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1.
J Med Virol ; 95(6): e28846, 2023 06.
Article in English | MEDLINE | ID: covidwho-20245127

ABSTRACT

Since the first SARS-CoV-2 outbreak in late 2019, the SARS-CoV-2 genome has harbored multiple mutations, especially spike protein mutations. The currently fast-spreading Omicron variant that manifests without symptoms or with upper respiratory diseases has been recognized as a serious global public health problem. However, its pathological mechanism is largely unknown. In this work, rhesus macaques, hamsters, and BALB/C mice were employed as animal models to explore the pathogenesis of Omicron (B.1.1.529). Notably, Omicron (B.1.1.529) infected the nasal turbinates, tracheae, bronchi, and lungs of hamsters and BALB/C mice with higher viral loads than in those of rhesus macaques. Severe histopathological damage and inflammatory responses were observed in the lungs of Omicron (B.1.1.529)-infected animals. In addition, viral replication was found in multiple extrapulmonary organs. Results indicated that hamsters and BALB/c mice are potential animal models for studies on the development of drugs/vaccines and therapies for Omicron (B.1.1.529).


Subject(s)
COVID-19 , SARS-CoV-2 , Mice , Animals , Cricetinae , Macaca mulatta , Mice, Inbred BALB C , Bronchi
2.
Sci Adv ; 9(22): eadf0211, 2023 06 02.
Article in English | MEDLINE | ID: covidwho-20242861

ABSTRACT

The emergence of a series of SARS-CoV-2 variants has necessitated the search for broad-spectrum antiviral targets. The aryl hydrocarbon receptor (AhR) senses tryptophan metabolites and is an immune regulator. However, the role of AhR in SARS-CoV-2 infection and whether AhR can be used as the target of antiviral therapy against SARS-CoV-2 and its variants are yet unclear. Here, we show that infection with SARS-CoV-2 activates AhR signaling and facilitates viral replication by interfering with IFN-I-driven antiviral immunity and up-regulating ACE2 receptor expression. The pharmacological AhR blockade or AhR knockout reduces SARS-CoV-2 and its variants' replication in vitro. Drug targeting of AhR with AhR antagonists markedly reduced SARS-CoV-2 and its variants' replication in vivo and ameliorated lung inflammation caused by SARS-CoV-2 infection in hamsters. Overall, AhR was a SARS-CoV-2 proviral host factor and a candidate host-directed broad-spectrum target for antiviral therapy against SARS-CoV-2 and its variants, including Delta and Omicron, and potentially other variants in the future.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Proviruses/metabolism , Receptors, Aryl Hydrocarbon/genetics , Receptors, Aryl Hydrocarbon/metabolism , SARS-CoV-2/metabolism
3.
Emerg Microbes Infect ; 12(1): 2203782, 2023 Dec.
Article in English | MEDLINE | ID: covidwho-2296691

ABSTRACT

Multiple clinical and epidemiological studies have shown an interconnection between coronavirus disease 2019 (COVID-19) and diabetes, but experimental evidence is still lacking. Understanding the interplay between them is important because of the global health burden of COVID-19 and diabetes. We found that C57BL/6J mice were susceptible to the alpha strain of SARS-CoV-2. Moreover, diabetic C57BL/6J mice with leptin receptor gene deficiency (db/db mice) showed a higher viral load in the throat and lung and slower virus clearance in the throat after infection than C57BL/6J mice. Histological and multifactor analysis revealed more advanced pulmonary injury and serum inflammation in SARS-CoV-2 infected diabetic mice. Moreover, SARS-CoV-2 infected diabetic mice exhibited more severe insulin resistance and islet cell loss than uninfected diabetic mice. By RNA sequencing analysis, we found that diabetes may reduce the collagen level, suppress the immune response and aggravate inflammation in the lung after infection, which may account for the greater susceptibility of diabetic mice and their more severe lung damage after infection. In summary, we successfully established a SARS-CoV-2 infected diabetic mice model and demonstrated that diabetes and COVID-19 were risk factors for one another.


