Metformin mitigates insulin signaling variations induced by COVID-19 vaccine boosters in type 2 diabetes (preprint)

Diabetes is associated with an increased risk of Coronavirus disease 2019 (COVID-19) vulnerability and mortality. COVID-19 vaccines significantly reduce the risks of serious COVID-19 outcomes, but the impact of COVID-19 vaccines including their effectiveness and adverse effects in patients with diabetes are not well known yet. Here, we showed that 61.1% patients with type 2 diabetes, but not healthy controls, exhibited aggravated insulin resistance towards the booster shots of the COVID-19 vaccine. Furthermore, we showed that COVID-19 vaccination once a week also impaired insulin sensitivity in healthy mice after four weeks. We further showed that metformin, a common anti-diabetic medication, improved the impaired insulin signaling induced by COVID-19 vaccination in mice. This study suggests clinical implications for the close monitoring of glycemic control in diabetic patients after receiving COVID-19 vaccines and indicates the beneficial action of metformin in counteracting insulin signaling variations induced by COVID-19 vaccination in diabetic patients.

Genomic Surveillance for SARS-CoV-2 - China, September 26, 2022 to January 29, 2023.

Introduction: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has generated 2,431 variants over the course of its global transmission over the past 3 years. To better evaluate the genomic variation of SARS-CoV-2 before and after the optimization of coronavirus disease 2019 (COVID-19) prevention and control strategies, we analyzed the genetic evolution branch composition and genomic variation of SARS-CoV-2 in both domestic and imported cases in China (the data from Hong Kong and Macau Special Administrative Regions and Taiwan, China were not included) from September 26, 2022 to January 29, 2023. Methods: Analysis of the number of genome sequences, sampling time, dynamic changes of evolutionary branches, origin, and clinical typing of SARS-CoV-2 variants submitted by 31 provincial-level administrative divisions (PLADs) and Xinjiang Production and Construction Corps (XPCC) was conducted to assess the accuracy and timeliness of SARS-CoV-2 variant surveillance. Results: From September 26, 2022 to January 29, 2023, 20,013 valid genome sequences of domestic cases were reported in China, with 72 evolutionary branches. Additionally, 1,978 valid genome sequences of imported cases were reported, with 169 evolutionary branches. The prevalence of the Omicron variants of SARS-CoV-2 in both domestic and imported cases was consistent with that of international epidemic variants. Conclusions: This study provides an overview of the prevalence of Omicron variants of SARS-CoV-2 in China. After optimizing COVID-19 prevention and control strategies, no novel Omicron variants of SARS-CoV-2 with altered biological characteristics or public health significance have been identified since December 1, 2022.

Control of SARS-CoV-2 infection by MT1-MMP-mediated shedding of ACE2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. Angiotensin-converting enzyme 2 (ACE2) is an entry receptor for SARS-CoV-2. The full-length membrane form of ACE2 (memACE2) undergoes ectodomain shedding to generate a shed soluble form (solACE2) that mediates SARS-CoV-2 entry via receptor-mediated endocytosis. Currently, it is not known how the physiological regulation of ACE2 shedding contributes to the etiology of COVID-19 in vivo. The present study identifies Membrane-type 1 Matrix Metalloproteinase (MT1-MMP) as a critical host protease for solACE2-mediated SARS-CoV-2 infection. SARS-CoV-2 infection leads to increased activation of MT1-MMP that is colocalized with ACE2 in human lung epithelium. Mechanistically, MT1-MMP directly cleaves memACE2 at M706-S to release solACE218-706 that binds to the SARS-CoV-2 spike proteins (S), thus facilitating cell entry of SARS-CoV-2. Human solACE218-706 enables SARS-CoV-2 infection in both non-permissive cells and naturally insusceptible C57BL/6 mice. Inhibition of MT1-MMP activities suppresses solACE2-directed entry of SARS-CoV-2 in human organoids and aged mice. Both solACE2 and circulating MT1-MMP are positively correlated in plasma of aged mice and humans. Our findings provide in vivo evidence demonstrating the contribution of ACE2 shedding to the etiology of COVID-19.

