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1.
Trials ; 24(1): 389, 2023 Jun 09.
Article in English | MEDLINE | ID: covidwho-20238656

ABSTRACT

BACKGROUND: Viral pneumonia has always been a problem faced by clinicians because of its insidious onset, strong infectivity, and lack of effective drugs. Patients with advanced age or underlying diseases may experience more severe symptoms and are prone to severe ventilation dysfunction. Reducing pulmonary inflammation and improving clinical symptoms is the focus of current treatment. Low-intensity pulsed ultrasound (LIPUS) can mitigate inflammation and inhibit edema formation. We aimed to investigate the efficacy of therapeutic LIPUS in improving lung inflammation in hospitalized patients with viral pneumonia. METHODS: Sixty eligible participants with clinically confirmed viral pneumonia will be assigned to either (1) intervention group (LIPUS stimulus), (2) control group (null stimulus), or (3) self-control group (LIPUS stimulated areas versus non-stimulated areas). The primary outcome will be the difference in the extent of absorption and dissipation of lung inflammation on computed tomography. Secondary outcomes include changes in lung inflammation on ultrasonography images, pulmonary function, blood gas analysis, fingertip arterial oxygen saturation, serum inflammatory factor levels, the sputum excretion volume, time to the disappearance of pulmonary rales, pneumonia status score, and course of pneumonia. Adverse events will be recorded. DISCUSSION: This study is the first clinical study of the efficacy of therapeutic LIPUS in the treatment of viral pneumonia. Given that the current clinical recovery mainly depends on the body's self-limiting and conventional symptomatic treatment, LIPUS, as a new therapy method, might be a major advance in the treatment of viral pneumonia. TRIAL REGISTRATION: ChiCTR2200059550 Chinese Clinical Trial Registry, May 3, 2022.


Subject(s)
COVID-19 , Pneumonia, Viral , Humans , SARS-CoV-2 , Pneumonia, Viral/drug therapy , Inflammation , Ultrasonic Waves , Treatment Outcome , Randomized Controlled Trials as Topic
2.
Heliyon ; 9(6): e16847, 2023 Jun.
Article in English | MEDLINE | ID: covidwho-20230952

ABSTRACT

The ongoing coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused millions of cases of infections, leading to a global health emergency. The SARS-CoV-2 spike (S) protein plays the most important role in viral infection, and S1 subunit and its receptor-binding domain (RBD) are widely considered the most attractive vaccine targets. The RBD is highly immunogenic and its linear epitopes are important for vaccine development and therapy, but linear epitopes on the RBD have rarely been reported. In this study, 151 mouse monoclonal antibodies (mAbs) against the SARS-CoV-2 S1 protein were characterized and used to identify epitopes. Fifty-one mAbs reacted with eukaryotic SARS-CoV-2 RBD. Sixty-nine mAbs reacted with the S proteins of Omicron variants B.1.1.529 and BA.5, indicating their potential as rapid diagnostic materials. Three novel linear epitopes of RBD, R6 (391CFTNVYADSFVIRGD405), R12 (463PFERDISTEIYQAGS477), and R16 (510VVVLSFELLHAPAT523), were identified; these were highly conserved in SARS-CoV-2 variants of concern and could be detected in the convalescent serum of COVID-19 patients. From pseudovirus neutralization assays, some mAbs including one detecting R12 were found to possess neutralizing activity. Together, from the reaction of mAbs with eukaryotic RBD (N501Y), RBD (E484K), and S1 (D614G), we found that a single amino acid mutation in the SARS-CoV-2 S protein may cause a structural alteration, exerting substantial impact on mAb recognition. Our results could, therefore, help us better understand the function of the SARS-CoV-2 S protein and develop diagnostic tools for COVID-19.

