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2.
Immun Inflamm Dis ; 10(6): e612, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1866537

ABSTRACT

INTRODUCTION: Surrogate rapid serological assay was urgently demanded for accessibly interpretation of immunity potency and duration of neutralizing antibody against SARS-CoV-2. The longitudinal trajectory of antibody profile with a reliable large-scale assay was crucial to judge the protective immune status, avoid futile therapy and provide insight into the booster vaccination minimizing the risk of COVID-19. METHODS: A total of 195 volunteers were enrolled for a two-doses procedure (0 and 28 days) of inactive vaccination, as well as ten COVID-19 convalescents. The serum was collected at six time point and detected by chemiluminescent immunoassay with SARS-CoV-2 neutralizing antibody (Nab), SARS-CoV-2 RBD immunoglobulin G (IgG) antibody (RBD IgG) and RBD total antibody. The diagnostic results and the correlation of antibody level were evaluated among three serological (Nab, RBD IgG, and RBD total antibody) assay, as well as with an authorized cPass kit (Nab). Referred to the assay-specific threshold, the seroconversion rate and dynamic titer of antibody were exhibited from 0 to 56 days since vaccination. RESULTS: There was no difference observed with diagnostic results between neutralizing and RBD IgG antibody (p > 0.05). Both diagnostic results of neutralizing and RBD IgG antibody testing differentiated from RBD total antibody assay (p < 0.05). The coefficient of correlation (R) was above 0.90 among the levels of those three antibodies, more than 0.60 in comparison with neutralizing antibody by cPass enzyme-linked immunoassay. The "S" varying pattern for various antibodies level was observed with time extension after vaccination. The seroconversion rate was below 11.1% in 2 weeks after the priming dose, while the value climbed to 81% in 1 week after the boosting dose. The seroconversion rate was maintained around 91%. The inactive vaccine elicited 81-fold higher antibody levels after finished the vaccination schedule than that at the basic point. Besides, the level of neutralizing antibody induced by vaccine was found with a 0.2-fold ratio by comparison with that in COVID-19 convalescents. CONCLUSION: The humoral immune response products including SARS-CoV-2 neutralizing, RBD IgG antibody and total antibody and the varying pattern of the antibody profile could be rapidly detected by CILA method. Meanwhile, the continuing and dynamic determination was attributed to evaluate the protection effect of humoral immunity against the SARS-CoV-2 infection.


Subject(s)
COVID-19 , Viral Vaccines , Antibodies, Neutralizing , Antibodies, Viral , Humans , Immunoassay , Immunoglobulin G , SARS-CoV-2 , Viral Vaccines/pharmacology
3.
Nano Today ; 43: 101445, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1851860

ABSTRACT

Aluminum oxyhydroxide (AlOOH) adjuvants are widely used in human vaccines. However, the interaction mechanisms at the material-bio interface, and further understandings on physicochemical property-dependent modulation of the immune responses still remain uncertain. Herein, a library of AlOOH nanorods with well-defined aspect ratios is designed to explore the mechanisms of adjuvanticity. The aspect ratios of AlOOH nanorods were demonstrated to be intrinsically modulated by the hydroxide supersaturation level during crystal growth, leading to the differences in surface free energy (SFE). As a result, higher aspect ratio AlOOH nanoadjuvants with lower SFE exhibited more hydrophobic surface, resulting in more membrane depolarization, cellular uptake and dendritic cell (DC) activation. By using hepatitis B surface antigen (HBsAg) virus-like particles (VLPs) or SARS-CoV-2 spike protein receptor-binding domain (RBD) as model antigens, AlOOH nanorods with higher aspect ratio were determined to elicit more potent humoral immune responses, which could be attributed to the enhanced DC activation and the efficient antigen trafficking to the draining lymph nodes. Our findings highlight the critical role of aspect ratio of AlOOH nanorods in modulating adjuvanticity, and further provide a design strategy for engineered nanoadjuvants for prophylactic vaccines.