Multi-Model Fusion-Based Hierarchical Extraction for Chinese Epidemic Event.

In recent years, Coronavirus disease 2019 (COVID-19) has become a global epidemic, and some efforts have been devoted to tracking and controlling its spread. Extracting structured knowledge from involved epidemic case reports can inform the surveillance system, which is important for controlling the spread of outbreaks. Therefore, in this paper, we focus on the task of Chinese epidemic event extraction (EE), which is defined as the detection of epidemic-related events and corresponding arguments in the texts of epidemic case reports. To facilitate the research of this task, we first define the epidemic-related event types and argument roles. Then we manually annotate a Chinese COVID-19 epidemic dataset, named COVID-19 Case Report (CCR). We also propose a novel hierarchical EE architecture, named multi-model fusion-based hierarchical event extraction (MFHEE). In MFHEE, we introduce a multi-model fusion strategy to tackle the issue of recognition bias of previous EE models. The experimental results on CCR dataset show that our method can effectively extract epidemic events and outperforms other baselines on this dataset. The comparative experiments results on other generic datasets show that our method has good scalability and portability. The ablation studies also show that the proposed hierarchical structure and multi-model fusion strategy contribute to the precision of our model. Supplementary Information: The online version contains supplementary material available at 10.1007/s41019-022-00203-6.

Surveillance and Analysis of SARS-CoV-2 Variant Importation - China, January-June 2022.

Introduction: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant is the dominant circulating strain worldwide. To assess the importation of SARS-CoV-2 variants in the mainland of China during the Omicron epidemic, the genomic surveillance data of SARS-CoV-2 from imported coronavirus disease 2019 (COVID-19) cases in the mainland of China during the first half of 2022 were analyzed. Methods: Sequences submitted from January to July 2022, with a collection date before June 30, 2022, were incorporated. The proportions of SARS-CoV-2 variants as well as the relationships between the origin and destination of each Omicron imported case were analyzed. Results: 4,946 sequences of imported cases were submitted from 27 provincial-level administrative divisions (PLADs), and the median submission interval was within 1 month after collection. In 3,851 Omicron sequences with good quality, 1 recombinant (XU) and 4 subvariants under monitoring (BA.4, BA.5, BA.2.12.1, and BA.2.13) were recorded, and 3 of them (BA.4, BA.5, and BA.2.12.1) caused local transmissions in the mainland of China later than that recorded in the surveillance. Omicron subvariants dominated in the first half of 2022 and shifted from BA.1 to BA.2 then to BA.4 and BA.5. The percentage of BA.2 in the imported SARS-CoV-2 surveillance data was far higher than that in the Global Initiative on Sharing All Influenza Data (GISAID). The imported cases from Hong Kong Special Administrative Region, China, accounted for 32.30% of Omicron cases sampled, and 98.71% of them were BA.2. Conclusions: The Omicron variant showed the intra-Omicron evolution in the first half of 2022, and all of the Omicron subvariants were introduced into the mainland of China multiple times from multiple different locations.

Source tracing of the COVID-19 infection case in Guangxi, China

The study describing the process of discovery and source tracing of a native case of coronavirus disease 2019 (COVID-19) infection on Jan 2021, in Guangxi, China, to provide methodology for source investigation better in the future. Following the Epidemiological Investigation Plan for COVID-19 (version 7), information of the native COVID-19 case and related close contacts were collected. Real time reverse transcription-quantitative polymerase chain reaction was performed to detect the nucleic acids of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in samples collected from the infection case, related close contacts, and the environment, combined with serum specific antibody detection. The positive nucleic acid samples were undergone whole genome sequencing, phylogenetic analysis and analyses of variation of amino acids. The whole genome sequence from the native case and the imported asymptomatic infected case from Indonesia containing 25 nucleotide mutation sites belong to L-Lineage European Branch II. 3. The imported asymptomatic case was the source of infection of this native case. The possible route of infection was that native case was exposed to contaminated environment by imported case, due to improper personal protective equipment. A focus on local outbreaks of COVID-19 caused by SARS-CoV-2-infected people from outside China is needed.