3.
J Infect Dis ; 2023 May 18.
Article in English | MEDLINE | ID: covidwho-2327151

ABSTRACT

BACKGROUND: An orally aerosolised adenovirus type-5 vector-based COVID-19 vaccine (Ad5-nCoV) has recently been authorized for boosting immunization in China. Our study aims to assess the environmental impact of the use of aerosolised Ad5-nCoV. METHODS: We collected air samples from rooms, swabs from the setting desks of the vaccine nebuliser, mask samples from participants and blood samples of nurses who administered the inoculation in the clinical trials. The viral load of adenovirus type-5 vector in the samples and the antibody levels against the wild-type SARS-CoV-2 strain in serum were detected. RESULTS: Only one (4.00%) air samples collected before the initiation of vaccination was positive, which were almost positive during and after the vaccination (97.96%, 100%, respectively). All nurses in the trial A showed at least four-fold increase of the neutralizing antibody against the SARS-CoV-2 after the initiation of the study. In trial B, the positive proportion of the mask samples was 72.97% at 30 minutes after vaccination, 8.11% at day 1, and 0% at days 3, 5, and 7, respectively. CONCLUSION: The vaccination with the orally aerosolised Ad5-nCoV could have some spillage of the vaccine vector viral particles in the environment and cause human exposure.

4.
BMC Nephrol ; 24(1): 120, 2023 05 01.
Article in English | MEDLINE | ID: covidwho-2327007

ABSTRACT

OBJECTIVE: To estimate the incidence of thromboembolism in children with primary nephrotic syndrome with Meta-analysis. METHODS: Relevant studies published from January 1, 1980 to December 31, 2021 were retrieved from Pubmed, Web of science, Cochrane library, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database(VIP) and Wangfang Database. Quality evaluation of the literatures included was conducted according to Agency for Healthcare Research and Quality(AHRQ) assessment tool, followed by data extraction and Meta-analysis with software RevMan 5.3. RESULTS: A total of seven studies involving 3675 subjects were included. The overall prevalence was 4.9% with 95% CI of 2.83 to 7.05.However, a significant heterogeneity (P < 0.001) was observed with I2 = 89%. The prevalence of venous thromboembolism was 3.3% with 95% CI of 1.7 to 4.9. The prevalence of arterial thromboembolism was 0.5% with 95% CI of 0.2 to 1.4. CONCLUSION: Children with nephrotic syndrome are prone to thromboembolism, and it may lead to disability or death, therefore prevention measures is critical to decreasing the prevalence of thromboembolism.


Subject(s)
Nephrotic Syndrome , Thromboembolism , Humans , Child , Incidence , China , Prevalence
5.
Molecules ; 28(9)2023 May 08.
Article in English | MEDLINE | ID: covidwho-2316555

ABSTRACT

Mitochondria (MITO) play a significant role in various physiological processes and are a key organelle associated with different human diseases including cancer, diabetes mellitus, atherosclerosis, Alzheimer's disease, etc. Thus, detecting the activity of MITO in real time is becoming more and more important. Herein, a novel class of amphiphilic aggregation-induced emission (AIE) active probe fluorescence (AC-QC nanoparticles) based on a quinoxalinone scaffold was developed for imaging MITO. AC-QC nanoparticles possess an excellent ability to monitor MITO in real-time. This probe demonstrated the following advantages: (1) lower cytotoxicity; (2) superior photostability; and (3) good performance in long-term imaging in vitro. Each result of these indicates that self-assembled AC-QC nanoparticles can be used as effective and promising MITO-targeted fluorescent probes.


Subject(s)
Nanoparticles , Neoplasms , Humans , Fluorescent Dyes/pharmacology , Mitochondria , Fluorescence
6.
Green Energy & Environment ; 2022.
Article in English | EuropePMC | ID: covidwho-2297177

ABSTRACT

Air-borne pollutants in particulate matter (PM) form, produced either physically during industrial processes or certain biological routes, have posed a great threat to human health. Particularly during the current COVID-19 pandemic, effective filtration of the virus is an urgent matter worldwide. In this review, we first introduce some fundamentals about PM, including its source and classification, filtration mechanisms, and evaluation parameters. Advanced filtration materials and their functions are then summarized, among which polymers and MOFs are discussed in detail together with their antibacterial performance. The discussion on the application is divided into end-of-pipe treatment and source control. Finally, we conclude this review with our prospective view on future research in this area. Graphical Image 1

