Impact of COVID-19 prevention and control on tuberculosis and scarlet fever in China's Guizhou.

China has implemented a series of long-term measures to control the spread of COVID-19, however, the effects of these measures on other chronic and acute respiratory infectious diseases remain unclear. Tuberculosis (TB) and scarlet fever (SF) serve as representatives of chronic and acute respiratory infectious diseases, respectively. In China's Guizhou province, an area with a high prevalence of TB and SF, approximately 40,000 TB cases and hundreds of SF cases are reported annually. To assess the impact of COVID-19 prevention and control on TB and SF in Guizhou, the exponential smoothing method was employed to establish a prediction model for analyzing the influence of COVID-19 prevention and control on the number of TB and SF cases. Additionally, spatial aggregation analysis was utilized to describe spatial changes in TB and SF before and after the COVID-19 outbreak. The parameters of the TB and SF prediction models are R2 = 0.856, BIC = 10.972 and R2 = 0.714, BIC = 5.325, respectively. TB and SF cases declined rapidly at the onset of COVID-19 prevention and control measures, with the number of SF cases decreasing for about 3-6 months and the number of TB cases remaining in decline for 7 months after the 11th month. The spatial aggregation of TB and SF did not change significantly before and after the COVID-19 outbreak but exhibited a marked decrease. These findings suggest that China's COVID-19 prevention and control measures also reduced the prevalence of TB and SF in Guizhou. These measures may have a long-term positive impact on TB, but a short-term effect on SF. Areas with high TB prevalence may continue to experience a decline due to the implementation of COVID-19 preventive measures in the future.

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.

Comprehensive Landscape of Heparin Therapy for COVID-19

The pandemic coronavirus disease 2019 (COVID-19), caused by the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is rapidly spreading globally. Clinical observations found that systemic symptoms caused by SARS-CoV-2 infection are attenuated when using the anticoagulant agent heparin, indicating that heparin may play other roles in managing COVID-19, in addition to prevention of pulmonary thrombosis. Several biochemical studies show strong binding of heparin and heparin-like molecules to the Spike protein, which resulted in inhibition of viral infection to cells. The clinical observations and in vitro studies argue for a potential multiple-targeting effects of heparin. However, adverse effects of heparin administration and some of the challenges using heparin therapy for SARS-CoV-2 infection need to be considered. This review discusses the pharmacological mechanisms of heparin regarding its anticoagulant, anti-inflammatory and direct antiviral activities, providing current evidence concerning the effectiveness and safety of heparin therapy for this major public health emergency.

Emerging patterns of substance abuse and related treatment in China.

PURPOSE OF REVIEW: The situation of China drug use has seen dramatic changes in recent years. The aim of this review is to give a perspective of the current situation of drug abuse, the problems associated with it, and the strategy to control it in China. RECENT FINDINGS: The number of registered drug users and newly discovered drug users had declined for 5 consecutive years, Moreover, the scaling down of drug trafficking and drug-related crimes had been seen for recent years. There are four main drug treatment modalities in China. The drug abuse and its related problems in China face new challenges, including the impact of the coronavirus disease 2019 pandemic, the role of compulsory treatment is overemphasized, the voluntary treatment facilities and community treatment cannot meet the requirements of Chinese society, and the coordination among government departments in drug control and treatment in China need to improved. SUMMARY: With years of the joint efforts, the overall drug situation kept improving. The drug abuse and its related problems in China still is a problem, and require effective and immediate interventions.

Computational Investigations for Identification of Bioactive Molecules from Baccaurea ramiflora and Bergenia ciliata as Inhibitors of SARS-CoV-2 Mpro