How sustainable are the biodegradable medical gowns via environmental and social life cycle assessment?

The growing disposable medical gown consumption due to the COVID-19 pandemic has driven tons of waste to landfills and posed plastic pollution. Investigating the pros and cons of biodegradable gowns over conventional counterparts can guide disposable medical gowns to be environmentally and socially sustainable. This work presents environmental and social life cycle assessments (E− and S-LCA) of biodegradable gowns to compare their environmental and social performances with conventional ones. The E-LCA evaluates the full-spectrum environmental impacts from gown production to end-of-life waste management processes, while the S-LCA assesses their associated influence on economic growth, employment, and worker welfare. The social impacts are evaluated based on the economic input-output analysis results of the economic sectors or gown life cycle stages involved in the gown value chain. Results show that biodegradable gown production poses 10.76% higher ecotoxicity than conventional alternatives contributed by pro-oxidant manufacturing. Integrating the landfill gas (LFG) capture and utilization processes into biodegradable gown waste treatment can reduce 48.81% of life cycle land use and over 5.67% of total greenhouse gas emissions. However, integrating this process in sanitary landfills to treat disinfected gown wastes can increase technical complexity, which enhances 70% of safety risks and 40% frequency of forced labor. Industrial composting biodegradable gowns can reduce over 20.5% of particulate matter formation versus sanitary landfills. Overall, fossil-based gowns possess full-spectrum environmental and social advantages over biodegradable counterparts treated by industrial composting and sanitary landfills. If improving the efficiencies of LFG capture by 85%, biogenic methane oxidation by 43%, and heat generation by 85%, biodegradable gowns can outperform conventional counterparts in reducing GHG emissions and fossil fuel use.

Protective health behaviors and fear of social isolation during the COVID-19 pandemic: a public opinion perspective.

When coronavirus disease (COVID-19) news along with protective health recommendations first came to people's life, such ambiguous information became a public opinion. Performing protective behaviors can be regarded as an approval of the majority opinion as people have to alter their established health positions and practices. So far, the association between public opinion and protective health behaviors is unclear especially in the pandemic context. This study utilized a survey data collected between 1 and 10 April 2020 in Germany (n = 101), Austria (n = 261), Switzerland (n = 26), and China (n = 267). We compared the protective health behaviors between the Chinese and European participants, as well as examined the associations between the protective health behaviors, peer influence, and fear of social isolation. Protective health behaviors were found similar between Chinese and European participants, although being independent from peer influence and fear of social isolation were related to protective health behaviors in the Chinese sample. Our cross-national findings are consistent with previous studies, suggesting that both official and unofficial health communication show stronger influences in Asian populations. Findings from this study provide advice for public communication strategies to promote protective health behaviors during pandemics.

An imported human case with the SARS-CoV-2 omicron subvariant BA.2.75 in Yunnan province, China.

The Omicron variants spread rapidly worldwide after being initially detected in South Africa in November 2021. It showed increased transmissibility and immune evasion with far more amino acid mutations in the Spike (S) protein than the previously circulating variant of concern (VOC). Notably, on 15 July 2022, we monitored the first VOC/Omicron subvariant BA.2.75 in China from an imported case. Moreover, nowadays, this subvariant still is predominant in India. It has nine additional mutations in the S protein compared to BA.2, three of which (W152R, G446S, and R493Q reversion) might contribute to higher transmissibility and immune escape. This subvariant could cause wider spread and pose a threat to the global situation. Our timely reporting and continuous genomic analysis are essential to fully elucidate the characteristics of the subvariant BA.2.75 in the future.