7.
Transboundary and Emerging Diseases ; 2023, 2023.
Article in German | ProQuest Central | ID: covidwho-2296316

ABSTRACT

Porcine deltacoronavirus (PDCoV) is an emerging swine coronavirus that causes severe diarrhea to pigs of all ages, especially the suckling piglets under one-week-old. We previously isolated a highly pathogenic PDCoV strain, CZ2020, from a diarrheal piglet and have passaged it for over 100 passages. The adaptability of the CZ2020 increased gradually in vitro as the passage increased. Amino acid mutations were observed in pp1a, pp1ab, spike, envelop, and membrane proteins, and the spike protein accounts for 66.7% of all amino acid mutations. Then, the high passage strains, CZ2020-F80 and CZ2020-F100, were selected for evaluation of the pathogenicity in three-day-old piglets to examine whether these amino acid changes affected their virulence. At 2 days postchallenge (DPC), 2/5 piglets started to show typical diarrhea, and at 4 DPC, severe diarrhea was observed in the CZ2020-challenged piglets. Viral RNA could be detected at 1 DPC in rectal swabs and reached its highest at 4 DPC in the CZ2020-challenged group. CZ2020-F80- and CZ2020-F100-challenged groups have one piglet exhibiting mild diarrhea at 4 and 6 DPC, respectively. Compared with the CZ2020-challenged group, the piglets in CZ2020-F80- and F100-challenged groups had lower viral loads in rectal swabs, intestines, and other organs. No obvious histopathological lesions were observed in the intestines of CZ2020-F80- and F100-challenged piglets. Virulent PDCoV infection could also induce strong interferons and proinflammatory cytokines in vitro and in vivo. These data indicate that the strains, CZ2020-F80 and CZ2020-F100, were significantly attenuated via serial passaging in vitro and have the potential for developing attenuated vaccine candidates.

8.
Frontiers in public health ; 11, 2023.
Article in English | EuropePMC | ID: covidwho-2295927

ABSTRACT

Background The 2019 coronavirus disease (COVID-19) pandemic increased the risks of mental health challenges, especially anxiety and depression. However, the impact of COVID-19 on mental health during pregnancy has not been fully established. Therefore, we investigated the impact of the COVID-19 pandemic on maternal mental health. Methods Two cohorts of pregnant women at their first antenatal care in the First Affiliated Hospital of Chongqing Medical University were enrolled in this study. One cohort was enrolled before the COVID-19 outbreak, from 1 June to 31 December 2019 (n = 5,728, pre-COVID-19 group), while the other was enrolled during the COVID-19 pandemic, from 24 January to 23 March 2020 (n = 739, COVID-19 pandemic group). Symptoms of depression, anxiety, and somatization disorders were assessed by the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and Patient Health Questionnaire-15 (PHQ-15), with a cutoff point of 10 for moderate-to-severe depression, anxiety, and somatoform symptoms. The propensity score matching method (1:1) was used to balance differences in demographic characteristics between groups. A chi-square analysis was performed to compare differences in demographic characteristics between the groups. Results Prevalence of moderate-to-severe depression, anxiety, and somatoform symptoms among pregnant women at their first antenatal care visit during the COVID-19 pandemic (9.5, 2.2, and 20.8%, respectively) was significantly lower than those before the pandemic (16.3, 4.4, and 25.7%, respectively) (p < 0.05). Compared with the same period before the pandemic, during the pandemic, the number of women newly registered for antenatal care decreased by nearly 50%. There were significant differences in the distributions of demographic characteristics between the groups (p < 0.05). After matching the demographic characteristics, differences in the prevalence of maternal mental health disorders between the groups reversed dramatically. Prevalence of moderate-to-severe depression, anxiety, and somatoform symptoms during the COVID-19 pandemic in this population (2.3, 9.6, and 20.8%, respectively) was significantly higher than those before the pandemic (0.3, 3.9, and 10%, respectively) (p < 0.05). Conclusion The COVID-19 pandemic increased mental health risks among pregnant women. As a large proportion of pregnant women with mental health challenges delay their prenatal care or change healthcare facilities after the outbreak of public health emergencies, there is a need to establish a balanced healthcare system in medical institutions at all levels.

