Longitudinal analyses using 18F-Fluorodeoxyglucose positron emission tomography with computed tomography as a measure of COVID-19 severity in the aged, young, and humanized ACE2 SARS-CoV-2 hamster models.

This study compared disease progression of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in three different models of golden hamsters: aged (≈60 weeks old) wild-type (WT), young (6 weeks old) WT, and adult (14-22 weeks old) hamsters expressing the human-angiotensin-converting enzyme 2 (hACE2) receptor. After intranasal (IN) exposure to the SARS-CoV-2 Washington isolate (WA01/2020), 2-deoxy-2-[fluorine-18]fluoro-D-glucose positron emission tomography with computed tomography (18F-FDG PET/CT) was used to monitor disease progression in near real time and animals were euthanized at pre-determined time points to directly compare imaging findings with other disease parameters associated with coronavirus disease 2019 (COVID-19). Consistent with histopathology, 18F-FDG-PET/CT demonstrated that aged WT hamsters exposed to 105 plaque forming units (PFU) developed more severe and protracted pneumonia than young WT hamsters exposed to the same (or lower) dose or hACE2 hamsters exposed to a uniformly lethal dose of virus. Specifically, aged WT hamsters presented with a severe interstitial pneumonia through 8 d post-exposure (PE), while pulmonary regeneration was observed in young WT hamsters at that time. hACE2 hamsters exposed to 100 or 10 PFU virus presented with a minimal to mild hemorrhagic pneumonia but succumbed to SARS-CoV-2-related meningoencephalitis by 6 d PE, suggesting that this model might allow assessment of SARS-CoV-2 infection on the central nervous system (CNS). Our group is the first to use (18F-FDG) PET/CT to differentiate respiratory disease severity ranging from mild to severe in three COVID-19 hamster models. The non-invasive, serial measure of disease progression provided by PET/CT makes it a valuable tool for animal model characterization.

An ultra-sensitive one-pot RNA-templated DNA ligation rolling circle amplification-assisted CRISPR/Cas12a detector assay for rapid detection of SARS-CoV-2

Rapid, sensitive, and one-pot diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays an extremely important role in point-of-care testing (POCT). Herein, we report an ultra-sensitive and rapid one-pot enzyme-catalyzed rolling circle amplification-assisted CRISPR/FnCas12a assay, termed OPERATOR. OPERATOR employs a single well-designed single-strand padlock DNA, containing a protospacer adjacent motif (PAM) site and a sequence complementary to the target RNA which procedure converts and amplifies genomic RNA to DNA by RNA-templated DNA ligation and multiply-primed rolling circle amplification (MRCA). The MRCA amplicon of single-stranded DNA is cleaved by the FnCas12a/crRNA complex and detected via a fluorescence reader or lateral flow strip. OPERATOR presents outstanding advantages including ultra-sensitivity (1.625 copies per reaction), high specificity (100%), rapid reaction speed (∼30 min), easy operation, low cost, and on-spot visualization. Furthermore, we established a POCT platform by combining OPERATOR with rapid RNA release and a lateral flow strip without professional equipment. The high performance of OPERATOR in SARS-CoV-2 tests was confirmed using both reference materials and clinical samples, and the results suggest that is readily adaptable for point-of-care testing of other RNA viruses.

An ultra-sensitive one-pot RNA-templated DNA ligation rolling circle amplification-assisted CRISPR/Cas12a detector assay for rapid detection of SARS-CoV-2.

Rapid, sensitive, and one-pot diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays an extremely important role in point-of-care testing (POCT). Herein, we report an ultra-sensitive and rapid one-pot enzyme-catalyzed rolling circle amplification-assisted CRISPR/FnCas12a assay, termed OPERATOR. OPERATOR employs a single well-designed single-strand padlock DNA, containing a protospacer adjacent motif (PAM) site and a sequence complementary to the target RNA which procedure converts and amplifies genomic RNA to DNA by RNA-templated DNA ligation and multiply-primed rolling circle amplification (MRCA). The MRCA amplicon of single-stranded DNA is cleaved by the FnCas12a/crRNA complex and detected via a fluorescence reader or lateral flow strip. OPERATOR presents outstanding advantages including ultra-sensitivity (1.625 copies per reaction), high specificity (100%), rapid reaction speed (∼30 min), easy operation, low cost, and on-spot visualization. Furthermore, we established a POCT platform by combining OPERATOR with rapid RNA release and a lateral flow strip without professional equipment. The high performance of OPERATOR in SARS-CoV-2 tests was confirmed using both reference materials and clinical samples, and the results suggest that is readily adaptable for point-of-care testing of other RNA viruses.