Subject(s)
COVID-19 , Diabetes Mellitus, Experimental , Mice , Animals , SARS-CoV-2 , Mice, Inbred C57BL , Inflammation
4.
BMC Public Health ; 23(1): 542, 2023 03 22.
Article in English | MEDLINE | ID: covidwho-2288668

ABSTRACT

BACKGROUND: COVID-19, which is caused by SARS-CoV-2, is a major global health threat. The dominant variant of SARS-CoV-2 has changed over time due to continuous evolution. We aimed to evaluate the coverage of SARS-CoV-2 vaccination among employees in China, explore their willingness to receive the SARS-CoV-2 variant vaccine and examine the potential factors influencing vaccination coverage and willingness. METHODS: A cross-sectional epidemiological survey was conducted online from January 1, 2022, to January 30, 2022. The information collected in the survey included sociodemographic characteristics, lifestyle habits, vaccination coverage, willingness to be vaccinated against SARS-CoV-2 variants and the reasons for vaccination and willingness. Multivariable logistic regression models were used to assess the associations of potential factors with the rate of vaccination and the willingness to be vaccinated. RESULTS: Among 62,395 eligible participants, the coverage of SARS-CoV-2 vaccination was 98.9% for at least one dose and 70.1% for a booster. The great majority of vaccinated individuals (94.4%) voluntarily received the vaccine. A total of 60,694 respondents (97.7%) were willing to be vaccinated against SARS-CoV-2 variants, mainly due to confidence in the effectiveness of vaccines (92.8%). A total of 1431 respondents were unwilling to be vaccinated, mainly because of concerns about the adverse effects of vaccines (77.6%). Longer education duration was associated with a higher rate of SARS-CoV-2 vaccination and willingness to be vaccinated. General or poor health status and having no history of influenza vaccination were associated with a lower rate of SARS-CoV-2 vaccination and willingness to be vaccinated. Additionally, we observed a significant positive association of abuse experience with the willingness to be vaccinated. CONCLUSION: Although the rate of SARS-CoV-2 vaccination and the willingness to be vaccinated were relatively high in the study population, there were still some respondents with vaccine hesitancy. Relevant strategies based on significant related factors should be developed and implemented to encourage vaccination.


Subject(s)
COVID-19 Vaccines , Humans , COVID-19 Vaccines/administration & dosage , Male , Female , Adult , Middle Aged , Patient Acceptance of Health Care , Logistic Models , Occupational Groups , China
5.
iScience ; 26(3): 106245, 2023 Mar 17.
Article in English | MEDLINE | ID: covidwho-2268794

ABSTRACT

The COVID-19 pandemic has spread worldwide, and rapid detection of the SARS-CoV-2 virus is crucial for infection surveillance and epidemic control. This study developed a centrifugal microfluidics-based multiplex reverse transcription recombinase polymerase amplification (RT-RPA) assay for endpoint fluorescence detection of the E, N, and ORF1ab genes of SARS-CoV-2. The microscope slide-shaped microfluidic chip could simultaneously accomplish three target genes and one reference human gene (i.e., ACTB) RT-RPA reactions in 30 min, and the sensitivity was 40 RNA copies/reaction for the E gene, 20 RNA copies/reaction for the N gene, and 10 RNA copies/reaction for the ORF1ab gene. The chip demonstrated high specificity, reproducibility, and repeatability. Chip performance was also evaluated using real clinical samples. Thus, this rapid, accurate, on-site, and multiplexed nucleic acid test microfluidic chip would significantly contribute to detecting patients with COVID-19 in low-resource settings and point-of-care testing (POCT) and, in the future, could be used to detect emerging new variants of SARS-CoV-2.

6.
Biosensors (Basel) ; 13(2)2023 Feb 10.
Article in English | MEDLINE | ID: covidwho-2283586

ABSTRACT

Myeloperoxidase (MPO) has been demonstrated to be a biomarker of neutrophilic inflammation in various diseases. Rapid detection and quantitative analysis of MPO are of great significance for human health. Herein, an MPO protein flexible amperometric immunosensor based on a colloidal quantum dot (CQD)-modified electrode was demonstrated. The remarkable surface activity of CQDs allows them to bind directly and stably to the surface of proteins and to convert antigen-antibody specific binding reactions into significant currents. The flexible amperometric immunosensor provides quantitative analysis of MPO protein with an ultra-low limit of detection (LOD) (31.6 fg mL-1), as well as good reproducibility and stability. The detection method is expected to be applied in clinical examination, POCT (bedside test), community physical examination, home self-examination and other practical scenarios.


