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1.
Biosensors ; 12(1):31, 2022.
Article in English | MDPI | ID: covidwho-1613612

ABSTRACT

C-reactive protein (CRP) is a non-specific biomarker of inflammation and may be associated with cardiovascular disease. In recent studies, systemic inflammatory responses have also been observed in cases of coronavirus disease 2019 (COVID-19). Molecularly imprinted polymers (MIPs) have been developed to replace natural antibodies with polymeric materials that have low cost and high stability and could thus be suitable for use in a home-care system. In this work, a MIP-based electrochemical sensing system for measuring CRP was developed. Such a system can be integrated with microfluidics and electronics for lab-on-a-chip technology. MIP composition was optimized using various imprinting template (CRP peptide) concentrations. Tungsten disulfide (WS2) was doped into the MIPs. Doping not only enhances the electrochemical response accompanying the recognition of the template molecules but also raises the top of the sensing range from 1.0 pg/mL to 1.0 ng/mL of the imprinted peptide. The calibration curve of the WS2-doped peptide-imprinted polymer-coated electrodes in the extended-gate field-effect transistor platform was obtained and used for the measurement of CRP concentration in real human serum.

2.
Pediatr Allergy Immunol ; 2021 Dec 02.
Article in English | MEDLINE | ID: covidwho-1546397

ABSTRACT

BACKGROUND: Clinical presentations of coronavirus disease 2019 (COVID-19) among children with asthma have rarely been investigated. This study aimed to assess clinical manifestations and outcome of COVID-19 among children with asthma, and whether the use of asthma medications was associated with outcomes of interest. METHODS: The Global Asthma Network (GAN) conducted a global survey among GAN centers. Data collection was between November 2020 and April 2021. RESULTS: Fourteen GAN centers from 10 countries provided data on 169 children with asthma infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 was asymptomatic in 58 (34.3%), mild in 93 (55.0%), moderate in 14 (8.3%), and severe/critical in 4 (2.4%). Thirty-eight (22.5%) patients had exacerbation of asthma and 21 (12.4%) were hospitalized for a median of 7 days (interquartile range 3-16). Those who had moderate or more severe COVID-19 were significantly more likely to have exacerbation of asthma as compared to those who were asymptomatic or had mild COVID-19 (adjusted odds ratio (adjOR) 3.97, 95% CI 1.23-12.84). Those who used inhaled bronchodilators were significantly more likely to have a change of asthma medications (adjOR 2.39, 95% CI 1.02-5.63) compared to those who did not. Children who used inhaled corticosteroids (ICS) did not differ from those who did not use ICS with regard to being symptomatic, severity of COVID-19, asthma exacerbation, and hospitalization. CONCLUSIONS: Over dependence on inhaled bronchodilator may be inappropriate. Use of ICS may be safe and should be continued in children with asthma during the pandemic of COVID-19.

3.
Front Immunol ; 12: 717496, 2021.
Article in English | MEDLINE | ID: covidwho-1512035

ABSTRACT

The antibody repertoire is a critical component of the adaptive immune system and is believed to reflect an individual's immune history and current immune status. Delineating the antibody repertoire has advanced our understanding of humoral immunity, facilitated antibody discovery, and showed great potential for improving the diagnosis and treatment of disease. However, no tool to date has effectively integrated big Rep-seq data and prior knowledge of functional antibodies to elucidate the remarkably diverse antibody repertoire. We developed a Rep-seq dataset Analysis Platform with an Integrated antibody Database (RAPID; https://rapid.zzhlab.org/), a free and web-based tool that allows researchers to process and analyse Rep-seq datasets. RAPID consolidates 521 WHO-recognized therapeutic antibodies, 88,059 antigen- or disease-specific antibodies, and 306 million clones extracted from 2,449 human IGH Rep-seq datasets generated from individuals with 29 different health conditions. RAPID also integrates a standardized Rep-seq dataset analysis pipeline to enable users to upload and analyse their datasets. In the process, users can also select set of existing repertoires for comparison. RAPID automatically annotates clones based on integrated therapeutic and known antibodies, and users can easily query antibodies or repertoires based on sequence or optional keywords. With its powerful analysis functions and rich set of antibody and antibody repertoire information, RAPID will benefit researchers in adaptive immune studies.

