Factors influencing neutralizing antibody titers elicited by coronavirus disease 2019 vaccines.

The World Health Organization has highlighted the importance of an international standard (IS) for severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) neutralizing antibody titer detection to calibrate diagnostic techniques. We applied an IS to calibrate neutralizing antibody titers (NTs) (international units/mL) in response to coronavirus disease 2019 (COVID-19) vaccination. Moreover, the association between different factors and neutralizing antibodies was analyzed. A total of 1,667 serum samples were collected from participants receiving different COVID-19 vaccines. Antibody titers were determined by a microneutralization assay using live viruses in a biosafety level 3 (BSL-3) laboratory and a commercial serological MeDiPro kit. The titer determined using the MeDiPro kit was highly correlated with the NT determined using live viruses and calibrated using IS. Fever and antipyretic analgesic treatment were related to neutralizing antibody responses in ChAdOx1-S and BNT162b2 vaccinations. Individuals with diabetes showed a low NT elicited by MVC-COV1901. Individuals with hypertension receiving the BNT162b2 vaccine had lower NTs than those without hypertension. Our study provided the international unit (IU) values of NTs in vaccinated individuals for the development of vaccines and implementation of non-inferiority trials. Correlation of the influencing factors with NTs can provide an indicator for selecting COVID-19 vaccines based on personal attributes.

Titers and breadth of neutralizing antibodies against SARS-CoV-2 variants after heterologous booster vaccination in health care workers primed with two doses of ChAdOx1 nCov-19: A single-blinded, randomized clinical trial.

OBJECTIVES: We conducted a single-blinded, randomized trial to evaluate the safety, reactogenicity, and immunogenicity of heterologous booster vaccination in health care workers (HCW) who had received two doses of ChAdOx1 nCov-19. METHODS: HCW who had at least 90 days after the second dose were enrolled to receive one of the four vaccines: BNT162b2 (30 µg), half-dose mRNA-1273 (50 µg), mRNA-1273 (100 µg), and MVC-COV1901 (15 µg). The primary outcomes were humoral and cellular immunogenicity and secondary outcomes assessed safety and reactogenicity at 28 days post-booster. RESULTS: MVC-COV1901 Three hundred and forty HCW were enrolled: 83 received BNT162b2 (2 excluded), 85 half-dose mRNA-1273, 85 mRNA-1273, and 85 MVC-COV1901. mRNA vaccines had more reactogenicity than protein vaccine. The fold-rise of anti-spike IgG geometric mean titer was 8.4 (95% CI 6.8-10.4) for MVC-COV1901, 32.2 (27.2-38.1) for BNT162b2, 47.6 (40.8-55.6) for half-dose mRNA-1273 and 63.2 (53.6-74.6) for mRNA-1273. The live virus microneutralization assays (LVMNA) against the wild type, alpha and delta variants were consistent with anti-spike IgG for all booster vaccines. The LVMNA in the four groups against omicron BA.1 variant were 6.4 to 13.5 times lower than those against the wild type. All booster vaccines induced a comparable T cell response. CONCLUSIONS: Third dose booster not only increases neutralizing antibody titer but also enhances antibody breadth against SARS-CoV-2 variants. mRNA vaccines are preferred booster vaccines for those who received primary series of ChAdOx1 nCov-19.

An outbreak of human Rhinovirus-A21 infection in a psychiatric ward during COVID-19 pandemic.

A cluster of acute respiratory illnesses involving 12 inpatients and 3 healthcare workers occurred in a psychiatric ward. Eight of them were identified as HRV-A21. Fever and cough were the most common symptoms. The study also provides further evidence of the impact of HRV on lower respiratory tract illness.

