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1.
Frontiers in Pediatrics ; 10:932734, 2022.
Article in English | MEDLINE | ID: covidwho-2039693

ABSTRACT

Background: Social distancing and school closures during the COVID-19 pandemic reduced the physical activities of the preschool children living in China. However, the effects of home-based exercise on the physical fitness of Chinese preschool children during COVID-19 school closures are still unknown. This study aimed to investigate the effects of home-based exercise on the physical fitness of Chinese preschool children during COVID-19 school closure. Methods: In this retrospective analysis, data from 1,608 Chinese preschool children (aged 3-5.5 years) in a second-tier city of Guangdong Province of China (Zhongshan city) were extracted from three successive National Physical Fitness Measurement (NPFM) from 2019 to 2021. NPFM consists of weight, height, and six subtests of physical fitness including 10-m shuttle run test (SRT), standing long jump (SLJ), balance beam walking (BBW), sit-and-reach (SR), tennis throwing (TT), and double-leg timed hop (DTH) tests. The change differences or change ratios of all the items in NPFM between any two successive years from 2019 to 2021 were compared. The exercise profiles about home-based and outdoor exercise before, during, and after COVID-19 school closure were obtained from 185 preschool children via retrospective telephone survey. Results: Between 2019 and 2021, 1,608 preschool children were included in this study. We observed larger changes in SLJ, SR, TT, and DTH tests during school closure than after school closure. But the children showed lower reduction rates in the completion time of SRT and BBW. During school closure, higher change ratios in SLJ and TT were observed in the children primarily participating in home-based exercise than those primarily participating in outdoor exercise. However, no statistical differences were observed in the changes in SRT and BBW between home-based and outdoor training groups. Conclusion: The home-based exercise program might be an alternative approach to improve the physical fitness of preschool children during COVID-19 school closure, but could not be beneficial to speed-agility and balance functions. A specific guideline geared toward a home-based exercise program during the COVID-19 outbreak is highly needed.

2.
Signal Transduct Target Ther ; 7(1):327, 2022.
Article in English | PubMed | ID: covidwho-2036782
3.
Academic Voices: A Conversation on New Approaches to Teaching and Learning in the post-COVID World ; : 269-281, 2022.
Article in English | Scopus | ID: covidwho-2035550

ABSTRACT

This chapter tells the story of 13 higher education (HE) practitioners (academics and academic developers) from 10 universities across Australia and New Zealand leveraging the COVID-19 disruption as a ‘disorienting dilemma’ that precipitated transformation from a Community of Practice (CoP) to a Community for Practice (CfP). The aim is to show how the group commenced as a CoP to ‘Talk About Teaching and Learning’ (TATAL) and support one another towards HE fellowships, and grew into a CfP that supports holistic growth that benefits each member based on their specific contexts, needs, and goals. With reflections woven throughout as evidence of transformation, the purpose of this chapter is to demonstrate how an interdisciplinary, multiuniversity group has created and nurtured a sustainable CfP. Experiential learning and reflective practice models, which are underpinned by considerations of action research and collaborative autoethnography, support and account for insights into the transformative changes. © 2022 Elsevier Ltd. All rights reserved.

4.
Sci Rep ; 12(1):15517, 2022.
Article in English | PubMed | ID: covidwho-2028729

ABSTRACT

Coronavirus disease 2019 (COVID-19) continues to significantly impact the global population, thus countermeasure platforms that enable rapid development of therapeutics against variants of SARS-CoV-2 are essential. We report use of a phage display human antibody library approach to rapidly identify neutralizing antibodies (nAbs) against SARS-CoV-2. We demonstrate the binding and neutralization capability of two nAbs, STI-2020 and STI-5041, against the SARS-CoV-2 WA-1 strain as well as the Alpha and Beta variants. STI-2020 and STI-5041 were protective when administered intravenously or intranasally in the golden (Syrian) hamster model of COVID-19 challenged with the WA-1 strain or Beta variant. The ability to administer nAbs intravenously and intranasally may have important therapeutic implications and Phase 1 healthy subjects clinical trials are ongoing.