In this study, a hybrid compound library of 72 phytocompounds from two antiviral medicinal plants (Baccaurea ramiflora and Bergenia ciliata) was computationally investigated for their inhibitory potential against SARS-CoV-2 Mpro. Molecular docking showed that 6-O-vanilloylicariside B5, 6-O-vanilloylisotachioside, leucoanthocyanidin 4-(2-galloyl), and p-hydroxybenzoyl bergenin has good binding affinity for Mpro. However, p-hydroxybenzoyl bergenin did not bind at the catalytic cavity. The RMSD and RMSF data obtained from 100 ns MD simulations revealed stable protein–ligand complexes for 6-O-vanilloylicariside B5, 6-O-vanilloylisotachioside, leucoanthocyanidin 4-(2-galloyl). Ligand trajectory study found 6-O-vanilloylisotachioside and leucoanthocyanidin 4-(2-galloyl) to be stable. Studies on ligand interaction profile and timeline interaction profile showed that 6-O-vanilloylisotachioside and leucoanthocyanidin 4-(2-galloyl) interacted with HIS41–CYS145 dyad and other crucial amino acids of the catalytic site cavity during the entire 100 ns MD simulations. Molecular mechanics generalized born solvent accessibility binding free energy calculations, density functional theory analysis, quantitative structure–property relationship studies, and ADMET profiling of 6-O-vanilloylisotachioside and leucoanthocyanidin 4-(2-galloyl) supported the results generated by molecular docking and MD simulations studies. Based on the current computational investigations, we conclude that that 6-O-vanilloylisotachioside of B. ramiflora and leucoanthocyanidin 4-(2-galloyl) of B. ciliata are two potential inhibitors of SARS-CoV-2 Mpro that are worthy of further investigations.

Simultaneous determination of multiple components in rat plasma by UHPLC-sMRM for pharmacokinetic studies after oral administration of Qingjin Yiqi Granules

As a Traditional Chinese Medicine prescription, Qingjin Yiqi Granules (QJYQ) provides an effective treatment for patients recovering from COVID-19. However, the pharmacokinetics characteristics of the main components of QJYQ in vivo are still unknown. An efficacious ultra-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was developed and validated for the simultaneous determination of 33 components in rat plasma after oral administration of QJYQ. The plasma samples were precipitated with 400 µL methanol/acetonitrile (1/1, v/v) and analyzed in scheduled multiple reaction monitoring mode. The linear relationship of the 33 components was good (r > 0.9928). The lower limit of quantification for 33 components ranged from 0.4–60.5 ng/mL. The average recoveries and matrix effects of the analytes ranged from 72.9% to 115.0% with RSD of 1.4%–15.0%. All inter-day and intra-day RSDs were within 15.0%. After oral administration (3.15 g/kg), the validated approach was effectively applied to the pharmacokinetics of main components of QJYQ. Finally, fifteen main constituents of QJYQ with large plasma exposure were obtained, including baicalin, wogonoside, wogonin, apigenin-7-O-glucuronide, verbenalin, isoferulic acid, hesperidin, liquiritin, harpagide, protocatechuic acid, p-Coumaric acid, ferulic acid, sinapic acid, liquiritin apioside and glycyrrhizic acid. The present research lays a foundation for clarifying the therapeutic material basis of QJYQ and provides a reference for further scientific research and clinical application of QJYQ.

Animal experiments on respiratory viruses and analogous studies of infection factors for interpersonal transmission.

Air pollution caused by SARS-CoV-2 and other viruses in human settlements will have a great impact on human health, but also a great risk of transmission. The transmission power of the virus can be represented by quanta number in the Wells-Riley model. In order to solve the problem of different dynamic transmission scenarios, only a single influencing factor is considered when predicting the infection rate, which leads to large differences in quanta calculated in the same space. In this paper, an analog model is established to define the indoor air cleaning index RL and the space ratio parameter. Based on infection data analysis and rule summary in animal experiments, factors affecting quanta in interpersonal communication were explored. Finally, by analogy, the factors affecting person-to-person transmission mainly include viral load of infected person, distance between individuals, etc., the more severe the symptoms, the closer the number of days of illness to the peak, and the closer the distance to the quanta. In summary, there are many factors that affect the infection rate of susceptible people in the human settlement environment. This study provides reference indicators for environmental governance under the COVID-19 epidemic, provides reference opinions for healthy interpersonal communication and human behavior, and provides some reference for accurately judging the trend of epidemic spread and responding to the epidemic.

Application of remote fetal heart rate monitoring via internet in late pregnancy during the COVID-19 pandemic.

