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SARS-CoV Spike (S) protein shares considerable homology with SARS-CoV-2 S, especially in the conserved S2 subunit (S2). S protein mediates coronavirus receptor binding and membrane fusion, and the latter activity can greatly influence coronavirus infection. We observed that SARS-CoV S is less effective in inducing membrane fusion compared with SARS-CoV-2 S. We identify that S813T mutation is sufficient in S2 interfering with the cleavage of SARS-CoV-2 S by TMPRSS2, reducing spike fusogenicity and pseudoparticle entry. Conversely, the mutation of T813S in SARS-CoV S increased fusion ability and viral replication. Our data suggested that residue 813 in the S was critical for the proteolytic activation, and the change from threonine to Serine at 813 position might be an evolutionary feature adopted by SARS-2-related viruses. This finding deepened the understanding of Spike fusogenicity and could provide a new perspective for exploring Sarbecovirus' evolution.
ABSTRACT
SARS-CoV-2 viruses engage ACE2 as a functional receptor with their spike protein. The S1 domain of the spike protein contains a C-terminal receptor binding domain (RBD) and an N-terminal domain (NTD). The NTD of other coronaviruses includes a glycan binding cleft. However, for the SARS-CoV-2 NTD, protein-glycan binding was only observed weakly for sialic acids with highly sensitive methods. Amino acid changes in the NTD of variants of concern (VoC) show antigenic pressure, which can be an indication of NTD-mediated receptor binding. Trimeric NTD proteins of SARS-CoV-2, alpha, beta, delta, and omicron did not reveal a receptor binding capability. Unexpectedly, the SARS-CoV-2 beta subvariant strain (501Y.V2-1) NTD binding to Vero E6 cells was sensitive to sialidase pretreatment. Glycan microarray analyses identified a putative 9-O-acetylated sialic acid as a ligand, which was confirmed by catch-and-release ESI-MS, STD-NMR analyses, and a graphene-based electrochemical sensor. The beta (501Y.V2-1) variant attained an enhanced glycan binding modality in the NTD with specificity toward 9-O-acetylated structures, suggesting a dual-receptor functionality of the SARS-CoV-2 S1 domain, which was quickly selected against. These results indicate that SARS-CoV-2 can probe additional evolutionary space, allowing binding to glycan receptors on the surface of target cells.
Subject(s)
COVID-19 , Sialic Acids , Humans , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , N-Acetylneuraminic AcidABSTRACT
The emergence of new SARS-CoV-2 variants and the dangers of long-covid necessitate the development of broad-acting therapeutics that can reduce viral burden. SARS-CoV-2 employs heparan sulfate (HS) as an initial cellular attachment factor, and therefore, there is interest in developing heparin as a therapeutic for SARS-CoV-2. Its use is, however, complicated by structural heterogeneity and the risk of causing bleeding and thrombocytopenia. Here, we describe the preparation of well-defined heparin mimetics by a controlled head-to-tail assembly of HS oligosaccharides having an alkyne or azide moiety by copper-catalyzed azide-alkyne cycloaddition (CuAAC). Alkyne- and azide-containing sulfated oligosaccharides were prepared from a common precursor by modifying an anomeric linker with 4-pentynoic acid and by enzymatic extension with an N-acetyl-glucosamine having an azide moiety at C-6 (GlcNAc6N3), respectively, followed by CuAAC. The process of enzymatic extension with GlcNAc6N3 followed by CuAAC with the desired alkyne-containing oligosaccharides could be repeated to give compounds composed of 20 and 27 monosaccharides, respectively. The heparin mimetics could inhibit the binding of the SARS-CoV-2 spike or RBD to immobilized heparin or to Vero E6 cells. The inhibitory potency increased with increasing chain length, and a compound composed of four sulfated hexasaccharides linked by triazoles had a similar potency as unfractionated heparin. Sequence analysis and HS microarray binding studies with a wide range of RBDs of variants of concern indicate that they have maintained HS-binding capabilities and selectivities. The heparin mimetics exhibit no or reduced binding to antithrombin-III and platelet factor 4, respectively, which are associated with side effects.
