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1.
Front Immunol ; 13: 952650, 2022.
Article in English | MEDLINE | ID: covidwho-2326989

ABSTRACT

Given pandemic risks of zoonotic SARS-CoV-2 variants and other SARS-like coronaviruses in the future, it is valuable to perform studies on conserved antigenic sites to design universal SARS-like coronavirus vaccines. By using antibodies obtained from convalescent COVID-19 patients, we succeeded in functional comparison of conserved antigenic sites at multiple aspects with each other, and even with SARS-CoV-2 unique antigenic sites, which promotes the cognition of process of humoral immune response to the conserved antigenic sites. The conserved antigenic sites between SARS-CoV-2 and SARS-CoV can effectively induce affinity maturation of cross-binding antibodies, finally resulting in broadly neutralizing antibodies against multiple variants of concern, which provides an important basis for universal vaccine design, however they are subdominant, putatively due to their lower accessibility relative to SARS-CoV-2 unique antigenic sites. Furthermore, we preliminarily design RBDs to improve the immunogenicity of these conserved antigenic sites. Our study focusing on conserved antigenic sites provides insights for promoting the development of universal SARS-like coronavirus vaccines, thereby enhancing our pandemic preparedness.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , Broadly Neutralizing Antibodies , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Spike Glycoprotein, Coronavirus/genetics
2.
Cell Rep Methods ; 2(10): 100313, 2022 Oct 24.
Article in English | MEDLINE | ID: covidwho-2086106

ABSTRACT

Wastewater surveillance has become essential for monitoring the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The quantification of SARS-CoV-2 RNA in wastewater correlates with the coronavirus disease 2019 (COVID-19) caseload in a community. However, estimating the proportions of different SARS-CoV-2 haplotypes has remained technically difficult. We present a phylogenetic imputation method for improving the SARS-CoV-2 reference database and a method for estimating the relative proportions of SARS-CoV-2 haplotypes from wastewater samples. The phylogenetic imputation method uses the global SARS-CoV-2 phylogeny and imputes based on the maximum of the posterior probability of each nucleotide. We show that the imputation method has error rates comparable to, or lower than, typical sequencing error rates, which substantially improves the reference database and allows for accurate inferences of haplotype composition. Our method for estimating relative proportions of haplotypes uses an initial step to remove unlikely haplotypes and an expectation maximization (EM) algorithm for obtaining maximum likelihood estimates of the proportions of different haplotypes in a sample. Using simulations with a reference database of >3 million SARS-CoV-2 genomes, we show that the estimated proportions reflect the true proportions given sufficiently high sequencing depth.

3.
Frontiers in immunology ; 13, 2022.
Article in English | EuropePMC | ID: covidwho-2046995

ABSTRACT

Given pandemic risks of zoonotic SARS-CoV-2 variants and other SARS-like coronaviruses in the future, it is valuable to perform studies on conserved antigenic sites to design universal SARS-like coronavirus vaccines. By using antibodies obtained from convalescent COVID-19 patients, we succeeded in functional comparison of conserved antigenic sites at multiple aspects with each other, and even with SARS-CoV-2 unique antigenic sites, which promotes the cognition of process of humoral immune response to the conserved antigenic sites. The conserved antigenic sites between SARS-CoV-2 and SARS-CoV can effectively induce affinity maturation of cross-binding antibodies, finally resulting in broadly neutralizing antibodies against multiple variants of concern, which provides an important basis for universal vaccine design, however they are subdominant, putatively due to their lower accessibility relative to SARS-CoV-2 unique antigenic sites. Furthermore, we preliminarily design RBDs to improve the immunogenicity of these conserved antigenic sites. Our study focusing on conserved antigenic sites provides insights for promoting the development of universal SARS-like coronavirus vaccines, thereby enhancing our pandemic preparedness.

4.
Cell reports methods ; 2022.
Article in English | EuropePMC | ID: covidwho-2034281

ABSTRACT

Wastewater surveillance has become essential for monitoring the spread of SARS-CoV-2. The quantification of SARS-CoV-2 RNA in wastewater correlates with the Covid-19 caseload in a community. However, estimating the proportions of different SARS-CoV-2 haplotypes has remained technically difficult. We present a phylogenetic imputation method for improving the SARS-CoV-2 reference database and a method for estimating the relative proportions of SARS-CoV-2 haplotypes from wastewater samples. The phylogenetic imputation method uses the global SARS-CoV-2 phylogeny and imputes based on the maximum of the posterior probability of each nucleotide. We show that the imputation method has error rates comparable to, or lower than, typical sequencing error rates which substantially improves the reference database and allows for accurate inferences of haplotype composition. Our method for estimating relative proportions of haplotypes uses an initial step to remove unlikely haplotypes and an Expectation-Maximization (EM) algorithm for obtaining maximum likelihood estimates of the proportions of different haplotypes in a sample. Using simulations with a reference database of >3 million SARS-CoV-2 genomes, we show that the estimated proportions reflect the true proportions given sufficiently high sequencing depth. Graphical Pipes et al. present a method for estimating the proportion of different SARS-CoV-2 haplotypes from shotgun sequencing of wastewater samples allowing researchers to obtain accurate results in real-time.