BACKGROUND: Internet-related technologies have rapidly developed and started to impact the traditional medical practices, which combined wireless communication technology as well as "cloud service" technology with electronic fetal heart monitoring have become a mainstream tendency. OBJECTIVE: To investigate the clinical application value of remote fetal heart rate monitoring mode (RFHRM) on late pregnancy during the coronavirus disease (COVID-19) pandemic. METHODS: From March 2021 to February 2022, we recruited 800 cases of pregnant women received prenatal examination at the Anhui Province Maternity and Child Healthcare Hospital. These pregnant women were randomly divided into two groups: the control group (n= 400), which was given traditional management, and the observation group (n= 400), which received remote monitoring technology on this basis. The two groups were compared with neonatal asphyxia, pregnancy outcomes, Edinburgh postnatal depression scale scores (EPDS), prenatal examination expenses and total time consumption. RESULTS: There were no statistically significant differences between the groups in pregnancy outcome and neonatal outcome (P> 0.05). However, total EPDS score of 12.5% pregnant women in the observation group were higher than 12. The TPE group had significantly higher mean EPDS scores compared with the RFHRM group (7.79 ± 3.58 vs 5.10 ± 3.07; P< 0.05). The results showed a significant difference in maternity expenses (2949.83 ± 456.07 vs 2455.37 ± 506.67; P< 0.05) and total time consumption (42.81 ± 7.60 vs 20.43 ± 4.16; P< 0.05) between the groups. CONCLUSION: Remote fetal heart rate monitoring via internet served as an innovative, acceptable, safe and effective reduced-frequency prenatal examination model without affecting the outcome of perinatology of pregnant women with different risk factors.

Change and convergence of innovation efficiency among listed health companies in China: Empirical study based on the DEA-Malmquist model.

This study investigates the present situation of and changing trend in the innovation efficiency of health industry enterprises in China. Based on panel data for 192 listed health companies in China from 2015 to 2020, we analyse innovation efficiency using the DEA-Malmquist index and test convergence using σ-convergence and ß-convergence models. From 2016 to 2019, comprehensive average innovation efficiency increased from 0.6207 to 0.7220 and average innovation efficiency decreased significantly in 2020. The average Malmquist index was 1.072. Innovation efficiency in China as a whole, North China, South China, and Northwest China showed σ-convergence. Except for the Northwest region, absolute ß-convergence was evident, and in China as a whole, North China, Northeast China, East China, and South China, conditional ß-convergence was evident. Overall innovation efficiency of these companies has increased annually but needs further improvement, and the COVID-19 pandemic has had a great negative impact on it. Innovation efficiency and trends in it vary across regions. Furthermore, we should pay attention to the impacts of innovation infrastructure and government scientific and technological support on innovation efficiency.

Centrifugal microfluidic-based multiplex recombinase polymerase amplification assay for rapid detection of SARS-CoV-2.

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.

Duration of SARS-CoV-2 Serum-Neutralizing Antibodies Against SARS-CoV-2 Dependent on the Individual.

We investigated the persistence of SARS-CoV-2-specific neutralizing antibodies in serum (CoV-2-SNAb) against the "WH-Human 1" coronavirus in 57 convalescent persons from January 2020 to January 2021. The CoV-2-SNAb response against authentic "WH-Human 1" showed a significant (p < 0.01) neutralizing high effect (≥95%) in the following manner: by 94.7% neutralization for up to 6 months, by 73.1% for up to 8 months, and by 31.7% for up to 10 months in correlation with a significant decrease in the concentration of the virus determined by SARS-CoV-2 spike protein extracellular domain and spike-receptor-binding domain (S-RBD). There was neutralizing effect (<95%) when the S-RBD optical density (OD) value was more than 1.0, showing a suitable threshold of S-RBD = 1.0 (antibody-tittering, OD). However, in some convalescent persons, no neutralizing effect (<95%) was observed although the SARS-CoV-2-specific neutralizing antibodies were bound to the S-RBD (OD >1.0). The neutralization of the virus in these cases may not involve S-RBD, but rather B- and T cell memory responses in overall immunity, using the threshold value (OD = 1.0) of S-RBD as a simple and effective method to determine the neutralization effect of the antibody efficacy and use of vaccination in combination with a standard pseudovirus neutralizing assay. We suggest that convalescent persons should contact their physicians 6-month postinfection to test the function of their serum neutralizing antibodies and determine whether administering a SARS-CoV-2 vaccine is necessary to prevent the development of severe illness in the future.

Isolation of a Novel Bat Rhabdovirus with Evidence of Human Exposure in China.