4.
Front Cell Infect Microbiol ; 12: 880915, 2022.
Article in English | MEDLINE | ID: covidwho-1847156

ABSTRACT

With the epidemic of betacoronavirus increasing frequently, it poses a great threat to human public health. Therefore, the research on the pathogenic mechanism of betacoronavirus is becoming greatly important. Murine hepatitis virus strain-3 (MHV-3) is a strain of betacoronavirus which cause tissue damage especially fulminant hepatic failure (FHF) in mice, and is commonly used to establish models of acute liver injury. Recently, MHV-3-infected mice have also been introduced to a mouse model of COVID-19 that does not require a Biosafety Level 3 (BSL-3) facility. FHF induced by MHV-3 is a type of severe liver damage imbalanced by regenerative hepatocellular activity, which is related to numerous factors. The complement system plays an important role in host defense and inflammation and is involved in first-line immunity and/or pathogenesis of severe organ disorders. In this study, we investigated the role of aberrant complement activation in MHV-3 infection-induced FHF by strategies that use C3-deficient mice and intervene in the complement system. Our results showed that mice deficient in C3 had more severe liver damage, a higher viral load in the liver and higher serum concentrations of inflammatory cytokines than wild-type controls. Treatment of C57BL/6 mice with C3aR antagonist or anti-C5aR antibody reduced liver damage, viral load, and serum IFN-γ concentration compared with the control group. These findings indicated that complement system acts as a double-edged sword during acute MHV-3 infection. However, its dysregulated activation leads to sustained inflammatory responses and induces extensive liver damage. Collectively, by investigating the role of complement activation in MHV-3 infection, we can further understand the pathogenic mechanism of betacoronavirus, and appropriate regulation of immune responses by fine-tuning complement activation may be an intervention for the treatment of diseases induced by betacoronavirus infection.


Subject(s)
COVID-19 , Liver Failure, Acute , Murine hepatitis virus , Animals , Complement Activation , Liver Failure, Acute/pathology , Mice , Mice, Inbred C57BL
5.
International Journal of Molecular Sciences ; 23(9):4485, 2022.
Article in English | ProQuest Central | ID: covidwho-1842816

ABSTRACT

Schizandrol A (SZA) and schizandrol B (SZB) are two active ingredients of Wuzhi capsule (WZC), a Chinese proprietary medicine commonly prescribed to alleviate tacrolimus (FK-506)-induced hepatoxicity in China. Due to their inhibitory effects on cytochrome P450 (CYP) 3A enzymes, SZA/SZB may display drug–drug interaction (DDI) with tacrolimus. To identify the extent of this DDI, the enzymes’ inhibitory profiles, including a 50% inhibitory concentration (IC50) shift, reversible inhibition (RI) and time-dependent inhibition (TDI) were examined with pooled human-liver microsomes (HLMs) and CYP3A5-genotyped HLMs. Subsequently, the acquired parameters were integrated into a physiologically based pharmacokinetic (PBPK) model to quantify the interactions between the SZA/SZB and the tacrolimus. The metabolic studies indicated that the SZB displayed both RI and TDI on CYP3A4 and CYP3A5, while the SZA only exhibited TDI on CYP3A4 to a limited extent. Moreover, our PBPK model predicted that multiple doses of SZB would increase tacrolimus exposure by 26% and 57% in CYP3A5 expressers and non-expressers, respectively. Clearly, PBPK modeling has emerged as a powerful approach to examine herb-involved DDI, and special attention should be paid to the combined use of WZC and tacrolimus in clinical practice.