Response and duration of serum anti-SARS-CoV-2 antibodies induced by the third dose of an inactivated vaccine: A prospective longitudinal cohort study at 21 serial time points over 641 days.

Given the prevalence of low-pathogenic but highly infectious Omicron variants, a cohort study was conducted to assess the response and duration of novel coronavirus-inactivated vaccine-induced antibodies 1 year after the third dose (Day 641). Blood samples were collected and anti-spike neutralizing antibodies (neutralizing antibody), total antibodies against the receptor-binding domain of the spike protein (total antibody), and immunoglobulin G antibodies against the spike protein (IgG antibody) were determined. Antibody kinetics and attenuation were evaluated. The results showed that the levels of neutralizing, total, and IgG antibodies on Day 641 were 98.05 IU/mL, 152.8 AU/mL, and 7.68 S/CO, respectively. Levels of anti-SARS-CoV-2 antibodies were higher in the younger subgroup than in the older subgroup at several time points after the second and third doses. The seropositive rate of neutralizing antibodies providing protection from infection or severe infection was 46.87% and 87.5%, and the seropositive rates of total antibody and IgG antibody were maintained at 100% and 90.63%, respectively. The half-lives of neutralizing, total, and IgG antibodies were 186.89, 363.04, and 417.50 days, respectively. Collectively, anti-SARS-CoV-2 antibodies may provide a certain degree of protection from infection 1 year after the third dose and high protection from severe infection.

Quantifying Social Interventions for Combating COVID-19 via a Symmetry-Based Model.

The COVID-19 pandemic has revealed new features in terms of substantial changes in rates of infection, cure, and death as a result of social interventions, which significantly challenges traditional SEIR-type models. In this paper we developed a symmetry-based model for quantifying social interventions for combating COVID-19. We found that three key order parameters, separating degree (S) for susceptible populations, healing degree (H) for mild cases, and rescuing degree (R) for severe cases, all display logistic dynamics, establishing a novel dynamic model named SHR. Furthermore, we discovered two evolutionary patterns of healing degree with a universal power law in 23 areas in the first wave. Remarkably, the model yielded a quantitative evaluation of the dynamic back-to-zero policy in the third wave in Beijing using 12 datasets of different sizes. In conclusion, the SHR model constitutes a rational basis by which we can understand this complex epidemic and policymakers can carry out sustainable anti-epidemic measures to minimize its impact.

Impact of vaccination against COVID-19 on the outcomes of in vitro fertilization-embryo transfer: a retrospective cohort study.

BACKGROUND: Vaccination against coronavirus disease 2019 (COVID-19) has become the primary approach in the fight against the spread of COVID-19. Studies have shown that vaccination against COVID-19 has adverse effects, particularly on human reproductive health, despite the fact that vaccination rates are still on the rise. However, few studies have reported whether vaccination affects the outcome of in vitro fertilization-embryo transfer (IVF-ET) or not. In this study, we compared the outcome of IVF-ET and the development of follicles and embryos between vaccinated and unvaccinated groups. METHODS: A single-center retrospective cohort study of 10,541 in vitro fertilization (IVF) cycles was conducted from June 2020 to August 2021. 835 IVF cycles with a history of vaccination against COVID-19 and 1670 IVF cycles that served as negative controls were selected and analyzed utilizing the Matchlt package of R software ( http://www.R-project.org/ ) and the nearest neighbor matching algorithm for propensity-matched analysis at a 1:2 ratio. RESULTS: The number of oocytes collected in the vaccinated group and the unvaccinated group were 8.00 (0, 40.00) and 9.00 (0, 77.00) ( P  = 0.073) and the good-quality embryo rates of the two groups were 0.56±0.32 and 0.56±0.31 averagely ( P  = 0.964). Clinical pregnancy rates for the vaccinated group and unvaccinated group were 42.4% (155/366) and 40.2% (328/816) ( P  = 0.486) and biochemical pregnancy rates were 7.1% (26/366) and 8.7% (71/816) ( P  = 0.355). Two other factors were analyzed in this study; vaccination among different genders and different types (inactivated vaccine or recombinant adenovirus vaccine) showed no statistically significant effect on the above outcomes. CONCLUSIONS: In our findings, vaccination against COVID-19 showed no statistically significant effect on the outcomes of IVF-ET and the development of follicles and embryos, nor did the gender of the vaccinated person or the formulation of vaccines show significant effects.