Subject(s)
Biosensing Techniques , Quantum Dots , Humans , Peroxidase , Biosensing Techniques/methods , Reproducibility of Results , Immunoassay/methods , Proteins , Limit of Detection , Biomarkers
7.
Int J Colorectal Dis ; 38(1): 31, 2023 Feb 09.
Article in English | MEDLINE | ID: covidwho-2237502

ABSTRACT

AIMS: To evaluate the impact of SARS-CoV-2 vaccine on IBD activity. METHODS: Adult IBD patients from five large IBD centers in China were enrolled and followed up for 6 months. Patients were divided into vaccinated and unvaccinated groups according to vaccination status. Demographic and clinical data were collected. RESULTS: A total of 280 individuals (213 UC and 67 CD patients) were enrolled in the study. The unvaccinated and vaccinated groups of UC patients were comparable for basic characteristics, including age (t = - 0.8, p = 0.425), sex (χ2 = 0.980, p = 0.322), course of disease (z = - 0.513, p = 0.608), surgical conditions (χ2 = 1.042, p = 0.838), disease extent (χ2 = 4.853, p = 0.088), or baseline drug therapy (χ2 = 7.784, p = 0.064). In the subgroup of UC patients, there was no association between vaccination and disease activities, according to the medium disease activity scores for two groups: unvaccinated patients having scores (IQR) 1(2.75), 1(2), 1(2), and 1(2) at baseline, 1, 3, and 6 months, respectively, whereas vaccinated patients having scores (IQR) 1(2), 1(2), 1(2), and 1(2). Similar conclusions were also derived in the subgroup of CD patients. There were also no statistically significant differences in age (t = - 1.48, p = 0.144), sex (χ2 = 0.003, p = 0.957), course of disease (z = - 0.074, p = 0.941), surgical conditions (χ2 = 0.613, p = 0.594), localization (χ2 = 6.261, p = 0.199), or baseline drug therapy (χ2 = 5.881, p = 0.114) between 2 groups of CD patients. The medium disease activity scores (IQR) of the unvaccinated group at baseline, 1, 3, and 6 months were 1(4), 1(3), 1(3), and 1(3), respectively, whereas those of vaccinated group were 2.5(3.75), 2.5(3.75), 3(2), and 2(2), respectively. Overall, very few participants in this study described worsening IBD disease activity requiring a change or addition of medication. CONCLUSIONS: SARS-CoV-2 vaccine has no adverse effect on disease activity in IBD population. IBD patients should be recommended to receive SARS-CoV-2 vaccine in time.


Subject(s)
COVID-19 , Colitis, Ulcerative , Crohn Disease , Inflammatory Bowel Diseases , Adult , Chlorocebus aethiops , Animals , Humans , Crohn Disease/drug therapy , Colitis, Ulcerative/drug therapy , COVID-19 Vaccines/therapeutic use , Vero Cells , COVID-19/prevention & control , SARS-CoV-2 , Inflammatory Bowel Diseases/drug therapy , China/epidemiology
8.
Hum Reprod ; 37(12): 2942-2951, 2022 Nov 24.
Article in English | MEDLINE | ID: covidwho-2051406