5.
Clinical and Translational Medicine ; 12(9):e1016, 2022.
Article in English | MEDLINE | ID: covidwho-2027332

ABSTRACT

BACKGROUND: To determine an appropriate dose of, and immunization schedule for, a vaccine SCoK against COVID-19 for an efficacy study;herein, we conducted randomized controlled trials to assess the immunogenicity and safety of this vaccine in adults. METHODS: These randomized, double-blind, placebo-controlled phase 1 and 2 trials of vaccine SCoK were conducted in Binhai District, Yan City, Jiangsu Province, China. Younger and older adult participants in phase 1 and 2 trials were sequentially recruited into different groups to be intramuscularly administered 20 or 40 mug vaccine SCoK or placebo. Participants were enrolled into our phase 1 and 2 studies to receive vaccine or placebo. RESULTS: No serious vaccine-related adverse events were observed in either trial. In both trials, local and systemic adverse reactions were absent or mild in most participants. In our phase 1 and 2 studies, the vaccine induced significantly increased neutralizing antibody responses to pseudovirus and live SARS-CoV-2. The vaccine induced significant neutralizing antibody responses to live SARS-CoV-2 on day 14 after the last immunization, with NT50s of 80.45 and 92.46 in participants receiving 20 and 40 mug doses, respectively;the seroconversion rates were 95.83% and 100%. The vaccine SCoK showed a similar safety and immunogenicity profiles in both younger participants and older participants. The vaccine showed better immunogenicity in phase 2 than in phase 1 clinical trial. Additionally, the incidence of adverse reactions decreased significantly in phase 2 clinical trial. The vaccine SCoK was well tolerated and immunogenic.

6.
Front Immunol ; 13:956369, 2022.
Article in English | PubMed | ID: covidwho-2022739

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused significant loss of life and property. In response to the serious pandemic, recently developed vaccines against SARS-CoV-2 have been administrated to the public. Nevertheless, the research on human immunization response against COVID-19 vaccines is insufficient. Although much information associated with vaccine efficacy, safety and immunogenicity has been reported by pharmaceutical companies based on laboratory studies and clinical trials, vaccine evaluation needs to be extended further to better understand the effect of COVID-19 vaccines on human beings. METHODS: We performed a comparative peptidome analysis on serum samples from 95 participants collected at four time points before and after receiving CoronaVac. The collected serum samples were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) to profile the serum peptides, and also subjected to humoral and cellular immune response analyses to obtain typical immunogenicity information. RESULTS: Significant difference in serum peptidome profiles by MALDI-TOF MS was observed after vaccination. By supervised statistical analysis, a total of 13 serum MALDI-TOF MS feature peaks were obtained on day 28 and day 42 of vaccination. The feature peaks were identified as component C1q receptor, CD59 glycoprotein, mannose-binding protein C, platelet basic protein, CD99 antigen, Leucine-rich alpha-2-glycoprotein, integral membrane protein 2B, platelet factor 4 and hemoglobin subunits. Combining with immunogenicity analysis, the study provided evidence for the humoral and cellular immune responses activated by CoronaVac. Furthermore, we found that it is possible to distinguish neutralizing antibody (NAbs)-positive from NAbs-negative individuals after complete vaccination using the serum peptidome profiles by MALDI-TOF MS together with machine learning methods, including random forest (RF), partial least squares-discriminant analysis (PLS-DA), linear support vector machine (SVM) and logistic regression (LR). CONCLUSIONS: The study shows the promise of MALDI-TOF MS-based serum peptidome analysis for the assessment of immune responses activated by COVID-19 vaccination, and discovered a panel of serum peptides biomarkers for COVID-19 vaccination and for NAbs generation. The method developed in this study can help not only in the development of new vaccines, but also in the post-marketing evaluation of developed vaccines.

7.
Allergy & Asthma Proceedings ; 43(5):419-430, 2022.
Article in English | MEDLINE | ID: covidwho-2022489

ABSTRACT

Background: Secretory immunoglobulin A (sIgA) plays an important role in antiviral protective immunity. Although salivary testing has been used for many viral infections, including severe acute respiratory syndrome (SARS) and Middle East Respiratory Syndrome (MERS), its use has not yet been well established with the SARS coronavirus 2 (SARS-CoV-2). Quantification of salivary IgA and IgG antibodies can elucidate mucosal and systemic immune responses after natural infection or vaccination. Here, we report the development and validation of a rapid enzyme-linked immunosorbent assay (ELISA) for anti-SARS-CoV-2 salivary IgA and serum IgG antibodies, and present quantitative results for immunized subjects both prior to or following COVID-19 infections. Objective: Total and serum SARS-CoV-2 spike-specific IgG responses were compared with salivary spike-specific IgA and IgG responses in samples obtained from patients recently infected with SARS-CoV-2 and from subjects recently immunized with COVID-19 vaccines.

