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1.
Sci China Life Sci ; 2022 Mar 10.
Article in English | MEDLINE | ID: covidwho-1739404

ABSTRACT

Signaling pathway alterations in COVID-19 of living humans as well as therapeutic targets of the host proteins are not clear. We analyzed 317 urine proteomes, including 86 COVID-19, 55 pneumonia and 176 healthy controls, and identified specific RNA virus detector protein DDX58/RIG-I only in COVID-19 samples. Comparison of the COVID-19 urinary proteomes with controls revealed major pathway alterations in immunity, metabolism and protein localization. Biomarkers that may stratify severe symptoms from moderate ones suggested that macrophage induced inflammation and thrombolysis may play a critical role in worsening the disease. Hyper activation of the TCA cycle is evident and a macrophage enriched enzyme CLYBL is up regulated in COVID-19 patients. As CLYBL converts the immune modulatory TCA cycle metabolite itaconate through the citramalyl-CoA intermediate to acetyl-CoA, an increase in CLYBL may lead to the depletion of itaconate, limiting its anti-inflammatory function. These observations suggest that supplementation of itaconate and inhibition of CLYBL are possible therapeutic options for treating COVID-19, opening an avenue of modulating host defense as a means of combating SARS-CoV-2 viruses.

2.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-325847

ABSTRACT

In this work, we propose a bi-directional long short-term memory (BiLSTM) network based COVID-19 detection method using breath/speech/cough signals. By using the acoustic signals to train the network, respectively, we can build individual models for three tasks, whose parameters are averaged to obtain an average model, which is then used as the initialization for the BiLSTM model training of each task. This initialization method can significantly improve the performance on the three tasks, which surpasses the official baseline results. Besides, we also utilize a public pre-trained model wav2vec2.0 and pre-train it using the official DiCOVA datasets. This wav2vec2.0 model is utilized to extract high-level features of the sound as the model input to replace conventional mel-frequency cepstral coefficients (MFCC) features. Experimental results reveal that using high-level features together with MFCC features can improve the performance. To further improve the performance, we also deploy some preprocessing techniques like silent segment removal, amplitude normalization and time-frequency mask. The proposed detection model is evaluated on the DiCOVA dataset and results show that our method achieves an area under curve (AUC) score of 88.44% on blind test in the fusion track.

3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-318459

ABSTRACT

Since beginning of this century, there have already been three zoonotic outbreaks caused by beta coronaviruses (CoV), SARS-CoV in 2002-2003, MERS-CoV in 2012, and the newly identified 2019-nCoV in late 2019, Wuhan, China. As to Feb 10 th , 2020, there are over 40,000 confirmed cases and over 900 deaths. However, little is known about the biology of this newly emerged virus. Here we developed a lentiviral based pseudovirus system for S protein of 2019-nCoV to study virus entry in BSL2 settings. First, we confirmed that human angiotensin converting enzyme 2 (hACE2) is the main entry receptor for 2019-nCoV. Second, we found that 2019-nCoV S protein mediated entry on 293/hACE2 cells was mainly through endocytosis, and PIKfyve, TPC2, and cathepsin L are critical for virus entry. Third, 2019-nCoV S protein is less stable than SARS-CoV, and it could trigger protease-independent and receptor dependent cell-cell fusion, which might help virus rapidly spread from cell to cell. Finally and more importantly, polyclonal anti-SARS S1 antibodies T62 effectively inhibited entry of SARS-CoV S pseudovirions, but almost had no effect on entry of 2019-nCoV S pseudovirions. Further studies using sera from one recovered SARS-CoV patient and five 2019-nCoV patients showed that there was only limited cross-neutralization activities between SARS-CoV and 2019-nCoV sera, suggesting that recovery from one infection might not protect against the other. Our results present potential targets for development of drugs and vaccines for 2019-nCoV.

