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1.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325038

ABSTRACT

In order to identify the clinical characteristics of patients with Corona Virus Disease 2019 (COVID-19) and find out the characteristic effects of 2019 New Coronavirus (SARS-CoV-2) infection on changes in clinical and laboratory data, we analyzed the medical records of 80 suspected cases who admitted in the national designated hospital due to the relevant clinical manifestations of SARS-CoV-2 infection from January 22 to February 13, 2020. 62 (77.5%) confirmed cases and 18 (22.5%) negative cases were confirmed by SARS-CoV-2 nucleic acid test. Epidemiological investigation and statistical analysis were carried out on the clinical and laboratory data of all suspected cases of COVID-19, the specific indicators were found, and the clinical characteristics of COVID-19 were described. Compared with the patients with negative nucleic acid test, the patients with positive nucleic acid test showed shorter time of onset of symptoms, higher plasma CO 2 level, lower eosinophil ratio, lower platelet count and hematocrit, lower serum sodium level, higher serum creatinine, higher blood urea and plasma albumin levels (all P <0.05). Our results might provide some suggestions in diagnosis, clinical treatment and prevention for COVID-19.

2.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-312183

ABSTRACT

Abstract There is a heated debate on whether the cancer survivors have worse outcomes in corona virus disease 2019 (COVID-2019). This study showed that both cancer survivors and cancer patients have decreased lymphocytes, partially explaining why these patients were associated with poorer prognosis in severe acute respiratory syndrome coronavirus 2 infection (SARS-CoV-2) in principle. Therefore, patients with cancer history, whether they are going active treatment or not, deserve special attention.

3.
Bioconjug Chem ; 32(11): 2420-2431, 2021 11 17.
Article in English | MEDLINE | ID: covidwho-1526037

ABSTRACT

The heparan sulfate (HS) mimetic pixatimod (PG545) is a highly potent inhibitor of angiogenesis, tumor growth, and metastasis currently in clinical trials for cancer. PG545 has also demonstrated potent antiviral activity against numerous HS-dependent viruses, including SARS-CoV-2, and shows promise as an antiviral drug for the treatment of COVID-19. Structurally, PG545 consists of a fully sulfated tetrasaccharide conjugated to the steroid 5α-cholestan-3ß-ol. The reported synthesis of PG545 suffers from a low yield and poor selectivity in the critical glycosylation step. Given its clinical importance, new efficient routes for the synthesis of PG545 and analogues were developed. Particular attention was given to improving the key glycosylation step by using more stable protecting groups and optimized glycosyl donors.


Subject(s)
COVID-19 , Angiogenesis Inhibitors , Cell Line, Tumor , Heparitin Sulfate , Humans , Neovascularization, Pathologic
4.
Front Med (Lausanne) ; 8: 764493, 2021.
Article in English | MEDLINE | ID: covidwho-1450820

ABSTRACT

[This corrects the article DOI: 10.3389/fmed.2020.584342.].

5.
Cell Discov ; 7(1): 49, 2021 Jul 06.
Article in English | MEDLINE | ID: covidwho-1298837

ABSTRACT

SARS-CoV-2 infection causes a wide spectrum of clinical manifestations in humans, and olfactory dysfunction is one of the most predictive and common symptoms in COVID-19 patients. However, the underlying mechanism by which SARS-CoV-2 infection leads to olfactory disorders remains elusive. Herein, we demonstrate that intranasal inoculation with SARS-CoV-2 induces robust viral replication in the olfactory epithelium (OE), not the olfactory bulb (OB), resulting in transient olfactory dysfunction in humanized ACE2 (hACE2) mice. The sustentacular cells and Bowman's gland cells in the OE were identified as the major target cells of SARS-CoV-2 before invasion into olfactory sensory neurons (OSNs). Remarkably, SARS-CoV-2 infection triggers massive cell death and immune cell infiltration and directly impairs the uniformity of the OE structure. Combined transcriptomic and quantitative proteomic analyses revealed the induction of antiviral and inflammatory responses, as well as the downregulation of olfactory receptor (OR) genes in the OE from the infected animals. Overall, our mouse model recapitulates olfactory dysfunction in COVID-19 patients and provides critical clues for understanding the physiological basis for extrapulmonary manifestations of COVID-19.