ABSTRACT

STUDY QUESTION: Does inoculation with inactivated vaccines against coronavirus disease 2019 (Covid-19) before frozen-thawed embryo transfer (FET) affect live birth and neonatal outcomes? SUMMARY ANSWER: Inactivated Covid-19 vaccines did not undermine live birth and neonatal outcomes of women planning for FET. WHAT IS KNOWN ALREADY: Accumulating reports are now available indicating the safe use of mRNA vaccines against Covid-19 in pregnant and lactating women, and a few reports indicate that they are not associated with adverse effects on ovarian stimulation or early pregnancy outcomes following IVF. Evidence about the safety of inactivated Covid-19 vaccines is very limited. STUDY DESIGN, SIZE, DURATION: This is a retrospective cohort analysis from Reproductive Medical Center of a tertiary teaching hospital. Clinical records and vaccination record of 2574 couples with embryos transferred between 1 March 2021 and 30 September 2021 were screened for eligibility of this study. PARTICIPANTS/MATERIALS, SETTING, METHODS: Clinical and vaccination data of infertile couples planning for FET were screened for eligibility of the study. The reproductive and neonatal outcomes of FET women inoculated with inactivated Covid-19 vaccines or not were compared. The primary outcomes were live birth rate per embryo transfer cycle and newborns' birth height and weight. Secondary outcomes included rates of ongoing pregnancy, clinical pregnancy, biochemical pregnancy and spontaneous miscarriage. Multivariate logistical regression and propensity score matching (PSM) analyses were performed to minimize the influence of confounding factors. Subgroup analyses, including single dose versus double dose of the vaccines and the time intervals between the first vaccination and embryo transfer, were also performed. MAIN RESULTS AND THE ROLE OF CHANCE: Vaccinated women have comparable live birth rates (43.6% versus 45.0% before PSM, P = 0.590; and 42.9% versus 43.9% after PSM, P = 0.688), ongoing pregnancy rates (48.2% versus 48.1% before PSM, P = 0.980; and 52.2% versus 52.7% after PSM, P = 0.875) and clinical pregnancy rate (55.0% versus 54.8% before PSM, P = 0.928; and 54.7% versus 54.2% after PSM, P = 0.868) when compared with unvaccinated counterparts. The newborns' birth length (50.0 ± 1.6 versus 49.0 ± 2.9 cm before PSM, P = 0.116; and 49.9 ± 1.7 versus 49.3 ± 2.6 cm after PSM, P = 0.141) and birth weight (3111.2 ± 349.9 versus 3030.3 ± 588.5 g before PSM, P = 0.544; and 3053.8 ± 372.5 versus 3039.2 ± 496.8 g after PSM, P = 0.347) were all similar between the two groups. Neither single dose nor double dose of vaccines, as well as different intervals between vaccination and embryo transfer showed any significant impacts on reproductive and neonatal outcomes. LIMITATIONS, REASONS FOR CAUTION: The main findings might be limited by retrospective design. Besides, inoculations of triple dose of Covid-19 vaccines were not available by the time of data collection, thus the results cannot reflect the safe use of triple dose of inactivated Covid-19 vaccines. Finally, history of Covid-19 infection was based on patients' self-report rather than objective laboratory tests. WIDER IMPLICATIONS OF THE FINDINGS: Eligible individuals of inactivated vaccines against Covid-19 should not postpone vaccination plan because of their embryo transfer schedule, or vice versa. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Medical Key Discipline of Guangzhou (2021-2023). All authors had nothing to disclose. TRIAL REGISTRATION NUMBER: N/A.


Subject(s)
COVID-19 , Live Birth , Pregnancy , Humans , Infant, Newborn , Female , COVID-19 Vaccines/adverse effects , Retrospective Studies , COVID-19/prevention & control , Lactation , Embryo Transfer/methods , Pregnancy Rate , Birth Rate , Vaccines, Inactivated , Fertilization in Vitro/methods
9.
Nat Commun ; 13(1): 5459, 2022 09 17.
Article in English | MEDLINE | ID: covidwho-2036822

ABSTRACT

The recently emerged Omicron (B.1.1.529) variant has rapidly surpassed Delta to become the predominant circulating SARS-CoV-2 variant, given the higher transmissibility rate and immune escape ability, resulting in breakthrough infections in vaccinated individuals. A new generation of SARS-CoV-2 vaccines targeting the Omicron variant are urgently needed. Here, we developed a subunit vaccine named RBD-HR/trimer by directly linking the sequence of RBD derived from the Delta variant (containing L452R and T478K) and HR1 and HR2 in SARS-CoV-2 S2 subunit in a tandem manner, which can self-assemble into a trimer. In multiple animal models, vaccination of RBD-HR/trimer formulated with MF59-like oil-in-water adjuvant elicited sustained humoral immune response with high levels of broad-spectrum neutralizing antibodies against Omicron variants, also inducing a strong T cell immune response in vivo. In addition, our RBD-HR/trimer vaccine showed a strong boosting effect against Omicron variants after two doses of mRNA vaccines, featuring its capacity to be used in a prime-boost regimen. In mice and non-human primates, RBD-HR/trimer vaccination could confer a complete protection against live virus challenge of Omicron and Delta variants. The results qualified RBD-HR/trimer vaccine as a promising next-generation vaccine candidate for prevention of SARS-CoV-2, which deserved further evaluation in clinical trials.