Bats are well-recognized reservoirs of zoonotic viruses. Several spillover events from bats to humans have been reported, causing severe epidemic or endemic diseases including severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), SARS-CoV, Middle East respiratory syndrome-CoV (MERS-CoV), henipaviruses, and filoviruses. In this study, a novel rhabdovirus species, provisionally named Rhinolophus rhabdovirus DPuer (DPRV), was identified from the horseshoe bat (Rhinolophus affinis) in Yunnan province, China, using next-generation sequencing. DPRV shedding in the spleen, liver, lung, and intestinal contents of wild bats with high viral loads was detected by real-time quantitative PCR, indicating that DPRV has tropism for multiple host tissues. Furthermore, DPRV can replicate in vitro in multiple mammalian cell lines, including BHK-21, A549, and MA104 cells, with the highest efficiency in hamster kidney cell line BHK-21, suggesting infectivity of DPRV in these cell line-derived hosts. Ultrastructure analysis revealed a characteristic bullet-shaped morphology and tightly clustered distribution of DPRV particles in the intracellular space. DPRV replicated efficiently in suckling mouse brains and caused death of suckling mice; death rates increased with passaging of DPRV in suckling mice. Moreover, 421 serum samples were collected from individuals who lived near the bat collection site and had fever symptoms within 1 year. DPRV-specific antibodies were detected in 20 (4.75%) human serum samples by indirect immunofluorescence assay. Furthermore, 10 (2.38%) serum samples were DPRV positive according to plaque reduction neutralization assay, which revealed potential transmission of DPRV from bats to humans and highlighted the potential public health risk. Potential vector association with DPRV was not found with negative viral RNA in bloodsucking arthropods. IMPORTANCE We identified a novel rhabdovirus from the horseshoe bat (Rhinolophus thomasi) in China with probable infectivity in humans. DPRV was isolated in vitro from several mammalian cell lines, indicating wide host tropism, excluding bats, of DPRV. DPRV replicated in the brains of suckling mice, and the death rate of suckling mice increased with passaging of DPRV in vivo. Serological tests indicated the possible infectivity of DPRV in humans and the potential transmission to humans. The present findings provide preliminary evidence for the potential risk of DPRV to public health. Additional studies with active surveillance are needed to address interspecies transmission and determine the pathogenicity of DPRV in humans.

A new polysaccharide platform constructs self-adjuvant nanovaccines to enhance immune responses.

BACKGROUND: Nanovaccines have shown the promising potential in controlling and eradicating the threat of infectious diseases worldwide. There has been a great need in developing a versatile strategy to conveniently construct diverse types of nanovaccines and induce potent immune responses. To that end, it is critical for obtaining a potent self-adjuvant platform to assemble with different types of antigens into nanovaccines. RESULTS: In this study, we identified a new natural polysaccharide from the rhizomes of Bletilla striata (PRBS), and used this polysaccharide as a platform to construct diverse types of nanovaccines with potent self-adjuvant property. In the construction process of SARS-CoV-2 nanovaccine, PRBS molecules and RBD protein antigens were assembled into ~ 300 nm nanoparticles by hydrogen bond. For HIV nanovaccine, hydrophobic effect dominantly drove the co-assembly between PRBS molecules and Env expression plasmid into ~ 350 nm nanospheres. Importantly, PRBS can potently activate the behaviors and functions of multiple immune cells such as macrophages, B cells and dendritic cells. Depending on PRBS-mediated immune activation, these self-adjuvant nanovaccines can elicit significantly stronger antigen-specific antibody and cellular responses in vivo, in comparison with their corresponding traditional vaccine forms. Moreover, we also revealed the construction models of PRBS-based nanovaccines by analyzing multiple assembly parameters such as bond energy, bond length and interaction sites. CONCLUSIONS: PRBS, a newly-identified natural polysaccharide which can co-assemble with different types of antigens and activate multiple critical immune cells, has presented a great potential as a versatile platform to develop potent self-adjuvant nanovaccines.

Corrigendum: Fc engineered ACE2-Fc is a potent multifunctional agent targeting SARS-CoV2.

[This corrects the article .].

How do temperature, humidity, and air saturation state affect the COVID-19 transmission risk?

Environmental parameters have a significant impact on the spread of respiratory viral diseases (temperature (T), relative humidity (RH), and air saturation state). T and RH are strongly correlated with viral inactivation in the air, whereas supersaturated air can promote droplet deposition in the respiratory tract. This study introduces a new concept, the dynamic virus deposition ratio (α), that reflects the dynamic changes in viral inactivation and droplet deposition under varying ambient environments. A non-steady-state-modified Wells-Riley model is established to predict the infection risk of shared air space and highlight the high-risk environmental conditions. Findings reveal that a rise in T would significantly reduce the transmission of COVID-19 in the cold season, while the effect is not significant in the hot season. The infection risk under low-T and high-RH conditions, such as the frozen seafood market, is substantially underestimated, which should be taken seriously. The study encourages selected containment measures against high-risk environmental conditions and cross-discipline management in the public health crisis based on meteorology, government, and medical research.