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BACKGROUND: Delays in colonoscopy work-up for red flag signs or symptoms of colorectal cancer (CRC) during the COVID-19 pandemic are not well characterized. AIMS: To examine colonoscopy uptake and time to colonoscopy after red flag diagnosis, before and during the COVID-19 pandemic. METHODS: Cohort study of adults ages 50-75 with iron deficiency anemia (IDA), hematochezia, or abnormal stool blood test receiving Veterans Health Administration (VHA) care from April 2019 to December 2020. Index date was first red flag diagnosis date, categorized into "pre" (April-December 2019) and "intra" (April-December 2020) policy implementation prioritizing diagnostic procedures, allowing for a 3-month "washout" (January-March 2020) period. Outcomes were colonoscopy completion and time to colonoscopy pre- vs. intra-COVID-19, examined using multivariable Cox models with hazard ratios (aHRs) and 95% confidence intervals (CIs). RESULTS: There were 52,539 adults with red flag signs or symptoms (pre-COVID: 25,154; washout: 7527; intra-COVID: 19,858). Proportion completing colonoscopy was similar pre- vs. intra-COVID-19 (27.0% vs. 26.5%; p = 0.24). Median time to colonoscopy among colonoscopy completers was similar for pre- vs. intra-COVID-19 (46 vs. 42 days), but longer for individuals with IDA (60 vs. 49 days). There was no association between time period and colonoscopy completion (aHR: 0.99, 95% CI 0.95-1.03). CONCLUSIONS: Colonoscopy work-up of CRC red flag signs and symptoms was not delayed within VHA during the COVID-19 pandemic, possibly due to VHA policies supporting prioritization and completion. Further work is needed to understand how COVID-19 policies on screening and surveillance impact CRC-related outcomes, and how to optimize colonoscopy completion after a red flag diagnosis.
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OBJECTIVES: We conducted a systematic and comprehensive bibliometric analysis of COVID-19-related medical imaging to determine the current status and indicate possible future directions. METHODS: This research provides an analysis of Web of Science Core Collection (WoSCC) indexed articles on COVID-19 and medical imaging published between 1 January 2020 and 30 June 2022, using the search terms "COVID-19" and medical imaging terms (such as "X-ray" or "CT"). Publications based solely on COVID-19 themes or medical image themes were excluded. CiteSpace was used to identify the predominant topics and generate a visual map of countries, institutions, authors, and keyword networks. RESULTS: The search included 4444 publications. The journal with the most publications was European Radiology, and the most co-cited journal was Radiology. China was the most frequently cited country in terms of co-authorship, with the Huazhong University of Science and Technology being the institution contributing with the highest number of relevant co-authorships. Research trends and leading topics included: assessment of initial COVID-19-related clinical imaging features, differential diagnosis using artificial intelligence (AI) technology and model interpretability, diagnosis systems construction, COVID-19 vaccination, complications, and predicting prognosis. CONCLUSIONS: This bibliometric analysis of COVID-19-related medical imaging helps clarify the current research situation and developmental trends. Subsequent trends in COVID-19 imaging are likely to shift from lung structure to function, from lung tissue to other related organs, and from COVID-19 to the impact of COVID-19 on the diagnosis and treatment of other diseases. Key Points ⢠We conducted a systematic and comprehensive bibliometric analysis of COVID-19-related medical imaging from 1 January 2020 to 30 June 2022. ⢠Research trends and leading topics included assessment of initial COVID-19-related clinical imaging features, differential diagnosis using AI technology and model interpretability, diagnosis systems construction, COVID-19 vaccination, complications, and predicting prognosis. ⢠Future trends in COVID-19-related imaging are likely to involve a shift from lung structure to function, from lung tissue to other related organs, and from COVID-19 to the impact of COVID-19 on the diagnosis and treatment of other diseases.