5.
Biosens Bioelectron ; 194: 113629, 2021 Dec 15.
Article in English | MEDLINE | ID: covidwho-1401251

ABSTRACT

Accurate and accessible nucleic acid diagnostics is critical to reducing the spread of COVID-19 and resuming socioeconomic activities. Here, we present an integrated platform for the direct detection of SARS-CoV-2 RNA targets near patients. Termed electrochemical system integrating reconfigurable enzyme-DNA nanostructures (eSIREN), the technology leverages responsive molecular nanostructures and automated microfluidics to seamlessly transduce target-induced molecular activation into an enhanced electrochemical signal. Through responsive enzyme-DNA nanostructures, the technology establishes a molecular circuitry that directly recognizes specific RNA targets and catalytically enhances signaling; only upon target hybridization, the molecular nanostructures activate to liberate strong enzymatic activity and initiate cascading reactions. Through automated microfluidics, the system coordinates and interfaces the molecular circuitry with embedded electronics; its pressure actuation and liquid-guiding structures improve not only analytical performance but also automated implementation. The developed platform establishes a detection limit of 7 copies of RNA target per µl, operates against the complex biological background of native patient samples, and is completed in <20 min at room temperature. When clinically evaluated, the technology demonstrates accurate detection in extracted RNA samples and direct swab lysates to diagnose COVID-19 patients.


Subject(s)
Biosensing Techniques , COVID-19 , Nanostructures , Humans , Microfluidics , RNA, Viral/genetics , SARS-CoV-2
6.
World J Pediatr ; 17(4): 375-384, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1338281

ABSTRACT

BACKGROUND: Severe cases of coronavirus disease 2019 (COVID-19) among pediatric patients are more common in children less than 1 year of age. Our aim is to address the underlying role of immunity and inflammation conditions among different age groups of pediatric patients. METHODS: We recruited pediatric patients confirmed of moderate COVID-19 symptoms, admitted to Wuhan Children's Hospital from January 28th to April 1st in 2020. Patients were divided into four age groups (≤ 1, 1-6, 7-10, and 11-15 years). Demographic information, clinical characteristics, laboratory results of lymphocyte subsets test, immune and inflammation related markers were all evaluated. RESULTS: Analysis included 217/241 (90.0%) of patients with moderate clinical stage disease. Average recovery time of children more than 6 years old was significantly shorter than of children younger than 6 years (P = 0.001). Reduced neutrophils and increased lymphocytes were significantly most observed among patients under 1 year old (P < 0.01). CD19+ B cells were the only significantly elevated immune cells, especially among patients under 1 year old (cell proportion: n = 12, 30.0%, P < 0.001; cell count: n = 13, 32.5%, P < 0.001). While, low levels of immune related makers, such as immunoglobulin (Ig) G (P < 0.001), IgA (P < 0.001), IgM (P < 0.001) and serum complement C3c (P < 0.001), were also mostly found among patients under 1 year old, together with elevated levels of inflammation related markers, such as tumor necrosis factor γ (P = 0.007), interleukin (IL)-10 (P = 0.011), IL-6 (P = 0.008), lactate dehydrogenase (P < 0.001), and procalcitonin (P = 0.007). CONCLUSION: The higher rate of severe cases and long course of COVID-19 among children under 1 year old may be due to the lower production of antibodies and serum complements of in this age group.