Titers and capacity of neutralizing antibodies against SARS-CoV-2 variants after heterologous booster vaccination in health care workers primed with two doses of ChAdOx1 nCov-19: a single-blinded, randomized clinical trial (preprint)

Background Booster vaccination is important because of waning immunity and variant immune evasion. We conducted a single-blinded, randomized trial to evaluate the safety, reactogenicity, and immunogenicity of heterologous booster vaccination in health care workers (HCW) who had received two doses of ChAdOx1 nCov-19. Methods and findings HCW at least 90 days after the second dose were enrolled to receive one of the four vaccines: BNT162b2, half-dose mRNA-1273, mRNA-1273, and MVC-COV1901. The primary outcomes were humoral and cellular immunogenicity and the secondary outcomes safety and reactogenicity 28 days post-booster. 340 HCW were enrolled: 83 received BNT162b2 (2 excluded), 85 half-dose mRNA-1273, 85 mRNA-1273, and 85 MVC-COV1901. mRNA vaccines had more reactogenicity than protein vaccine. Anti-spike IgG increased by a fold of 8.4 for MCV-COV1901, 32.2 for BNT162b2, 47.6 for half-dose mRNA-1273 and 63.2 for mRNA1273. The live virus microneutralization assay (LVMNA) against the wild type, alpha and delta variants were consistent with anti-spike IgG for all booster vaccines. The LVMNA in the four groups against omicron variant were 6.4 to 13.5 times lower than those against the wild type. Serum neutralizing antibody against omicron variant was undetectable in 60% of the participants who received MCV-COV1901 as a booster by LVMNA. By using pseudovirus neutralizing assay, we found that neutralization activity in the four groups against omicron variant were 4.6 to 5.2 times lower than that against the D614G. All booster vaccines induced comparable T cell response. Conclusions Third dose booster not only increases neutralizing antibody titer but also enhances antibody capacity against SARS-CoV-2 variants. mRNA vaccines are preferred booster vaccines for those after primary series of ChAdOx1 nCov-19.

Potential inhibitor for blocking binding between ACE2 and SARS-CoV-2 spike protein with mutations.

At the time of writing, more than 440 million confirmed coronavirus disease 2019 (COVID-19) cases and more than 5.97 million COVID-19 deaths worldwide have been reported by the World Health Organization since the start of the outbreak of the pandemic in Wuhan, China. During the COVID-19 pandemic, many variants of SARS-CoV-2 have arisen because of high mutation rates. N501Y, E484K, K417N, K417T, L452R and T478K in the receptor binding domain (RBD) region may increase the infectivity in several variants of SARS-CoV-2. In this study, we discovered that GB-1, developed from Chiehyuan herbal formula which obtained from Tian Shang Sheng Mu of Chiayi Puzi Peitian Temple, can inhibit the binding between ACE2 and RBD with Wuhan type, K417N-E484K-N501Y and L452R-T478K mutation. In addition, GB-1 inhibited the binding between ACE2 and RBD with a single mutation (E484K or N501Y), except the K417N mutation. In the compositions of GB-1, glycyrrhizic acid can inhibit the binding between ACE2 and RBD with Wuhan type, except K417N-E484K-N501Y mutation. Our results suggest that GB-1 could be a potential candidate for the prophylaxis of different variants of SARS-CoV-2 infection because of its inhibition of binding between ACE2 and RBD with different mutations (L452R-T478K, K417N-E484K-N501Y, N501Y or E484K).

Priority Weights for Predicting the Success of Hotel Sustainable Business Models

This study proposes the use of consistent fuzzy preference relations to evaluate the structure of hotel sustainable business model (HSBM) dimensions and the corresponding hierarchy of evaluation indicators, and predict the overall probability of success. As fuzzy preference relations require, a group of hotel professionals in Taiwan was asked to process pairwise comparisons using linguistic variables to determine the weights of dimensions and indicators. According to the results, finances were found to be the most important dimension, followed by human capital. The number of local cultural events in the hotel was identified as the most important indicator. The predictive values revealed the possibility for successful HSBM implementation, shedding light on the vision of sustainability for the hotel industry. The results of the present study contribute to the literature on sustainability by determining the importance and weights of dimensions and indicators for hotel business models, providing an example of the use of this strategic tool in generating and modifying sustainable business models for the hotel industry.