4.
Microbiol Spectr ; 10(1): e0155021, 2022 02 23.
Article in English | MEDLINE | ID: covidwho-1685499

ABSTRACT

Mycoplasma pneumoniae is a common pathogen causing respiratory disease in children. We sought to investigate the epidemiology of M. pneumoniae among outpatient children with mild respiratory tract infections (RTIs) during the coronavirus disease 2019 (COVID-19) pandemic. Eligible patients were prospectively enrolled from January 2020 to June 2021. Throat swabs were tested for M. pneumoniae RNA. M. pneumoniae IgM was tested by a colloidal gold assay. Macrolide resistance and the effect of the COVID-19 countermeasures on M. pneumoniae prevalence were assessed. Symptom scores, treatments, and outcomes were evaluated. Eight hundred sixty-two eligible children at 15 centers in China were enrolled. M. pneumoniae was detected in 78 (9.0%) patients. Seasonally, M. pneumoniae peaked in the first spring and dropped dramatically to extremely low levels over time until the next summer. Decreases in COVID-19 prevalence were significantly associated with decreases in M. pneumoniae prevalence (r = 0.76, P = 0.001). The macrolide resistance rate was 7.7%. The overall sensitivity and specificity of the colloidal gold assay used in determining M. pneumoniae infection were 32.1% and 77.9%, respectively. No more benefits for improving the severity of symptoms and outcomes were observed in M. pneumoniae-infected patients treated with a macrolide than in those not treated with a macrolide during follow-up. The prevalences of M. pneumoniae and macrolide resistance in outpatient children with mild RTIs were at low levels in the early stage of the COVID-19 pandemic but may have rebounded recently. The colloidal gold assay for M. pneumoniae IgM may be not appropriate for diagnosis of M. pneumoniae infection. Macrolides should be used with caution among outpatients with mild RTIs. IMPORTANCE This is the first and largest prospective, multicenter, active, population-based surveillance study of the epidemiology of Mycoplasma pneumoniae among outpatient children with mild respiratory tract infections (RTIs) during the COVID-19 pandemic. Nationwide measures like strict face mask wearing and restrictions on population movement implemented to prevent the spread of COVID-19 might also effectively prevent the spread of M. pneumoniae. The prevalence of M. pneumoniae and the proportion of drug-resistant M. pneumoniae isolates in outpatient children with mild RTIs were at low levels in the early stage of the COVID-19 pandemic but may have rebounded recently. The colloidal gold assay for M. pneumoniae IgM may be not appropriate for screening and diagnosis of M. pneumoniae infection. Macrolides should be used with caution among outpatients with mild RTIs.


Subject(s)
Mycoplasma pneumoniae/isolation & purification , Pneumonia, Mycoplasma/microbiology , Respiratory Tract Infections/microbiology , Adolescent , Adult , Anti-Bacterial Agents/therapeutic use , COVID-19/epidemiology , Child , Child, Preschool , China/epidemiology , Drug Resistance, Bacterial , Female , Humans , Infant , Macrolides/therapeutic use , Male , Mycoplasma pneumoniae/genetics , Mycoplasma pneumoniae/physiology , Outpatients/statistics & numerical data , Pneumonia, Mycoplasma/drug therapy , Pneumonia, Mycoplasma/epidemiology , Prospective Studies , Respiratory Tract Infections/drug therapy , Respiratory Tract Infections/epidemiology , Young Adult
5.
Infect Drug Resist ; 14: 5395-5401, 2021.
Article in English | MEDLINE | ID: covidwho-1581593