8.
Cell Discov ; 8, 2022.
Article in English | PMC | ID: covidwho-2008266

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs), especially the latest Omicron, have exhibited severe antibody evasion. Broadly neutralizing antibodies with high potency against Omicron are urgently needed for understanding the working mechanisms and developing therapeutic agents. In this study, we characterized the previously reported F61, which was isolated from convalescent patients infected with prototype SARS-CoV-2, as a broadly neutralizing antibody against all VOCs including Omicron BA.1, BA.1.1, BA.2, BA.3 and BA.4 sublineages by utilizing antigen binding and cell infection assays. We also identified and characterized another broadly neutralizing antibody D2 with epitope distinct from that of F61. More importantly, we showed that a combination of F61 with D2 exhibited synergy in neutralization and protecting mice from SARS-CoV-2 Delta and Omicron BA.1 variants. Cryo-Electron Microscopy (Cryo-EM) structures of the spike-F61 and spike-D2 binary complexes revealed the distinct epitopes of F61 and D2 at atomic level and the structural basis for neutralization. Cryo-EM structure of the Omicron-spike-F61-D2 ternary complex provides further structural insights into the synergy between F61 and D2. These results collectively indicated F61 and F61-D2 cocktail as promising therapeutic antibodies for combating SARS-CoV-2 variants including diverse Omicron sublineages.

9.
Frontiers in Cellular and Infection Microbiology ; 12, 2022.
Article in English | EMBASE | ID: covidwho-2005850

ABSTRACT

Purpose: The Corona Virus Disease 2019 (COVID-19) pandemic has become a challenge of world. The latest research has proved that Xuanfei Baidu granule (XFBD) significantly improved patient’s clinical symptoms, the compound drug improves immunity by increasing the number of white blood cells and lymphocytes, and exerts anti-inflammatory effects. However, the analysis of the effective monomer components of XFBD and its mechanism of action in the treatment of COVID-19 is currently lacking. Therefore, this study used computer simulation to study the effective monomer components of XFBD and its therapeutic mechanism. Methods: We screened out the key active ingredients in XFBD through TCMSP database. Besides GeneCards database was used to search disease gene targets and screen intersection gene targets. The intersection gene targets were analyzed by GO and KEGG. The disease-core gene target-drug network was analyzed and molecular docking was used for verification. Molecular dynamics simulation verification was carried out to combine the active ingredient and the target with a stable combination. The supercomputer platform was used to measure and analyze the number of hydrogen bonds, the binding free energy, the stability of protein target at the residue level, the solvent accessible surface area, and the radius of gyration. Results: XFBD had 1308 gene targets, COVID-19 had 4600 gene targets, the intersection gene targets were 548. GO and KEGG analysis showed that XFBD played a vital role by the signaling pathways of immune response and inflammation. Molecular docking showed that I-SPD, Pachypodol and Vestitol in XFBD played a role in treating COVID-19 by acting on NLRP3, CSF2, and relieve the clinical symptoms of SARS-CoV-2 infection. Molecular dynamics was used to prove the binding stability of active ingredients and protein targets, CSF2/I-SPD combination has the strongest binding energy. Conclusion: For the first time, it was found that the important active chemical components in XFBD, such as I-SPD, Pachypodol and Vestitol, reduce inflammatory response and apoptosis by inhibiting the activation of NLRP3, and reduce the production of inflammatory factors and chemotaxis of inflammatory cells by inhibiting the activation of CSF2. Therefore, XFBD can effectively alleviate the clinical symptoms of COVID-19 through NLRP3 and CSF2.