6.
Front Med (Lausanne) ; 7: 584342, 2020.
Article in English | MEDLINE | ID: covidwho-914432

ABSTRACT

Background and Aim: Liver test abnormalities are common in COVID-19 patients. The aim of our study was to determine risk factors for different liver injury patterns and to evaluate the relationship between liver injury patterns and prognosis in patients with COVID-19. Methods: We retrospectively analyzed patients admitted between January 1st to March 10th, with laboratory-confirmed COVID-19 and followed them up to April 20th, 2020. Information of clinical features of patients was collected for analysis. Results: As a result, a total of 838 hospitalized patients with confirmed COVID-19, including 48.8% (409/838) patients with normal liver function and 51.2% (429/838) patients with liver injury were analyzed. Abnormal liver function tests are associated with organ injuries, hypoxia, inflammation, and the use of antiviral drugs. Hepatocellular injury pattern was associated with hypoxia. The mortality of the hepatocellular injury pattern, cholestatic pattern and mixed pattern were 25, 28.2, and 22.3%, respectively, while the death rate was only 6.1% in the patients without liver injury. Multivariate analyses showed that liver injury with cholestatic pattern and mixed pattern were associated with increased mortality risk. Conclusions: Our study confirmed that hepatocellular injury pattern that may be induced by hypoxia was not risk factor for mortality in SARS-COV-2 infection, while liver injury with mixed pattern and cholestatic pattern that might be induced by SARS-CoV-2 directly might be potential risk factors for increased mortality in COVID-19 patients.

7.
J Dig Dis ; 21(9): 512-518, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-670044

ABSTRACT

OBJECTIVE: Abnormal liver function is a common form of extra-pulmonary organ damage in patients with coronavirus disease 2019 (COVID-19). Patients with severe COVID-19 have a higher probability and progression of liver injury than those without severe disease. We aimed to evaluate the prognosis of liver injury in patients with COVID-19. METHODS: We retrospectively included 502 patients with laboratory-confirmed SARS-CoV-2 infection. Clinical features and survival of patients with and without liver injury were compared. Cox proportional hazards models were used to determine the variables that might have an effect on survival. RESULTS: Among the 502 patients enrolled, 301 patients had abnormal liver function with increased neutrophil count, C-reactive protein, creatinine, troponin I (TnI), D-dimer, lactose dehydrogenase and creatine kinase. Patients with abnormal liver functions had a higher mortality rate (28.9% vs 9.0%, P < 0.001), a higher ratio of male sex (65.1% vs 40.8%, P < 0.001) and a higher chance of developing systemic inflammatory response syndrome (53.5% vs 41.3%, P = 0.007). Among patients with abnormal liver functions, patients with grade 2 liver damage (with both abnormal alanine aminotransferase or aspartate aminotransferase levels and abnormal alkaline phosphatase or gamma-glutamyl transpeptidase levels) had a higher ratio of male patients, elevated neutrophil count, procalcitonin, D-dimer levels and mortality rate. Multivariate Cox regression analyses suggested that the grade of liver damage (hazard ratio: 1.377, 95% confidence interval: 1.000-1.896, P = 0.049) was an independent predictor of death. CONCLUSIONS: Patients with COVID-19 and abnormal liver functions have a higher mortality than those with normal liver functions. Liver damage is an independent prognostic factor of COVID-19.


Subject(s)
Alanine Transaminase/blood , Aspartate Aminotransferases/blood , C-Reactive Protein/analysis , Coronavirus Infections , Fibrin Fibrinogen Degradation Products/analysis , Hepatic Insufficiency , Pandemics , Pneumonia, Viral , Betacoronavirus/isolation & purification , COVID-19 , China/epidemiology , Coronavirus Infections/blood , Coronavirus Infections/diagnosis , Coronavirus Infections/mortality , Coronavirus Infections/physiopathology , Female , Hepatic Insufficiency/blood , Hepatic Insufficiency/diagnosis , Hepatic Insufficiency/etiology , Humans , Leukocyte Count/methods , Male , Middle Aged , Mortality , Outcome and Process Assessment, Health Care , Pneumonia, Viral/blood , Pneumonia, Viral/diagnosis , Pneumonia, Viral/mortality , Pneumonia, Viral/physiopathology , Procalcitonin/blood , Prognosis , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index
8.
Cell ; 182(5): 1271-1283.e16, 2020 09 03.
Article in English | MEDLINE | ID: covidwho-666099

ABSTRACT

There is an urgent need for vaccines against coronavirus disease 2019 (COVID-19) because of the ongoing SARS-CoV-2 pandemic. Among all approaches, a messenger RNA (mRNA)-based vaccine has emerged as a rapid and versatile platform to quickly respond to this challenge. Here, we developed a lipid nanoparticle-encapsulated mRNA (mRNA-LNP) encoding the receptor binding domain (RBD) of SARS-CoV-2 as a vaccine candidate (called ARCoV). Intramuscular immunization of ARCoV mRNA-LNP elicited robust neutralizing antibodies against SARS-CoV-2 as well as a Th1-biased cellular response in mice and non-human primates. Two doses of ARCoV immunization in mice conferred complete protection against the challenge of a SARS-CoV-2 mouse-adapted strain. Additionally, ARCoV is manufactured as a liquid formulation and can be stored at room temperature for at least 1 week. ARCoV is currently being evaluated in phase 1 clinical trials.