ABSTRACT

Purpose: This study detects SARS-CoV-2 in the ocular surface through one-step reverse-transcription droplet digital PCR (one-step RT-ddPCR) and evaluates the possibility of the ocular surface as a possible transmission route. Methods: A single-center prospective observational study was designed to investigate the viral loads in ocular surface. Specimens including the conjunctival swabs, nasopharyngeal swabs and blood were synchronously collected at a single time point for all COVID-19 patients. SARS-CoV-2 loads in nasopharyngeal swabs were tested by real-time polymerase chain reaction (PCR); the blood samples and conjunctival swabs were tested by real-time PCR and one-step RT-ddPCR. Results: Sixty-eight COVID-19 patients confirmed by nasopharyngeal real-time PCR were recruited. In the single time point test, 40 cases showed positive SARS-CoV-2 detection in either the blood, tears, or nasopharynx, of which four cases were triple-positive, 10 were dual-positive, and 26 were single-positive. The positive rate of nasopharyngeal swab real-time PCR test was 22.1% (15/68). The positive rate of blood and conjunctival swabs by one-step RT-ddPCR was 38.2% (26/68) and 25% (17/68), respectively, whereas real-time PCR was all negative. Positive conjunctival swabs were significantly correlated with positive nasopharyngeal swabs (P = 0.028). The sampling lags from illness onset to sampling day in 3 out of 4 triple-positive patients and in 9 out of 10 dual-positive patients were respectively less than 9 days and less than 20 days. Conclusion: Our results indicate that the positive rate of SARS-CoV-2 on the ocular surface is much higher than expected. Transmission possibility through the ocular surface may be greatly underestimated.

6.
Nurs Open ; 9(1): 358-366, 2022 01.
Article in English | MEDLINE | ID: covidwho-1437067

ABSTRACT

AIM: To explore the experiences of patients with cancers in hospitals during the COVID-19 pandemic. DESIGN: A qualitative research study. METHODS: Using a phenomenological approach, we enrolled 22 patients with cancers in the Hunan Cancer Hospital from 20 February 2020 to 10 April 2020. The interviews were conducted face-to-face and were analysed by Colaizzi's 7-step method. This study aligns with the COREQ checklist. RESULTS: The experiences of patients with cancers in hospitals during the COVID-19 pandemic can be categorized into four major themes: (1) emotional changes; (2) delays in visiting hospital; (3) barriers to accessing medical care services, and (4) inconvenience related to logistics services.


Subject(s)
COVID-19 , Neoplasms , Hospitals , Humans , Neoplasms/epidemiology , Pandemics , Qualitative Research , SARS-CoV-2
8.
Eur J Med Chem ; 225: 113818, 2021 Dec 05.
Article in English | MEDLINE | ID: covidwho-1385491

ABSTRACT

Cathepsin C, an important lysosomal cysteine protease, mediates the maturation process of neutrophil serine proteases, and participates in the inflammation and immune regulation process associated with polymorphonuclear neutrophils. Therefore, cathepsin C is considered to be an attractive target for treating inflammatory diseases. With INS1007 (trade name: brensocatib) being granted a breakthrough drug designation by FDA for the treatment of Adult Non-cystic Fibrosis Bronchiectasis and Coronavirus Disease 2019, the development of cathepsin C inhibitor will attract attentions from medicinal chemists in the future soon. Here, we summarized the research results of cathepsin C as a therapeutic target, focusing on the development of cathepsin C inhibitor, and provided guidance and reference opinions for the upcoming development boom of cathepsin C inhibitor.


Subject(s)
Anti-Inflammatory Agents/chemistry , Cathepsin C/antagonists & inhibitors , Drug Discovery , Protease Inhibitors/chemistry , Anti-Inflammatory Agents/therapeutic use , COVID-19/drug therapy , COVID-19/pathology , COVID-19/virology , Cathepsin C/genetics , Cathepsin C/metabolism , Humans , Papillon-Lefevre Disease/genetics , Papillon-Lefevre Disease/pathology , Protease Inhibitors/metabolism , Protease Inhibitors/therapeutic use , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/pathology , SARS-CoV-2/isolation & purification , Serine Endopeptidases/metabolism
9.
Nat Commun ; 12(1): 4876, 2021 08 12.
Article in English | MEDLINE | ID: covidwho-1356557