Subject(s)
COVID-19 , Viral Vaccines , Animals , Antibodies, Neutralizing , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Mice , Mice, Inbred BALB C , Protein Subunits , SARS-CoV-2 , Vaccines, Subunit , Water
10.
Hum Reprod ; 37(9): 2054-2062, 2022 08 25.
Article in English | MEDLINE | ID: covidwho-1961049

ABSTRACT

STUDY QUESTION: Do inactivated coronavirus disease-2019 (COVID-19) vaccines affect IVF outcomes among the vaccine recipients? SUMMARY ANSWER: The receipt of inactivated COVID-19 vaccines before ovarian stimulation has little effect on the outcomes of IVF, including ovarian stimulation outcomes, embryo development and pregnancy rates. WHAT IS KNOWN ALREADY: Limited studies have reported that COVID-19 vaccines do not affect ovarian function, embryo development or pregnancy outcomes. STUDY DESIGN, SIZE, DURATION: This was a retrospective cohort study performed at the Third Affiliated Hospital of Guangzhou Medical University on 240 women vaccinated with either CoronaVac or Sinopharm COVID-19 before ovarian stimulation in the exposed group and 1343 unvaccinated women before ovarian stimulation in the unexposed group. All participants received fresh embryo transfers between 1 March 2021 and 15 September 2021. The included women were followed up until 12 weeks of gestation. PARTICIPANTS/MATERIALS, SETTING, METHODS: Vaccination information of all subjects was followed up by a nurse, and the IVF data were obtained from the IVF data system. The following aspects were compared between the vaccinated and the unvaccinated groups: parameters of ovarian stimulation, embryo development and pregnancy rates. Regression analyses were performed to control for confounders of embryo development and pregnancy rates. Propensity score matching (PSM) was performed to balance the baseline parameters of the two groups. The primary outcome was the ongoing pregnancy rate. MAIN RESULTS AND THE ROLE OF CHANCE: Liner regression analysis revealed that the number of oocytes retrieved (regression coefficient (B) = -0.299, P = 0.264), embryos suitable for transfer (B = -0.203, P = 0.127) and blastocysts (B = -0.250, P = 0.105) were not associated with the status of vaccination before ovarian stimulation, after adjusting for the confounders. The ongoing pregnancy rate in the women of the vaccinated group was not significantly lower than that in the unvaccinated group (36.3% vs 40.7%, P = 0.199) (adjust odd ratio = 0.91, 95% CI = 0.68-1.22, P = 0.52). After PSM, the rates of ongoing pregnancy (36.0% vs 39.9%, P = 0.272), implantation (35.4% vs 38.3%, P = 0.325), biochemical pregnancy (47.3% vs 51.6%, P = 0.232), clinical pregnancy (44.4% vs 47.4%, P = 0.398) and early miscarriage (15.0% vs 12.1%, P = 0.399) were not significantly different between the vaccinated and the unvaccinated groups. LIMITATIONS, REASONS FOR CAUTION: This is a retrospective study of women with infertility. The results from the present study warrant confirmation by prospective studies with a larger cohort. WIDER IMPLICATIONS OF THE FINDINGS: This is the first study with a large sample size on the effect of inactivated COVID-19 vaccines on ongoing pregnancy rates of women undergoing IVF. The present results showed that vaccination has no detrimental effect on IVF outcomes. Therefore, women are recommended to receive COVID-19 vaccines before undergoing their IVF treatment. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the National Key Research and Development Program of China (No. 2018YFC1003803 to J.L.), the Guangzhou Science and Technology Plan Project (No. 202102010076 to H.L.) and the Medical Key Discipline of Guangzhou (2021-2023), as well as the Sino-German Center for Research Promotion Rapid Response Funding Call for Bilateral Collaborative Proposals between China and Germany in COVID-19 Related Research (No. C-0032 to Xingfei Pan). The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.


Subject(s)
COVID-19 Vaccines , COVID-19 , COVID-19/prevention & control , Female , Fertilization in Vitro/methods , Humans , Ovulation Induction/methods , Pregnancy , Pregnancy Rate , Prospective Studies , Retrospective Studies , Vaccination
11.
Viruses ; 14(5)2022 05 12.
Article in English | MEDLINE | ID: covidwho-1869809

ABSTRACT

A new antibody diagnostic assay with more rapid and robust properties is demanded to quantitatively evaluate anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunity in a large population. Here, we developed a nanometer-scale fluorescent biosensor system consisting of CdSe-ZnS quantum dots (QDs) coupled with the highly sensitive B-cell epitopes of SARS-CoV-2 that could remarkably identify the corresponding antibody with a detection limit of 100 pM. Intriguingly, we found that fluorescence quenching of QDs was stimulated more obviously when coupled with peptides than the corresponding proteins, indicating that the energy transfer between QDs and peptides was more effective. Compared to the traditional enzyme-linked immunosorbent assay (ELISA), the B-cell-epitope-based QD-biosensor could robustly distinguish coronavirus disease 2019 (COVID-19) antibody-positive patients from uninfected individuals with a higher sensitivity (92.3-98.1% positive rates by QD-biosensor vs. 78.3-83.1% positive rates by ELISAs in 207 COVID-19 patients' sera) in a more rapid (5 min) and labor-saving manner. Taken together, the 'QD-peptides' biosensor provided a novel real-time, quantitative, and high-throughput method for clinical diagnosis and home-use tests.