10.
Frontiers in Chemistry ; 10, 2022.
Article in English | Web of Science | ID: covidwho-2005848

ABSTRACT

Cytokine-mediated inflammatory response is considered a cause of skin lesion in COVID-19 patients. Complanatuside is a flavonol glycoside isolated from Astragalus complanatus. Flavonoids from Astragalus complanatus were reported to have anti-inflammatory and anticancer activities but the potential protective effect of complanatuside on cytokine-induced inflammatory damage in skin keratinocytes is not known. The aim of this study is to explore the inhibitory effect of complanatuside on inflammation and its underlying mechanisms in skin epithelial HaCaT cells treated with inflammatory cytokines. The combination of IFN-gamma, TNF-alpha, and IL-6 decreased cell viability, increased cell death, and pyroptosis in HaCaT cells. Treatment with complanatuside alleviated the effects of the cytokine combination on HaCaT cells. Complanatuside down-regulated pyroptosis related to NLRP3, GSDMD, and ASC. The effects of complanatuside were related to vast reductions in the levels of iNOS, COX-2, and ROS. Results of the present study indicate that complanatuside inhibited inflammation and protected the cells from inflammatory cell damage in HaCaT cells treated with the combination of IFN-gamma, TNF-alpha, and IL-6. Complanatuside may be a promising candidate for inhibiting COVID-19 related skin inflammatory damage.

11.
Journal of Virology ; : e0081422, 2022.
Article in English | MEDLINE | ID: covidwho-2001773

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted between humans and minks, and some mutations in the spike (S) protein, especially in the receptor-binding domain (RBD), have been identified in mink-derived viruses. Here, we examined binding of the mink angiotensin-converting enzyme 2 (ACE2) receptor to mink-derived and important human-originating variants, and we demonstrated that most of the RBD variants increased the binding affinities to mink ACE2 (mkACE2). Cryo-electron microscopy structures of the mkACE2-RBD Y453F (with a Y-to-F change at position 453) and mkACE2-RBD F486L complexes helped identify the key residues that facilitate changes in mkACE2 binding affinity. Additionally, the data indicated that the Y453F and F486L mutations reduced the binding affinities to some human monoclonal antibodies, and human vaccinated sera efficiently prevented infection of human cells by pseudoviruses expressing Y453F, F486L, or N501T RBD. Our findings provide an important molecular mechanism for the rapid adaptation of SARS-CoV-2 in minks and highlight the potential influence of the main mink-originating variants for humans. IMPORTANCE Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a broad range of hosts. Mink-derived SARS-CoV-2 can transmit back to humans. There is an urgent need to understand the binding mechanism of mink-derived SARS-CoV-2 variants to mink receptor. In this study, we identified all mutations in the receptor-binding domain (RBD) of spike (S) protein from mink-derived SARS-CoV-2, and we demonstrated the enhanced binding affinity of mink angiotensin-converting enzyme 2 (ACE2) to most of the mink-derived RBD variants as well as important human-originating RBD variants. Cryo-electron microscopy structures revealed that the Y453F and F486L mutations enhanced the binding forces in the interaction interface. In addition, Y453F and F486L mutations reduced the binding affinities to some human monoclonal antibodies, and the SARS-CoV-2 pseudoviruses with Y453F, F486L, or N501T mutations were neutralized by human vaccinated sera. Therefore, our results provide valuable information for understanding the cross-species transmission mechanism of SARS-CoV-2.

12.
Inflammatory Bowel Diseases ; 23:23, 2022.
Article in English | MEDLINE | ID: covidwho-2001299

ABSTRACT

BACKGROUND: The safety of a third dose of SARS-CoV-2 mRNA vaccination in patients with inflammatory bowel disease is unknown. METHODS: We compared symptoms following a third SARS-CoV-2 mRNA vaccine dose with symptoms after the second dose in IBD. RESULTS: The study group included 594 patients (70% female, 58% BNT162b2). Overall, 41% reported symptoms after a third dose. Symptom frequency and severity were lower after the third dose relative to the second dose for every organ system, except for gastrointestinal symptoms which were marginally worse. CONCLUSION: The frequency and severity of symptoms after a third mRNA vaccine dose are generally similar or milder than after a second dose for most organ systems.

13.
Protein Science ; 31(9), 2022.
Article in English | Web of Science | ID: covidwho-1995551

ABSTRACT

SARS-CoV-2 nsp10-nsp16 complex is a 2 '-O-methyltransferase (MTase) involved in viral RNA capping, enabling the virus to evade the immune system in humans. It has been considered a valuable target in the discovery of antiviral therapeutics, as the RNA cap formation is crucial for viral propagation. Through cross-screening of the inhibitors that we previously reported for SARS-CoV-2 nsp14 MTase activity against nsp10-nsp16 complex, we identified two compounds (SS148 and WZ16) that also inhibited nsp16 MTase activity. To further enable the chemical optimization of these two compounds towards more potent and selective dual nsp14/nsp16 MTase inhibitors, we determined the crystal structure of nsp10-nsp16 in complex with each of SS148 and WZ16. As expected, the structures revealed the binding of both compounds to S-adenosyl-L-methionine (SAM) binding pocket of nsp16. However, our structural data along with the biochemical mechanism of action determination revealed an RNA-dependent SAM-competitive pattern of inhibition for WZ16, clearly suggesting that binding of the RNA first may help the binding of some SAM competitive inhibitors. Both compounds also showed some degree of selectivity against human protein MTases, an indication of great potential for chemical optimization towards more potent and selective inhibitors of coronavirus MTases.