Genetic characterization of SARS-CoV-2 from cross-border trucks and containers in Kashgar Prefecture, Xinjiang Uygur Autonomous Region, China

Kashgar is a prefecture in Xinjiang Uygur Autonomous Region. China. Kashgar Prefecture (KP) is a land-cargo port connecting China with central Asian countries and Europe. Frequent transportation of cargo has increased the risk of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) introduction into China, which has increased the pressure on coronavirus disease-2019 (COVID-19) prevention and control. In November 2020, an imported virus-induced COVID-19 outbreak occurred in KP. To investigate the genetic characterization of SARS-CoV-2 that contaminated the trucks and containers, and the potential of border rapid logistics system to serve as carriers for SARS-CoV-2 transmission, thirty-five SARS-CoV-2-positive nucleic-acid samples collected from KP cross-border trucks and containers from 6-10 November 2020 were subjected into SARS-CoV-2 genomic sequencing and comparative analyses. The results showed that the median (minimum to maximum) Ct value of ORF1ab was 37.64 (28.91-39.81) . and that of the N gene was 36.50 (26.35-39.30), and the median (minimum to maximum) of the reads mapping ratio to SARS-CoV-2 was 51.95% (0.86%-99.31%), which indicated low viral loads in these environmental samples. Eighteen of 35 samples had genomic coverage >70%. According to the Pango nomenclature, 18 SARS-CoV-2 sequences belonged to six lineages (B.1, B.I.1, B.1.9. B.1.1.220, B.1.153 and B.1.465), three of which (B.I. B.1.1 and 8.1.153) were found in case samples from the same period of four China-neighboring countries. Analyses of nucleotide mutations and phylogenetic trees showed that the genome sequences of SARS-CoV-2 collected from the same location were similar. Four of 18 sequences were in a sub-lineage with the representative strain of COVID-19 outbreak in KP, one of which had 1 or 2 differences in nucleotide mutation sites with the strain that caused the COVID-19 outbreak in KP, which indicated high homology in the viral genome. We showed that cross-border trucks and containers were contaminated by various genotypes of SARS-CoV-2 from other countries during the outbreak in KP. and in which contained the parental virus of the KP cases. These trucks and containers served as carriers for SARS-CoV-2 introduction from other countries to cause local transmission. Our results provide important references for COVID-19 prevention-and-control strategies in border ports and tracing of outbreak sources in China.

A local COVID - 19 outbreak in Dalian caused by imported cold - chain products contaminated by SARS-CoV-2

On December 15, 2020, four dock workers tested positive for severe acute respiratory syndrome-coronavirus 2 (SARS-COV-2) nucleic acids and were reported by Dalian. Up until then, Dalian City had not reported local cases for 136 consecutive days. In this coronavirus disease 2019 (COVID-19) outbreak (referred to as the "Dalian COVID-19 outbreak"), samples from all infected persons (83) and part from the ship cargoes in contact With them during December 15, 2020 to January 8, 2021 were collected. Confirmed cases accounted for 61.45% (51/83) and asymptomatic infections accounted for 38.55% (32/83). Through high-throughput sequencing, 76 SARS-CoV-2 whole-genome sequences were obtained, of which 72 (86.75%) were from clinical samples, and 4 from cold-chain food packaging surface samples on cargo ship A of country R. Refer to Wuhan reference strain (NC_045512), genome analysis revealed 12-16 nucleotide mutations in 76 whole genomes sharing 12 nucleotide mutations and belong to the SARS-CoV-2 branch of B.1.1. Viral genomics and field epidemiological investigations showed that the Dalian COVID-19 outbreak was a local epidemic caused by dock workers infected with imported cold - chain products contaminated with SARS - CoV - 2. During transmission, 3 Virus generations and three relatively independent transmission chains were formed.

Effects of Chinese medicine for COVID-19 rehabilitation: a multicenter observational study.

