The practice of drug emergency supply in China from a policy mix perspective (preprint)

Background This study aims to analyze relevant policy texts, explore and determine the focal points and inadequacies of the Chinese government in guaranteeing supplies of medicines, and provide advice on how to make better policies about drug supply when public health emergencies occur.Methods We selected 559 documents that guided the support of drug supply during emergencies issued by governments at both the national and provincial levels from December 1, 2019, to February 28, 2023. In addition, we developed a four-dimensional analysis framework of the issuing agency, issuing period, policy tools, and drug supply chain to analyze specific policy items, determine their basic characteristics, and quantitatively analyze them from a policy mix perspective.Results The analysis using policy tools showed that the national government tended to call on stakeholders in all aspects of drug supply to fulfil their responsibilities, and both national and provincial governments tended to use incentive tools, such as opening up urgent drug supply tracks and applying financial incentives to promote drug supply. However, managing stakeholders’ behaviors in drug supply and the capacity building to guarantee drug supply are still lacking and require improvement. From the perspective of the drug supply chain, the national government has paid much attention to the distribution of drugs, whereas attention to the supply of drug substances has been lacking. As various stages of the COVID-19 pandemic, the number of policies related to drug supply increased slowly after a surge at the beginning of the pandemic and then rapidly decreased. From the policy mix perspective, the analysis showed that incentives were lacking in drug research and development, and capacity building was not discussed much in the drug manufacturing process.Conclusions We suggest enhancing the complementarity and cohesion of the policy content issued by national and provincial governments, strengthening the coordination and connection between policymaking bodies, optimizing the internal structure of policy tools, improving the performance of various policy strategies, and using appropriate policy tools to create policies suited to various stages of emergencies and drug supply chains.

Rapid screening of benzyl dodecyl dimethyl ammonium bromide co-metabolic degrading bacteria based on NIR hyperspectral imaging technology.

As a typical disinfectant, the use of benzyl dodecyl dimethyl ammonium bromide (BDAB) has dramatically increased since the emergence of SARS-CoV-2, posing a threat to environmental balance and human health. Screening BDAB co-metabolic degrading bacteria is required for efficient microbial degradation. Conventional methods for screening co-metabolic degrading bacteria are laborious and time-consuming, especially when the number of strains is large. This study aimed to develop a novel method for the rapid screening of BDAB co-metabolic degrading bacteria from the cultured solid medium using near-infrared hyperspectral imaging (NIR-HSI) technology. Based on NIR spectra, the concentration of BDAB in the solid medium can be well predicted by partial least squares regression (PLSR) models, non-destructively and rapidly, with Rc2 > 0.872 and Rcv2 > 0.870. The results show that the predicted BDAB concentrations decrease after degrading bacteria utilization, comparing with the regions where no degrading bacteria grew. The proposed method was applied to directly identify the BDAB co-metabolic degrading bacteria cultured on the solid medium, and two kinds of co-metabolic degrading bacteria RQR-1 and BDAB-1 were correctly identified. This method provides a high-efficiency method for screening BDAB co-metabolic degrading bacteria from a large number of bacteria.

Safety and immunogenicity of heterologous boosting with orally aerosolised or intramuscular Ad5-nCoV vaccine and homologous boosting with inactivated vaccines (BBIBP-CorV or CoronaVac) in children and adolescents: a randomised, open-label, parallel-controlled, non-inferiority, single-centre study.