Subject(s)
Biosensing Techniques , COVID-19 , Quantum Dots , Antibodies , COVID-19/diagnosis , Epitopes, B-Lymphocyte , Humans , Peptides , SARS-CoV-2
12.
Inf Process Manag ; 59(4): 102989, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1867286

ABSTRACT

Systematic processing helps individuals identify misinformation during the COVID-19 pandemic and serves as an individual-level measure to fight the infodemic. Highly educated people tend to engage in systematic processing more than their less educated counterparts. We follow a major part of the risk information seeking and processing (RISP) model to explicate this gap. An online survey (N = 1,568) conducted during the early stage of the pandemic in China showed that current knowledge and perceived information gathering capacity both positively mediated the association between education level and systematic processing. Although informational subjective norms were positively associated with systematic processing, we did not observe a significant difference in these norms between highly and less educated individuals. The results clarify the psychological mechanism underlying the education-based difference in systematic processing of the COVID-19 information and corroborate a relevant part of the RISP model. Moreover, our findings offer practical implications for facilitating individuals with less educational attainment to engage in systematic processing, thereby alleviating the negative impact of exposure to misinformation on them. These insights not only apply to managing the infodemic in China, but also inform the global recovery from the infodemic.

13.
Cell Mol Immunol ; 19(5): 577-587, 2022 05.
Article in English | MEDLINE | ID: covidwho-1830043

ABSTRACT

Neutrophil extracellular traps (NETs) can capture and kill viruses, such as influenza viruses, human immunodeficiency virus (HIV), and respiratory syncytial virus (RSV), thus contributing to host defense. Contrary to our expectation, we show here that the histones released by NETosis enhance the infectivity of SARS-CoV-2, as found by using live SARS-CoV-2 and two pseudovirus systems as well as a mouse model. The histone H3 or H4 selectively binds to subunit 2 of the spike (S) protein, as shown by a biochemical binding assay, surface plasmon resonance and binding energy calculation as well as the construction of a mutant S protein by replacing four acidic amino acids. Sialic acid on the host cell surface is the key molecule to which histones bridge subunit 2 of the S protein. Moreover, histones enhance cell-cell fusion. Finally, treatment with an inhibitor of NETosis, histone H3 or H4, or sialic acid notably affected the levels of sgRNA copies and the number of apoptotic cells in a mouse model. These findings suggest that SARS-CoV-2 could hijack histones from neutrophil NETosis to promote its host cell attachment and entry process and may be important in exploring pathogenesis and possible strategies to develop new effective therapies for COVID-19.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Histones , Mice , N-Acetylneuraminic Acid , Protein Subunits/metabolism , Spike Glycoprotein, Coronavirus/chemistry , Virus Internalization
14.
Cell ; 185(13): 2265-2278.e14, 2022 06 23.
Article in English | MEDLINE | ID: covidwho-1803705

ABSTRACT

Breakthrough infections by SARS-CoV-2 variants become the global challenge for pandemic control. Previously, we developed the protein subunit vaccine ZF2001 based on the dimeric receptor-binding domain (RBD) of prototype SARS-CoV-2. Here, we developed a chimeric RBD-dimer vaccine approach to adapt SARS-CoV-2 variants. A prototype-Beta chimeric RBD-dimer was first designed to adapt the resistant Beta variant. Compared with its homotypic forms, the chimeric vaccine elicited broader sera neutralization of variants and conferred better protection in mice. The protection of the chimeric vaccine was further verified in macaques. This approach was generalized to develop Delta-Omicron chimeric RBD-dimer to adapt the currently prevalent variants. Again, the chimeric vaccine elicited broader sera neutralization of SARS-CoV-2 variants and conferred better protection against challenge by either Delta or Omicron SARS-CoV-2 in mice. The chimeric approach is applicable for rapid updating of immunogens, and our data supported the use of variant-adapted multivalent vaccine against circulating and emerging variants.