OBJECTIVES: This study aimed to evaluate the effects of Chinese Medicine (CM) on the health condition of the post-COVID-19 patients, particularly with the CM Syndrome diagnosis and Body Constitutions (BC), as well as related clinical characteristics. METHODS: 150 participants who had COVID-19 and discharged from Hong Kong public hospitals were recruited. They were provided with three to six months of CM treatments, during which assessments were made per month and at follow-up on their CM syndromes, BC, lung functions, and other medical conditions. This study was divided into two parts: (1) Retrospective survey: medical history of participants during COVID-19 hospitalization was collected during the baseline visit; (2) Prospective observation and assessments: clinical symptoms, lung functions, and BC status were evaluated in participants receiving CM treatment based on syndrome differentiation and clinical symptoms. RESULTS: The median hospitalization period was 16 days. Symptoms were presented in 145 (96.6%) patients at the day they were diagnosed with COVID-19. Fever, fatigue, and dry cough were the most common symptoms, exhibiting in 59.3% (89 of 150), 55.3% (83 of 150), and 46% (70 of 150) participants, respectively. Among the 150 post-COVID patients, majority (71.3%) were of the two particular post-COVID CM Syndromes (Qi Deficiency of Lung and Spleen, and Qi and Yin Deficiency). Upon CM treatment, there was an observable increase in participants reaching a balanced BC (i.e. healthy body conditions). The increase was observed to be more prominent in those without the particular CM Syndromes compared to those with the CM Syndromes. Main clinical symptoms in participants with the CM Syndromes decreased upon CM treatment. Occurrence of fatigue also dropped after CM treatment though not all accompanied clinical symptoms were resolved fully. Further to the improvement in terms of CM assessments, lung functions of the participants were found to show improvement after treatment. Both the performance in 6MWT and scores in the LFQ improved upon CM treatments (P < 0.05). CONCLUSION: This study provided evidence for individualized CM treatment on COVID-19 rehabilitation concerning the clinical symptoms improvements, lung functions improvement, and achieving a balanced BC. It is believed that CM may be a key to further promote rehabilitation and resolution of residual symptoms. Long-term large scale follow-up studies on sub-categorising post-COVID patients according to different CM syndromes would be required to further elucidate treatment of persistent symptoms that may be associated with long-COVID.

Genomic Surveillance for SARS-CoV-2 Variants of Concern from Imported COVID-19 Cases - the Mainland of China, 2021.

Introduction: After the epidemic in Wuhan City was brought under control in 2020, local outbreaks of coronavirus disease 2019 (COVID-19) in the mainland of China were mainly due to imported COVID-19 cases. The ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has continued to generate new variants. Some have been designated as variants of concern (VOCs) by the World Health Organization (WHO). To better assess the role of imported SARS-CoV-2 surveillance and the prevalence of VOCs in 2021, the genomic surveillance data of SARS-CoV-2 from imported COVID-19 cases of 2021 in the mainland of China were analyzed. Methods: The analyses included the number of sequence submissions, time of sequence deposition, and time of detection of the VOCs in order to determine the timeliness and sensitivity of the surveillance. The proportions of VOCs were analyzed and compared with data from the Global Initiative of Sharing All Influenza Data (GISAID). Results: A total of 3,355 sequences of imported cases were submitted from 29 provincial-level administrative divisions, with differences in the number of sequence submissions and median time of sequence deposition. A total of 2,388 sequences with more than 90% genomic coverage were used for lineage analysis. The epidemic trend from Alpha to Delta to Omicron in imported cases was consistent with that in the GISAID. In addition, VOCs from imported cases were usually identified after WHO designation and before causing local outbreaks. Conclusions: The global distribution of SARS-CoV-2 VOCs changed rapidly in 2021. Robust genomic surveillance of the imported SARS-CoV-2 in the mainland of China is of great significance.

Clinical features and prognosis of COVID-19 patients with metabolic syndrome: A multicenter, retrospective study Características clínicas y pronóstico de los pacientes con COVID-19 y síndrome metabólico: un estudio multicéntrico y retrospectivo