Subject(s)
Artificial Intelligence , COVID-19 , Humans , COVID-19 Vaccines , Bibliometrics , Diagnostic ImagingABSTRACT
BACKGROUND: Solid organ transplant (SOT) recipients are at increased risks of morbidity and mortality associated with COVID-19. OBJECTIVES: This study aimed to evaluate the immunogenicity of COVID-19 vaccines in SOT recipients. DATA SOURCES: Electronic databases were searched for eligible reports published from 1 December 2019 to 31 May 2022. STUDY ELIGIBILITY CRITERIA: We included reports evaluating the humoral immune response (HIR) or cellular immune response rate in SOT recipients after the administration of COVID-19 vaccines. PARTICIPANTS: SOT recipients who received COVID-19 vaccines. ASSESSMENT OF RISK OF BIAS: We used the Newcastle-Ottawa scale to assess bias in case-control and cohort studies. For randomised-controlled trials, the Jadad Scale was used. METHODS: We used a random-effects model to calculate the pooled rates of immune response with 95% CI. We used a risk ratio (RR) with 95% CI for a comparison of immune responses between SOT and healthy controls. RESULTS: A total of 91 reports involving 11 886 transplant recipients (lung: 655; heart: 539; liver: 1946; and kidney: 8746) and 2125 healthy controls revealed pooled HIR rates after the 1st, 2nd, and 3rd COVID-19 vaccine doses in SOT recipients were 9.5% (95% CI, 7-11.9%), 43.6% (95% CI, 39.3-47.8%) and 55.1% (95% CI, 44.7-65.6%), respectively. For specific organs, the HIR rates were still low after 1st vaccine dose (lung: 4.4%; kidney: 9.4%; heart: 13.2%; liver: 29.5%) and 2nd vaccine dose (lung: 28.4%; kidney: 37.6%; heart: 50.3%; liver: 64.5%). CONCLUSIONS: A booster vaccination enhances the immunogenicity of COVID-19 vaccines in SOT; however, a significant share of the recipients still has not built a detectable HIR after receiving the 3rd dose. This finding calls for alternative approaches, including the use of monoclonal antibodies. In addition, lung transplant recipients need urgent booster vaccination to improve the immune response.
Subject(s)
COVID-19 , Organ Transplantation , Vaccines , Humans , COVID-19 Vaccines , Transplant Recipients , COVID-19/prevention & controlABSTRACT
The long-term physical and mental sequelae of COVID-19 are a growing public health concern, yet there is considerable uncertainty about their prevalence, persistence and predictors. We conducted a comprehensive, up-to-date meta-analysis of survivors' health consequences and sequelae for COVID-19. PubMed, Embase and the Cochrane Library were searched through Sep 30th, 2021. Observational studies that reported the prevalence of sequelae of COVID-19 were included. Two reviewers independently undertook the data extraction and quality assessment. Of the 36,625 records identified, a total of 151 studies were included involving 1,285,407 participants from thirty-two countries. At least one sequelae symptom occurred in 50.1% (95% CI 45.4-54.8) of COVID-19 survivors for up to 12 months after infection. The most common investigation findings included abnormalities on lung CT (56.9%, 95% CI 46.2-67.3) and abnormal pulmonary function tests (45.6%, 95% CI 36.3-55.0), followed by generalized symptoms, such as fatigue (28.7%, 95% CI 21.0-37.0), psychiatric symptoms (19.7%, 95% CI 16.1-23.6) mainly depression (18.3%, 95% CI 13.3-23.8) and PTSD (17.9%, 95% CI 11.6-25.3), and neurological symptoms (18.7%, 95% CI 16.2-21.4), such as cognitive deficits (19.7%, 95% CI 8.8-33.4) and memory impairment (17.5%, 95% CI 8.1-29.6). Subgroup analysis showed that participants with a higher risk of long-term sequelae were older, mostly male, living in a high-income country, with more severe status at acute infection. Individuals with severe infection suffered more from PTSD, sleep disturbance, cognitive deficits, concentration impairment, and gustatory dysfunction. Survivors with mild infection had high burden of anxiety and memory impairment after recovery. Our findings suggest that after recovery from acute COVID-19, half of survivors still have a high burden of either physical or mental sequelae up to at least 12 months. It is important to provide urgent and appropriate prevention and intervention management to preclude persistent or emerging long-term sequelae and to promote the physical and psychiatric wellbeing of COVID-19 survivors.