BACKGROUND: Heterologous booster immunisation with orally administered aerosolised Ad5-nCoV vaccine (AAd5) has been shown to be safe and highly immunogenic in adults. Here, we aimed to assess the safety and immunogenicity of heterologous booster immunisation with orally administered AAd5 in children and adolescents aged 6-17 years who had received two doses of inactivated vaccine (BBIBP-CorV or CoronaVac). METHODS: We did a randomised, open-label, parallel-controlled, non-inferiority study to assess the safety and immunogenicity of heterologous booster immunisation with AAd5 (0·1 mL) or intramuscular Ad5-nCoV vaccine (IMAd5; 0·3 mL) and homologous booster immunisation with inactivated vaccine (BBIBP-CorV or CoronaVac; 0·5 mL) in children (aged 6-12 years) and adolescents (aged 13-17 years) who had received two doses of inactivated vaccine at least 3 months earlier in Hunan, China. Children and adolescents who were previously immunised with two-dose BBIBP-CorV or CoronaVac were recruited for eligibility screening at least 3 months after the second dose. A stratified block method was used for randomisation, and participants were stratified by age and randomly assigned (3:1:1) to receive AAd5, IMAd5, or inactivated vaccine. The study staff and participants were not masked to treatment allocation. Laboratory and statistical staff were masked during the study. In this interim analysis, adverse events within 14 days and geometric mean titre (GMT) of serum neutralising antibodies on day 28 after the booster vaccination, based on the per-protocol population, were used as the primary outcomes. The analysis of non-inferiority was based on comparison using a one-sided 97·5% CI with a non-inferiority margin of 0·67. This study was registered at ClinicalTrials.gov, NCT05330871, and is ongoing. FINDINGS: Between April 17 and May 28, 2022, 436 participants were screened and 360 were enrolled: 220 received AAd5, 70 received IMAd5, and 70 received inactivated vaccine. Within 14 days after booster vaccination, vaccine-related adverse reactions were reported: 35 adverse events (in 13 [12%] of 110 children and 22 [20%] of 110 adolescents) in 220 individuals in the AAd5 group, 35 (in 18 [51%] of 35 children and 17 [49%] of 35 adolescents) in 70 individuals in the IMAd5 group, and 13 (in five [14%] of 35 children and eight [23%] of 35 adolescents) in 70 individuals in the inactivated vaccine group. Solicited adverse reactions were also reported: 34 (13 [12%] of 110 children and 21 [10%] of 110 adolescents) in 220 individuals in the AAd5 group, 34 (17 [49%] of 35 children and 17 [49%] of 35 adolescents) in 70 individuals in the IMAd5 group, and 12 (five [14%] of 35 children and seven [20%] of 35 adolescents) in 70 individuals in the inactivated vaccine group. The GMTs of neutralising antibodies against ancestral SARS-CoV-2 Wuhan-Hu-1 (Pango lineage B) in the AAd5 group were significantly higher than the GMTs in the inactivated vaccine group (adjusted GMT ratio 10·2 [95% CI 8·0-13·1]; p<0·0001). INTERPRETATION: Our study shows that a heterologous booster with AAd5 is safe and highly immunogenic against ancestral SARS-CoV-2 Wuhan-Hu-1 in children and adolescents. FUNDING: National Key R&D Program of China.

Safety, immunogenicity, and efficacy of the mRNA vaccine CS-2034 as a heterologous booster versus homologous booster with BBIBP-CorV in adults aged ≥18 years: a randomised, double-blind, phase 2b trial.