Background Few studies have investigated the impacts of metabolic syndrome (MS) on coronavirus disease 2019 (COVID-19). We described the clinical features and prognosis of confirmed COVID-19 patients with MS during hospitalization and after discharge. Methods Two hundred and thirty-three COVID-19 patients from the hospitals in 8 cities of Jiangsu, China were retrospectively included. Clinical characteristics of COVID-19 patients were described and risk factors of severe illness were analyzed by logistic regression analysis. Results Forty-five (19.3%) of 233 COVID-19 patients had MS. The median age of COVID-19 patients with MS was significantly higher than non-MS patients (53.0 years vs. 46.0 years, P = 0.004). There were no significant differences of clinical symptoms, abnormal chest CT images, and treatment drugs between two groups. More patients with MS had severe illness (33.3% vs. 6.4%, P < 0.001) and critical illness (4.4% vs. 0.5%, P = 0.037) than non-MS patients. The proportions of respiratory failure and acute respiratory distress syndrome in MS patients were also higher than non-MS patients during hospitalization. Multivariate analysis showed that concurrent MS (odds ratio [OR] 7.668, 95% confidence interval [CI] 3.062–19.201, P < 0.001) and lymphopenia (OR 3.315, 95% CI 1.306–8.411, P = 0.012) were independent risk factors of severe illness of COVID-19. At a median follow-up of 28 days after discharge, bilateral pneumonia was found in 95.2% of MS patients, while only 54.7% of non-MS patients presented bilateral pneumonia. Conclusions 19.3% of COVID-19 patients had MS in our study. COVID-19 patients with MS are more likely to develop severe complications and have worse prognosis. More attention should be paid to COVID-19 patients with MS.

Clinical features and prognosis of COVID-19 patients with metabolic syndrome: A multicenter, retrospective study.

Background: Few studies have investigated the impacts of metabolic syndrome (MS) on coronavirus disease 2019 (COVID-19). We described the clinical features and prognosis of confirmed COVID-19 patients with MS during hospitalization and after discharge. Methods: Two hundred and thirty-three COVID-19 patients from the hospitals in 8 cities of Jiangsu, China were retrospectively included. Clinical characteristics of COVID-19 patients were described and risk factors of severe illness were analyzed by logistic regression analysis. Results: Forty-five (19.3%) of 233 COVID-19 patients had MS. The median age of COVID-19 patients with MS was significantly higher than non-MS patients (53.0 years vs. 46.0 years, P = 0.004). There were no significant differences of clinical symptoms, abnormal chest CT images, and treatment drugs between two groups. More patients with MS had severe illness (33.3% vs. 6.4%, P < 0.001) and critical illness (4.4% vs. 0.5%, P = 0.037) than non-MS patients. The proportions of respiratory failure and acute respiratory distress syndrome in MS patients were also higher than non-MS patients during hospitalization. Multivariate analysis showed that concurrent MS (odds ratio [OR] 7.668, 95% confidence interval [CI] 3.062-19.201, P < 0.001) and lymphopenia (OR 3.315, 95% CI 1.306-8.411, P = 0.012) were independent risk factors of severe illness of COVID-19. At a median follow-up of 28 days after discharge, bilateral pneumonia was found in 95.2% of MS patients, while only 54.7% of non-MS patients presented bilateral pneumonia. Conclusions: 19.3% of COVID-19 patients had MS in our study. COVID-19 patients with MS are more likely to develop severe complications and have worse prognosis. More attention should be paid to COVID-19 patients with MS.