ABSTRACT
Meplazumab, a humanized CD147 antibody, has shown favourable safety and efficacy in our previous clinical studies. In DEFLECT (NCT04586153), 167 patients with severe COVID-19 were enroled and randomized to receive three dosages of meplazumab and a placebo. Meplazumab at 0.12 mg/kg, compared to the placebo group, showed clinical benefits in significantly reducing mortality by 83.6% (2.4% vs. 14.6%, p = 0.0150), increasing the proportion of patients alive and discharged without supplemental oxygen (82.9% vs. 70.7%, p = 0.0337) and increasing the proportion of patients who achieved sustained clinical improvement (41.5% vs. 31.7%). The response rate in the 0.2 mg/kg group was relatively increased by 16.0% compared with the placebo group (53.7% vs. 46.3%). Meplazumab also reduced the viral loads and multiple cytokine levels. Compare with the placebo group, the 0.3 mg/kg significantly increased the virus negative rate by 40.6% (p = 0.0363) and reduced IL-8 level (p = 0.0460); the 0.2 mg/kg increased the negative conversion rate by 36.9%, and reduced IL-4 (p = 0.0365) and IL-8 levels (p = 0.0484). In this study, the adverse events occurred at a comparable rate across the four groups, with no unexpected safety findings observed. In conclusion, meplazumab promoted COVID-19 convalescence and reduced mortality, viral load, and cytokine levels in severe COVID-19 population with good safety profile.
Subject(s)
COVID-19 , Humans , Adult , SARS-CoV-2 , Interleukin-8 , CytokinesABSTRACT
BACKGROUND: Unhealthy behaviors of coronary heart disease (CHD) patients are closely related to the occurrence of major heart events, which increases the readmission rate and brings a heavy economic burden to families and society. Therefore, it is necessary for health care workers to take active preventive and therapeutic measures to keep or establish healthy behaviors of patients. Positive psychological intervention has been proved to be effective, but it has not been reported in the field of CHD in China. The purpose of this study is to explore the effects of positive event recording based on positive psychology on the healthy behaviors, readmission rate, and anxiety of patients with CHD, in order to provide new ideas for the development of secondary prevention strategies for CHD. METHODS: This is a prospective, single-center, randomized controlled trial (RCT). The subjects will be enrolled from the Department of Cardiology, the First Affiliated Hospital of Soochow University. There are 80 cases in total; according to the random number table, the subjects are randomly divided into the intervention group (n = 40) and the control group (n = 40). The patients in the intervention group will receive the intervention of recording positive events once a week for 3 months, while the patients in the control group receive conventional nursing. The primary outcomes will include healthy behaviors, readmission rate, and anxiety, and the secondary outcomes will include psychological capital, subjective well-being, and corresponding clinical laboratory indicators. The protocol was approved by the Medical Ethics Committee of Soochow University (approval no. SUDA20200604H01) and is performed in strict accordance with the Declaration of Helsinki formulated by the World Medical Association. All participants provide written informed consent. DISCUSSION: This study will verify whether positive event recording based on positive psychology can make patients maintain healthy behaviors, reduce readmission rate, and improve anxiety after PCI. Then, this study will provide new ideas and references for the development of secondary prevention strategies for patients with CHD. TRIAL REGISTRATION: Chinese Clinical Trials Registry 2000034538. Registered on 10 July 2020.