6.
Frontiers in psychiatry ; 13, 2022.
Article in English | EuropePMC | ID: covidwho-1837921

ABSTRACT

Background The novel coronavirus disease 2019 (COVID-19) pandemic causes great disruption to cancer care services, which might bring about psychological problems and further lower both physical and mental life quality in cancer patients. Until now, very few studies focused on the psychological distress of patients with advanced melanoma before or during the epidemic. This study aimed to elucidate the fear of progression (FoP), anxiety, depression, and related independent predictors in patients with advanced melanoma during the COVID-19 outbreak. Methods Two hundred and seventy-three patients with unresectable stage III or metastatic melanoma were recruited from February 2020 to November 2021, and completed the Fear of Progression Questionnaire-Short Form (FoP-Q-SF), State Trait Anxiety Inventory (STAI-6), and Patient Health Questionnaire (PHQ-9). Results One hundred and seventy-four (64.7%) patients experienced heighted FoP (FoP-Q-SF: 39.9 ± 11.0), 198 (72.5%) patients reported elevated anxiety (STAI-6: 13.1 ± 3.0), and 62 (22.7%) patients had increased depression (PHQ-9: 6.4 ± 6.1). In multivariate analysis, illness duration (OR = 0.987 for FoP;OR = 0.984 for depression), cancer stage (OR = 14.394 for anxiety) and disease progression (OR = 1.960 for FoP;OR = 23.235 for anxiety;OR = 1.930 for depression) were independent predictors for FoP, anxiety or depression. Additionally, the high levels of FoP, anxiety and depression were significantly positive correlated with each other (r = 0.466 for FoP and anxiety;r = 0.382 for FoP and depression;r = 0.309 for anxiety and depression). Conclusion Our study indicates that FoP, anxiety and depression are persisting among patients with advanced melanoma in the COVID-19 and post-COVID-19 era. Effective psycho-oncological interventions are needed for melanoma patients with psychological distress during the ongoing COVID-19 pandemic.

7.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-335525

ABSTRACT

Background: Currently, rapid and widespread testing is essential to promote early intervention and curb the ongoing COVID-19 pandemic. The reverse transcription-polymerase chain reaction (RT-PCR) for detecting novel coronavirus (SARS-CoV-2) is restricted to professional laboratories and well-trained personnel, thus, limiting its widespread use in in resource-limited conditions. Methods: To overcome these challenges, we developed a rapid and convenient assay using recombinase polymerase amplification (RPA) and clustered regularly interspaced short palindromic repeats (CRISPR) technology for the rapid detection SARS-CoV-2, which was named as Visual Detection of RPA-amplified Products (VDAP). The reaction conditions of the VDAP were optimized and selected using pure SARS-CoV-2 RNA standards and the sensitivity and specificity of the VDAP were further determined. Finally, the VDAP was verified on clinical specimens. Results: The VDAP was performed at 37 °C for 15 min, and the result was visible by the naked eye. The limits of detection (LODs) of the VDAP for the target ORF1ab and N genes are 70 and 500 copies, respectively. No cross-reactivity was observed with the RNA standard samples of four respiratory viruses or clinical samples of common respiratory viral infections. These results confirmed that the assay was highly specific. Thirty SARS-CoV-2 positive and 30 SARS-CoV-2 negative patient specimens were analyzed. We compared these results to RT-PCR, the overall sensitivity and specificity of the VDAP compared to RT-PCR for detection SARS-CoV-2 were 93.3% and 100.0%, respectively. Conclusions: The VDAP is a simple, highly specific, and convenient assay for the detection of SARS-CoV-2 in resource-limited conditions

8.
Nat Metab ; 4(5): 547-558, 2022 May.
Article in English | MEDLINE | ID: covidwho-1830111

ABSTRACT

The severity and mortality of COVID-19 are associated with pre-existing medical comorbidities such as diabetes mellitus. However, the underlying causes for increased susceptibility to viral infection in patients with diabetes is not fully understood. Here we identify several small-molecule metabolites from human blood with effective antiviral activity against SARS-CoV-2, one of which, 1,5-anhydro-D-glucitol (1,5-AG), is associated with diabetes mellitus. The serum 1,5-AG level is significantly lower in patients with diabetes. In vitro, the level of SARS-CoV-2 replication is higher in the presence of serum from patients with diabetes than from healthy individuals and this is counteracted by supplementation of 1,5-AG to the serum from patients. Diabetic (db/db) mice undergo SARS-CoV-2 infection accompanied by much higher viral loads and more severe respiratory tissue damage when compared to wild-type mice. Sustained supplementation of 1,5-AG in diabetic mice reduces SARS-CoV-2 loads and disease severity to similar levels in nondiabetic mice. Mechanistically, 1,5-AG directly binds the S2 subunit of the SARS-CoV-2 spike protein, thereby interrupting spike-mediated virus-host membrane fusion. Our results reveal a mechanism that contributes to COVID-19 pathogenesis in the diabetic population and suggest that 1,5-AG supplementation may be beneficial to diabetic patients against severe COVID-19.