BACKGROUND: Heterologous boosting is suggested to be of use in populations who have received inactivated COVID-19 vaccines. We aimed to assess the safety and immunogenicity of a heterologous vaccination with the mRNA vaccine CS-2034 versus the inactivated BBIBP-CorV as a fourth dose, as well as the efficacy against the SARS-CoV-2 omicron (BA.5) variant. METHODS: This trial contains a randomised, double-blind, parallel-controlled study in healthy participants aged 18 years or older (group A) and an open-label cohort in participants 60 years and older (group B), who had received three doses of inactivated whole-virion vaccines at least 6 months before enrolment. Pregnant women and people with major chronic illnesses or a history of allergies were excluded. Eligible participants in group A were stratified by age (18-59 years and ≥60 years) and then randomised by SAS 9.4 in a ratio of 3:1 to receive a dose of the mRNA vaccine (CS-2034, CanSino, Shanghai, China) or inactivated vaccine (BBIBP-CorV, Sinopharm, Beijing, China). Safety and immunogenicity against omicron variants of the fourth dose were evaluated in group A. Participants 60 years and older were involved in group B for safety observations. The primary outcome was geometric mean titres (GMTs) of the neutralising antibodies against omicron and seroconversion rates against BA.5 variant 28 days after the boosting, and incidence of adverse reactions within 28 days. The intention-to-treat group was involved in the safety analysis, while all patients in group A who had blood samples taken before and after the booster were involved in the immunogenicity analysis. This trial was registered at the Chinese Clinical Trial Registry Centre (ChiCTR2200064575). FINDINGS: Between Oct 13, and Nov 22, 2022, 320 participants were enrolled in group A (240 in the CS-2034 group and 80 in the BBIBP-CorV group) and 113 in group B. Adverse reactions after vaccination were more frequent in CS-2034 recipients (158 [44·8%]) than BBIBP-CorV recipients (17 [21·3%], p<0·0001). However, most adverse reactions were mild or moderate, with grade 3 adverse reactions only reported by eight (2%) of 353 participants receiving CS-2034. Heterologous boosting with CS-2034 elicited 14·4-fold (GMT 229·3, 95% CI 202·7-259·4 vs 15·9, 13·1-19·4) higher concentration of neutralising antibodies to SARS-CoV-2 omicron variant BA.5 than did homologous boosting with BBIBP-CorV. The seroconversion rates of SARS-CoV-2-specific neutralising antibody responses were much higher in the mRNA heterologous booster regimen compared with BBIBP-CorV homologous booster regimen (original strain 47 [100%] of 47 vs three [18·8%] of 16; BA.1 45 [95·8%] of 48 vs two [12·5%] 16; and BA.5 233 [98·3%] of 240 vs 15 [18·8%] of 80 by day 28). INTERPRETATION: Both the administration of mRNA vaccine CS-2034 and inactivated vaccine BBIBP-CorV as a fourth dose were well tolerated. Heterologous boosting with mRNA vaccine CS-2034 induced higher immune responses and protection against symptomatic SARS-CoV-2 omicron infections compared with homologous boosting, which could support the emergency use authorisation of CS-2034 in adults. FUNDING: Science and Technology Commission of Shanghai, National Natural Science Foundation of China, Jiangsu Provincial Science Fund for Distinguished Young Scholars, and Jiangsu Provincial Key Project of Science and Technology Plan. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Detergent modulates the conformational equilibrium of SARS-CoV-2 Spike during cryo-EM structural determination.

The Spike glycoprotein of SARS-CoV-2 mediates viral entry into the host cell via the interaction between its receptor binding domain (RBD) and human angiotensin-converting enzyme 2 (ACE2). Spike RBD has been reported to adopt two primary conformations, a closed conformation in which the binding site is shielded and unable to interact with ACE2, and an open conformation that is capable of binding ACE2. Many structural studies have probed the conformational space of the homotrimeric Spike from SARS-CoV-2. However, how sample buffer conditions used during structural determination influence the Spike conformation is currently unclear. Here, we systematically explored the impact of commonly used detergents on the conformational space of Spike. We show that in the presence of detergent, the Spike glycoprotein predominantly occupies a closed conformational state during cryo-EM structural determination. However, in the absence of detergent, such conformational compaction was neither observed by cryo-EM, nor by single-molecule FRET designed to visualize the movement of RBD in solution in real-time. Our results highlight the highly sensitive nature of the Spike conformational space to buffer composition during cryo-EM structural determination, and emphasize the importance of orthogonal biophysical approaches to validate the structural models obtained.