Cost-Effectiveness of Interventions for the Prevention and Control of COVID-19: A Systematic Review and Meta-Analysis (preprint)

Background: The COVID-19 pandemic is an unprecedented global crisis and has a profound impact on health-care systems, society and economy. The cost-effectiveness of different interventions for the prevention and control of COVID-19 remains debated. We aimed to quantitatively summarize the health economic evaluation evidence of prevention and control programs addressing COVID-19 globally.Methods: We did a systematic review and meta-analysis to assess the economic and health benefit of interventions of COVID-19. We searched PubMed, Embase, Web of Science and Cochrane Library of economic evaluation from 31 December, 2019 to 13 July, 2021 to identify relevant literatures. Two researchers screened titles and abstracts, extracted data from full-text articles, and did quality assessment by the Consolidated Health Economic Evaluation Reporting Standards checklist. Meta-analyses were done using random-effects models to estimate pooled incremental net benefit (INB). Heterogeneity was assessed using I^2 statistics, and publication bias was assessed by Egger’s test. This study is registered with PROSPERO, CRD42021267475.Findings Of 15542 studies identified, 50 articles were included in the systematic review, and 17 articles (9 studies about non-pharmacological interventions (NPIs), 4 studies about vaccinations and 4 studies about treatments) were included in the meta-analysis. The pooled INB of NPIs, vaccinations and treatments were $972·05 (95% CI $772·52 to $1171·59), $295·18 (95% CI $209·58 to $380·77) and $14854·90 (95% CI $1783·60 to $27926·20), respectively. The pooled INBs in subgroups of screening, and suppression were $2390·89 (95% CI $1932·92 to $2848·85) and $2156·00 (95% CI $1114·40 to $3197·59). Sensitivity analyses showed similar findings.Interpretation: NPIs, vaccinations and treatments are all cost-effective in combating COVID-19 pandemic. However, evidence almost from high-income and middle-income countries, further studies from lower-income countries are needed.Funding: National Natural Science Foundation of China (No. 71910107004, 91746205, 72122001, 71934002).Declaration of Interest: The authors declare no competing interests.

The Online Learning Academic Achievement of Chinese Students during the COVID-19 Pandemic: The Role of Self-Regulated Learning and Academic Entitlement

In the spring semester of 2020, all Chinese higher education institutions delivered courses online across the nation in response to the COVID-19. This study explores Chinese college students' self-regulated learning, academic entitlement, and academic achievement during the transitioning from face-to-face to online learning environments during this special time. Structure equation modeling was conducted, and results indicate that academic entitlement associates with students' online learning academic achievement. Whereas self-regulated learning does not relate to academic achievement in the online learning setting. Additionally, academic entitlement is marginally associated with academic achievement only among male students, while self-regulated learning is not a significant predictor for both genders. However, self-regulated learning is marginally linked with higher academic achievement among students who do not have previous online learning experiences but not among those who took online courses before.

Current status of epidemiology and research on COVID-19

In December 2019. an increasing number of pneumonia cases of unknown origin occurred in Wuhan, China. This pneumonia was subsequently identified to be caused by a novel coronavirus, and named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-Z). Since then, the epidemic has spread throughout the whole country. Coronavirus disease 2019 (COVID-19) also emerged in many other countries and regions around the world. The disease is transmitted mainly through respiratory droplets and close person-to-person contact. The incubation period for an initial COVID-19 infection is generally 1-14 days (3-7 days in most cases). Most patients with COVID-19 have mild symptoms, but some patients become seriously ill and develop dyspnea and/or hypoxemia, even acute respiratory distress syndrome. multiple organ failure. etc. Currently, medication or a vaccine for COVID-19 is lacking. Here, we summarize the biology, epidemiology, pathogenesis, prevention and treatment of COVID-19. In this way, we hope to provide comprehensive reference of COVID-19, as well as help for disease prevention and control, drug and vaccine development.