14.
National Science Review ; : 10, 2022.
Article in English | Web of Science | ID: covidwho-1985098

ABSTRACT

This paper presents an unprecedented SARS-CoV-2 variants gene detection platform MOPCS(Methodologies of Photonic CRISPR Sensing), which achieved high specificity and sensitivity at the same time by the innovative crossover of the unique sequence-specific recognizing ability of the CRISPR/Cas system and the superior sensitivity of the surface plasmon resonance sensing technique. The outbreak of the COVID-19 pandemic was partially due to the challenge of identifying asymptomatic and presymptomatic carriers of the virus, and thus highlights a strong motivation for diagnostics with high sensitivity that can be rapidly deployed. On the other hand, several concerning SARS-CoV-2 variants, including Omicron, are required to be identified as soon as the samples are identified as 'positive'. Unfortunately, a traditional PCR test does not allow their specific identification. Herein, for the first time, we have developed MOPCS (Methodologies of Photonic CRISPR Sensing), which combines an optical sensing technology-surface plasmon resonance (SPR) with the 'gene scissors' clustered regularly interspaced short palindromic repeat (CRISPR) technique to achieve both high sensitivity and specificity when it comes to measurement of viral variants. MOPCS is a low-cost, CRISPR/Cas12a-system-empowered SPR gene-detecting platform that can analyze viral RNA, without the need for amplification, within 38 min from sample input to results output, and achieve a limit of detection of 15 fM. MOPCS achieves a highly sensitive analysis of SARS-CoV-2, and mutations appear in variants B.1.617.2 (Delta), B.1.1.529 (Omicron) and BA.1 (a subtype of Omicron). This platform was also used to analyze some recently collected patient samples from a local outbreak in China, identified by the Centers for Disease Control and Prevention. This innovative CRISPR-empowered SPR platform will further contribute to the fast, sensitive and accurate detection of target nucleic acid sequences with single-base mutations.

15.
IEEE Frontiers in Education Conference (FIE) ; 2021.
Article in English | Web of Science | ID: covidwho-1978362

ABSTRACT

This paper aims to study the new changes in higher education in the post COVID-19 era and proposed an innovative Online-to-Offline (O2O) blending teaching model, named BOPPPS-SPOC by tracking a C programming language course. BOPPPS-SPOC indicates implementing BOPPPS mode for SPOC (Small Private Online Course). BOPPPS is an acronym for 6 components: Bridge in, Objective, Preassessment, Participatory learning, Post-assessment and Summary and it makes the classroom teaching arrangement more logic and rationality. The new changes are: (1) Teaching Methods: From separated online and offline teaching to an online-offline blending teaching. By adopting the new BOPPPS-SPOC method, the traditional offline and online independent teaching, implemented in a serial way, is optimized into offline and online blending teaching, implemented in a cross-parallel way, and it effectively expand the time and space scope of classroom teaching;(2) Course Evaluation: From single-dimensional evaluation to multi-dimensional evaluation. It focuses on the construction of a fusion evaluation system, mainly including the formative evaluation of teaching process and the sum. Finally, a survey from an authoritative research institution is conducted to 334 universities in China. It shows about 95% of students are able to adapt to an O2O blending teaching.