COVID-19-related conspiracy theories in China

Many COVID-19 conspiracy theories implicate China and its agents, whether implicitly or explicitly, as conspirators with potentially malicious intent behind the current pandemic. We set out to explore whether Chinese people believe in pandemic-related conspiracy theories, and if so, how do their secure (in-group identification) and defensive (collective narcissism) in-group positivity predict their conspiracy beliefs. We hypothesized that national identification would negatively predict the tendency to attribute responsibility to an in-group, thus predicting less risk-rejection conspiracy theory beliefs (e.g., COVID-19 is a hoax). In contrast, national collective narcissism would positively predict the tendency to attribute responsibility for the pandemic to an out-group, which in turn would validate conspiracy theories that acknowledge the risk of the pandemic (e.g., COVID-19 is a bioweapon). To test these predictions, we collected data in China (n = 1,200) in April 2020. Supporting our predictions, national identification was negatively associated with risk-rejection conspiracy beliefs via in-group attribution, whereas national collective narcissism was positively associated with risk-acceptance conspiracy beliefs via out-group attribution.

Specific pupylation as IDEntity reporter (SPIDER) for the identification of protein-biomolecule interactions.

Protein-biomolecule interactions play pivotal roles in almost all biological processes. For a biomolecule of interest, the identification of the interacting protein(s) is essential. For this need, although many assays are available, highly robust and reliable methods are always desired. By combining a substrate-based proximity labeling activity from the pupylation pathway of Mycobacterium tuberculosis and the streptavidin (SA)-biotin system, we developed the Specific Pupylation as IDEntity Reporter (SPIDER) method for identifying protein-biomolecule interactions. Using SPIDER, we validated the interactions between the known binding proteins of protein, DNA, RNA, and small molecule. We successfully applied SPIDER to construct the global protein interactome for m6A and mRNA, identified a variety of uncharacterized m6A binding proteins, and validated SRSF7 as a potential m6A reader. We globally identified the binding proteins for lenalidomide and CobB. Moreover, we identified SARS-CoV-2-specific receptors on the cell membrane. Overall, SPIDER is powerful and highly accessible for the study of protein-biomolecule interactions.

Roles of p53-Mediated Host-Virus Interaction in Coronavirus Infection.

The emergence of the SARS-CoV-2 coronavirus has garnered global attention due to its highly pathogenic nature and the resulting health crisis and economic burden. Although drugs such as Remdesivir have been considered a potential cure by targeting the virus on its RNA polymerase, the high mutation rate and unique 3' to 5' exonuclease with proofreading function make it challenging to develop effective anti-coronavirus drugs. As a result, there is an increasing focus on host-virus interactions because coronaviruses trigger stress responses, cell cycle changes, apoptosis, autophagy, and the dysregulation of immune function and inflammation in host cells. The p53 tumor suppressor molecule is a critical regulator of cell signaling pathways, cellular stress responses, DNA repair, and apoptosis. However, viruses can activate or inhibit p53 during viral infections to enhance viral replication and spread. Given its pivotal role in cell physiology, p53 represents a potential target for anti-coronavirus drugs. This review aims to summarize the relationship between p53 and coronaviruses from various perspectives, to shed light on potential targets for antiviral drug development and vaccine design.

Triacetyl Resveratrol Inhibits PEDV by Inducing the Early Apoptosis In Vitro.

PEDV represents an ancient Coronavirus still causing huge economic losses to the porcine breeding industry. Resveratrol has excellent antiviral effects. Triacetyl resveratrol (TCRV), a novel natural derivative of resveratrol, has been recently discovered, and its pharmacological effects need to be explored further. This paper aims to explore the relationship between PEDV and TCRV, which offers a novel strategy in the research of antivirals. In our study, Vero cells and IPEC-J2 cells were used as an in vitro model. First, we proved that TCRV had an obvious anti-PEDV effect and a strong inhibitory effect at different time points. Then, we explored the mechanism of inhibition of PEDV infection by TCRV. Our results showed that TCRV could induce the early apoptosis of PEDV-infected cells, in contrast to PEDV-induced apoptosis. Moreover, we observed that TCRV could promote the expression and activation of apoptosis-related proteins and release mitochondrial cytochrome C into cytoplasm. Based on these results, we hypothesized that TCRV induced the early apoptosis of PEDV-infected cells and inhibited PEDV infection by activating the mitochondria-related caspase pathway. Furthermore, we used the inhibitors Z-DEVD-FMK and Pifithrin-α (PFT-α) to support our hypothesis. In conclusion, the TCRV-activated caspase pathway triggered early apoptosis of PEDV-infected cells, thereby inhibiting PEDV infections.