Homologous booster immunization with an inactivated vaccine induced robust antibody response in healthcare workers: A retrospective study.

Coronavirus Disease 2019 (Covid-19) severely impacted the health, society, and economy around the world. With declining protective efficacy of primary vaccination and the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, a Covid-19 booster vaccination is being fully implemented globally. Many people received three doses of BBIBP-CorV inactivated vaccine in China and other developing countries. However, the antibody response and immune persistence of the homologous BBIBP-CorV booster vaccination is yet to be thoroughly evaluated, as previous studies focused within one month after the third dose. In this study, 97 participants were enrolled to analyze the antibody response and immune persistence within 6 months as well as the safety within 7 days after the third-dose of homologous BBIBP-CorV inactivated vaccine. The seroconversion rate for total antibody against the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) protein were both 100% at month 1 and month 6 after the third dose. The IgG against the RBD of the SARS-CoV-2 S protein seroconversion rate increased from 42.27% before the third dose to 100% 1 month after the third dose and then slightly decreased to 98.97% 5 months later. Positive IgM against the RBD of the SARS-CoV-2 S protein was rare and was observed in only one participant at month 1 after the third dose. The neutralizing antibody levels at month 1 and month 6 after the third dose increased 63.32-fold and 13.16-fold compared with those before the third dose, and the positive rate for neutralizing antibody was still 100% at month 6 after the third dose. Importantly, the antibody responses induced by the vaccine and immune persistence were not affected by sex or age. No serious adverse reactions were reported. Total antibody and IgG against the RBD of the SARS-CoV-2 S protein were highly correlated with neutralizing antibody, suggesting that total antibody and IgG against the RBD of the SARS-CoV-2 S protein could be used as predictors for neutralizing antibody. In conclusion, the third dose of homologous BBIBP-CorV inactivated vaccine induced a robust antibody response and moderate immune persistence. These finding are of great significance for development future vaccination strategies.

Characterization of SARS-CoV-2 Omicron BA.2.75 clinical isolates.

The prevalence of the Omicron subvariant BA.2.75 rapidly increased in India and Nepal during the summer of 2022, and spread globally. However, the virological features of BA.2.75 are largely unknown. Here, we evaluated the replicative ability and pathogenicity of BA.2.75 clinical isolates in Syrian hamsters. Although we found no substantial differences in weight change among hamsters infected with BA.2, BA.5, or BA.2.75, the replicative ability of BA.2.75 in the lungs is higher than that of BA.2 and BA.5. Of note, BA.2.75 causes focal viral pneumonia in hamsters, characterized by patchy inflammation interspersed in alveolar regions, which is not observed in BA.5-infected hamsters. Moreover, in competition assays, BA.2.75 replicates better than BA.5 in the lungs of hamsters. These results suggest that BA.2.75 can cause more severe respiratory disease than BA.5 and BA.2 in a hamster model and should be closely monitored.

Study on the Opening of School Sports Facilities under the National Fitness Programme

In recent years, with the continued promotion of the national fitness programme, the motivation of people of all ages to participate in daily fitness exercises has been significantly enhanced. The higher demand for national fitness obviously needs to be matched with more supply of sports venues and sports facilities. The lack of sports facilities in China has led to a growing conflict between the growing demand for sports and the relatively poor public sports services. As a major component of China's public sports facilities, school sports facilities are an important vehicle for the implementation of the national fitness programme. The opening of school sports facilities is directly related to the solid foundation of facilities and venues for the national fitness programme in China. This paper studies the opening of school sports facilities in the context of the national fitness programme, explores the difficulties and challenges faced by the opening of school sports facilities, and proposes practical countermeasures and suggestions for the opening of school sports facilities.

