19/immunology , Cytokines/genetics , Cytokines/immunology , SARS-CoV-2/immunology , Severity of Illness Index , Transcriptome/immunology , Adult , Aged , Biomarkers/blood , Chemokines/blood , Chemokines/genetics , Chemokines/immunology , Cytokines/blood , Female , Hospitalization/statistics & numerical data , Humans , Influenza, Human/blood , Influenza, Human/immunology , Male , Middle Aged
10.
Clin Chim Acta ; 511: 177-180, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-1385202

ABSTRACT

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.


Subject(s)
COVID-19/diagnosis , COVID-19/genetics , Polymerase Chain Reaction/standards , SARS-CoV-2/genetics , Saliva/virology , Specimen Handling/standards , Adult , Female , Humans , Male , Middle Aged , Nasopharynx/virology , Polymerase Chain Reaction/methods , Prospective Studies , SARS-CoV-2/isolation & purification , Specimen Handling/methods , Sputum/virology , Viral Load/methods , Viral Load/standards
12.
BMC Med ; 19(1): 191, 2021 08 09.
Article in English | MEDLINE | ID: covidwho-1344106

ABSTRACT

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.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Adult , COVID-19/diagnostic imaging , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prospective Studies , Retrospective Studies , SARS-CoV-2 , Tomography, X-Ray Computed
13.
Engineering (Beijing) ; 2021 Jun 12.
Article in English | MEDLINE | ID: covidwho-1267670

ABSTRACT

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.

15.
Front Endocrinol (Lausanne) ; 11: 623792, 2020.
Article in English | MEDLINE | ID: covidwho-1122326

ABSTRACT

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.


Subject(s)
COVID-19/epidemiology , Thyroid Diseases/epidemiology , Adult , Aged , COVID-19/blood , COVID-19/complications , COVID-19/therapy , China/epidemiology , Euthyroid Sick Syndromes/epidemiology , Female , Humans , Male , Middle Aged , Retrospective Studies , SARS-CoV-2/physiology , Severity of Illness Index , Thyroid Diseases/blood , Thyroid Diseases/complications , Thyroid Diseases/therapy , Thyroid Hormones/blood , Thyrotropin/blood
16.
Metabolism ; 118: 154739, 2021 05.
Article in English | MEDLINE | ID: covidwho-1117306

ABSTRACT

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.


Subject(s)
COVID-19/metabolism , Metabolome , SARS-CoV-2 , Adult , Aged , Amino Acids/blood , COVID-19/drug therapy , Cholesterol/blood , Female , Fructose/blood , Gas Chromatography-Mass Spectrometry , Humans , Hydroxybutyrates/blood , Lactic Acid/blood , Male , Middle Aged , Prospective Studies
17.
J Med Virol ; 93(7): 4446-4453, 2021 07.
Article in English | MEDLINE | ID: covidwho-1064383

ABSTRACT

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.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , Indoles/therapeutic use , Lopinavir/therapeutic use , Methylprednisolone/therapeutic use , Ritonavir/therapeutic use , China , Drug Combinations , Female , Fever/drug therapy , Humans , Length of Stay , Male , Middle Aged , Retrospective Studies , SARS-CoV-2/drug effects
18.
Int Immunopharmacol ; 90: 107120, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1065209

ABSTRACT

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.


Subject(s)
COVID-19/therapy , Cytokine Release Syndrome/therapy , Life Support Care/methods , Liver, Artificial , Lung/pathology , Lymphocytes/pathology , SARS-CoV-2/physiology , Aged , Alanine Transaminase/blood , Aspartate Aminotransferases/blood , Cytokines/blood , Female , Humans , Lung/diagnostic imaging , Male , Middle Aged
19.
Clin Transl Med ; 11(2): e297, 2021 02.
Article in English | MEDLINE | ID: covidwho-1049592

ABSTRACT

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.


Subject(s)
COVID-19/therapy , Menstruation , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , SARS-CoV-2/metabolism , Adolescent , Adult , Aged , Allografts , COVID-19/blood , COVID-19/mortality , Critical Illness , Disease-Free Survival , Female , Humans , Male , Middle Aged , Severity of Illness Index , Survival Rate
20.
Front Immunol ; 11: 586073, 2020.
Article in English | MEDLINE | ID: covidwho-1021888

ABSTRACT

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.


Subject(s)
COVID-19/therapy , Cytokine Release Syndrome/therapy , Cytokines/blood , Hemoperfusion , Liver/metabolism , Plasma Exchange , SARS-CoV-2 , Adult , Aged , Aged, 80 and over , COVID-19/complications , Cytokine Release Syndrome/etiology , Female , Humans , Male , Middle Aged
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