Human Rhinoviruses Prevailed Among Children in the Setting of Wearing Face Masks in Shanghai, 2020 (preprint)

Background: Human rhinovirus (HRV) is the predominant etiological agent of the common cold in children and adults. A recent study showed that the inhibitory effect of face masks on viral shedding of HRV was less prominent than that on other respiratory viruses. Considering that most Chinese people have worn face masks in public area since the outbreak of coronavirus disease 2019, we aimed to find out whether HRV prevailed among children in 2020 and demonstrate the details of the epidemiological features of HRV under such a special circumstance. Methods: We summarized the incidences of various respiratory virus infections in patients who visited the Children’s Hospital of Fudan University during 2018~2020, and genotyped HRV positive nasopharyngeal specimens collected from 316 inpatients and 72 outpatients that visited the hospital in 2020. Results: There was a major prevalence of HRV among children in the latter half of 2020, with a clear seasonality that HRV-As prevailed in summer while HRV-Cs in autumn. HRV-As were more prone to cause severe lower respiratory tract infections (LRTI), while HRV-Cs were closely associated with childhood wheezing. The predominant genotypes were A11, A28, A47, A82, A101, C40 and C43. Notably, A21, A82 and A101 took up larger proportions in severe cases than in non-severe cases. Conclusions: Our findings described a major prevalence of HRVs among children in 2020, which highlight the unique transmitting pattern of HRV and help to narrow the targets for antiviral strategies.

GB-2 blocking the interaction between ACE2 and wild type and mutation of spike protein of SARS-CoV-2.

Since the start of the outbreak of coronavirus disease 2019 in Wuhan, China, there have been more than 150 million confirmed cases of the disease reported to the World Health Organization. The beta variant (B.1.351 lineage), the mutation lineages of SARS-CoV-2, had increase transmissibility and resistance to neutralizing antibodies due to multiple mutations in the spike protein. N501Y, K417N and E484K, in the receptor binding domain (RBD) region may induce a conformational change of the spike protein and subsequently increase the infectivity of the beta variant. The L452R mutation in the epsilon variant (the B.1.427/B.1.429 variants) also reduced neutralizing activity of monoclonal antibodies. In this study, we discovered that 300 µg/mL GB-2, from Tian Shang Sheng Mu of Chiayi Puzi Peitian Temple, can inhibit the binding between ACE2 and wild-type (Wuhan type) RBD spike protein. GB-2 can inhibit the binding between ACE2 and RBD with K417N-E484K-N501Y mutation in a dose-dependent manner. GB-2 inhibited the binding between ACE2 and the RBD with a single mutation (K417N or N501Y or L452R) except the E484K mutation. In the compositions of GB-2, glycyrrhiza uralensis Fisch. ex DC., theaflavin and (+)-catechin cannot inhibit the binding between ACE2 and wild-type RBD spike protein. Theaflavin 3-gallate can inhibit the binding between ACE2 and wild-type RBD spike protein. Our results suggest that GB-2 could be a potential candidate for the prophylaxis of some SARS-CoV-2 variants infection in the further clinical study because of its inhibition of binding between ACE2 and RBD with K417N-E484K-N501Y mutations or L452R mutation.

Antibody titers measured by commercial assays are correlated with neutralizing antibody titers calibrated by international standards (preprint)

The World Health Organization (WHO) has highlighted the importance of an international standard (IS) for SARS-CoV-2 neutralizing antibody titer detection, with the aim of calibrating different diagnostic techniques. In this study, IS was applied to calibrate neutralizing antibody titers (IU/mL) and binding antibody titers (BAU/mL) in response to SARS-CoV-2 vaccines. Serum samples were collected from participants receiving the Moderna (n = 20) and Pfizer (n = 20) vaccines at three time points: pre-vaccination, after one dose, and after two doses. We obtained geometric mean titers of 1404.16 and 928.75 IU/mL for neutralizing antibodies after two doses of the Moderna and Pfizer vaccines, respectively. These values provide an important baseline for vaccine development and the implementation of non-inferiority trials. We also compared three commercially available kits from Roche, Abbott, and MeDiPro for the detection of COVID-19 antibodies based on binding affinity to S1 and/or RBD. Our results demonstrated that antibody titers measured by commercial assays are highly correlated with neutralizing antibody titers calibrated by IS.

Trends of injury mortality during the COVID-19 period in Guangdong, China: a population-based retrospective analysis.