Network structure of family function and self-management in patients with early chronic kidney disease amid the COVID-19 pandemic.

Background: Family function plays a pivotal role in self-management among patients with early chronic kidney disease (CKD), which has been especially important during the COVID-19 pandemic. Previous studies have investigated the relationships between family function and self-management using total scores through self-report questionnaires while ignoring the different components in both family function and self-management. The specific objective of this study was to explore the network structure of family function and self-management at the component level. Methods: A total of 360 patients with early CKD from three tertiary hospitals were enrolled in our cross-sectional survey from September to December 2021 in China. Components of family function were measured by the Family Adaptation Partnership Growth and Resolve Index, and components of self-management were measured by the Chronic Kidney Disease Self-management Instrument. Network analysis was used to establish the network structure. Results: Edges across the community of family function and self-management were mainly positive. Edges between F3 "Growth" and M1 "Self-integration", F2 "Partnership" and M3 "Seeking social support," F5 "Resolve" and M3 "Seeking social support" were the strongest. F3 "Growth" had the greatest positive bridge expected influence of family function community (0.12), and M3 "Seeking social support" had the greatest positive bridge expected influence of self-management community (0.16). Conclusion: We explored the potential pathways between different components of family function and self-management among patients with early CKD during the COVID-19 pandemic and found fine-grained relationships between them. The two nodes F3 "Growth" and M3 "Seeking social support" may provide a new idea from the perspective of family function for interventions to improve self-management.

Nasal swab is a good alternative sample for detecting SARS-CoV-2 with rapid antigen test: A meta-analysis.

BACKGROUND: We aim to determine if nasal samples have equivalent detection sensitivity to nasopharyngeal swabs for RAT and evaluate the diagnostic accuracy of nasal swabs with RAT. METHODS: PubMed and Web of Science were searched for eligible studies published before August 23, 2022. A bivariate random effects model was used to perform the quantitative synthesis. RESULTS: The pooled sensitivity, pooled specificity, positive likelihood ratio, negative likelihood ratio, and summary AUC on nasal swabs with RAT were 0.81 (95% CI, 0.77-0.85), 1.00 (95% CI: 0.99-1.00), 0.97 (95% CI, 0.95-0.98), 298.91 (95% CI, 144.71-617.42) and 0.19 (95% CI, 0.15-0.23), respectively. WHO required RAT kits to perform with a sensitivity of 0.80 and a specificity of 0.97, nasal swabs (0.81) achieved the required sensitivity while nasopharyngeal swabs (0.75) did not. The symptomatic population yielded higher pooled sensitivity than the asymptomatic population (0.86 versus 0.71), with a pooled sensitivity of 0.90 for five days of symptom onset. CONCLUSION: Nasal sampling had a great performance and yielded a high sensitivity in detecting SARS-CoV-2 using RAT, we believe that RAT performed with nasal swabs is a good alternative for detecting SARS-CoV-2, especially early in the onset of symptoms.

Network structure of family function and self-management in patients with early chronic kidney disease amid the COVID-19 pandemic

Background Family function plays a pivotal role in self-management among patients with early chronic kidney disease (CKD), which has been especially important during the COVID-19 pandemic. Previous studies have investigated the relationships between family function and self-management using total scores through self-report questionnaires while ignoring the different components in both family function and self-management. The specific objective of this study was to explore the network structure of family function and self-management at the component level. Methods A total of 360 patients with early CKD from three tertiary hospitals were enrolled in our cross-sectional survey from September to December 2021 in China. Components of family function were measured by the Family Adaptation Partnership Growth and Resolve Index, and components of self-management were measured by the Chronic Kidney Disease Self-management Instrument. Network analysis was used to establish the network structure. Results Edges across the community of family function and self-management were mainly positive. Edges between F3 "Growth” and M1 "Self-integration”, F2 "Partnership” and M3 "Seeking social support,” F5 "Resolve” and M3 "Seeking social support” were the strongest. F3 "Growth” had the greatest positive bridge expected influence of family function community (0.12), and M3 "Seeking social support” had the greatest positive bridge expected influence of self-management community (0.16). Conclusion We explored the potential pathways between different components of family function and self-management among patients with early CKD during the COVID-19 pandemic and found fine-grained relationships between them. The two nodes F3 "Growth” and M3 "Seeking social support” may provide a new idea from the perspective of family function for interventions to improve self-management.