Subject(s)
COVID-19 , Diabetes Mellitus, Experimental , Animals , Glucose , Humans , Mice , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
9.
Neuroimage ; 256: 119190, 2022 Aug 01.
Article in English | MEDLINE | ID: covidwho-1829283

ABSTRACT

This paper extends frequency domain quantitative electroencephalography (qEEG) methods pursuing higher sensitivity to detect Brain Developmental Disorders. Prior qEEG work lacked integration of cross-spectral information omitting important functional connectivity descriptors. Lack of geographical diversity precluded accounting for site-specific variance, increasing qEEG nuisance variance. We ameliorate these weaknesses. (i) Create lifespan Riemannian multinational qEEG norms for cross-spectral tensors. These norms result from the HarMNqEEG project fostered by the Global Brain Consortium. We calculate the norms with data from 9 countries, 12 devices, and 14 studies, including 1564 subjects. Instead of raw data, only anonymized metadata and EEG cross-spectral tensors were shared. After visual and automatic quality control, developmental equations for the mean and standard deviation of qEEG traditional and Riemannian DPs were calculated using additive mixed-effects models. We demonstrate qEEG "batch effects" and provide methods to calculate harmonized z-scores. (ii) We also show that harmonized Riemannian norms produce z-scores with increased diagnostic accuracy predicting brain dysfunction produced by malnutrition in the first year of life and detecting COVID induced brain dysfunction. (iii) We offer open code and data to calculate different individual z-scores from the HarMNqEEG dataset. These results contribute to developing bias-free, low-cost neuroimaging technologies applicable in various health settings.


Subject(s)
Brain Diseases , COVID-19 , Brain/diagnostic imaging , Brain Mapping , Electroencephalography/methods , Humans
10.
Biomed J ; 2022 May 05.
Article in English | MEDLINE | ID: covidwho-1821151

ABSTRACT

Despite the rising natural and vaccines mediated immunity, several countries have experienced a resurgence of the Coronavirus disease of 2019 (COVID-19) due to emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. From Alpha to Omicron, the variants of concern (VOC) have evolved several spike protein mutations that may have impact on virus characteristics, such as transmissibility and antigenicity. In this review, we describe the evolution of SARS-CoV-2, summarize current knowledge of epidemiological and clinical features of the variants, and discuss the response strategies in terms of vaccines to reduce the burden of COVID-19.

11.
Signal Transduct Target Ther ; 7(1): 139, 2022 04 27.
Article in English | MEDLINE | ID: covidwho-1815514

ABSTRACT

The SARS-CoV-2 Omicron variant shows substantial resistance to neutralization by infection- and vaccination-induced antibodies, highlighting the demands for research on the continuing discovery of broadly neutralizing antibodies (bnAbs). Here, we developed a panel of bnAbs against Omicron and other variants of concern (VOCs) elicited by vaccination of adenovirus-vectored COVID-19 vaccine (Ad5-nCoV). We also investigated the human longitudinal antibody responses following vaccination and demonstrated how the bnAbs evolved over time. A monoclonal antibody (mAb), named ZWD12, exhibited potent and broad neutralization against SARS-CoV-2 variants Alpha, Beta, Gamma, Kappa, Delta, and Omicron by blocking the spike protein binding to the angiotensin-converting enzyme 2 (ACE2) and provided complete protection in the challenged prophylactic and therapeutic K18-hACE2 transgenic mouse model. We defined the ZWD12 epitope by determining its structure in complex with the spike (S) protein via cryo-electron microscopy. This study affords the potential to develop broadly therapeutic mAb drugs and suggests that the RBD epitope bound by ZWD12 is a rational target for the design of a broad spectrum of vaccines.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Antibodies, Monoclonal/genetics , Antibodies, Viral , Broadly Neutralizing Antibodies , COVID-19/prevention & control , COVID-19 Vaccines/genetics , Cryoelectron Microscopy , Epitopes , Humans , Mice , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Vaccination , Viral Envelope Proteins
12.
Clin Infect Dis ; 2021 Oct 05.
Article in English | MEDLINE | ID: covidwho-1769226