9.
Environmental pollution (Barking, Essex : 1987) ; 2023.
Article in English | EuropePMC | ID: covidwho-2294389

ABSTRACT

Before and during the COVID-19 outbreak in the heated winter season of 2019, the carbonaceous fractions including organic carbon (OC), elemental carbon (EC), OC1–4, and EC1–5 were investigated between normal (November 1, 2019, to January 24, 2020) and lockdown (January 25, to February 29, 2020) periods in polluted regions of northern Henan Province. In comparison to urban site, four rural sites showed higher concentrations of carbonaceous components, especially secondary OC (SOC);the concentration of SOC in rural sites was 1.5–3.4 times that in the urban site. During the lockdown period, SOC in urban site decreased slightly, while it increased significantly in rural sites. NO2 has a significant effect on SOC generation, particularly in normal period when NO2 concentrations were high. Nevertheless, NO2 significantly decreased, and the elevated O3 (increased by 103–138%) contributed considerably to the generation of SOC during lockdown. Relative humidity (RH) promoted SOC production when RH was below 60%, but SOC was negatively correlated or uncorrelated with RH when RH exceeded 60%. Additionally, RH has a more pronounced effect on SOC during lockdown. The contribution of gasoline vehicle emissions decreases significantly in both urban and rural sites (3–12%) due to the significant reduction of anthropogenic activities during lockdown, although the urban site remained with the biggest contributions (37%). These results provide innovative insights into the variations in carbonaceous aerosols and SOC generation during the unique time when anthropogenic sources were significantly reduced and illustrate the differences in pollution characteristics and sources of carbonaceous fractions in different environments. Graphical Image 1

10.
Sci China Life Sci ; 66(7): 1589-1599, 2023 07.
Article in English | MEDLINE | ID: covidwho-2288738

ABSTRACT

The global COVID-19 pandemic emerged at the end of December 2019. Acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) are common lethal outcomes of bacterial lipopolysaccharide (LPS), avian influenza virus, and SARS-CoV-2. Toll-like receptor 4 (TLR4) is a key target in the pathological pathway of ARDS and ALI. Previous studies have reported that herbal small RNAs (sRNAs) are a functional medical component. BZL-sRNA-20 (Accession number: B59471456; Family ID: F2201.Q001979.B11) is a potent inhibitor of Toll-like receptor 4 (TLR4) and pro-inflammatory cytokines. Furthermore, BZL-sRNA-20 reduces intracellular levels of cytokines induced by lipoteichoic acid (LTA) and polyinosinic-polycytidylic acid (poly (I:C)). We found that BZL-sRNA-20 rescued the viability of cells infected with avian influenza H5N1, SARS-CoV-2, and several of its variants of concern (VOCs). Acute lung injury induced by LPS and SARS-CoV-2 in mice was significantly ameliorated by the oral medical decoctosome mimic (bencaosome; sphinganine (d22:0)+BZL-sRNA-20). Our findings suggest that BZL-sRNA-20 could be a pan-anti-ARDS ALI drug.


Subject(s)
Acute Lung Injury , COVID-19 , Influenza A Virus, H5N1 Subtype , Influenza in Birds , Respiratory Distress Syndrome , Mice , Humans , Animals , Lipopolysaccharides , Toll-Like Receptor 4/genetics , Toll-Like Receptor 4/metabolism , Influenza A Virus, H5N1 Subtype/metabolism , Pandemics , COVID-19/pathology , SARS-CoV-2/metabolism , Acute Lung Injury/chemically induced , Acute Lung Injury/drug therapy , Acute Lung Injury/genetics , Cytokines/metabolism , Lung/metabolism
11.
Emerg Microbes Infect ; 12(1): 2192815, 2023 Dec.
Article in English | MEDLINE | ID: covidwho-2288611