An efficient method for qualitation and quantitation of multi-components of the herbal medicine Qingjin Yiqi Granules.

Qingjin Yiqi Granules (QJYQ) is a Traditional Chinese Medicines (TCMs) prescription for the patients with post-COVID-19 condition. It is essential to carry out the quality evaluation of QJYQ. A comprehensive investigation was conducted by establishing deep-learning assisted mass defect filter (deep-learning MDF) mode for qualitative analysis, ultra-high performance liquid chromatography and scheduled multiple reaction monitoring method (UHPLC-sMRM) for precise quantitation to evaluate the quality of QJYQ. Firstly, a deep-learning MDF was used to classify and characterize the whole phytochemical components of QJYQ based on the mass spectrum (MS) data of ultra-high performance liquid chromatography quadrupole time of flight tandem mass spectrometry (UHPLC-Q-TOF/MS). Secondly, the highly sensitive UHPLC-sMRM data-acquisition method was established to quantify the multi-ingredients of QJYQ. Totally, nine major types of phytochemical compounds in QJYQ were intelligently classified and 163 phytochemicals were initially identified. Furthermore, fifty components were rapidly quantified. The comprehensive evaluation strategy established in this study would provide an effective tool for accurately evaluating the quality of QJYQ as a whole.

Key mutations on spike protein altering ACE2 receptor utilization and potentially expanding host range of emerging SARS-CoV-2 variants.

Increasing evidence supports inter-species transmission of SARS-CoV-2 variants from humans to domestic or wild animals during the ongoing COVID-19 pandemic, which is posing great challenges to epidemic control. Clarifying the host range of emerging SARS-CoV-2 variants will provide instructive information for the containment of viral spillover. The spike protein (S) of SARS-CoV-2 is the key determinant of receptor utilization, and therefore amino acid mutations on S will probably alter viral host range. Here, to evaluate the impact of S mutations, we tested 27 pseudoviruses of SARS-CoV-2 carrying different spike mutants by infecting Hela cells expressing different angiotensin-converting enzyme 2 (ACE2) orthologs from 20 animals. Of these 27 pseudoviruses, 20 bear single mutation and the other 7 were cloned from emerging SARS-CoV-2 variants, including D614G, Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), Lambda (B.1.429), and Mu (B.1.621). Using pseudoviral reporter assay, we identified that the substitutions of T478I and N501Y enabled the pseudovirus to utilize chicken ACE2, indicating potential infectivity to avian species. Furthermore, the S mutants of real SARS-CoV-2 variants comprising N501Y showed significantly acquired abilities to infect cells expressing mouse ACE2, indicating a critical role of N501Y in expanding SARS-CoV-2 host range. In addition, A262S and T478I significantly enhanced the utilization of various mammal ACE2. In summary, our results indicated that T478I and N501Y substitutions were two S mutations important for receptor adaption of SARS-CoV-2, potentially contributing to the spillover of the virus to many other animal hosts. Therefore, more attention should be paid to SARS-CoV-2 variants with these two mutations.

A transition programme to enhance ICU new graduate nurses' professional identity and intention to remain employed: A pre- and postevaluation.

AIMS: To investigate the effect of a transition programme including cognitive-behaviour-based preceptorship intervention on ICU new graduate nurses' (NGNs)' professional identity and their intention to remain employed. DESIGN: One-arm pre- and post-test design followed the TREND Statement. METHODS: NGNs' professional identity and intention to remain employed were measured at baseline (T1), postintervention (1 month, T2) and 6-month follow-up (T3). RESULTS: Fifty-three NGNs completed the programme, and their professional identity score significantly increased postintervention [from 111.5 (SD = 16.72) at T1 to 114.2 (SD = 9.12) at T2, p < 0.05], but decreased at T3 [105.8 (SD = 9.44) compared with T1 and T2, p < 0.05]. There was no significant difference in ICU NGNs' intention of remain employed outcomes at three time points (p > 0.05). The transition programme was effective to improve ICU NGNs' professional identity immediately after the intervention, but the increment did not maintain at the 6-month follow-up.