16.
8th International Conference on Artificial Intelligence and Security , ICAIS 2022 ; 1586 CCIS:306-316, 2022.
Article in English | Scopus | ID: covidwho-1971397

ABSTRACT

With the development of Deep Learning, image recognition technology has been applied in many aspects. And convolutional neural networks have played a key role in realizing image recognition under the increasing computing power and massive data. However, if developers want to implement the training of convolutional neural networks and achieve the subsequent applications in scenarios such as personal computers, IoT devices, and embedded platforms with low Graphics Processing Units(GPUs) memory, a large number of parameters during training of convolutional neural networks is a great challenge. Therefore, this paper uses depthwise separable convolution to optimize the classic convolutional neural network model VGG-16 to solve this problem. And the VGG-16-JS model is proposed using the Inception structure dimensionality reduction and depthwise separable convolution on the VGG-16 convolutional neural network model. Finally, this paper compares the classification success rates of VGG-16 and VGG-16-JS for the application scenario of the COVID-19 mask-wearing. A series of reliable experimental data show that the improved VGG-16-JS model significantly reduces the number of parameters required for model training without a significant drop in the success rate. It solves the GPU memory requirements for training neural networks to a certain extent. © 2022, The Author(s), under exclusive license to Springer Nature Switzerland AG.

17.
Gastroenterology ; 162(7):S-675-S-676, 2022.
Article in English | EMBASE | ID: covidwho-1967359

ABSTRACT

Background: Vaccination against SARS-CoV-2 is a highly effective strategy to protect against infection, which is predominantly mediated by vaccine-induced antibodies. Postvaccination antibodies are robustly produced by those with inflammatory bowel disease (IBD) even on immune-modifying therapies but are blunted by anti-TNF therapy. In contrast, T-cell response which primarily determines long-term efficacy against disease progression, , is less well understood. We aimed to assess the post-vaccination T-cell response and its relationship to antibody responses in patients with inflammatory bowel disease (IBD) on immunemodifying therapies. Methods: We evaluated IBD patients who completed SARS-CoV-2 vaccination using samples collected at four time points (dose 1, dose 2, 2 weeks after dose 2, 8 weeks after dose 2). T-cell clonal analysis was performed by T-cell Receptor (TCR) immunosequencing. The breadth (number of unique sequences to a given protein) and depth (relative abundance of all the unique sequences to a given protein) of the T-cell clonal response were quantified using reference datasets and were compared to antibody responses. Results: Overall, 303 subjects were included (55% female;5% with prior COVID) (Table). 53% received BNT262b (Pfizer), 42% mRNA-1273 (Moderna) and 5% Ad26CoV2 (J&J). The Spike-specific clonal response peaked 2 weeks after completion of the vaccine regimen (3- and 5-fold for breadth and depth, respectively);no changes were seen for non-Spike clones, suggesting vaccine specificity. Reduced T-cell clonal depth was associated with chronologic age, male sex, and immunomodulator treatment, and was preserved by nonanti- TNF biologic therapies;augmented clonal depth was associated with anti-TNF treatment (Figure). TCR depth and breadth were associated with vaccine type;after adjusting for age and gender, Ad26CoV2 (J&J) exhibited weaker metrics than mRNA-1273 (Moderna) (p= 0.01 for each) or BNT262b (Pfizer) (p=0.056 for depth). Antibody and T-cell responses were only modestly correlated;while those with robust humoral responses also had robust TCR clonal expansion, a substantial fraction of patients with high antibody levels had only a minimal T-cell clonal response (Figure). Conclusion: Age, sex and select immunotherapies are associated with the T-cell clonal response to SARS-CoV-2 vaccines, and T-cell responses are low in many patients despite high antibody levels. These factors, as well as differences seen by vaccine type may help guide reimmunization vaccine strategy in immune-impaired populations. Further study of the effects of anti-TNF therapy on vaccine responses are warranted. (Table Presented)