Subject(s)
COVID-19 , Percutaneous Coronary Intervention , Humans , SARS-CoV-2 , Psychology, Positive , Patient Readmission , Health Behavior , Percutaneous Coronary Intervention/adverse effects , Treatment Outcome , Randomized Controlled Trials as TopicABSTRACT
OBJECTIVE: A comparative analysis was performed to investigate the potential risk factors of Adverse Events Following Immunization (AEFI) after receiving different booster vaccines. METHODS: From 18 January 2021 to 21 January 2022, the Health Care Workers (HCWs) of Guizhou Provincial Staff Hospital (Guizhou Province, China) who received a third Booster vaccine, that was either homologous (i.e., (i) a total of three doses of Vero cell vaccine or (ii) three doses of CHO cell vaccine) or (iii) heterologous with two first doses of Vero cell vaccine, being either CHO cell vaccine or adenovirus type-5 (Ad5) vectored COVID-19 vaccine, were asked to complete a self-report questionnaire form to provide information on any AEFI that may have occurred in the first 3 days after vaccination with the booster. The frequency of AEFI corresponding to the three different booster vaccines was compared, and the risk factors for predicting AEFI were determined by multivariate logistic regression analysis. RESULTS: Of the 904 HCWs who completed the survey, 792 met the inclusion criteria. The rates of AEFI were 9.8% (62/635) in the homologous Vero cell booster group, 17.3% (13/75) in the homologous CHO cell booster group, and 20.7% (17/82) in the heterologous mixed vaccines booster group, and the rates were significantly different (c2 = 11.5, p = 0.004) between the three groups of vaccines. Multivariate logistic regression analysis showed that: (1) compared to the homologous Vero cell booster group, the risk of AEFI was about 2.1 times higher (OR = 2.095, 95% CI: 1.056-4.157, p = 0.034) in the CHO cell booster group and 2.5 times higher (OR = 2.476, 95% CI: 1.352-4.533, p = 0.003) in the mixed vaccines group; (2) the odds for women experiencing AEFI were about 2.8 times higher (OR = 2.792, 95% CI: 1.407-5.543, p = 0.003) than men; and (3) compared to the non-frontline HCWs, the risk of AEFI was about 2.6 times higher (OR = 2.648, 95% CI: 1.473-4.760, p = 0.001) in the doctors. CONCLUSION: The AEFI in all three booster groups are acceptable, and serious adverse events are rare. The risk of AEFI was higher in doctors, which may be related to the high stress during the COVID-19 epidemic. Support from government and non-governmental agencies is important for ensuring the physical and mental health of HCWs.
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Existing research suggests that COVID-19 lockdowns tend to contribute to a decrease in overall urban crime rates. Most studies have compared pre-lockdown and post-lockdown periods to lockdown periods in Western cities. Few have touched on the fine variations during lockdowns. Equally rare are intracity studies conducted in China. This study tested the relationship between violent crime and COVID-19 lockdown policies in ZG City in southern China. The distance from the isolation location to the nearest violent crime site, called "the nearest crime distance", is a key variable in this study. Kernel density mapping and the Wilcoxon signed-rank test are used to compare the pre-lockdown and post-lockdown periods to the lockdown period. Panel logistic regression is used to test the fine variations among different stages during the lockdown. The result found an overall decline in violent crime during the lockdown and a bounce-back post-lockdown. Violent crime moved away from the isolation location during the lockdown. This outward spread continued for the first two months after the lifting of the lockdown, suggesting a lasting effect of the lockdown policy. During the lockdown, weekly changes in COVID-19 risk ratings at the district level in ZG City also affected changes in the nearest crime distance. In particular, an increase in the risk rating increased that distance, and a drop in the risk rating decreased that distance. These findings add new results to the literature and could have policy implications for joint crime and pandemic prevention and control.
Subject(s)
COVID-19 , Humans , COVID-19/epidemiology , Communicable Disease Control , Violence , Crime , Pandemics/prevention & controlABSTRACT