COVID-19-related conspiracy theories in China: The role of secure versus defensive in-group positivity and responsibility attributions

Many COVID-19 conspiracy theories implicate China and its agents, whether implicitly or explicitly, as conspirators with potentially malicious intent behind the current pandemic. We set out to explore whether Chinese people believe in pandemic-related conspiracy theories, and if so, how do their secure (in-group identification) and defensive (collective narcissism) in-group positivity predict their conspiracy beliefs. We hypothesized that national identification would negatively predict the tendency to attribute responsibility to an in-group, thus predicting less risk-rejection conspiracy theory beliefs (e.g., COVID-19 is a hoax). In contrast, national collective narcissism would positively predict the tendency to attribute responsibility for the pandemic to an out-group, which in turn would validate conspiracy theories that acknowledge the risk of the pandemic (e.g., COVID-19 is a bioweapon). To test these predictions, we collected data in China (n = 1,200) in April 2020. Supporting our predictions, national identification was negatively associated with risk-rejection conspiracy beliefs via in-group attribution, whereas national collective narcissism was positively associated with risk-acceptance conspiracy beliefs via out-group attribution. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

SARS-CoV-2 ORF8 Protein Induces Endoplasmic Reticulum Stress-like Responses and Facilitates Virus Replication by Triggering Calnexin: an Unbiased Study.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the viral pathogen responsible for the worldwide coronavirus disease 2019 (COVID-19) pandemic. The novel SARS-CoV-2 ORF8 protein is not highly homologous with known proteins, including accessory proteins of other coronaviruses. ORF8 contains a 15-amino-acid signal peptide in the N terminus that localizes the mature protein to the endoplasmic reticulum. Oligomannose-type glycosylation has been identified at the N78 site. Here, the unbiased molecular functions of ORF8 are also demonstrated. Via an immunoglobulin-like fold in a glycan-independent manner, both exogenous and endogenous ORF8 interacts with human calnexin and HSPA5. The key ORF8-binding sites of Calnexin and HSPA5 are indicated on the globular domain and the core substrate-binding domain, respectively. ORF8 induces species-dependent endoplasmic reticulum stress-like responses in human cells exclusively via the IRE1 branch, including intensive HSPA5 and PDIA4 upregulation, with increases in other stress-responding effectors, including CHOP, EDEM and DERL3. ORF8 overexpression facilitates SARS-CoV-2 replication. Both stress-like responses and viral replication induced by ORF8 have been shown to result from triggering the Calnexin switch. Thus, ORF8 serves as a key unique virulence gene of SARS-CoV-2, potentially contributing to COVID-19-specific and/or human-specific pathogenesis. IMPORTANCE Although SARS-CoV-2 is basically regarded as a homolog of SARS-CoV, with their genomic structure and the majority of their genes being highly homologous, the ORF8 genes of SARS-CoV and SARS-CoV-2 are distinct. The SARS-CoV-2 ORF8 protein also shows little homology with other viral or host proteins and is thus regarded as a novel special virulence gene of SARS-CoV-2. The molecular function of ORF8 has not been clearly known until now. Our results reveal the unbiased molecular characteristics of the SARS-CoV-2 ORF8 protein and demonstrate that it induces rapidly generated but highly controllable endoplasmic reticulum stress-like responses and facilitates virus replication by triggering Calnexin in human but not mouse cells, providing an explanation for the superficially known in vivo virulence discrepancy of ORF8 between SARS-CoV-2-infected patients and mouse.

Prediction and Verification of Curcumin as a Potential Drug for Inhibition of PDCoV Replication in LLC-PK1 Cells.