18.
Gastroenterology ; 162(7):S-279, 2022.
Article in English | EMBASE | ID: covidwho-1967266

ABSTRACT

BACKGROUND: In response to COVID-19 vaccination, cytotoxic and cytokine effector T cell immune responses are elicited in the T-cell compartment, based on recognition of epitopes presented by Class I or Class II MHC molecules, respectively. The levels of these distinct T-cell responses may have significant implications for immunization strategies and risk assessment. Knowledge of these two responses after vaccination is still largely unknown, especially in the context of immunomodulatory treatment regimens. METHODS: We performed T-cell receptor (TCR) immunosequencing (Adaptive Biotechnologies, Seattle WA) of IBD patients (N=303) and health care worker controls (HCW, N=224) at up to four time points (prior to dose 1, prior to dose 2, 2 weeks after dose 2, 8 weeks after dose 2). Two metrics of TCR response, breadth (# of unique antigen-specific sequences) and depth (expansion of antigen-specific sequences), were calculated for all sequences and Class I- and Class II-specific sequences, and compared to demographics, IBD treatment, and vaccine type. Subjects with exceptional Class I or Class II responses were calculated as significant residuals relative to the Class I vs. Class II regression line. Similar associations were observed for both breadth and depth: breadth is presented here for brevity. RESULTS: Both Class I- and Class II-specific T-cell responses peaked 2 weeks after dose 2, and significantly correlated with lower age, female gender, and mRNA vaccine type (mRNA-1273/Moderna and BNT262b/Pfizer, versus vector vaccine AD26CoV2/J&J) (FIGURE). Class II responses comprised ~85% of detected TCR response in both IBD and HCW subjects. Among IBD patients, there was a significant elevation of the class I response with anti-TNF treatment (p=0.04). This effect was most pronounced at later timepoints, suggesting that anti-TNF permitted a more persistent Class I-specific response. Among patients with exceptionally high or low Class I TCR response, there were significant differences in TCR metrics across vaccine types (p=0.0035). 21% of AD26CoV2 patients were highly Class I-biased (Zscore>1, 9.4% and 7.3% for BNT162 and mRNA-1273, respectively), and this was correlated with lower anti-spike serology 2 and 8 weeks after vaccination (p<1E-10). Conversely, mRNA- 1273 patients were Class I-deficient, representing 25.3% of patients but 44.1% of highly Class I-deficient patients (Zscore<1, 0% for AD26CoV2). CONCLUSION: The T-cell clonal response to SARS-CoV-2 vaccine is Class II-predominant, but the Class I-response is augmented by anti-TNF therapy and vector vaccine type. These factors may help guide reimmunization vaccine strategy in immune-impaired populations, and warrant further study of the effects of anti-TNF therapies on vaccine efficacy.(Figure Presented)Figure: TCR response time course (left);effect of anti-TNF (middle);effect of vaccine type (right). Breadth was predominantly Class II for most patients, with maximum response at 2 weeks after full vaccination (left). The balance of Class I vs. Class II response was significantly biased towards Class I at 8 weeks after full vaccination for patients receiving anti-TNF treatment for IBD (asterisk, p=0.036). Patients receiving AD26CoV2 vaccines were significantly increased in Class I responses, while patients receiving mRNA-1273 vaccines were significantly reduced for Class I responses (t-tests: p=0.0036 at 8 weeks [asterisk], p=0.051 at 2 weeks).

19.
Gastroenterology ; 162(7):S-162-S-163, 2022.
Article in English | EMBASE | ID: covidwho-1967253

ABSTRACT

Background:Symptoms after SARS-CoV-2 primary vaccination among patients with inflammatory bowel disease (IBD) are generally similar to the general population,although symptoms after the second dose are more frequent and severe than after the first dose.Postvaccination symptoms after a 3rd mRNA vaccine dose in the predominantly immune-compromised IBD population is unknown.Methods:Adults with IBD participating in the prospective Coronavirus Risk Associations and Longitudinal Evaluation in IBD (CORALE-IBD) vaccine registry who received a 3rd mRNA vaccine dose were asked to complete a detailed symptom survey 1 week after vaccination.Symptoms were assessed across 11 organ systems,and graded as mild,moderate,or severe,or requiring hospitalization.“Severe+” referred to those with severe symptoms or who required hospitalization.We stratified by age (<or> 50 years) given prior distinct symptom profiles after dose 2 (D2).We also evaluated whether severe+ symptoms after D2 predicted severe+ symptoms after dose 3 (D3).Results:We included 524 participants (70% female, mean age 45 years) who received a 3rd mRNA vaccine through October 11, 2021.Most had Crohn's disease (71%), and 89% were on biologic therapies.Most (58%) had received primary vaccination with BNT562b2,and only 3.5% reported prior COVID infection at the time of initial vaccination.Overall, 97% of subjects received a 3rd dose with the same mRNA vaccine as in their initial series with the remainder receiving the other mRNA vaccine type.No participants received a 3rd dose with the Ad26.CoV.2 (J&J) vaccine. Overall, 41% reported symptoms after a 3rd dose,with symptoms generally more frequent and severe among those <55 years (Table).The most frequent postvaccination symptom was injection site pain (39%).Common systemic symptoms included fatigue/malaise (34%),headache (23%),and muscle, bone or joint symptoms (13%).These were all less frequent after D3 than after D2 (Figure).Gastrointestinal symptoms were reported by 8.8%, which was slightly more frequent than after D2 (7.8%).Among those with postvaccination symptoms, the proportion with severe symptoms after D3 was lower than D2 for fatigue/ malaise, headache, dizziness and lightheadedness, fever/chills, and rheumatologic symptoms, but was slightly higher than D2 for gastrointestinal symptoms.Severe+ symptoms were seen in 17% after D2 and in 14% after D3. Of those with severe+ symptoms after D2, 34% had severe+ symptoms after D3.In contrast, about 22% had severe+ symptoms after D3 but did not report severe+ symptoms after D2.Conclusion:The frequency and severity of symptoms after a 3rd mRNA vaccine dose are generally similar or lower than those after a second dose.Furthermore, prior severe+ symptoms after D2 do not necessarily predict severe+ symptoms after D3. Further evaluation of postvaccination gastrointestinal symptoms in this population is warranted. (Figure Presented) (Table Presented)