Subject(s)
COVID-19/immunology , Pneumonia, Viral/immunology , SARS-CoV-2/immunology , Systemic Inflammatory Response Syndrome/immunology , Adolescent , Biomarkers/blood , COVID-19/epidemiology , Child , Child, Preschool , China/epidemiology , Cytokines/immunology , Female , Hospitals, Pediatric , Humans , Infant , Lymphocyte Subsets , Male , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Severity of Illness Index , Systemic Inflammatory Response Syndrome/epidemiology
7.
Adv Sci (Weinh) ; 8(18): e2101155, 2021 09.
Article in English | MEDLINE | ID: covidwho-1316191

ABSTRACT

Accessible and adaptable nucleic acid diagnostics remains a critical challenge in managing the evolving COVID-19 pandemic. Here, an integrated molecular nanotechnology that enables direct and programmable detection of SARS-CoV-2 RNA targets in native patient specimens is reported. Termed synergistic coupling of responsive equilibrium in enzymatic network (SCREEN), the technology leverages tunable, catalytic molecular nanostructures to establish an interconnected, collaborative architecture. SCREEN mimics the extraordinary organization and functionality of cellular signaling cascades. Through programmable enzyme-DNA nanostructures, SCREEN activates upon interaction with different RNA targets to initiate multi-enzyme catalysis; through system-wide favorable equilibrium shifting, SCREEN directly transduces a single target binding into an amplified electrical signal. To establish collaborative equilibrium coupling in the architecture, a computational model that simulates all reactions to predict overall performance and optimize assay configuration is developed. The developed platform achieves direct and sensitive RNA detection (approaching single-copy detection), fast response (assay reaction is completed within 30 min at room temperature), and robust programmability (across different genetic loci of SARS-CoV-2). When clinically evaluated, the technology demonstrates robust and direct detection in clinical swab lysates to accurately diagnose COVID-19 patients.


Subject(s)
COVID-19/virology , DNA, Catalytic/genetics , Nanostructures/chemistry , SARS-CoV-2/genetics , Humans , Limit of Detection , Molecular Diagnostic Techniques/methods , Nanotechnology/methods , Pandemics/prevention & control , RNA, Viral/genetics , Specimen Handling/methods
8.
J Adv Nurs ; 77(12): 4805-4814, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1309773

ABSTRACT

AIMS: To explore the experiences of community-dwelling older adults in Wuhan during the coronavirus disease 2019 lockdown. DESIGN: An empirical phenomenological approach was used to conduct a qualitative study. METHODS: We performed semi-structured, in-depth telephone interviews between July 24 and August 2, 2020. A purposive sample of 18 participants (≥65 years old) who lived in Wuhan during the lockdown was recruited, including both infected and uninfected people. Data summarization and theme categories refinement were performed following Colaizzi's phenomenological approach. RESULTS: Four main theme categories emerged. First, the 'Challenges' posed by the epidemic. Older adults were challenged with barriers in seeing a doctor and daily life inconveniences. And they experienced negative emotions, whether infected or not. The second domain was 'multi-dimensional support', which helped older people went through the difficult period. The third domain was 'resilience amid challenges'. Although they experienced physical and psychological distress, most of them could self-adjust and achieve transcendence from the unique experience. Lastly, the remaining impact after the epidemic affected older adults. Some still had mental burdens, while others thought they have benefited from the quarantine time (e.g. regular diet, learning new skills). CONCLUSION: The epidemic and lockdown of the city brought significant physical and mental challenges to community-dwelling older adults. Active adaptation and multifaceted support helped them through this period. However, the mental burdens after the epidemic still require attention. These experiences would provide guidelines for the protection of vulnerable populations during public health emergencies. IMPACT: The results of the study suggested that certain social dynamics and individual behaviours helped the elderly to better cope with the stressful lockdown period. The findings in this study provided guidelines on how to reduce the negative effects on older adults during the pandemic and enlighten studies concerning the well-being of older adults or other vulnerable people in future crises.


Subject(s)
COVID-19 , Aged , Communicable Disease Control , Humans , Independent Living , Quarantine , SARS-CoV-2
9.
Int J Mol Sci ; 22(13)2021 Jun 28.
Article in English | MEDLINE | ID: covidwho-1288900