ABSTRACT

The re-emerging mpox (formerly monkeypox) virus (MPXV), a member of Orthopoxvirus genus together with variola virus (VARV) and vaccinia virus (VACV), has led to public health emergency of international concern since July 2022. Inspired by the unprecedent success of coronavirus disease 2019 (COVID-19) mRNA vaccines, the development of a safe and effective mRNA vaccine against MPXV is of high priority. Based on our established lipid nanoparticle (LNP)-encapsulated mRNA vaccine platform, we rationally constructed and prepared a panel of multicomponent MPXV vaccine candidates encoding different combinations of viral antigens including M1R, E8L, A29L, A35R, and B6R. In vitro and in vivo characterization demonstrated that two immunizations of all mRNA vaccine candidates elicit a robust antibody response as well as antigen-specific Th1-biased cellular response in mice. Importantly, the penta- and tetra-component vaccine candidates AR-MPXV5 and AR-MPXV4a showed superior capability of inducing neutralizing antibodies as well as of protecting from VACV challenge in mice. Our study provides critical insights to understand the protection mechanism of MPXV infection and direct evidence supporting further clinical development of these multicomponent mRNA vaccine candidates.


Subject(s)
COVID-19 , Monkeypox , Animals , Mice , COVID-19/prevention & control , Vaccines, Synthetic/genetics , Vaccinia virus/genetics , Monkeypox virus , COVID-19 Vaccines , Antibodies, Viral
12.
J Affect Disord ; 329: 343-349, 2023 05 15.
Article in English | MEDLINE | ID: covidwho-2288408

ABSTRACT

BACKGROUND: The outbreak of COVID-19 disarranged lives across mainland China. No study has examined changes in psychological symptoms of healthcare professionals in the intensive care unit (ICU) before and after the outbreak of COVID-19. The aim of this study was to estimate changes in psychological symptoms of ICU healthcare professionals before and after the COVID-19 outbreak, and to analyze factors related to psychological symptoms. METHODS: Two waves' administrations were implemented between December 13 and December 14, 2018, and between April 5 and April 7, 2020, respectively. The symptom checklist-90 (SCL-90) were used to evaluate psychological symptoms. Multiple logistical regression was used to reveal the risk of psychological symptoms. RESULTS: A total of 3902 and 3908 ICU healthcare professionals took part in the first and second surveys. The mean total score of the SCL-90 was 179.27 (70.02) at wave 1 and 147.75 (58.40) at wave 2, respectively. The proportion of psychological symptoms was 55.6 % (95%CI = 54.0-57.1) at wave 1. But rates of psychological symptoms decreased to 36.6 % (95%CI = 35.1-38.2) at wave 2. ICU healthcare professionals with western economic belt and 6-10 years of work were more likely to develop psychological symptoms, while ICU healthcare professionals with the later survey and doctoral degree were less likely to develop psychological symptoms. CONCLUSION: Although COVID-19 period benefited psychological symptoms of ICU healthcare professionals, psychological symptoms still had a related high prevalence. Regular screening and appropriate interventions should still be implemented to decrease the risk for psychological symptoms among Chinese ICU healthcare professionals.


Subject(s)
COVID-19 , Health Personnel , Intensive Care Units , Humans , COVID-19/epidemiology , Cross-Sectional Studies , Delivery of Health Care , Disease Outbreaks , East Asian People , Health Personnel/psychology
13.
Molecules ; 28(6)2023 Mar 10.
Article in English | MEDLINE | ID: covidwho-2261562