OBJECTIVE: We aimed to ascertain the trends of injury mortality during the COVID-19 period in southern China. METHODS: We conducted a population-based retrospective analysis to compare the mortality changes of all-cause injury and transport injuries, poisoning, falls, fire/heat/hot substances, drowning, self-harm and interpersonal violence, which were further stratified by sex and age. Comparisons were made between the COVID-19 period (between January 2020 and June 2020) and control period (between January 2019 and June 2019) in Guangdong province. We used the negative binomial models to explore the associations of deaths during the COVID-19 period, according to the different sex and age strata. RESULTS: The all-cause injury mortality in Guangdong province decreased significantly from 28.65 per 100 000 population during the control period to 23.24 per 100 000 population during COVID-19 pandemic period. Similar results were found in specific injury categories. Mortality of self-harm increased by 139.26% in the 10-14 year group during the COVID-19 period as compared with the control period. Although mortality changes in some groups were not statistically significant, some increases were noteworthy during the COVID-19 period (ie, self-harm, transport injury and falls) in the 70-79 year group. The corresponding increase in mortality rate was 16.83%, 3.32% and 4.92%, respectively. CONCLUSION: The mortality of all-cause injury, transport injury and drowning during the COVID-19 pandemic was consistently decreased. However, the increase in mortality associated with falls, fire/heat/hot substance injury and self-harm in specific age populations warrant the targeted control and prevention measures for the population at risk.

Prevention and Control of COVID-19 by Primary Health Care Facilities in China: A Field- Survey-Based Qualitative Study in Three Typical Cities (preprint)

Background In fulfilling the COVID-19 containment, primary health care (PHC) facilities in China played an important role. We sought to investigate the exact tasks performed at the PHC facilities and the processes of COVID-19 prevention and control.Methods Semi-structured face-to-face interviews for primary care physicians (PCPs) and a simple survey for residents were conducted in the field survey. Based-on purposive stratified sampling, 32 PCPs were selected from 22 PHC facilities in Wuhan as a high-risk city, in Shanghai as medium-risk city and in Zunyi as low-risk city. In the field survey, semi-structured face-to-face interviews were conducted with PCPs to summarize the tasks of COVID-19 prevention and control at the PHC facilities. A simple survey was used to investigate the local residents’ awareness about COVID-19 prevention and control.Results In pre-outbreak period, the PHC facilities mainly engaged in storing medical supplies; in out-break period, they were responsible for screening, transferring, quarantine and treatment; in regular prevention and control period, attention was given to the employees and items of cold-chain & fresh food markets, etc. In Wuhan, PHC facilities focused on graded diagnoses and treatments of patients; in Shanghai, they were mainly engaged in at-home/centralized quarantine; in Zunyi, they focused on the screening of high-risk individuals. In urban areas, COVID-19 were more likely to be transmitted; in urban-rural areas, it was difficult to perform screening on the migrant populations; in rural areas, the risk was much lower. The community residents had satisfactory compliance with the preventive measures.Conclusion We identified differences in the prevention and control tasks performed at the PHC facilities in China. During the different phases of the pandemic, the tasks were adjusted depending on the gradually comprehensive understanding of COVID-19. Among the cities at different risk levels, screening, quarantine, transferring or treatment was chosen to be a priority accordingly. Located in different intra-city geographic locations at different risk levels, the PHC facilities conducted their own tasks accordingly. Additionally, compliance on the part of the local community residents could not be overemphasized in COVID-19 prevention and control.

Potential Simultaneous Inhibitors of Angiotensin-Converting Enzyme 2 and Transmembrane Protease, Serine 2.

Outbreak of coronavirus disease 2019 occurred in Wuhan and has rapidly spread to almost all parts of world. GB-1, the herbal formula from Tian Shang Sheng Mu of Chiayi Puzi Peitian Temple, is used for the prophylaxis of SARS-CoV-2 in Taiwan. In this study, we investigated that the effect of GB-1 and the index compounds of GB-1 on the ACE2 and TMPRSS2 expression through in vitro and in vivo study. In our result, GB-1 can inhibit ACE2 and TMPRSS2 protein expression in HepG2 cells, 293T cells, and Caco-2 cells without cytotoxicity. For the mouse model, GB-1 treatment could decrease ACE2 and TMPRSS2 expression levels of the lung and kidney tissue without adverse effects, including nephrotoxicity and hepatotoxicity. In the compositions of GB-1, 0.5-1 mg/ml of Glycyrrhiza uralensis Fisch. ex DC. extract could not inhibit ACE2 mRNA and protein expression in HepG2 cells. In addition, theaflavin-3-gallate could inhibit protein expression of ACE2 and TMPRSS2 without significant cytotoxicity. Our results suggest that GB-1 and theaflavin-3-gallate could act as potential candidates for prophylaxis or treatment of SARS-CoV-2 infection through inhibiting protein expression of ACE2 and TMPRSS2 for the further study.