ABSTRACT

A group of clinically approved cancer therapeutic tyrosine kinase inhibitors was screened to test their effects on the expression of angiotensin-converting enzyme 2 (ACE2), the cell surface receptor for SARS-CoV-2. Here, we show that the receptor tyrosine kinase inhibitor imatinib (also known as STI571, Gleevec) can inhibit the expression of the endogenous ACE2 gene at both the transcript and protein levels. Treatment with imatinib resulted in inhibition of cell entry of the viral pseudoparticles (Vpps) in cell culture. In FVB mice orally fed imatinib, tissue expression of ACE2 was reduced, specifically in the lungs and renal tubules, but not in the parenchyma of other organs such as the heart and intestine. Our finding suggests that receptor tyrosine kinases play a role in COVID-19 infection and can be therapeutic targets with combined treatments of the best conventional care of COVID-19.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , Down-Regulation/drug effects , Imatinib Mesylate/pharmacology , SARS-CoV-2/physiology , Virus Internalization/drug effects , Angiotensin-Converting Enzyme 2/chemistry , Angiotensin-Converting Enzyme 2/genetics , Animals , COVID-19/pathology , COVID-19/virology , Cell Line , Cell Survival/drug effects , Chlorocebus aethiops , Female , Genes, Reporter , Humans , Mice , Promoter Regions, Genetic , SARS-CoV-2/isolation & purification
10.
Sens Actuators B Chem ; 343: 130139, 2021 Sep 15.
Article in English | MEDLINE | ID: covidwho-1240621

ABSTRACT

Owing to the over-increasing demands in resisting and managing the coronavirus disease 2019 (COVID-19) pandemic, development of rapid, highly sensitive, accurate, and versatile tools for monitoring total antibody concentrations at the population level has been evolved as an urgent challenge on measuring the fatality rate, tracking the changes in incidence and prevalence, comprehending medical sequelae after recovery, as well as characterizing seroprevalence and vaccine coverage. To this end, herein we prepared highly luminescent quantum dot nanobeads (QBs) by embedding numerous quantum dots into polymer matrix, and then applied it as a signal-amplification label in lateral flow immunoassay (LFIA). After covalently linkage with the expressed recombinant SARS-CoV-2 spike protein (RSSP), the synthesized QBs were used to determine the total antibody levels in sera by virtue of a double-antigen sandwich immunoassay. Under the developed condition, the QB-LFIA can allow the rapid detection of SARS-CoV-2 total antibodies within 15 min with about one order of magnitude improvement in analytical sensitivity compared to conventional gold nanoparticle-based LFIA. In addition, the developed QB-LFIA performed well in clinical study in dynamic monitoring of serum antibody levels in the whole course of SARS-CoV-2 infection. In conclusion, we successfully developed a promising fluorescent immunological sensing tool for characterizing the host immune response to SARS-CoV-2 infection and confirming the acquired immunity to COVID-19 by evaluating the SRAS-CoV-2 total antibody level in the crowd.

11.
Sci Adv ; 7(12)2021 03.
Article in English | MEDLINE | ID: covidwho-1140315

ABSTRACT

Despite the importance of nucleic acid testing in managing the COVID-19 pandemic, current detection approaches remain limited due to their high complexity and extensive processing. Here, we describe a molecular nanotechnology that enables direct and sensitive detection of viral RNA targets in native clinical samples. The technology, termed catalytic amplification by transition-state molecular switch (CATCH), leverages DNA-enzyme hybrid complexes to form a molecular switch. By ratiometric tuning of its constituents, the multicomponent molecular switch is prepared in a hyperresponsive state-the transition state-that can be readily activated upon the binding of sparse RNA targets to turn on substantial enzymatic activity. CATCH thus achieves superior performance (~8 RNA copies/µl), direct fluorescence detection that bypasses all steps of PCR (<1 hour at room temperature), and versatile implementation (high-throughput 96-well format and portable microfluidic assay). When applied for clinical COVID-19 diagnostics, CATCH demonstrated direct and accurate detection in minimally processed patient swab samples.