Importance: People exposed to coronavirus disease 2019 (COVID-19) and a series of imperative containment measures could be psychologically stressed, yet the burden of and factors associated with mental health symptoms remain unclear. Objective: To investigate the prevalence of and risk factors associated with mental health symptoms in the general population in China during the COVID-19 pandemic. Design, Setting, and Participants: This large-sample, cross-sectional, population-based, online survey study was conducted from February 28, 2020, to March 11, 2020. It involved all 34 province-level regions in China and included participants aged 18 years and older. Data analysis was performed from March to May 2020. Main Outcomes and Measures: The prevalence of symptoms of depression, anxiety, insomnia, and acute stress among the general population in China during the COVID-19 pandemic was evaluated using the Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, Insomnia Severity Index, and Acute Stress Disorder Scale. Logistic regression analyses were used to explore demographic and COVID-19-related risk factors. Results: Of 71â¯227 individuals who clicked on the survey link, 56â¯932 submitted the questionnaires, for a participation rate of 79.9%. After excluding the invalid questionnaires, 56â¯679 participants (mean [SD] age, 35.97 [8.22] years; 27â¯149 men [47.9%]) were included in the study; 39â¯468 respondents (69.6%) were aged 18 to 39 years. During the COVID-19 pandemic, the rates of mental health symptoms among the survey respondents were 27.9% (95% CI, 27.5%-28.2%) for depression, 31.6% (95% CI, 31.2%-32.0%) for anxiety, 29.2% (95% CI, 28.8%-29.6%) for insomnia, and 24.4% (95% CI, 24.0%-24.7%) for acute stress. Participants with confirmed or suspected COVID-19 and their family members or friends had a high risk for symptoms of depression (adjusted odds ratios [ORs], 3.27 [95% CI, 1.84-5.80] for patients; 1.53 [95% CI, 1.26-1.85] for family or friends), anxiety (adjusted ORs, 2.48 [95% CI, 1.43-4.31] for patients; 1.53 [95% CI, 1.27-1.84] for family or friends), insomnia (adjusted ORs, 3.06 [95% CI, 1.73-5.43] for patients; 1.62 [95% CI, 1.35-1.96] for family or friends), and acute stress (adjusted ORs, 3.50 [95% CI, 2.02-6.07] for patients; 1.77 [95% CI, 1.46-2.15] for family or friends). Moreover, people with occupational exposure risks and residents in Hubei province had increased odds of symptoms of depression (adjusted ORs, 1.96 [95% CI, 1.77-2.17] for occupational exposure; 1.42 [95% CI, 1.19-1.68] for Hubei residence), anxiety (adjusted ORs, 1.93 [95% CI, 1.75-2.13] for occupational exposure; 1.54 [95% CI, 1.30-1.82] for Hubei residence), insomnia (adjusted ORs, 1.60 [95% CI, 1.45-1.77] for occupational exposure; 1.20 [95% CI, 1.01-1.42] for Hubei residence), and acute stress (adjusted ORs, 1.98 [95% CI, 1.79-2.20] for occupational exposure; 1.49 [95% CI, 1.25-1.79] for Hubei residence). Both centralized quarantine (adjusted ORs, 1.33 [95% CI, 1.10-1.61] for depression; 1.46 [95% CI, 1.22-1.75] for anxiety; 1.63 [95% CI, 1.36-1.95] for insomnia; 1.46 [95% CI, 1.21-1.77] for acute stress) and home quarantine (adjusted ORs, 1.30 [95% CI, 1.25-1.36] for depression; 1.28 [95% CI, 1.23-1.34] for anxiety; 1.24 [95% CI, 1.19-1.30] for insomnia; 1.29 [95% CI, 1.24-1.35] for acute stress) were associated with the 4 negative mental health outcomes. Being at work was associated with lower risks of depression (adjusted OR, 0.85 [95% CI, 0.79-0.91]), anxiety (adjusted OR, 0.92 [95% CI, 0.86-0.99]), and insomnia (adjusted OR, 0.87 [95% CI, 0.81-0.94]). Conclusions and Relevance: The results of this survey indicate that mental health symptoms may have been common during the COVID-19 outbreak among the general population in China, especially among infected individuals, people with suspected infection, and people who might have contact with patients with COVID-19. Some measures, such as quarantine and delays in returning to work, were also associated with mental health among the public. These findings identify populations at risk for mental health problems during the COVID-19 pandemic and may help in implementing mental health intervention policies in other countries and regions.