The Equilibrium and Pandemic Waves of COVID-19 in the US (preprint)

Importance: Removing the epidemic waves and reducing the instability level of an endemic critical point of COVID-19 dynamics are fundamental to the control of COVID-19 in the US. Objective: To develop new mathematic models and investigate when and how will the COVID-19 in the US be evolved to endemic. Design, Setting, and Participants: To solve the problem of whether mass vaccination against SARS-CoV-2 will ultimately end the COVID-19 pandemic, we defined a set of nonlinear ordinary differential equations as a mathematical model of transmission dynamics of COVID-19 with vaccination. Multi-stability analysis was conducted on the data for the daily reported new cases of infection from January 12, 2021 to December 12, 2022 across 50 states in the US using the developed dynamic model of COVID-19 and limit cycle theory. Main Outcomes and Measures: Eigenvalues and the reproduction number under the disease-free equilibrium point and endemic equilibrium point were used to assess the stability of the disease-free equilibrium point and endemic equilibrium point. Both analytic analysis and numerical methods were used to determine the instability level of new cases of COVID-19 in the US under the different types of equilibrium points and to investigate how the system moves back and forth between stable and unstable states of the system and how the pandemic COVD-19 will evolve to endemic in the US. Results: Multi-stability analysis identified two types of critical equilibrium points, disease-free endemic equilibrium points in the COVID-19 transmission dynamic system. The transmissional, recovery, vaccination rates and vaccination effectiveness during the major transmission waves of COVID-19 across 50 states in the US were estimated. These parameters in the model varied over time and across the 50 states. The eigenvalues and the reproduction numbers R0 and R0end in the disease-free equilibrium point and endemic equilibrium point were estimated to assess stability and classify equilibrium points. They also varied from state to state. The impacts of the transmission and vaccination parameters on the stability of COVID-19 were simulated, and stability attractor regions of these parameters were found and ranked for all 50 states in the US. The US experienced five major epidemic waves, endemic equilibrium points of which across 50 states were all in unstable states. However, the combination of re-infection and vaccination (hybrid immunity) may provide strong protection against COVID-19 infection, and stability analysis showed that these unstable equilibrium points were toward stable points. Theoretical analysis and real data analysis showed that additional epidemic waves may be possible in the future, but COVID-19 across all 50 sates in the US is rapidly moving toward stable endemicity. Conclusions and Relevance: Both stability analysis and observed epidemic waves in the US indicated that the pandemic might not end with the disappearance of the virus. However, after enough people gained immune protection from vaccination and from natural infection, COVID-19 would become an endemic disease, as the stability analysis showed. Educating the population about multiple epidemic waves of the transmission dynamics of COVID-19 and designing optimal vaccine rollout are crucial for controlling the pandemic of COVID-19 and its evolving to endemic.

A new PEDV strain CH/HLJJS/2022 can challenge current detection methods and vaccines.

BACKGROUND: Porcine epidemic diarrhea virus (PEDV) variant strains cause great economic losses to the global swine industry. However, vaccines do not provide sufficient protection against currently circulating strains due to viral mutations. This study traced the molecular characteristics of the most recent isolates in China and aimed to provide a basis for the prevention and treatment of PEDV. METHODS: We obtained samples from a Chinese diarrheal swine farm in 2022. Reverse transcription polymerase chain reaction and immunofluorescence were used to determine the etiology, and the full-length PEDV genome was sequenced. Nucleotide similarity was calculated using MEGA to construct a phylogenetic tree and DNASTAR. Mutant amino acids were aligned using DNAMAN and modeled by SWISS-MODEL, Phyre2 and FirstGlance in JMOL for protein tertiary structure simulation. Additionally, TMHMM was used for protein function prediction. RESULTS: A PEDV virulent strain CH/HLJJS/2022 was successfully isolated in China. A genome-wide based phylogenetic analysis suggests that it belongs to the GII subtype, and 96.1-98.9% homology existed in the whole genomes of other strains. For the first time, simultaneous mutations of four amino acids were found in the highly conserved membrane (M) and nucleocapsid (N) proteins, as well as eight amino acid mutations that differed from the vast majority of strains in the spike (S) protein. Three of the mutations alter the S-protein spatial structure. In addition, typing markers exist during strain evolution, but isolates are using the fusion of specific amino acids from multiple variant strains to add additional features, as also demonstrated by protein alignments and 3D models of numerous subtype strains. CONCLUSION: The newly isolated prevalent strain CH/HLJJS/2022 belonged to the GII subtype, and thirteen mutations different from other strains were found, including mutations in the highly conserved m and N proteins, and in the S1° and COE neutralizing epitopes of the S protein. PEDV is breaking through original cognitions and moving on a more complex path. Surveillance for PEDV now and in the future and improvements derived from mutant strain vaccines are highly warranted.