Subject(s)
COVID-19 Nucleic Acid Testing , COVID-19 , Lab-On-A-Chip Devices , Microfluidic Analytical Techniques , Point-of-Care Testing , SARS-CoV-2/genetics , COVID-19/diagnosis , COVID-19/genetics , COVID-19 Nucleic Acid Testing/instrumentation , COVID-19 Nucleic Acid Testing/methods , Humans , Limit of Detection
12.
Ann Palliat Med ; 10(1): 672-680, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1136693

ABSTRACT

BACKGROUND: The novel 2019 coronavirus (COVID-19) has largely abated in China; however, sporadic or imported cases are still a concern, while in other countries, the COVID-19 pandemic persists as a major health crisis. METHODS: All patients enrolled in this study were diagnosed with COVID-19 from February 21, 2020 to April 14, 2020 in Wuhan. We retrospectively analyzed the patients admitted to the ICU (137 patients) and general wards (114 patients) of Wuhan Leishenshan Hospital in China. The population characteristics, symptoms, and laboratory examination results between the patients in the ICU and those in the general wards were compared. Furthermore, the differences between the deceased patients in the ICU and those discharged from the ICU were compared. RESULTS: There were significant differences between the two groups in terms of symptoms, including fever, shortness of breath, no presence of complications, presence of 1 complication, and presence of 3 or more complications (P<0.05). There were also significant differences between the patients in terms of the laboratory examination results including elevated urea nitrogen, creatinine, direct bilirubin, aspartate aminotransferase, total protein, albumin, creatine kinase, lactate dehydrogenase, procalcitonin, erythrocyte sedimentation rate, white blood cells, C-reactive protein, prothrombin time, activated partial thromboplastin time, fibrinogen, D-dimer, interleukin 6, interleukin 8, interleukin 10, interleukin 2 receptor, tumor necrosis factor-α, troponin I, phosphokinase isoenzyme-MB, and B-type natriuretic peptide; and decreased platelets, lymphocyte absolute value, and eosinophil absolute value (<0.05). There were 45 patients who died in ICU and 57 improved and discharged patients. There were significant differences between the two groups in the number of patients that had 1 complication and 3 or more complications (P<0.05). There were also significant differences in the laboratory examination results between the patients including elevated urea nitrogen, total bilirubin, direct bilirubin, aspartate aminotransferase, procalcitonin, white blood cells, interleukin 8, interleukin 10, phosphokinase isoenzyme-MB, and B-type natriuretic peptide; and decreased platelets and eosinophil absolute value (P<0.05). CONCLUSIONS: Our findings highlight that the identified determinants may help to improve treatment of COVID-19 patients, to predict the risk of developing severe illness and to optimizing arrangement of health resources.


Subject(s)
COVID-19/blood , COVID-19/mortality , Hospitalization , Intensive Care Units , Adolescent , Adult , Aged , Aged, 80 and over , Aspartate Aminotransferases/blood , Bilirubin/blood , Blood Cell Count , Blood Coagulation Tests , Blood Proteins/analysis , Blood Sedimentation , Blood Urea Nitrogen , Creatine Kinase/blood , Creatinine/analysis , Cytokines/blood , Female , Fever/virology , Humans , L-Lactate Dehydrogenase/blood , Male , Middle Aged , Natriuretic Peptide, Brain/blood , Procalcitonin/blood , Retrospective Studies , Young Adult
13.
Indian J Tuberc ; 67(4S): S16-S22, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-1125266