ABSTRACT

While the printed circuit board (PCB) has been widely considered as the building block of integrated electronics, the world is switching to pursue new ways of merging integrated electronic circuits with textiles to create flexible and wearable devices. Herein, as an alternative for PCB, we described a non-printed integrated-circuit textile (NIT) for biomedical and theranostic application via a weaving method. All the devices are built as fibers or interlaced nodes and woven into a deformable textile integrated circuit. Built on an electrochemical gating principle, the fiber-woven-type transistors exhibit superior bending or stretching robustness, and were woven as a textile logical computing module to distinguish different emergencies. A fiber-type sweat sensor was woven with strain and light sensors fibers for simultaneously monitoring body health and the environment. With a photo-rechargeable energy textile based on a detailed power consumption analysis, the woven circuit textile is completely self-powered and capable of both wireless biomedical monitoring and early warning. The NIT could be used as a 24/7 private AI "nurse" for routine healthcare, diabetes monitoring, or emergencies such as hypoglycemia, metabolic alkalosis, and even COVID-19 patient care, a potential future on-body AI hardware and possibly a forerunner to fabric-like computers.


Subject(s)
Biosensing Techniques/instrumentation , Precision Medicine/instrumentation , Textiles , Wearable Electronic Devices , Wireless Technology/instrumentation , Biosensing Techniques/methods , COVID-19/diagnosis , COVID-19/prevention & control , COVID-19/virology , Equipment Design , Humans , Monitoring, Physiologic/instrumentation , Monitoring, Physiologic/methods , Precision Medicine/methods , SARS-CoV-2/physiology , Sweat/physiology
10.
Pediatr Investig ; : e12282, 2021 Aug 12.
Article in English | MEDLINE | ID: covidwho-1353594

ABSTRACT

IMPORTANCE: The Coronavirus disease 2019 (COVID-19) global pandemic poses a considerable challenge for pediatricians. OBJECTIVE: This study aimed to identify the epidemiological characteristics and clinical features of pediatric patients with COVID-19 in China. METHODS: This multicenter retrospective study included pediatric patients from 46 hospitals in China, covering 12 provinces and two municipalities. Epidemiological, demographic, clinical, laboratory, treatment, and outcome data were analyzed. RESULTS: In total, 211 pediatric patients with COVID-19 were included in this study. The median age was 7.0 years (range: 22 days to 18 years). Approximately 16.3% of the patients exhibited asymptomatic infections, 23.0% had upper respiratory tract infections, and 60.7% had pneumonia, including two with severe pneumonia and one with critical illness. Approximately 78.7% of the pediatric patients occurred in familial clusters. The most three common symptoms or signs at onset in children with COVID-19 were fever (54.5%), cough (49.3%), and pharyngeal congestion (20.8%). Only 17.6% of the patients presented with decreased lymphocyte count, whereas 13.6% had increased lymphocyte count. Among the patients with pneumonia who exhibited abnormal chest computed tomography findings, 18.2% (23/127) of the patients had no other symptoms. Generally, the chest radiographs showed abnormalities that affected both lungs (49.6%); ground-glass opacity (47.2%) was the most common manifestation. The cure and improvement rates were 86.7% (183/211) and 13.3% (28/211), respectively. Only one patient with an underlying condition received invasive mechanical ventilation; none of the patients died. INTERPRETATION: Similar to adults, children of all age groups are susceptible to COVID-19. Fortunately, most pediatric patients have mild symptoms or remain asymptomatic, despite the high incidence of pneumonia. Decreased proportions of white blood cells and lymphocytes are less frequent in children than in adults.

11.
Cell ; 184(17): 4380-4391.e14, 2021 08 19.
Article in English | MEDLINE | ID: covidwho-1275186

ABSTRACT

Despite the discovery of animal coronaviruses related to SARS-CoV-2, the evolutionary origins of this virus are elusive. We describe a meta-transcriptomic study of 411 bat samples collected from a small geographical region in Yunnan province, China, between May 2019 and November 2020. We identified 24 full-length coronavirus genomes, including four novel SARS-CoV-2-related and three SARS-CoV-related viruses. Rhinolophus pusillus virus RpYN06 was the closest relative of SARS-CoV-2 in most of the genome, although it possessed a more divergent spike gene. The other three SARS-CoV-2-related coronaviruses carried a genetically distinct spike gene that could weakly bind to the hACE2 receptor in vitro. Ecological modeling predicted the co-existence of up to 23 Rhinolophus bat species, with the largest contiguous hotspots extending from South Laos and Vietnam to southern China. Our study highlights the remarkable diversity of bat coronaviruses at the local scale, including close relatives of both SARS-CoV-2 and SARS-CoV.