ABSTRACT

Suramin was originally used as an antiparasitic drug in clinics. Here, we demonstrate that suramin can bind to the N-terminal domain of SARS-CoV-2 nucleocapsid protein (N-NTD) and disturb its interaction with RNA. The BLI experiments showed that N-NTD interacts suramin with a dissociate constant (Kd = 2.74 µM) stronger than that of N-NTD with ssRNA-16 (Kd = 8.37 µM). Furthermore, both NMR titration experiments and molecular docking analysis suggested that suramin mainly binds to the positively charged cavity between the finger and the palm subdomains of N-NTD, and residues R88, R92, R93, I94, R95, K102 and A156 are crucial for N-NTD capturing suramin. Besides, NMR dynamics experiments showed that suramin-bound N-NTD adopts a more rigid structure, and the loop between ß2-ß3 exhibits fast motion on the ps-ns timescale, potentially facilitating suramin binding. Our findings not only reveal the molecular basis of suramin disturbing the association of SARS-CoV-2 N-NTD with RNA but also provide valuable structural information for the development of drugs against SARS-CoV-2.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/metabolism , Suramin/pharmacology , Nucleocapsid Proteins/chemistry , Molecular Docking Simulation , Models, Molecular , RNA, Viral/genetics
14.
Am J Nucl Med Mol Imaging ; 13(1): 43-50, 2023.
Article in English | MEDLINE | ID: covidwho-2268859

ABSTRACT

Molecular imaging can dynamically and quantitatively record the biochemical changes in a systemic view. In this research, SARS-CoV-2 pseudovirus was intramuscularly injected to simulate the vaccination with inactivated virus. New Zealand white rabbits were evaluated with 18F-FDG PET for inflammation and 68Ga-cyc-DX600 PET for ACE2 fluctuation, which were performed before and at 3, 7 and 14 days post injection (d P.I.); furthermore, one rabbit was vaccinated with two cycles with interval of 14 days for a longer period evaluation. Different with the vaccination-induced inflammatory response that was random and individual, ACE2 regulation was systemic and organ-specific: the liver and spleen were of a moderate decrease post injection but rebound at 14 d P.I., while there were a downward trend in heart, testis and bone marrow; besides, similar pattern of ACE2 regulation were recorded after the second injection with a relatively greater volatility. In conclusion, ACE2 PET gave a more comprehensive view on host response post vaccination, hold substantial promise in continuous monitoring of coronavirus vaccine administration and effectiveness.

15.
J Asthma ; : 1-9, 2022 Jun 07.
Article in English | MEDLINE | ID: covidwho-2249294

ABSTRACT

OBJECTIVE: Short-acting bronchodilators for asthma and chronic obstructive pulmonary disease (COPD) exacerbations are commonly delivered by nebulizers although administration using metered dose inhaler with space chamber (MDI spacer) has been shown to be equally efficacious. There are few studies examining patients' and healthcare providers' attitudes on the two administration methods in adults. This study explores patients' and healthcare providers' attitudes on the use of nebulizer versus MDI spacer for acute asthma and COPD exacerbations in adults.Methods: Patients admitted for asthma or COPD exacerbations, doctors, and nurses in a university-affiliated hospital were surveyed from 1 April 2021 to 30 September 2021 regarding their views on the effectiveness, ease of use, preparation and administration, side effects, and infection risk of the two administration methods. RESULTS: Ninety-nine patients, 103 doctors, and 650 nurses completed the survey. 60.6% of patients perceived nebulizer to be more effective. Patients who found nebulizer more comfortable were more likely to prefer nebulizer (OR 43.97, p = 0.01), while those who associated it with a greater infection risk were less likely to prefer nebulizer (OR 0.15, p = 0.03). 49.5% of doctors and 49.1% of nurses perceived nebulizer to be more effective, compared to 10.7% and 34.5%, respectively, for MDI spacer. Effectiveness and patient comfort influenced doctors' and nurses' preference for nebulizer while ease of preparation and administration influenced nurses' preference only. CONCLUSIONS: Patients and healthcare providers perceived nebulizer to be more effective. Factors unique to each group influenced their preference for nebulizer.