Subject(s)
COVID-19 , Vaccines , Animals , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Mice , SARS-CoV-2/genetics
15.
Cell ; 185(10): 1728-1744.e16, 2022 05 12.
Article in English | MEDLINE | ID: covidwho-1767964

ABSTRACT

As the emerging variants of SARS-CoV-2 continue to drive the worldwide pandemic, there is a constant demand for vaccines that offer more effective and broad-spectrum protection. Here, we report a circular RNA (circRNA) vaccine that elicited potent neutralizing antibodies and T cell responses by expressing the trimeric RBD of the spike protein, providing robust protection against SARS-CoV-2 in both mice and rhesus macaques. Notably, the circRNA vaccine enabled higher and more durable antigen production than the 1mΨ-modified mRNA vaccine and elicited a higher proportion of neutralizing antibodies and distinct Th1-skewed immune responses. Importantly, we found that the circRNARBD-Omicron vaccine induced effective neutralizing antibodies against the Omicron but not the Delta variant. In contrast, the circRNARBD-Delta vaccine protected against both Delta and Omicron or functioned as a booster after two doses of either native- or Delta-specific vaccination, making it a favorable choice against the current variants of concern (VOCs) of SARS-CoV-2.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Macaca mulatta , Mice , RNA, Circular/genetics , SARS-CoV-2/genetics , Vaccines, Synthetic/genetics , mRNA Vaccines
16.
Front Public Health ; 10: 773271, 2022.
Article in English | MEDLINE | ID: covidwho-1731865

ABSTRACT

BACKGROUND: Non-pharmaceutical interventions were implemented in most countries to reduce the transmission of COVID-19. We aimed to describe the incidence of influenza in four countries in the 2019-2020 season and examined the effect of these non-pharmaceutical interventions on the incidence of influenza. METHODS: We used the network surveillance data from 2015 to 2020 to estimate the percentage increase in influenza cases to explore the effect of non-pharmaceutical interventions implemented to control the COVID-19 on the incidence of influenza in China, the United States, Japan, and Singapore. RESULTS: We found that the incidence of influenza has been almost zero and reached a persistent near-zero level for a continuous period of six months since epidemiologic week 14 of 2020 in the four countries. Influenza incidence decreased by 77.71% and 60.50% in the early days of COVID-19 in the 2019-2020 season compared to the same period in preceding years in Japan and Singapore, respectively. Furthermore, influenza incidence decreased by 60.50-99.48% during the period of compulsory interventions in the 2019-2020 season compared to the same period in preceding years in the four countries. CONCLUSION: These findings suggest that the application of non-pharmaceutical interventions, even everyday preventive action, was associated with a reduction of influenza incidence, which highlights that more traditional public health interventions need to be reasserted and universalized to reduce influenza incidence.


Subject(s)
COVID-19 , Influenza, Human , COVID-19/epidemiology , COVID-19/prevention & control , China/epidemiology , Humans , Incidence , Influenza, Human/epidemiology , Influenza, Human/prevention & control , SARS-CoV-2
17.
Front Psychol ; 13: 837820, 2022.
Article in English | MEDLINE | ID: covidwho-1705623

ABSTRACT

Individuals' unverified information sharing on social media, namely, sharing information without verification, is a major cause of the widespread misinformation amid the COVID-19 pandemic. The association between perceived information overload and unverified information sharing has been well documented in the cognitive overload approach. However, little is known about the underlying mechanism of this process. This study aims to explore the mediating role of anxiety and the moderating role of perceived herd between perceived information overload and unverified information sharing on WeChat. Anxiety demonstrates people's emotional response to the pandemic, whereas perceived herd describes a willingness to share certain information if it has been shared by many. The results of an online survey in China (N = 525) showed that perceived information overload was positively associated with unverified information sharing. In addition, this relationship was partially mediated by anxiety. Moreover, perceived herd positively moderated the link between anxiety and unverified information sharing, such that the indirect effect of perceived information overload on unverified information sharing via anxiety was significant in conditions where the level of perceived herd was high, whereas the indirect effect was not significant in conditions where the level of perceived herd was low. The moderated mediation model extends the cognitive overload approach and indicates that unverified information sharing is not only an individual strategy to cope with information overload but also a herding behavior to manage anxiety. Practical implications for curbing people's tendencies toward unverified information sharing on social media are discussed.