ABSTRACT

BACKGROUND: The longitudinal antigen-specific immunity in COVID-19 convalescents is crucial for long-term protection upon individual re-exposure to SARS-CoV-2, and even more pivotal for ultimately achieving population-level immunity. To better understand the features of immune memory in individuals with different disease severities at one year post-disease onset we conducted this cohort study. METHODS: We conducted a systematic antigen-specific immune evaluation in 101 COVID-19 convalescents, who had asymptomatic, mild, moderate, or severe disease, through two visits at months 6 and 12 post-disease onset. The SARS-CoV-2-specific antibodies, comprising NAb, IgG, and IgM, were assessed by mutually corroborated assays, i.e. neutralization, enzyme-linked immunosorbent assay (ELISA), and microparticle chemiluminescence immunoassay (MCLIA). Meanwhile, the T-cell memory against SARS-CoV-2 spike, membrane and nucleocapsid proteins was tested through enzyme-linked immunospot assay (ELISpot), intracellular cytokine staining (ICS), and tetramer staining-based flow cytometry, respectively. RESULTS: SARS-CoV-2-specific IgG antibodies, and also NAb can persist among over 95% COVID-19 convalescents from 6 months to 12 months after disease onset. At least 19/71 (26%) of COVID-19 convalescents (double positive in ELISA and MCLIA) had detectable circulating IgM antibody against SARS-CoV-2 at 12m post-disease onset. Notably, the percentages of convalescents with positive SARS-CoV-2-specific T-cell responses (at least one of the SARS-CoV-2 antigen S1, S2, M and N protein) were 71/76 (93%) and 67/73 (92%) at 6m and 12m, respectively. Furthermore, both antibody and T-cell memory levels of the convalescents were positively associated with their disease severity. CONCLUSIONS: SARS-CoV-2-specific cellular and humoral immunities are durable at least until one year after disease onset.

13.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-331070

ABSTRACT

Background: An ongoing outbreak of coronavirus disease 2019 (COVID-19) is spreading, there are few reports on exploring individualized nutritional therapy for critical coronavirus disease 2019 (COVID-19) patients. Case presentation: To explore individualized nutritional therapy for critical coronavirus disease 2019 (COVID-19) patients.A nutritional treatment plan was created through nutritional risk screening and nutritional assessment, and an individualized nutritional treatment was implemented through multidisciplinary collaboration. The patient’s gastrointestinal symptoms were corrected, and her nutrition-related indicators such as albumin and body weight were improved. She was cured and discharged. Conclusion: Nutritional therapy is beneficial to improve the nutritional status and clinical outcome of critical COVID- 19 patients.