ABSTRACT

National tuberculosis programmes (NTPs) should aim for achieving a very high proportion of cure of all tuberculosis (TB) cases. Ineffective chemotherapy of TB that keeps a substantial proportion of patients alive without cure may amplify resistance during treatment and promote transmission of TB. In 2017, the World Health Organization (WHO) recommended that in patients who require TB retreatment, the retreatment regimen that comprised 8 months of isoniazid, rifampicin and ethambutol supplemented by streptomycin for the initial 2 months, and pyrazinamide for the initial 3 months (2SHRZE/HRZE/5HRE) should no longer be prescribed and drug susceptibility testing (DST) should be conducted to inform the choice of treatment regimen. While GeneXpert MTB/RIF assay may detect rifampicin resistance, it does not detect isoniazid resistance. A 6-month regimen consisting of rifampicin, isoniazid, pyrazinamide and ethambutol may be used for the treatment of previously treated cases in whom rifampicin resistance has been excluded but DST of isoniazid is not available. WHO recommended to treat isoniazid-resistant, rifampicin-susceptible TB (Hr-TB) with rifampicin, ethambutol, pyrazinamide and levofloxacin for a duration of 6 months. In several low- and middle-income countries, the majority of Hr-TB cases are detected after the initiation of treatment with first-line regimens. If patients have an unsatisfactory response to first-line treatment with persistent positive sputum, modification of regimens needs to be done very carefully. Adding a fluoroquinolone in cases with undetected rifampicin resistance runs the risk of acquired fluoroquinolone resistance. Recently, WHO advises NTPs to phase out the injectable-containing short regimen for multidrug-resistant and rifampicin-resistant TB (MDR-/RR-TB) and recommends that the preferred treatment option is a shorter, all-oral, bedaquiline-containing regimen. WHO emphasizes that access to rapid DST, especially for ruling out fluoroquinolone resistance, is required before starting the bedaquiline-containing shorter regimen. The problem is that access to rapid DST for ruling out fluoroquinolone resistance is limited in low- and middle-income countries. The use of WHO-recommended bedaquiline-containing regimens in the treatment of MDR-/RR-TB patients with undetected resistance to fluoroquinolones runs a high risk of acquired bedaquiline resistance, especially in settings with a high prevalence of fluoroquinolone resistance. It is crucial to mitigate the risks of both primary and acquired resistance of rifampicin, fluoroquinolone and bedaquiline by rational design of regimens and effective management of TB patients.


Subject(s)
Antitubercular Agents/therapeutic use , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Pulmonary/drug therapy , Developing Countries , Humans
14.
J Biomol Struct Dyn ; : 1-16, 2021 Mar 09.
Article in English | MEDLINE | ID: covidwho-1123184

ABSTRACT

A novel acute viral pneumonia induced by SARS-CoV-2 exploded at the end of 2019, causing a severe medical and economic crisis. For developing specific pharmacotherapy against SARS-CoV-2, an in silico virtual screening was developed for the available in-house molecules. The conserved domain analysis was performed to identify the highly conserved and exposed amino acid regions in the SARS-CoV-2-S RBD sites. The Protein-Protein interaction analyses demonstrated the higher affinity between the SARS-CoV-2-S and ACE2 due to varieties of significant interactions between them. The computational alanine scanning mutation study has recognized the highly stabilized amino acids in the SARS-CoV-2-S RBD/ACE2 complex. The cumulative sequence investigations have inferred that Lys417, Phe486, Asn487, Tyr489, and Gln493 are perhaps the iconic target amino acids to develop a drug molecule or vaccine against SARS-CoV-2 infection. Most of the selected compounds include luteolin, zhebeirine, 3-dehydroverticine, embelin, andrographolide, ophiopogonin D, crocin-1, sprengerinin A, B, C, peimine, etc. were exhibited distinguish drug actions through the strong hydrogen bonding with the hot spots of the RBD. Besides, the 100 ns molecular dynamics simulation and free energy binding analysis showed the significant efficacy of luteolin to inhibit the infection of SARS-CoV-2.Communicated by Ramaswamy H. Sarma.

15.
Evol Med Public Health ; 2020(1): 264-278, 2020.
Article in English | MEDLINE | ID: covidwho-1104860

ABSTRACT

The COVID-19 pandemic has brought science into the public eye and to the attention of governments more than ever before. Much of this attention is on work in epidemiology, virology and public health, with most behavioural advice in public health focusing squarely on 'proximate' determinants of behaviour. While epidemiological models are powerful tools to predict the spread of disease when human behaviour is stable, most do not incorporate behavioural change. The evolutionary basis of our preferences and the cultural evolutionary dynamics of our beliefs drive behavioural change, so understanding these evolutionary processes can help inform individual and government decision-making in the face of a pandemic. Lay summary: The COVID-19 pandemic has brought behavioural sciences into the public eye: Without vaccinations, stopping the spread of the virus must rely on behaviour change by limiting contact between people. On the face of it, "stop seeing people" sounds simple. In practice, this is hard. Here we outline how an evolutionary perspective on behaviour change can provide additional insights. Evolutionary theory postulates that our psychology and behaviour did not evolve to maximize our health or that of others. Instead, individuals are expected to act to maximise their inclusive fitness (i.e, spreading our genes) - which can lead to a conflict between behaviours that are in the best interests for the individual, and behaviours that stop the spread of the virus. By examining the ultimate explanations of behaviour related to pandemic-management (such as behavioural compliance and social distancing), we conclude that "good of the group" arguments and "one size fits all" policies are unlikely to encourage behaviour change over the long-term. Sustained behaviour change to keep pandemics at bay is much more likely to emerge from environmental change, so governments and policy makers may need to facilitate significant social change - such as improving life experiences for disadvantaged groups.