5.
J Virol Methods ; 309: 114597, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-1966905

ABSTRACT

Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has become disaster for human society. As the pandemic becomes more regular, we should develop more rapid and accurate detection methods to achieve early diagnosis and treatment. Antigen detection methods based on spike protein has great potential, however, it has not been effectively developed, probably due to the torturing conformational complexity. By utilizing cross-blocking data, we clustered SARS-CoV-2 receptor binding domain (RBD)-specific monoclonal antibodies (mAbs) into 6 clusters. Subsequently, the antigenic sites for representative mAbs were identified by RBDs with designed residue substitutions. The sensitivity and specificity of selected antibody pairs was demonstrated using serial diluted samples of SARS-CoV-2 S protein and SARS-CoV S protein. Furthermore, pseudovirus system was constructed to determine the detection capability against SARS-CoV-2 and SARS-CoV. 6 RBD-specific mAbs, recognizing different antigenic sites, were identified as potential candidates for optimal antibody pairs for detection of SARS-CoV-2 S protein. By considering relative spatial position, accessibility and conservation of corresponding antigenic sites, affinity and the presence of competitive antibodies in clinical samples, 6H7-6G3 was rationally identified as optimal antibody pair for detection of both SARS-CoV-2 and SARS-CoV. Furthermore, our results showed that 6H7 and 6G3 effectively bind to SARS-CoV-2 variants of concern (VOCs). Taken together, we identified 6H7-6G3 antibody pair as a promising rapid antigen diagnostic tool in containing COVID-19 pandemic caused by multiple VOCs. Moreover, our results also provide an important reference in screening of antibody pairs detecting antigens with complex conformation.


Subject(s)
COVID-19 , Spike Glycoprotein, Coronavirus , Antibodies, Monoclonal , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/diagnosis , COVID-19 Testing , Humans , Pandemics , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics
6.
J Affect Disord ; 311: 425-431, 2022 08 15.
Article in English | MEDLINE | ID: covidwho-1851384

ABSTRACT

BACKGROUND: Recent research suggested that COVID-19-related multiple mental health problems were associated with an increased risk for suicidal ideations (SIs), but population-based data demonstrating these associations are scarce. This study aimed to estimate the cumulative effects of psychological risk factors on SIs during the outbreak and remission periods of COVID-19 using a cumulative risk model, as well as sex differences. METHODS: A total of 68,685 college students in China participated in the survey during two phases of the pandemic (T1 and T2). Mental health risks (acute stress, depression, anxiety, insomnia, and obsessive-compulsive symptoms) and sociodemographic characteristics were measured at T1, and SIs were assessed at T1 and T2. Hierarchical regression analysis was used to determine the combined effect of multiple mental health problems on SIs at T1 and T2. RESULTS: The prevalence of SIs increased from the early periods of the COVID-19 pandemic (7.6%) to the later periods (10.0%). Depression was a powerful risk factor for SIs during the COVID-19 pandemic. Individuals with >3 mental risks would be most likely to experience rapidly increasing SIs during the early periods of the COVID-19 pandemic. Sex exerted different effects on the cumulative risk model of SIs. CONCLUSIONS: Interventions, such as mental health education and improving utilization of student support services, should be implemented. There is a crucial need for early intervention and prevention efforts aimed at males with greater than three mental health problems.