16.
Anal Chim Acta ; 1248: 340938, 2023 Apr 01.
Article in English | MEDLINE | ID: covidwho-2242732

ABSTRACT

CRISPR-Cas12a (Cpf1) is widely used for pathogen detection. However, most Cas12a nucleic acid detection methods are limited by a PAM sequence requirement. Moreover, preamplification and Cas12a cleavage are separate. Here, we developed a one-step RPA-CRISPR detection (ORCD) system unrestricted by the PAM sequence with high sensitivity and specificity that offers one-tube, rapid, and visually observable detection of nucleic acids. In this system, Cas12a detection and RPA amplification are performed simultaneously, without separate preamplification and product transfer steps, and 0.2 copies/µL of DNA and 0.4 copies/µL of RNA can be detected. In the ORCD system, the activity of Cas12a is the key to the nucleic acid detection; specifically, reducing Cas12a activity increases the sensitivity of ORCD assay detection of the PAM target. Furthermore, by combining this detection technique with a nucleic acid extraction-free method, our ORCD system can be used to extract, amplify and detect samples within 30 min, as verified with tests of 82 Bordetella pertussis clinical samples with a sensitivity and specificity of 97.30% and 100% compared with PCR. We also tested 13 SARS-CoV-2 samples with RT-ORCD, and the results were consistent with RT-PCR.


Subject(s)
COVID-19 , Nucleic Acids , Humans , SARS-CoV-2 , RNA , Biological Assay , Nucleic Acid Amplification Techniques
17.
J Med Virol ; 2022 Oct 13.
Article in English | MEDLINE | ID: covidwho-2237619

ABSTRACT

The ongoing coronavirus disease 2019 (COVID-19) pandemic has a significant global social and economic impact, and the emergence of new and more destructive mutant strains highlights the need for accurate virus detection. Here, 90 monoclonal antibodies (MAbs) that exclusively reacted with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid protein (NP) were generated. These MAbs did not cross-react with NPs of common human coronaviruses (HCoVs, i.e., 229E, OC43, HKU1, and NL63) and Middle East Respiratory Syndrome Coronavirus. Subsequently, overlapped peptides in individual fragments (N1-N4) of NP were synthesized. N1-3 (25-GSNQNGERSGARSKQ-39), N3-1 (217-AALALLLLDRLNQL-230), and N4-8 (393-TLLPAADLDDFSKQL-407) were identified as major epitopes using enzyme-linked immunoassay (ELISA) and recognized by 47, 1, and 18 MAbs, respectively. The 24 remaining MAbs exhibited no reactivity with all synthetic peptides. Among MAb-epitope pairs, only MAbs targeting epitope N1-3 displayed no cross-reaction with NPs of SARS-CoV-1 and other SARS-related CoVs. All Omicron variants contained a three-amino acid deletion (31ERS33) in the N1-3 region. Thus, MAbs targeting N1-3 failed to recognize these variants. Furthermore, a double-antibody sandwich ELISA for antigen detection was established using the optimal MAbs. Overall, a series of MAbs targeting SARS-CoV-2 NP was prepared, characterized with epitope mapping, and applied for the detection of SARS-CoV-2 antigens, and some novel B-cell epitopes of the viral NP were identified.

18.
J Med Virol ; : e28287, 2022 Nov 07.
Article in English | MEDLINE | ID: covidwho-2234636

ABSTRACT

Respiratory syncytial virus (RSV) is the most important virus that causes lower respiratory tract disease in children; efficient viral identification is an important component of disease prevention and treatment. Here, we developed and evaluated a ready-to-use (RTU) nucleic acid extraction-free direct reagent for identification of RSV (RTU-Direct test) in clinical samples. The limit of detection (LOD) of the RSV RTU-Direct test was consistent with the LOD of the standard test using extracted nucleic acids. The virus inactivation ability of RTU-Direct reagent was confirmed by viral infectivity assays involving RTU-Direct-treated samples containing RSV and human coronavirus OC43. RSV RNA stability was significantly better in RTU-Direct reagent than in conventional virus transport medium (VTM) at room temperature and 4°C (p < 0.05). The clinical performance of the RTU-Direct test was evaluated using 155 respiratory specimens from patients with suspected RSV infection. Positive agreement between the RTU-Direct test and the VTM standard test was 100% (42/42); negative agreement was 99.1% (112/113), and the kappa statistic was 0.968 (p < 0.001). The distributions of Ct values did not significantly differ between the RTU-Direct test and the standard test (p > 0.05). Overall, the RTU-Direct reagent can improve the efficiency and biosafety of RSV detection, while reducing the cost of detection.