Porcine deltacoronavirus (PDCoV) is an emerging swine enteropathogenic coronavirus (CoV) that causes lethal watery diarrhea in neonatal pigs and poses economic and public health burdens. Currently, there are no effective antiviral agents against PDCoV. Curcumin is the active ingredient extracted from the rhizome of turmeric, which has a potential pharmacological value because it exhibits antiviral properties against several viruses. Here, we described the antiviral effect of curcumin against PDCoV. At first, the potential relationships between the active ingredients and the diarrhea-related targets were predicted through a network pharmacology analysis. Twenty-three nodes and 38 edges were obtained using a PPI analysis of eight compound-targets. The action target genes were closely related to the inflammatory and immune related signaling pathways, such as the TNF signaling pathway, Jak-STAT signaling pathway, and so on. Moreover, IL-6, NR3C2, BCHE and PTGS2 were identified as the most likely targets of curcumin by binding energy and 3D protein-ligand complex analysis. Furthermore, curcumin inhibited PDCoV replication in LLC-PK1 cells at the time of infection in a dose-dependent way. In poly (I:C) pretreated LLC-PK1 cells, PDCoV reduced IFN-ß production via the RIG-I pathway to evade the host's antiviral innate immune response. Meanwhile, curcumin inhibited PDCoV-induced IFN-ß secretion by inhibiting the RIG-I pathway and reduced inflammation by inhibiting IRF3 or NF-κB protein expression. Our study provides a potential strategy for the use of curcumin in preventing diarrhea caused by PDCoV in piglets.

Prevalence and risk factors for anxiety and depression among community dwelling patients with cervical spondylosis during the COVID-19 pandemic.

Background: The emergence of COVID-19 and its unfavorable consequences lead to disease fear and other related mental health problems for individuals worldwide. This study aimed to analyze the prevalence and relevant factors of anxiety and depression among community dwelling cervical spondylosis (CS) patients, and to explore the relationship between fear of COVID-19 and anxiety and depression, so as to provide scientific basis for improving their mental health. Methods: A community-based cross-sectional study was conducted among a cohort of 556 CS patients by using convenient sampling. These participants were asked to complete a demographic questionnaire, the Hospital Anxiety and Depression Scale (HADS), and the Fear of COVID-19 Scale (FCV-19S). The Chi-square test was used to determine the differences among categorical variables. Binary stepwise logistic regression was used to determine predictors of anxiety and depression. Results: The median HADS-A score was 5 (interquartile interval 2-7), and the median HADS-D score was 4 (interquartile interval 2-8). In this study, the prevalence of anxiety and depression was 25.0% and 26.6%, respectively. Gender and comorbid chronic diseases were predictors of depressive symptoms. In addition, fear of COVID-19 was related to depression and anxiety among community dwelling CS patients. Conclusion: Approximately one quarter of community dwelling CS patients were suffering depression or anxiety. Our findings could provide a basis for the development of psychological crisis intervention strategies for CS patients under public health emergencies in the future.

Remote scoring models of rigidity and postural stability of Parkinson's disease based on indirect motions and a low-cost RGB algorithm.

Background and objectives: The Movement Disorder Society's Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS III) is mostly common used for assessing the motor symptoms of Parkinson's disease (PD). In remote circumstances, vision-based techniques have many strengths over wearable sensors. However, rigidity (item 3.3) and postural stability (item 3.12) in the MDS-UPDRS III cannot be assessed remotely since participants need to be touched by a trained examiner during testing. We developed the four scoring models of rigidity of the neck, rigidity of the lower extremities, rigidity of the upper extremities, and postural stability based on features extracted from other available and touchless motions. Methods: The red, green, and blue (RGB) computer vision algorithm and machine learning were combined with other available motions from the MDS-UPDRS III evaluation. A total of 104 patients with PD were split into a train set (89 individuals) and a test set (15 individuals). The light gradient boosting machine (LightGBM) multiclassification model was trained. Weighted kappa (k), absolute accuracy (ACC ± 0), and Spearman's correlation coefficient (rho) were used to evaluate the performance of model. Results: For model of rigidity of the upper extremities, k = 0.58 (moderate), ACC ± 0 = 0.73, and rho = 0.64 (moderate). For model of rigidity of the lower extremities, k = 0.66 (substantial), ACC ± 0 = 0.70, and rho = 0.76 (strong). For model of rigidity of the neck, k = 0.60 (moderate), ACC ± 0 = 0.73, and rho = 0.60 (moderate). For model of postural stability, k = 0.66 (substantial), ACC ± 0 = 0.73, and rho = 0.68 (moderate). Conclusion: Our study can be meaningful for remote assessments, especially when people have to maintain social distance, e.g., in situations such as the coronavirus disease-2019 (COVID-19) pandemic.