14.
BMC Infect Dis ; 22(1): 157, 2022 Feb 15.
Article in English | MEDLINE | ID: covidwho-1745485

ABSTRACT

OBJECTIVE: Reliable high-throughput serological assays for SARS-CoV-2 antibodies present an important role in the strength and duration of immunity after vaccination. The study investigated the analytical and clinical performances of neutralizing antibodies (NTAb) assay by chemiluminescent (CLIA), and SARS-CoV-2 neutralizing antibody after vaccination in real world. METHODS: The analytical performances of CLIA for SARS-CoV-2 NTAb were evaluated, followed by the sensitivity and specificity identified with a PRNT test from 50 volunteers. Then, a cohort of vaccine recipients (n = 37) were tracked with SARS-CoV-2 NTAb assay at prior to vaccination, one, three and six months post two doses. In real world, a total of 737 cases were recruited from physical examination center in Shenzhen Luohu People's Hospital (from Jun to August 2021) to analyze vaccination status. RESULTS: Serological assays on the CLIA were found with excellent characteristics including imprecision, repeatability and linearity. Besides, it was robust to icterus, lipemia and hemolysis. The good sensitivity and specificity were obtained at 98% and 100%, respectively. NTAb results showed a high correlation with PRNT50 titers (r 0.61). Until July 2021, the BBIBP-CorV (76.3%) and Sinovac CoronaVac (20.5%) were the predominant vaccines injection in Shenzhen, China. Adolescent less than 18 years was the main unvaccinated group (52.1%). The seropositive rate of inactive SRAR-CoV-2 vaccines exceeded 97% after inoculation. The NTAb generated by Sinovac CoronaVac with the schedule of 0-56 days was found significantly lower than that by BBIBP-CorV (P < 0.001). The follow-up of NTAb changes in a cohort and the dynamic variation of NTAb in real world disclosed steep downward by almost three times for NTAb level occurred at three months post twice vaccinations. The seropositive ratio was at least 50% over 6 months. CONCLUSIONS: SARS-CoV-2 neutralizing antibodies assay show excellent analytical and clinical performances, and a high correlation with neutralizing activity. Anti-epidemic measures and the urgent trial of SARS-CoV-2 vaccine was calling for adolescents.


Subject(s)
COVID-19 Vaccines , COVID-19 , Adolescent , Antibodies, Neutralizing , Antibodies, Viral , Humans , Luminescence , SARS-CoV-2 , Vaccination
15.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-330228

ABSTRACT

Background MVC-COV1901 is a subunit SARS-CoV-2 vaccine based on the prefusion spike protein S-2P and adjuvanted with CpG 1018 and aluminum hydroxide. Although MVC-COV1901 has been licensed for emergency use for adults in Taiwan, the safety and immunogenicity of MVC-COV1901 in adolescents remained unknown. As young people play an important role in SARS-CoV-2 transmission and epidemiology, a vaccine approved for adolescents and eventually, children, will be important in mitigating the COVID-19 pandemic. Methods This study is a prospective, double-blind, multi-center phase 2 trial evaluating the safety, tolerability and immunogenicity of two doses of the SARS-CoV-2 vaccine MVC-COV1901 in adolescents. Healthy adolescents from age of 12 to 17 years were recruited and randomly assigned (6:1) to receive two intramuscular doses of either MVC-COV1901 or placebo at 28 days apart. The primary outcomes were safety and immunogenicity from the day of first vaccination (Day 1) to 28 days after the second vaccination (Day 57), and immunogenicity of MVC COV1901 in adolescents as compared to young adult vaccinees in terms of neutralizing antibody titers and seroconversion rate. The secondary outcomes were safety and immunogenicity of MVC-COV1901 as compared to placebo in adolescents in terms of immunoglobulin titers and neutralizing antibody titers over the study period. Results Between July 21, 2021 and December 22, 2021, a total of 399 adolescent participants were included for safety evaluation after enrollment to receive at least one dose of either MVC-COV1901 (N=341) or placebo (N=58). Of these, 334 and 46 participants went on to receive two doses of either MVC-COV1901 or placebo, respectively, and were included in the per protocol set (PPS) for immunogenicity analysis. Adverse events were mostly mild and were similar in MVC-COV1901 and placebo groups. The most commonly reported adverse events were pain/tenderness and malaise/fatigue. All immunogenicity endpoints in the adolescent group were non-inferior to the endpoints seen in the young adult and placebo groups. Conclusions The safety and immunogenicity data presented here showed that MVC-COV1901 has similar safety profile and non-inferior immunogenicity in adolescents compared to young adults. ClinicalTrials.gov registration NCT04951388.