Subject(s)
COVID-19/virology , Chiroptera/virology , Coronavirus/genetics , Evolution, Molecular , SARS-CoV-2/genetics , Amino Acid Sequence , Angiotensin-Converting Enzyme 2/chemistry , Angiotensin-Converting Enzyme 2/metabolism , Animals , Asia, Southeastern , China , Coronavirus/classification , Coronavirus/isolation & purification , Ecological and Environmental Phenomena , Genome, Viral , Humans , Models, Molecular , Phylogeny , SARS-CoV-2/physiology , Sequence Alignment , Sequence Analysis, RNA , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism , Viral Zoonoses
12.
BMC Endocr Disord ; 21(1): 111, 2021 May 27.
Article in English | MEDLINE | ID: covidwho-1244921

ABSTRACT

BACKGROUND: Low free triiodothyronine (FT3) levels are related to a poor prognosis deterioration in patients with COVID-19 presenting with non-thyroidal illness syndrome (NTI). This study was designed to explore whether free thyroxin (FT4) or thyroid stimulating hormone (TSH) levels affected the mortality of patients with COVID-19 presenting with NTI. METHODS: Patients with COVID-19 complicated with NTI who were treated at our hospital were included in this retrospective study. Patients were divided into low TSH and normal TSH groups, as well as low and normal-high FT4 group, according to the reference range of TSH or FT4 levels. The 90-day mortality and critical illness rates were compared among patients with low and normal TSH levels, as well as among patients with low FT4 levels and normal-high FT4 levels; in addition, differences in demographic and laboratory data were compared. A Kaplan-Meier analysis and Cox proportional hazards models were used to assess the associations of TSH and FT4 levels with mortality. RESULTS: One hundred fifty patients with low FT3 levels and without a history of thyroid disease were included, 68% of whom had normal FT4 and TSH levels. Critical illness rates (74.07% VS 37.40%, P = 0.001) and mortality rates (51.85% VS 22.76%, P = 0.002) were significantly higher in the low TSH group than in the normal TSH group. Although no significant difference in the critical illness rate was found (P = 0.296), the mortality rate was significantly higher in the low FT4 group (P = 0.038). Low TSH levels were independently related to 90-day mortality (hazard ratio = 2.78, 95% CI:1.42-5.552, P = 0.003). CONCLUSIONS: Low FT4 and TSH concentrations were associated with mortality in patients with COVID-19 presenting with NTI; moreover, low TSH levels were an independent risk factor for mortality in these patients.


Subject(s)
COVID-19/epidemiology , COVID-19/mortality , Euthyroid Sick Syndromes/epidemiology , SARS-CoV-2 , Thyrotropin/blood , Thyroxine/blood , Adult , Aged , Aged, 80 and over , COVID-19/blood , Cohort Studies , Comorbidity , Euthyroid Sick Syndromes/blood , Female , Humans , Male , Middle Aged , Prognosis , Proportional Hazards Models , Retrospective Studies , Risk Factors , Thyrotropin/deficiency , Thyroxine/deficiency
14.
Atmosphere ; 12(4):422, 2021.
Article in English | MDPI | ID: covidwho-1154281

ABSTRACT

The absence of motor vehicle traffic and suspended human activities during the COVID-19 lockdown period in China produced a unique experiment to assess the efficiency of air pollution mitigation. Herein, we synthetically analyzed monitoring data of atmospheric pollutants together with meteorological parameters to investigate the impact of human activity pattern changes on air quality in Guiyang, southwestern China. The results show that the Air Quality Index (AQI) during the lockdown period decreased by 7.4% and 23.48% compared to pre-lockdown levels and the identical lunar period during the past 3 years, respectively, which exhibited optimal air quality due to reduced emissions. The sharp decrease in NO2 concentration reduced the “titration” effect and elevated the O3 concentration by 31.94% during the lockdown period. Meteorological conditions significantly impacted air quality, and serious pollution events might also occur under emission reductions. Falling wind speeds and increasing relative humidity were the direct causes of the pollution event on February 1st. The “first rain” increases the hygroscopicity of atmospheric particulate matter and then elevate its concentration, while continuous rainfall significantly impacted the removal of atmospheric particulate matter. As impacted by the lockdown, the spatial distribution of the NO2 concentration sharply decreased on the whole, while the O3 concentration increased significantly. The implications of this study are as follows: Measures should be formulated to prevent O3 pollution when emission reduction measures are being adopted to improve air quality, and an emphasis should be placed on the impact of secondary aerosols formation by gas-particle conversion.