20.
Gastroenterology ; 162(7):S-160, 2022.
Article in English | EMBASE | ID: covidwho-1967250

ABSTRACT

Background: Vaccine-induced protection against SARS-CoV-2 infection is predominantly mediated by humoral immunity;protection against disease progression is primarily determined by cellular immunity. Patients with inflammatory bowel disease (IBD) have high rates of post-vaccination anti-Spike IgG [IgG(S)] seroconversion, but postvaccination immune responses relative to non-IBD controls have not been well described. We aimed to assess post-vaccination humoral (antibody) and cellular (T-cell) responses in IBD relative to healthcare worker (HCW) controls. Methods: We evaluated IBD patients enrolled in a US registry referred from 26 centers at 2, 8, and 16 weeks after completing 2 doses of SARSCoV- 2 mRNA vaccination and compared results to non-IBD non-immunosuppressed HCW participating in a parallel study. We analyzed plasma antibodies to the receptor binding domain of the viral spike protein using the SARS-CoV-2 IgG-II assay (Abbott Labs, Abbott Park, IL);IgG(S) > 50 AU/mL was defined as positive. Those with prior COVID were excluded. We also performed T-cell clonal analysis by T-cell receptor (TCR) immunosequencing at 8 weeks (Adaptive Biotechnologies, Seattle, WA). The breadth (number of unique sequences to a given protein) and depth (relative abundance of all the unique sequences to a given protein) of the T-cell clonal response were quantified using reference datasets. Analyses were adjusted for age, sex and vaccine type. Results: Overall, 1805 subjects were included (IBD n=1074 (65% Crohn's disease, 35% ulcerative colitis);HCW n=731). Age and sex were similar between both cohorts;Hispanic ethnicity and Asian race were less common among IBD than HCW (Table). Vaccine type included BNT162b2 (Pfizer) (75% of IBD, 98% of HCW) and the remainder mRNA-1274 (Moderna). IBD treatments included anti- TNF (46%), other biologics (33%), other immune suppressing therapy (9%), and no immune suppression (12%). Postvaccination antibody levels were lower among IBD than HCW both before and after adjusting for vaccine type (p<0.0001 each timepoint;Figure). After further restricting the IBD cohort to those on no immune-suppressive therapies, antibodies remained lower in IBD vs HCW at 2w (p=0.008) and 8w (p<0.0001), but not 16w (p=0.07). Among 321 subjects with available whole cell samples at 8 weeks (IBD n=163, HCW =158), Spikespecific TCR responses were similar between IBD and HCW for both clonal breadth and depth in both unadjusted and adjusted analyses;sub-analyses of those on biologics yielded similar results. Conclusion: Patients with IBD have dampened humoral responses, but similar cellular responses, after SARS-CoV-2 mRNA vaccination relative to HCW. These findings suggest a potentially greater risk of infection, but not of disease progression, among those with IBD, and should be considered to help guide booster dosing strategies for the IBD population. (Figure Presented) (Figure Presented) Figure: Post-vaccination immune responses: (A) Antibody responses are lower in IBD relative to non-IBD healthcare workers at 2, 8, and 16 weeks (p<0.0001 at each timepoint). In contrast, post-vaccination Spike-specific T-cell receptor clonal breadth (B1) and clonal depth (B2) at 8 weeks are similar in IBD compared to healthcare workers.

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