18.
Ann Am Thorac Soc ; 19(1): 58-65, 2022 01.
Article in English | MEDLINE | ID: covidwho-1605425

ABSTRACT

Rationale: Both genetic variants and chronic obstructive pulmonary disease (COPD) contribute to the risk of incident severe coronavirus disease (COVID-19). Whether genetic risk of incident severe COVID-19 is the same regardless of preexisting COPD is unknown. Objectives: In this study, we aimed to investigate the potential interaction between genetic risk and COPD in relation to severe COVID-19. Methods: We constructed a polygenic risk score for severe COVID-19 by using 112 single-nucleotide polymorphisms in 430,582 participants from the UK Biobank study. We examined the associations of genetic risk and COPD with severe COVID-19 by using logistic regression models. Results: Of 430,582 participants, 712 developed severe COVID-19 as of February 22, 2021, of whom 19.8% had preexisting COPD. Compared with participants at low genetic risk, those at intermediate genetic risk (odds ratio [OR], 1.34; 95% confidence interval [CI], 1.09-1.66) and high genetic risk (OR, 1.50; 95% CI, 1.18-1.92) had higher risk of severe COVID-19 (P for trend = 0.001), and the association was independent of COPD (P for interaction = 0.76). COPD was associated with a higher risk of incident severe COVID-19 (OR, 1.37; 95% CI, 1.12-1.67; P = 0.002). Participants at high genetic risk and with COPD had a higher risk of severe COVID-19 (OR, 2.05; 95% CI, 1.35-3.04; P < 0.001) than those at low genetic risk and without COPD. Conclusions: The polygenic risk score, which combines multiple risk alleles, can be effectively used in screening for high-risk populations of severe COVID-19. High genetic risk correlates with a higher risk of severe COVID-19, regardless of preexisting COPD.


Subject(s)
COVID-19 , Pulmonary Disease, Chronic Obstructive , Humans , Polymorphism, Single Nucleotide , Pulmonary Disease, Chronic Obstructive/epidemiology , Pulmonary Disease, Chronic Obstructive/genetics , Risk Factors , SARS-CoV-2
19.
Clin Lab ; 67(11)2021 Nov 01.
Article in English | MEDLINE | ID: covidwho-1513105

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a highly contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that brings a significant public health challenge. A rapid and simple method is necessary for testing suspected samples and screening the population. METHODS: To better monitor sample effectiveness, this study described a method to detect nucleocapsid protein gene (N gene) of SARS-CoV-2 and human ACTB gene employing real-time duplex reverse transcription multienzyme isothermal rapid amplification (RT-MIRA) assays. RESULTS: The established real-time duplex RT-MIRA assays showed that no cross-reactions were observed to other pathogens and the detection limit was 100 copies/reaction. Using simulated clinical samples to test established assays further and the amplification process took no more than 20 minutes at 42°C. CONCLUSIONS: RT-MIRA assays are faster and easier than reverse transcription real-time polymerase chain reaction (RT-PCR). It is expected to be further optimized and evaluated in the detection of SARS-CoV-2 confirmed cases.


Subject(s)
COVID-19 , Reverse Transcription , Humans , Nucleic Acid Amplification Techniques , SARS-CoV-2 , Sensitivity and Specificity
20.
Cancer Research on Prevention and Treatment ; 47(4):227-234, 2020.
Article in Chinese | CAB Abstracts | ID: covidwho-1408605

ABSTRACT

In the current pandemic of SARS-Cov-2 (formally known as novel coronavirus disease 2019, COVID-19), the cancer treatment is particularly a challenge that must be overcome as soon as possible. Currently, the clinical data on the prevalence of SARS-Cov-2 in cancer patients is very limited, alone with constant evolving situations. To obtain existing evidence, we reviewed a wide range of medical literature and relevant websites including the National Health Commission of China. With the actual situation of Hubei Cancer Hospital, we formulated the interim guideline which was developed by all contributors from different disciplines after fully discussion, to provide the reference for treatment options on cancer patients, especially the cancer patients recovered from COVID-19 infection. This guideline highlighted the multidisciplinary team (MDT) diagnostic model, the assessment between risks and benefits prior to treatment, individualized service for patients' medical needs, and the acceptability in ethics and patients' socio-economic conditions.

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