Subject(s)
COVID-19 , Suicidal Ideation , Anxiety/psychology , COVID-19/epidemiology , Depression/psychology , Female , Humans , Male , Mental Health , Pandemics , Students/psychology , Universities
7.
Cell Rep ; 39(8): 110862, 2022 05 24.
Article in English | MEDLINE | ID: covidwho-1821171

ABSTRACT

The rapidly spreading Omicron variant is highly resistant to vaccines, convalescent sera, and neutralizing antibodies (nAbs), highlighting the urgent need for potent therapeutic nAbs. Here, a panel of human nAbs from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) convalescent patients show diverse neutralization against Omicron, of which XMA01 and XMA04 maintain nanomolar affinities and excellent neutralization (half maximal inhibitory concentration [IC50]: ∼20 ng/mL). nAb XMA09 shows weak but unattenuated neutralization against all variants of concern (VOCs) as well as SARS-CoV. Structural analysis reveals that the above three antibodies could synergistically bind to the receptor-binding domains (RBDs) of both wild-type and Omicron spikes and defines the critical determinants for nAb-mediated broad neutralizations. Three nAbs confer synergistic neutralization against Omicron, resulting from the inter-antibody interaction between XMA04 and XMA01(or XMA09). Furthermore, the XMA01/XMA04 cocktail provides synergistic protection against Beta and Omicron variant infections in hamsters. In summary, our results provide insights for the rational design of antibody cocktail therapeutics or universal vaccines against Omicron.


Subject(s)
COVID-19 , Vaccines , Animals , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/therapy , Cricetinae , Humans , Immunization, Passive , SARS-CoV-2 , COVID-19 Serotherapy
8.
Psychiatry Res ; 304: 114153, 2021 10.
Article in English | MEDLINE | ID: covidwho-1336864

ABSTRACT

This study aimed to evaluate the sleep-related problems and predictors of probable clinical insomnia among college students during the COVID-19 remission period in China. 146,102 college students from 22 colleges/universities in Guangdong province participated in this study from 1th to 15th June, 2020. Self-administered questionnaires were used to assess demographic characteristics. Sleep-related problems, depression and anxiety symptoms were measured by Youth Self-Rating Insomnia Scale, Patient Health Questionnaire-9 and Generalized Anxiety Disorder Scale-7, respectively. The prevalence of difficulty in initiating sleep, difficulty in maintaining sleep, early morning awakening, sleep insufficiency, unrefreshing sleep and daytime functioning impairment were 7.2%, 3.4%, 3.5%, 9.6%, 14.6%, and 7.6%, respectively. 16.9% students had varying degrees of insomnia and 6.3% were considered as displaying probable clinical insomnia. Moreover, being urban residents, having a history of physical or mental illness, and probable clinical depression or anxiety were significant risk factors of probable clinical insomnia, while college senior degree and 7-8 hours' sleep duration per day was the protective factor for probable clinical insomnia. Unrefreshing sleep was the most prominent sleep problem among college students during COVID-19 remission in China. Good sleep hygiene practices are strongly suggested to develop in the time of prolonged home isolation.


Subject(s)
COVID-19 , Sleep Initiation and Maintenance Disorders , Adolescent , Anxiety/epidemiology , China/epidemiology , Cross-Sectional Studies , Depression/epidemiology , Humans , Pandemics , SARS-CoV-2 , Sleep Initiation and Maintenance Disorders/epidemiology , Students , Surveys and Questionnaires
9.
J Affect Disord ; 281: 597-604, 2021 02 15.
Article in English | MEDLINE | ID: covidwho-952061

ABSTRACT

BACKGROUND: Growing evidence supports a clear association between COVID-19 pandemic and mental health. However, little is known about the longitudinal course of psychopathology in young adults at different stages of the pandemic. METHODS: This large-scale, longitudinal, population-based survey was conducted among college students in China. The rates of three mental health problems (acute stress, anxiety, and depressive symptoms), and their change patterns at two phases of the pandemic (early vs under-control) were measured. Predictors of changes in mental health symptoms were examined utilizing multivariate regression. RESULTS: Among the 164,101 college students who participated in the first wave survey (T1=during onset of outbreak), 68,685 (41.9%) completed a follow-up survey (T2=during remission). In the follow-up survey, the prevalence of probable acute stress (T1: 34.6%; T2: 16.4%) decreased, while the rates of depressive (T1: 21.6%; T2: 26.3%) and anxiety symptoms (T1: 11.4%; T2: 14.7%) increased. Senior students, with suspected or conformed cases in their community and COVID-19 related worries (all AORs > 1.20, ps < 0.001) were found to have a higher risk of developing mental health problems in at least one wave. Less physical exercise, low perceived social support, and a dysfunctional family were found to negatively impact psychological symptoms. CONCLUSIONS: Acute stress, anxiety, and depressive symptoms have been prevalent among college students during the COVID-19 epidemic, and showed a significant increase after the initial stage of the outbreak. Some college students, especially those with the risk factors noted above, exhibited persistent or delayed symptoms.


Subject(s)
COVID-19/psychology , Mental Health , Pandemics , Students/psychology , Anxiety/epidemiology , China/epidemiology , Depression/epidemiology , Humans , Longitudinal Studies , Young Adult
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