16.
Preprint in English | medRxiv | ID: ppmedrxiv-22272325

ABSTRACT

BackgroundMVC-COV1901 is a subunit SARS-CoV-2 vaccine based on the prefusion spike protein S-2P and adjuvanted with CpG 1018 and aluminum hydroxide. Although MVC-COV1901 has been licensed for emergency use for adults in Taiwan, the safety and immunogenicity of MVC-COV1901 in adolescents remained unknown. As young people play an important role in SARS-CoV-2 transmission and epidemiology, a vaccine approved for adolescents and eventually, children, will be important in mitigating the COVID-19 pandemic. MethodsThis study is a prospective, double-blind, multi-center phase 2 trial evaluating the safety, tolerability and immunogenicity of two doses of the SARS-CoV-2 vaccine MVC-COV1901 in adolescents. Healthy adolescents from age of 12 to 17 years were recruited and randomly assigned (6:1) to receive two intramuscular doses of either MVC-COV1901 or placebo at 28 days apart. The primary outcomes were safety and immunogenicity from the day of first vaccination (Day 1) to 28 days after the second vaccination (Day 57), and immunogenicity of MVC COV1901 in adolescents as compared to young adult vaccinees in terms of neutralizing antibody titers and seroconversion rate. The secondary outcomes were safety and immunogenicity of MVC-COV1901 as compared to placebo in adolescents in terms of immunoglobulin titers and neutralizing antibody titers over the study period. ResultsBetween July 21, 2021 and December 22, 2021, a total of 399 adolescent participants were included for safety evaluation after enrollment to receive at least one dose of either MVC-COV1901 (N=341) or placebo (N=58). Of these, 334 and 46 participants went on to receive two doses of either MVC-COV1901 or placebo, respectively, and were included in the per protocol set (PPS) for immunogenicity analysis. Adverse events were mostly mild and were similar in MVC-COV1901 and placebo groups. The most commonly reported adverse events were pain/tenderness and malaise/fatigue. All immunogenicity endpoints in the adolescent group were non-inferior to the endpoints seen in the young adult and placebo groups. ConclusionsThe safety and immunogenicity data presented here showed that MVC-COV1901 has similar safety profile and non-inferior immunogenicity in adolescents compared to young adults. ClinicalTrials.gov registrationNCT04951388.

17.
J Environ Chem Eng ; 10(2): 107206, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1729897

ABSTRACT

The surface contamination of SARS-CoV-2 is becoming a potential source of virus transmission during the pandemic of COVID-19. Under the cold environment, the infection incidents would be more severe with the increase of virus survival time. Thus, the disinfection of contaminated surfaces in both ambient and cold environments is a critical measure to restrain the spread of the virus. In our study, it was demonstrated that the 254 nm ultraviolet-C (UVC) is an efficient method to inactivate a coronavirus, mouse hepatitis virus strain A59 (MHV-A59). The inactivation rate to MHV-A59 coronavirus was up to 99.99% when UVC doses were 2.90 and 14.0 mJ/cm2 at room temperature (23 °C) and in cold environment (-20 °C), respectively. Further mechanistic study demonstrated that UVC could induce spike protein damage to partly impede virus attachment and genome penetration processes, which contributes to 12% loss of viral infectivity. Additionally, it can induce genome damage to significantly interrupt genome replication, protein synthesis, virus assembly and release processes, which takes up 88% contribution to viral inactivation. With these mechanistic understandings, it will greatly contribute to the prevention and control of the current SARS-CoV-2 transmissions in cold chains (low temperature-controlled product supply chains), public area such as airport, school, and warehouse.