Culture-Based Virus Isolation To Evaluate Potential Infectivity of Clinical Specimens Tested for COVID-19.

Real-time reverse transcription-PCR (RT-PCR) is currently the most sensitive method to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19). However, the correlation between detectable viral RNA and culturable virus in clinical specimens remains unclear. Here, we performed virus culture for 60 specimens that were confirmed to be positive for SARS-CoV-2 RNA by real-time RT-PCR. The virus could be successfully isolated from 12 throat and nine nasopharyngeal swabs and two sputum specimens. The lowest copy number required for virus isolation was determined to be 5.4, 6.0, and 5.7 log10 genome copies/ml sample for detecting the nsp12, E, and N genes, respectively. We further examined the correlation of genome copy number and virus isolation in different regions of the viral genome, demonstrating that culturable specimens are characterized by high copy numbers with a linear correlation observed between copy numbers of amplicons targeting structural and nonstructural regions. Overall, these results indicate that in addition to the copy number, the integrity of the viral genome should be considered when evaluating the infectivity of clinical SARS-CoV-2 specimens.

[Care Strategies and Trends in Taiwan During the COVID-19 Pandemic].

The ongoing COVID-19 pandemic has currently spread to over 100 countries, infecting over thirty million people and causing nearly one million deaths. The COVID-19 pandemic is the most serious pandemic crisis faced by the world medical system for at least a century. To address the impacts of pandemic prevention and control measures and of societal concerns regarding risks of contraction in healthcare environments, related policies and management must be adopted to provide effective care and future prevention. The author introduces the prevention policies implemented during the pandemic under coordinated medical systems, the National Health Insurance program, pandemic management, and national and international governmental organizations to provide readers with a reference for the current situation of the pandemic in Taiwan and the world.

A model based on CT radiomic features for predicting RT-PCR becoming negative in coronavirus disease 2019 (COVID-19) patients (preprint)

Background: Coronavirus disease 2019 (COVID-19) has emerged as a global pandemic. According to the diagnosis and treatment guidelines of China, negative reverse transcription-polymerase chain reaction (RT-PCR) is the key criterion for discharging COVID-19 patients. However, repeated RT-PCR tests lead to medical waste and prolonged hospital stays for COVID-19 patients during the recovery period. Our purpose is to assess a model based on chest computed tomography (CT) radiomic features and clinical characteristics to predict RT-PCR negativity during clinical treatment. Methods: : From February 10 to March 10, 2020, 203 mild COVID-19 patients in Fangcang Shelter Hospital were retrospectively included (training: n=141; testing: n=62), and clinical characteristics were collected. Lung abnormalities on chest CT images were segmented with a deep learning algorithm. CT quantitative features and radiomic features were automatically extracted. Clinical characteristics and CT quantitative features were compared between RT-PCR-negative and RT-PCR-positive groups. Univariate logistic regression and Spearman correlation analyses identified the strongest features associated with RT-PCR negativity, and a multivariate logistic regression model was established. The diagnostic performance was evaluated for both cohorts. Results: : The RT-PCR-negative group had a longer time interval from symptom onset to CT exams than the RT-PCR-positive group (median 23 vs. 16 days, p<0.001). There was no significant difference in the other clinical characteristics or CT quantitative features. In addition to the time interval from symptom onset to CT exams, nine CT radiomic features were selected for the model. ROC curve analysis revealed AUCs of 0.811 and 0.812 for differentiating the RT-PCR-negative group, with sensitivity/specificity of 0.765/0.625 and 0.784/0.600 in the training and testing datasets, respectively. Conclusion: The model combining CT radiomic features and clinical data helped predict RT-PCR negativity during clinical treatment, indicating the proper time for RT-PCR retesting.