16.
Curr Med Sci ; 41(1): 46-50, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-1081788

ABSTRACT

Positive nucleic acid (NA) results have been found in recovered and discharged COVID-19 patients, but the proportion is unclear. This study was designed to analyze the recurrent positive rate of NA results after consecutively negative results, and the relationship between the specific antibody production and positive NA rate. According to Strengthening the Reporting of Observational Studies in Epidemiology guidelines, data of inpatients in Sino-French New City Branch of Tongji Hospital between Jan. 28 and Mar. 6, 2020 were collected. A total of 564 COVID-19 patients over 14 years old who received the examinations of NA and antibodies against SARS-CoV-2 were included. Days of viral shedding and specific antibodies were recorded and assessed. Among NA tests in respiratory samples (throat swabs, nasopharyngeal swabs, sputum and flushing fluid in alveoli), the patients with all-negative NA results accounted for 17.20%, those with single-positive results for 46.63%, and those with multiple-positive results for 36.17% respectively. Besides, the recurrent positive NA results after consecutively negative results appeared in 66 patients (11.70%). For multiple-positive patients, median viral shedding duration was 20 days (range: 1 to 57 days). Of the 205 patients who received 2 or more antibody tests, 141 (68.78%) had decreased IgG and IgM concentrations. IgM decreased to normal range in 24 patients, with a median of 44 days from symptom onset. Viral shedding duration was not significantly correlated with gender, age, disease severity, changes in pulmonary imaging, and antibody concentration. It is concluded that antibody level and antibody change had no significant correlation with the positive rate of NA tests and the conversion rate after continuous negative NA tests. In order to reduce the recurrent positive proportion after discharge, 3 or more consecutive negative NA test results with test interval more than 24 h every time are suggested for the discharge or release from quarantine.


Subject(s)
Antibodies, Viral/analysis , COVID-19/diagnosis , SARS-CoV-2/physiology , Adult , Aged , Aged, 80 and over , COVID-19/immunology , Female , Guidelines as Topic , Humans , Immunoglobulin G/analysis , Immunoglobulin M/analysis , Male , Middle Aged , Respiratory System/virology , Retrospective Studies , SARS-CoV-2/immunology , Virus Shedding
17.
Journal of Modern Laboratory Medicine ; 35(4):94-96, 2020.
Article in Chinese | GIM | ID: covidwho-1073551

ABSTRACT

Objective: To explore the application value of peripheral blood lymphocytes and their subgroups in patients with novel coronavirus pneumonia (COVID-19).

18.
SciFinder; 2020.
Preprint | SciFinder | ID: ppcovidwho-5331

ABSTRACT

A review on diagnosis and treatment of new coronavirus pneumonia using "Three-factor adaptation" guide in the Zhongshan area.

19.
SciFinder; 2020.
Preprint | SciFinder | ID: ppcovidwho-3711

ABSTRACT

A review. Relying on 60 thousand blogs and 15 thousand hot blog reviews in Sina micro-blog from Jan. 1st to Feb. 29th in 2020, this article launches the anal. of the public opinion to the topic about novel coronavirus pneumonia based on distributed crawler technol., distributed database system, SnowNLP sentiment anal. model and K-Means algorithm. This anal. can show visually the spatial and temporal evolution process of Internaet public opinion in the events of this epidemic situation. On spatial dimension, we find that the area which has the most serious epidemic has the most comments and the lowest emotional value through geog. statistical anal.

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