18.
Biochem Genet ; 2022 Mar 02.
Article in English | MEDLINE | ID: covidwho-1718783

ABSTRACT

Severe Acute Respiratory Syndrome Coronavirus Type 2 (SARS-CoV-2) is an enveloped single-stranded RNA virus that can lead to respiratory symptoms and damage many organs such as heart, kidney, intestine, brain and liver. It has not been clearly documented whether myocardial injury is caused by direct infection of cardiomyocytes, lung injury, or other unknown mechanisms. The gene expression profile of GSE150392 was obtained from the Gene Expression Omnibus (GEO) database. The processing of high-throughput sequencing data and the screening of differentially expressed genes (DEGs) were implemented by R software. The R software was employed to analyze the Gene Ontology (GO) analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The protein-protein interaction (PPI) network of the DEGs was constructed by the STRING website. The Cytoscape software was applied for the visualization of PPI network and the identification of hub genes. The statistical analysis was performed by the GraphPad Prism software to verify the hub genes. A total of 516 up-regulated genes and 191 down-regulated genes were screened out. The top 1 enrichment items of GO in biological process (BP), Cellular Component (CC), and Molecular Function (MF) were type I interferon signaling pathway, sarcomere, and receptor ligand activity, respectively. The top 10 enrichment pathways, including TNF signaling pathway, were identified by KEGG enrichment analysis. A PPI network was established, consisting of 613 nodes and 3,993 edges. The 12 hub genes were confirmed as statistically significant, which was verified by GSE151879 dataset. In conclusion, the hub genes of human iPSC-cardiomyocytes infected with SARS-CoV-2 were identified through bioinformatics analysis, which may be used as biomarkers for further research.

19.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-329581

ABSTRACT

Emerging in December 2019, coronavirus disease 2019 (COVID-19) eventually became a pandemic and has posed a tremendous threat to global public health. However, the origins of SARS-CoV-2, the causative agent of COVID-19, remain to be determined. It has reported that a certain number of the early case clusters had a contact history with Huanan Seafood Market. Therefore, surveillance of SARS-CoV-2 within the market is of vital importance. Herein, we presented the SARS-CoV-2 detection results of 1380 samples collected from the environment and the animals within the market in early 2020. By SARS-CoV-2-specific RT-qPCR, 73 environmental samples tested positive for SARS-CoV-2 and three live viruses were successfully isolated. The viruses from the market shared nucleotide identity of 99.980% to 99.993% with the human isolate HCoV/Wuhan/IVDC-HB-01. In contrast, no virus was detected in the animal swabs covering 18 species of animals in the market. The SARS-COV-2 nucleic acids in the positive environmental samples showed significant correlation of abundance of Homo sapiens with SARS-CoV-2. In summary, this study provided convincing evidence of the prevalence of SARS-CoV-2 in the Huanan Seafood Market during the early stage of COVID-19 outbreak.

20.
J Clin Lab Anal ; 36(4): e24325, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1712111

ABSTRACT

BACKGROUND: Currently, mass vaccine inoculation against coronavirus disease-2019 (COVID-19) has been being implemented globally. Rapid and the large-scale detection of serum neutralizing antibodies (NAbs) laid a foundation for assessing the immune response against SARS-CoV-2 infection and vaccine. Additional assessments include the duration of antibodies and the optimal time for a heightened immune response. METHODS: The performance of five surrogate NAbs-three chemiluminescent immunoassay (CLIA) and two enzyme-linked immunosorbent assays (ELISAs)-and specific IgM and IgG assays were compared using COVID-19-vaccinated serum (n = 164). Conventional virus neutralization test (cVNT) was used as a criterion and the diagnostic agreement and correlation of the five assays were evaluated. We studied the antibody responses after the two-dose vaccine in volunteers up to 6 months. RESULTS: The sensitivity and specificity of five surrogate NAb assays ranged from 84% to 100%. Our cVNT results indicated great consistency with the surrogate assays. At 28 days after primary vaccination, the seropositivities of the NAbs, IgG, and IgM were 6%, 4%, and 13%, respectively. After the booster dose, seropositivities reached 14%, 65%, and 97%, respectively. Six months after receipt of the second dose, the NAb positive rate was eventually maintained at 66%. In all COVID-19 convalescents, patients were detected with 100% NAb sat three months after discharge. CONCLUSION: COVID-19 vaccine induced a humoral immune response lasting at least six months. Rapid serological detection was used as a proxy for identifying changes in immunity levels and as a guide to whether an individual may require a booster vaccination.


Subject(s)
COVID-19 Vaccines , COVID-19 , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , Humans , Immunoglobulin G , Immunoglobulin M , SARS-CoV-2 , Serologic Tests , Vaccination
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