Subject(s)
RNA, Messenger/genetics , RNA, Viral/genetics , Vaccines, Synthetic/immunology , Viral Vaccines/immunology , Animals , Antibodies, Neutralizing/immunology , Binding Sites , COVID-19 Vaccines , Chlorocebus aethiops , Coronavirus Infections/genetics , Coronavirus Infections/immunology , Coronavirus Infections/prevention & control , Female , HEK293 Cells , HeLa Cells , Humans , Immunogenicity, Vaccine , Injections, Intramuscular , Macaca fascicularis , Male , Mice , Mice, Inbred ICR , Nanoparticles/chemistry , RNA, Messenger/metabolism , RNA, Viral/metabolism , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism , Th1 Cells/immunology , Vaccine Potency , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/genetics , Vero Cells , Viral Vaccines/administration & dosage , Viral Vaccines/genetics
9.
Eur Respir J ; 55(6)2020 06.
Article in English | MEDLINE | ID: covidwho-622479

ABSTRACT

BACKGROUND: During the outbreak of coronavirus disease 2019 (COVID-19), consistent and considerable differences in disease severity and mortality rate of patients treated in Hubei province compared to those in other parts of China have been observed. We sought to compare the clinical characteristics and outcomes of patients being treated inside and outside Hubei province, and explore the factors underlying these differences. METHODS: Collaborating with the National Health Commission, we established a retrospective cohort to study hospitalised COVID-19 cases in China. Clinical characteristics, the rate of severe events and deaths, and the time to critical illness (invasive ventilation or intensive care unit admission or death) were compared between patients within and outside Hubei. The impact of Wuhan-related exposure (a presumed key factor that drove the severe situation in Hubei, as Wuhan is the epicentre as well the administrative centre of Hubei province) and the duration between symptom onset and admission on prognosis were also determined. RESULTS: At the data cut-off (31 January 2020), 1590 cases from 575 hospitals in 31 provincial administrative regions were collected (core cohort). The overall rate of severe cases and mortality was 16.0% and 3.2%, respectively. Patients in Hubei (predominantly with Wuhan-related exposure, 597 (92.3%) out of 647) were older (mean age 49.7 versus 44.9 years), had more cases with comorbidity (32.9% versus 19.7%), higher symptomatic burden, abnormal radiologic manifestations and, especially, a longer waiting time between symptom onset and admission (5.7 versus 4.5 days) compared with patients outside Hubei. Patients in Hubei (severe event rate 23.0% versus 11.1%, death rate 7.3% versus 0.3%, HR (95% CI) for critical illness 1.59 (1.05-2.41)) have a poorer prognosis compared with patients outside Hubei after adjusting for age and comorbidity. However, among patients outside Hubei, the duration from symptom onset to hospitalisation (mean 4.4 versus 4.7 days) and prognosis (HR (95%) 0.84 (0.40-1.80)) were similar between patients with or without Wuhan-related exposure. In the overall population, the waiting time, but neither treated in Hubei nor Wuhan-related exposure, remained an independent prognostic factor (HR (95%) 1.05 (1.01-1.08)). CONCLUSION: There were more severe cases and poorer outcomes for COVID-19 patients treated in Hubei, which might be attributed to the prolonged duration of symptom onset to hospitalisation in the epicentre. Future studies to determine the reason for delaying hospitalisation are warranted.


Subject(s)
Coronavirus Infections/mortality , Hospitalization , Pneumonia, Viral/mortality , Adult , Aged , Betacoronavirus , COVID-19 , Cardiovascular Diseases/epidemiology , China , Cohort Studies , Comorbidity , Coronavirus Infections/complications , Coronavirus Infections/diagnostic imaging , Cough/etiology , Diabetes Mellitus/epidemiology , Disease Outbreaks , Dyspnea/etiology , Fatigue/etiology , Female , Fever/etiology , Geography , Humans , Hypertension/epidemiology , Intensive Care Units/statistics & numerical data , Lung/diagnostic imaging , Male , Middle Aged , Pandemics , Pharyngitis/etiology , Pneumonia, Viral/complications , Pneumonia, Viral/diagnostic imaging , Prognosis , Proportional Hazards Models , Respiration, Artificial/statistics & numerical data , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index , Time Factors , Time-to-Treatment/statistics & numerical data , Tomography, X-Ray Computed
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