16.
Anal Biochem ; 617: 114118, 2021 03 15.
Article in English | MEDLINE | ID: covidwho-1064675

ABSTRACT

Remdesivir (RDV) is a phosphoramidate prodrug designed to have activity against a broad spectrum of viruses. Following IV administration, RDV is rapidly distributed into cells and tissues and simultaneously metabolized into GS-441524 and GS-704277 in plasma. LC-MS/MS methods were validated for determination of the 3 analytes in human plasma that involved two key aspects to guarantee their precision, accuracy and robustness. First, instability issues of the analytes were overcome by diluted formic acid (FA) treatment of the plasma samples. Secondly, a separate injection for each analyte was performed with different ESI modes and organic gradients to achieve sensitivity and minimize carryover. Chromatographic separation was achieved on an Acquity UPLC HSS T3 column (2.1 × 50 mm, 1.8 µm) with a run time of 3.4 min. The calibration ranges were 4-4000, 2-2000, and 2-2000 ng/mL, respectively for RDV, GS-441524 and GS-704277. The intraday and interday precision (%CV) across validation runs at 3 QC levels for all 3 analytes was less than 6.6%, and the accuracy was within ±11.5%. The long-term storage stability in FA-treated plasma was established to be 392, 392 and 257 days at -70 °C, respectively for RDV, GS-441524 and GS-704277. The validated method was successfully applied in COVID-19 related clinical studies.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/blood , Drug Monitoring/methods , Furans/blood , Pyrroles/blood , Tandem Mass Spectrometry/methods , Triazines/blood , Adenosine/analogs & derivatives , Adenosine Monophosphate/blood , Alanine/blood , COVID-19/drug therapy , Chromatography, High Pressure Liquid/methods , Humans , Limit of Detection
17.
Preprint | SciFinder | ID: ppcovidwho-4669

ABSTRACT

A review. Plasma exchange is a blood purification technol. in vitro, which removes plasma together with macromol. substances such as autoantibodies, immune complexes and toxins to reduce the harm of these substances to the body. At present, plasma exchange technol. is widely used in the treatment of a variety of diseases. This paper discusses the application of plasmapheresis in the treatment of viral diseases. These disease includes viral hepatitis, influenza A, severe acute respiratory syndromes, middle east respiratory syndrome and coronavirus disease 2019.

18.
19.
Infect Dis Poverty ; 9(1): 163, 2020 Dec 02.
Article in English | MEDLINE | ID: covidwho-954569