Durability of neutralization against Omicron subvariants after vaccination and breakthrough infection.

Booster immunizations and breakthrough infections can elicit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariant neutralizing activity. However, the durability of the neutralization response is unknown. We characterize the sensitivity of BA.1, BA.2, BA.2.75, BA.4/BA.5, BF.7, BQ.1.1, and XBB against neutralizing antibodies from vaccination, hybrid immunity, and breakthrough infections 4-6 months after vaccination and infection. We show that a two-dose CoronaVac or a third-dose ZF2001 booster elicits limited neutralization against Omicron subvariants 6 months after vaccination. Hybrid immunity as well as Delta, BA.1, and BA.2 breakthrough infections induce long-term persistence of the antibody response, and over 70% of sera neutralize BA.1, BA.2, BA.4/BA.5, and BF.7. However, BQ.1.1 and XBB, followed by BA.2.75, are more resistant to neutralization, with neutralizing titer reductions of ∼9- to 41-fold, ∼16- to 63-fold, and ∼4- to 25-fold, respectively. These data highlight additional vaccination in CoronaVac- or ZF2001-vaccinated individuals and provide insight into the durability of neutralization against Omicron subvariants.

Durability of neutralization against Omicron subvariants after vaccination and breakthrough infection

Booster immunizations and breakthrough infections can elicit SARS-CoV-2 Omicron subvariants neutralizing activity. However, the durability of the neutralization response is unknown. We characterize the sensitivity of BA.1, BA.2, BA.2.75, BA.4/BA.5, BF.7, BQ.1.1, and XBB against neutralizing antibodies from vaccination, hybrid immunity, and breakthrough infections 4–6 months after vaccination and infection. We show that a two-dose CoronaVac or a third-dose ZF2001 booster elicits limited neutralization against Omicron subvariants 6 months after vaccination. Hybrid immunity as well as Delta, BA.1, and BA.2 breakthrough infections induce long-term persistence of the antibody response, and over 70% of sera neutralize BA.1, BA.2, BA.4/BA.5, and BF.7. However, BQ.1.1 and XBB, followed by BA.2.75, are more resistant to neutralization, with neutralizing titer reductions of ∼9- to 41-fold, ∼16- to 63-fold, and ∼4- to 25-fold, respectively. These data highlight additional vaccination in CoronaVac- or ZF2001-vaccinated individuals and provide insight into the durability of neutralization against Omicron subvariants. Graphical Zhu et al. report that a two-dose CoronaVac or ZF2001 booster elicits limited neutralization against Omicron subvariants 6 months after vaccination. Hybrid immunity and Delta, BA.1 and BA.2 breakthrough infection induce neutralization against earlier Omicron variants, but not for BQ.1.1 and XBB, up to 5 months after vaccination or infection.

Willingness to Use Mobile Health Devices in the Post-COVID-19 Era: Nationwide Cross-sectional Study in China.