Antecedentes: Pocos estudios han investigado el impacto del síndrome metabólico (SM) en la enfermedad por coronavirus 2019 (COVID-19). Describimos las características clínicas y el pronóstico de los pacientes con COVID-19 confirmados con SM durante la hospitalización y después del alta. Métodos: Se incluyó de forma retrospectiva a 233 pacientes con COVID-19 de los hospitales de 8 ciudades de Jiangsu (China). Se describieron sus características clínicas y se analizaron los factores de riesgo de enfermedad grave mediante un análisis de regresión logística. Resultados: De los 233 pacientes, 45 (19,3%) tenían EM. La mediana de edad de estos pacientes con EM fue significativamente mayor que la de los pacientes sin él (53,0 años frente a 46,0 años; p = 0,004). No hubo diferencias significativas en cuanto a los síntomas clínicos, las imágenes de TC torácica anormales y los fármacos de tratamiento entre los 2 grupos. Hubo más pacientes con EM que tuvieron enfermedades graves (33,3% frente a 6,4%; p < 0,001) y críticas (4,4% frente a 0,5%; p = 0,037) que los pacientes sin EM. Las proporciones de insuficiencia respiratoria y síndrome de dificultad respiratoria aguda en los pacientes con EM también fueron mayores que en los pacientes sin EM durante la hospitalización. El análisis multivariante mostró que la EM concurrente (odds ratio [OR] 7,668; intervalo de confianza [IC] del 95%: 3,062-19,201; p < 0,001) y la linfopenia (OR 3,315; IC del 95%: 1,306-8,411; p = 0,012) eran factores de riesgo independientes de COVID-19 grave. En una mediana de seguimiento de 28 días tras el alta, se encontró neumonía bilateral en el 95,2% de los pacientes con EM, mientras que solo la presentaron el 54,7% de los pacientes sin EM. Conclusiones: El 19,3% de los pacientes con COVID-19 tenían EM en nuestro estudio. Los pacientes con COVID-19 y EM son más propensos a desarrollar complicaciones graves y tienen peor pronóstico. Se debe prestar más atención a los pacientes con COVID-19 y EM.

The E484K Substitution in a SARS-CoV-2 Spike Protein Subunit Vaccine Resulted in Limited Cross-Reactive Neutralizing Antibody Responses in Mice.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), especially emerging variants, poses an increased threat to global public health. The significant reduction in neutralization activity against the variants such as B.1.351 in the serum of convalescent patients and vaccinated people calls for the design of new potent vaccines targeting the emerging variant. However, since most vaccines approved and in clinical trials are based on the sequence of the original SARS-CoV-2 strain, the immunogenicity and protective efficacy of vaccines based on the B.1.351 variant remain largely unknown. In this study, we evaluated the immunogenicity, induced neutralization activity, and protective efficacy of wild-type spike protein nanoparticle (S-2P) and mutant spike protein nanoparticle (S-4M-2P) carrying characteristic mutations of B.1.351 variant in mice. Although there was no significant difference in the induction of spike-specific IgG responses in S-2P- and S-4M-2P-immunized mice, neutralizing antibodies elicited by S-4M-2P exhibited noteworthy, narrower breadth of reactivity with SARS-CoV-2 variants compared with neutralizing antibodies elicited by S-2P. Furthermore, the decrease of induced neutralizing antibody breadth at least partly resulted from the amino acid substitution at position 484. Moreover, S-4M-2P vaccination conferred insufficient protection against live SARS-CoV-2 virus infection, while S-2P vaccination gave definite protection against SARS-CoV-2 challenge in mice. Together, our study provides direct evidence that the E484K substitution in a SARS-CoV-2 subunit protein vaccine limited the cross-reactive neutralizing antibody breadth in mice and, more importantly, draws attention to the unfavorable impact of this mutation in spike protein of SARS-CoV-2 variants on the induction of potent neutralizing antibody responses.

Parent-Child Relationships and Academic Performance of College Students: Chain-Mediating Roles of Gratitude and Psychological Capital.

This study used the Social Cognitive Theory and Broaden-and-Build Theory to propose and validate a chain mediation model. In total, 417 Chinese college students were studied to explore the effects of parent-child relationships on their academic performance. In addition, we investigated the chain-mediating roles of gratitude and psychological capital. The results showed that (1) the parent-child relationship significantly and positively affected the academic performance of college students; (2) gratitude partially mediated the parent-child relationship and the academic performance of college students; (3) psychological capital partially mediated the parent-child relationship and the academic performance of college students; and (4) gratitude and psychological capital exerted a chain-mediating effect between parent-child relationships and the academic performance of college students. Based on the results of the study, we conclude that the parent-child relationship not only directly affects the academic performance of college students but also indirectly affects it through the chain mediation of gratitude and psychological capital. Moreover, we proposed reasonable suggestions on how colleges and universities can guide students to deal with parent-child relationships, strengthen gratitude education, and improve psychological capital.