Anti-SARS-CoV-2 IgM Secondary Response Was Suppressed by Preexisting Immunity in Vaccinees: A Prospective, Longitudinal Cohort Study over 456 Days.

To obtain more insight into IgM in anti-SARS-CoV-2 immunity a prospective cohort study was carried out in 32 volunteers to longitudinally profile the kinetics of the anti-SARS-CoV-2 IgM response induced by administration of a three-dose inactivated SARS-CoV-2 vaccine regimen at 19 serial time points over 456 days. The first and second doses were considered primary immunization, while the third dose was considered secondary immunization. IgM antibodies showed a low secondary response that was different from the other three antibodies (neutralizing, total, and IgG antibodies). There were 31.25% (10/32) (95% CI, 14.30-48.20%) of participants who never achieved a positive IgM antibody conversion over 456 days after vaccination. The seropositivity rate of IgM antibodies was 68.75% (22/32) (95% CI, 51.80-85.70%) after primary immunization. Unexpectedly, after secondary immunization the seropositivity response rate was only 9.38% (3/32) (95% CI, 1.30-20.10%), which was much lower than that after primary immunization (p = 0.000). Spearman's correlation analysis indicated a poor correlation of IgM antibodies with the other three antibodies. IgM response in vaccinees was completely different from the response patterns of neutralizing, total, and IgG antibodies following both the primary immunization and the secondary immunization and was suppressed by pre-existing immunity induced by primary immunization.

Evaluating the Value of Anti-SARS-CoV-2 Antibody-Based Tests for COVID-19 Diagnosis.

BACKGROUND: The early detection of COVID-19 patients is fundamental for containing the pandemic. A reverse-transcriptase quantitative polymerase chain reaction (RT-PCR), which detects SARS-CoV-2 RNA, is the gold standard diagnostic test, although it can contribute to false-negative results. Consequently, supplementary diagnostic tests are urgently needed. METHODS: To assess the value of anti-SARS-CoV-2 antibody-based tests for confirming COVID-19, a retrospective study was conducted on 3120 inbound overseas travelers who underwent a 14-day government quarantine in Xiamen from August 2020 to October 2020. The diagnostic accuracy of the total antibody that detected the anti-SARS-CoV-2 antibody and the RT-PCR that detected SARS-CoV-2 RNA was determined in comparison to the clinical diagnosis. RESULTS: The COVID-19 positive rate was 3.14% (98/3120). The sensitivity and specificity of the RT-PCR test on the first day of quarantine were 14.29% and 100%, respectively, and the sensitivity and specificity of the total antibody were 93.88% and 99.40%, respectively. The kappa value between an RT-PCR on the first day of quarantine and a clinical diagnosis was 0.24 (95% CI, 0.14-0.35), indicating poor consistency. The kappa value between total antibodies and a clinical diagnosis was 0.88 (95% CI, 0.83-0.93), indicating perfect consistency. There were no differences in the positive rates of an RT-PCR in symptomatic COVID-19 (7.41% (2/27)) and asymptomatic COVID-19 (16.90 (12/71) (p = 0.338). Similarly, the positive rate of the total antibody tests showed no difference in symptomatic COVID-19 (96.30% (26/27)) and asymptomatic COVID-19 (92.96% (66/71)) (p = 0.676). CONCLUSION: SARS-CoV-2 antibodies are developed by the body in response to an infection or after vaccination; this can easily lead to a missed diagnosis. In the context of low sensitivity for an RT-PCR, SARS-CoV-2 antibody detection is an effective adjunct to RT-PCR detection, which can improve the diagnostic accuracy of COVID-19 and provide an effective complement to the false-negative results of an RT-PCR.