BACKGROUND: Despite the increased development and use of mobile health (mHealth) devices during the COVID-19 pandemic, there is little knowledge of willingness of the Chinese people to use mHealth devices and the key factors associated with their use in the post-COVID-19 era. Therefore, a more comprehensive and multiangle investigation is required. OBJECTIVE: We aimed to probe Chinese attitudes regarding the use of mHealth and analyze possible associations between the attitude of willingness to use mHealth devices and some factors based on the socioecological model. METHODS: A survey was conducted using quota sampling to recruit participants from 148 cities in China between June 20 and August 31, 2022. Data from the survey were analyzed using multiple stepwise regression to examine the factors associated with willingness to use mHealth devices. Standardized regression coefficients (ß) and 95% CIs were calculated using multiple stepwise regression. RESULTS: The survey contained a collection of 21,916 questionnaires and 21,897 were valid questionnaires, with a 99.91% effective response rate. The median score of willingness to use mHealth in the post-COVID-19 era was 70 points on a scale from 0 to 100. Multiple stepwise regression results showed that the female gender (ß=.03, 95% CI 1.04-2.35), openness personality trait (ß=.05, 95% CI 0.53-0.96), higher household per capita monthly income (ß=.03, 95% CI 0.77-2.24), and commercial and multiple insurance (ß=.04, 95% CI 1.77-3.47) were factors associated with the willingness to use mHealth devices. In addition, people with high scores of health literacy (ß=.13, 95% CI 0.53-0.68), self-reported health rating (ß=.22, 95% CI 0.24-0.27), social support (ß=.08, 95% CI 0.40-0.61), family health (ß=.03, 95% CI 0.03-0.16), neighbor relations (ß=.12, 95% CI 2.09-2.63), and family social status (ß=.07, 95% CI 1.19-1.69) were more likely to use mHealth devices. CONCLUSIONS: On the basis of the theoretical framework of socioecological model, this study identified factors specifically associated with willingness of the Chinese people to use mHealth devices in the post-COVID-19 era. These findings provide reference information for the research, development, promotion, and application of future mHealth devices.

Neutralization sensitivity, fusogenicity, and infectivity of Omicron subvariants.

BACKGROUND: The emergence of SARS-CoV-2 Omicron subvariants has raised questions regarding resistance to immunity by natural infection or immunization. We examined the sensitivity of Delta and Omicron subvariants (BA.1, BA.1.1, BA.2, BA.2.12.1, BA.4/5, and BA.3) to neutralizing antibodies from BBIBP-CorV-vaccinated and BBIBP-CorV- or ZF2001-boosted individuals, as well as individuals with Delta and BA.1 breakthrough infections, and determined their fusogenicity and infectivity. METHODS: In this cross-sectional study, serum samples from two doses of BBIBP-CorV-vaccinated individuals 1 (n = 36), 3 (n = 36), and 7 (n = 37) months after the second dose; BBIBP-CorV- (n = 25) or ZF2001-boosted (n = 30) individuals; and fully vaccinated individuals with Delta (n = 30) or BA.1 (n = 26) infection were collected. The serum-neutralizing reactivity and potency of bebtelovimab were assessed against D614G, Delta, and Omicron subvariants (BA.1, BA.1.1, BA.2, BA.2.12.1, BA.4/5, and BA.3) through a pseudovirus neutralization assay. The fusogenicity and infectivity of D614G, Delta, and Omicron subvariants were determined by cell-cell fusion assay and pseudovirus infection assay, respectively. RESULTS: Omicron subvariants markedly escaped vaccine-elicited neutralizing antibodies after two doses of BBIBP-CorV with comparable efficiency. A third dose vaccination of BBIBP-CorV or ZF2001 increased neutralizing antibody titers and breadth against Delta and three Omicron subvariants. Delta and BA.1 breakthrough infections induced comparable neutralizing antibody titers against D614G and Delta variants, whereas BA.1 breakthrough infections elicited a stronger and broader antibody response against three Omicron subvariants than Delta breakthrough infections. BA.2.12.1 and BA.4/5 are more resistant to immunity induced by breakthrough infections. Bebtelovimab had no significant loss of potency against the Delta and Omicron subvariants. Cell culture experiments showed Omicron subvariants to be less fusogenic and have higher infectivity than D614G and Delta with comparable efficiency. CONCLUSIONS: These findings have important public health implications and highlight the importance of repeated exposure to SARS-CoV-2 antigens to broaden the neutralizing antibody response against Omicron subvariants.