ABSTRACT

BACKGROUND: There is an urgent need to better understand the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), for that the coronavirus disease 2019 (COVID-19) continues to cause considerable morbidity and mortality worldwide. This paper was to differentiate COVID-19 from other respiratory infectious diseases such as avian-origin influenza A (H7N9) and influenza A (H1N1) virus infections. METHODS: We included patients who had been hospitalized with laboratory-confirmed infection by SARS-CoV-2 (n = 83), H7N9 (n = 36), H1N1 (n = 44) viruses. Clinical presentation, chest CT features, and progression of patients were compared. We used the Logistic regression model to explore the possible risk factors. RESULTS: Both COVID-19 and H7N9 patients had a longer duration of hospitalization than H1N1 patients (P < 0.01), a higher complication rate, and more severe cases than H1N1 patients. H7N9 patients had higher hospitalization-fatality ratio than COVID-19 patients (P = 0.01). H7N9 patients had similar patterns of lymphopenia, neutrophilia, elevated alanine aminotransferase, C-reactive protein, lactate dehydrogenase, and those seen in H1N1 patients, which were all significantly different from patients with COVID-19 (P < 0.01). Either H7N9 or H1N1 patients had more obvious symptoms, like fever, fatigue, yellow sputum, and myalgia than COVID-19 patients (P < 0.01). The mean duration of viral shedding was 9.5 days for SARS-CoV-2 vs 9.9 days for H7N9 (P = 0.78). For severe cases, the meantime from illness onset to severity was 8.0 days for COVID-19 vs 5.2 days for H7N9 (P < 0.01), the comorbidity of chronic heart disease was more common in the COVID-19 patients than H7N9 (P = 0.02). Multivariate analysis showed that chronic heart disease was a possible risk factor (OR > 1) for COVID-19, compared with H1N1 and H7N9. CONCLUSIONS: The proportion of severe cases were higher for H7N9 and SARS-CoV-2 infections, compared with H1N1. The meantime from illness onset to severity was shorter for H7N9. Chronic heart disease was a possible risk factor for COVID-19.The comparison may provide the rationale for strategies of isolation and treatment of infected patients in the future.


Subject(s)
COVID-19/pathology , COVID-19/virology , Influenza, Human/pathology , Influenza, Human/virology , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19/mortality , Child , Child, Preschool , Comorbidity , Disease Progression , Female , Hospitalization , Humans , Influenza A Virus, H1N1 Subtype/pathogenicity , Influenza A Virus, H7N9 Subtype/pathogenicity , Influenza, Human/diagnosis , Influenza, Human/mortality , Lung/diagnostic imaging , Lung/pathology , Male , Middle Aged , Risk Factors , SARS-CoV-2/pathogenicity , Virus Shedding , Young Adult
20.
Andrology ; 9(1): 107-114, 2021 01.
Article in English | MEDLINE | ID: covidwho-908746

ABSTRACT

BACKGROUND: A novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causing the pandemic of coronavirus disease 2019 (COVID-19), may attack testes by angiotensin-converting enzyme 2. OBJECTIVE: To assess whether SARS-CoV-2 infection can affect sex-related hormones and testicular function in recovering patients. MATERIALS AND METHODS: The patients were separately classified according to the duration of viral shedding (long-term positive vs normal-term group, with the former cases having a duration > 50 days) and disease severity (moderate vs severe group). Differences in sex-related hormone levels were compared between groups and linear regression analysis was used to compare the associations of testosterone (T) and estradiol with various clinical and laboratory factors. RESULTS: A total of 39 COVID-19-infected patients were included in this study. The mean T level was in the normal reference range while the mean estradiol level was above the normal limit. There were no significant differences between the long-term positive and normal-term groups in T (P = .964), follicle-stimulating hormone (FSH; P = .694), luteinizing hormone (LH; P = .171), prolactin (PRL; P = .836), or T/LH (P = .512). However, estradiol was higher in the normal-term group than the long-term positive group (P < .001). Moreover, there were also no significant differences between the moderate and severe groups in sex-related hormones, duration of viral shedding, or serum biochemical or inflammation indicators. Additionally, regression analyses showed that there were no associations between the T level and the clinical and laboratory factors, while estradiol was negatively associated with the duration of viral shedding. CONCLUSION: In males infected with SARS-CoV-2, most sex-related hormones (T, FSH and LH levels) remain within the normal reference ranges after recovery from COVID-19, and no significant associations were observed between T level and disease duration or severity. At present, there is insufficient evidence to show that SARS-CoV-2 causes hypogonadism and sterility, but the potential risk should not be ignored.


Subject(s)
COVID-19/blood , Estradiol/blood , SARS-CoV-2/pathogenicity , Testis/metabolism , Testosterone/blood , Aged , Biomarkers/blood , COVID-19/diagnosis , COVID-19/therapy , COVID-19/virology , Case-Control Studies , Follicle Stimulating Hormone, Human/blood , Host-Pathogen Interactions , Humans , Luteinizing Hormone/blood , Male , Middle Aged , Prolactin/blood , Remission Induction , Severity of Illness Index , Time Factors , Virus Shedding
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