In silico analysis and preclinical findings uncover potential targets of anti-cervical carcinoma and COVID-19 in laminarin, a promising nutraceutical.

Until today, the coronavirus disease 2019 (COVID-19) pandemic has caused 6,043,094 deaths worldwide, and most of the mortality cases have been related to patients with long-term diseases, especially cancer. Autophagy is a cellular process for material degradation. Recently, studies demonstrated the association of autophagy with cancer development and immune disorder, suggesting autophagy as a possible target for cancer and immune therapy. Laminarin is a polysaccharide commonly found in brown algae and has been reported to have pharmaceutic roles in treating human diseases, including cancers. In the present report, we applied network pharmacology with systematic bioinformatic analysis, including gene ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, reactome pathway analysis, and molecular docking to determine the pharmaceutic targets of laminarin against COVID-19 and cervical cancer via the autophagic process. Our results showed that the laminarin would target ten genes: CASP8, CFTR, DNMT1, HPSE, KCNH2, PIK3CA, PIK3R1, SERPINE1, TLR4, and VEGFA. The enrichment analysis suggested their involvement in cell death, immune responses, apoptosis, and viral infection. In addition, molecular docking further demonstrated the direct binding of laminarin to its target proteins, VEGFA, TLR4, CASP8, and PIK3R1. The present findings provide evidence that laminarin could be used as a combined therapy for treating patients with COVID-19 and cervical cancer.

Spillover Effect of Economic Policy Uncertainty on the Stock Market in the Post-Epidemic Era

In the post-epidemic era, global economic policies have been uncertain and the stock market has been volatile. It is crucial to investigate the spillover effect of economic policy uncertainty (EPU) on the stock market for accurately hedging risks and seizing recovery opportunities. This paper applies the DY spillover index and network analysis to study the spillover effect between the U.S. EPU and the U.S. and Asian stock markets. The empirical results show a significant spillover effect in both the U.S. and Asian stock markets, with EPU as the recipient of risk spillover and stock indices as the transmitters. The stock markets in Japan and South Korea react more strongly to shifts in the U.S. EPU. All transmitters attain their maximum values in both the TO and FROM directions in 2020. The from-direction spillover indices of the U.S. stock market are less volatile in 2020 than those of the Asian stock market, indicating that the outbreak of the COVID-19 epidemic has a greater impact on the Asian stock market than the U.S. stock market. These conclusions have substantial implications for asset management, investment diversification and aversion to unsystematic risk in major economic shocks.

Evaluation of the cycle threshold values of RT-PCR for SARS-CoV-2 in COVID-19 patients in predicting epidemic dynamics and monitoring surface contamination.

To evaluate the application of cycle threshold (Ct) values of coronavirus disease 2019 (COVID-19) patients in predicting epidemic dynamics and monitoring surface contamination. The Ct value of reverse transcriptase-polymerase chain reaction for SARS­CoV-2 from COVID-19 patients inbound overseas in Xiamen, China was collected from October 2020 to December 2021, and the correlation of patients' Ct values with epidemic dynamics and surface contamination was evaluated. The results showed that there was an extreme inverse correlation of positivity rate in the current calendar month (ORF1ab, r = -0.692, P = 0.004; N,r = -0.629, P = 0.012) and the following calendar month (ORF1ab,r = -0.801, P = 0.001; N,r = -0.620, P = 0.018) with the median Ct values. Ct value showed better performance for monitoring surface contamination, with the area under the curve value 0.808(95 %CI: 0.748-0.869) for ORF1ab and 0.807(95 %CI:0.746-0.868) for the N gene. The patients' ORF1ab Ct value< 29.09 or N Ct value< 28.03 were 11.25 times and 10.48 times more likely to result in surface contamination than those with ORF1ab Ct value ≥ 29.09 or N Ct value≥ 28.03 (OR:11.25,95 % CI: 5.52-22.35; OR:10.48,95 % CI:5.29-20.70). Ct values were associated with the positivity rate in the current or following calendar month and predicted the epidemic dynamics. The Ct values can be used as a predictor for monitoring surface contamination to develop public health responses to COVID-19.