19.
J Med Virol ; 2022 Sep 16.
Article in English | MEDLINE | ID: covidwho-2232486

ABSTRACT

Coronavirus disease 2019 (COVID-19) remains a serious global threat. The metabolic analysis had been successfully applied in the efforts to uncover the pathological mechanisms and biomarkers of disease severity. Here we performed a quasi-targeted metabolomic analysis on 56 COVID-19 patients from Sierra Leone in western Africa, revealing the metabolomic profiles and the association with disease severity, which was confirmed by the targeted metabolomic analysis of 19 pairs of COVID-19 patients. A meta-analysis was performed on published metabolic data of COVID-19 to verify our findings. Of the 596 identified metabolites, 58 showed significant differences between severe and nonsevere groups. The pathway enrichment of these differential metabolites revealed glutamine and glutamate metabolism as the most significant metabolic pathway (Impact = 0.5; -log10P = 1.959). Further targeted metabolic analysis revealed six metabolites with significant intergroup differences, with glutamine/glutamate ratio significantly associated with severe disease, negatively correlated with 10 clinical parameters and positively correlated with SPO2 (rs = 0.442, p = 0.005). Mini meta-analysis indicated elevated glutamate was related to increased risk of COVID-19 infection (pooled odd ratio [OR] = 2.02; 95% confidence interval [CI]: 1.17-3.50) and severe COVID-19 (pooled OR = 2.28; 95% CI: 1.14-4.56). In contrast, elevated glutamine related to decreased risk of infection and severe COVID-19, the pooled OR were 0.30 (95% CI: 0.20-0.44), and 0.44 (95% CI: 0.19-0.98), respectively. Glutamine and glutamate metabolism are associated with COVID-19 severity in multiple populations, which might confer potential therapeutic target of COVID-19, especially for severe patients.

20.
Microb Pathog ; 176: 106009, 2023 Mar.
Article in English | MEDLINE | ID: covidwho-2221158

ABSTRACT

Bovine coronavirus (BCoV) is one of the important pathogens that cause calf diarrhea (CD), winter dysentery (WD), and the bovine respiratory disease complex (BRDC), and spreads worldwide. An infection of BCoV in cattle can lead to death of young animals, stunted growth, reduced milk production, and milk quality, thus bringing serious economic losses to the bovine industry. Therefore, it is necessary to prevent and control the spread of BCoV. Here, a systematic review and meta-analysis was conducted to assess the prevalence of BCoV in cattle in China before 2022. A total of 57 articles regarding the prevalence of BCoV in cattle in China were collected from five databases (PubMed, ScienceDirect, CNKI, VIP, and Wan Fang). Based on the inclusion criteria, a total of 15,838 samples were included, and 6,136 were positive cases. The overall prevalence of BCoV was 30.8%, with the highest prevalence rate (60.5%) identified in South China and the lowest prevalence (15.6%) identified in Central China. We also analyzed other subgroup information, included sampling years, sample sources, detection methods, breeding methods, age, type of cattle, presence of diarrhea, and geographic and climatic factors. The results indicated that BCoV was widely prevalent in China. Among all subgroups, the sample sources, detection methods, breeding methods, and presence or absence of diarrheal might be potential risk factors responsible for BCoV prevalence. It is recommended to strengthen the detection of BCoV in cattle, in order to effectively control the spread of BCoV.


Subject(s)
Cattle Diseases , Coronavirus, Bovine , Dysentery , Cattle , Animals , Prevalence , Cattle Diseases/epidemiology , Diarrhea/veterinary , China/epidemiology , Feces
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