Subject(s)
Anxiety , Coronavirus Infections , Depression , Pandemics , Pneumonia, Viral , Sleep Initiation and Maintenance Disorders , Stress, Psychological , Adult , Anxiety/diagnosis , Anxiety/epidemiology , Anxiety/physiopathology , Betacoronavirus/isolation & purification , COVID-19 , China/epidemiology , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Coronavirus Infections/psychology , Depression/diagnosis , Depression/epidemiology , Depression/physiopathology , Female , Humans , Male , Mental Health/statistics & numerical data , Mental Status Schedule/statistics & numerical data , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Pneumonia, Viral/psychology , Prevalence , Quarantine/psychology , Return to Work/psychology , Risk Factors , SARS-CoV-2 , Sleep Initiation and Maintenance Disorders/diagnosis , Sleep Initiation and Maintenance Disorders/epidemiology , Sleep Initiation and Maintenance Disorders/physiopathology , Stress, Psychological/diagnosis , Stress, Psychological/epidemiology , Stress, Psychological/physiopathologyABSTRACT
The rapid mutation and spread of SARS-CoV-2 variants urge the development of effective mucosal vaccines to provide broad-spectrum protection against the initial infection and thereby curb the transmission potential. Here, we designed a chimeric triple-RBD immunogen, 3Ro-NC, harboring one Delta RBD and two Omicron RBDs within a novel protein scaffold. 3Ro-NC elicits potent and broad RBD-specific neutralizing immunity against SARS-CoV-2 variants of concern. Notably, intranasal immunization with 3Ro-NC plus the mucosal adjuvant KFD (3Ro-NC + KFDi.n) elicits coordinated mucosal IgA and higher neutralizing antibody specificity (closer antigenic distance) against the Omicron variant. In Omicron-challenged human ACE2 transgenic mice, 3Ro-NC + KFDi.n immunization significantly reduces the tissue pathology in the lung and lowers the viral RNA copy numbers in both the lung (85.7-fold) and the nasal turbinate (13.6-fold). Nasal virologic control is highly correlated with RBD-specific secretory IgA antibodies. Our data show that 3Ro-NC plus KFD is a promising mucosal vaccine candidate for protection against SARS-CoV-2 Omicron infection, pathology and transmission potential.
Subject(s)
COVID-19 Vaccines , COVID-19 , Animals , Humans , Mice , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/genetics , COVID-19 Vaccines/immunology , Immunity, Mucosal , Administration, IntranasalABSTRACT
OBJECTIVE: A retrospective survey was conducted of adverse events following immunization (AEFI) experienced by health care workers (HCWs) in a relatively remote ethnic region in southwest China (Guizhou Province) who received COVID-19 vaccines. METHODS: From 18 January 2021 to 21 January 2022, all HCWs of Guizhou Provincial Staff Hospital, China, who received at least one dose of inactivated COVID-19 vaccine (Vero cell), recombinant novel coronavirus vaccine (CHO cell), or one dose of adenovirus type-5 (Ad5) vectored COVID-19 vaccine were asked to complete a self-report questionnaire to provide information on any adverse events that may have occurred in the first 3 days after injection. The frequency of AEFI corresponding to the three types of vaccines were compared and the potential risks of AEFI due to the three different vaccines were predicted by multivariate logistic regression analysis. RESULTS: Of the 904 HCWs who completed the survey, the rates of AEFI were 10.1% (80/794) due to Vero cell, 16.3% (13/80) due to CHO cell, and 46.67% (14/30) due to Ad5 vectored vaccines, and the rates were significantly different (χ2 = 38.7, p < 001) between the three vaccines. Multivariate logistic regression models predict that (1) compared to the Ad 5 vectored group, the risk of AEFI occurrence in the Vero cell group was reduced by about 85.9% (OR = 0.141, 95% CI: 0.065-0.306, p < 0.001) and in the CHO cell group by about 72.1% (OR = 0.279, 95% CI: 0.107-0.723, p = 0.009), (2) the odds for women experiencing AEFI were about 2.1 (OR = 2.093, 95% CI: 1.171-3.742, p = 0.013) times as high as those of men, and (3) the risk of AEFI for HCWs with a Bachelor's degree or above was about 2.2 (OR = 2.237, 95% CI: 1.434-3.489, p = 0.001) times higher than in HCWs who do not have a Bachelor's degree. CONCLUSIONS: 1. The inactivated COVID-19 vaccine (Vero cell), recombinant novel coronavirus vaccine (CHO cell), and adenovirus type-5 (Ad5) vectored COVID-19 vaccine made in China are safe and relatively broad-spectrum. 2. The prevalence of AEFI is more common in women healthcare workers. 3. The risk of AEFI was higher in those with a Bachelor's degree or above and may be related to the psychological and social effects triggered by the global COVID-19 pandemic.
ABSTRACT
Dynamic changes of the paired heavy and light chain B cell receptor (BCR) repertoire provide an essential insight into understanding the humoral immune response post-SARS-CoV-2 infection and vaccination. However, differences between the endogenous paired BCR repertoire kinetics in SARS-CoV-2 infection and previously recovered/naïve subjects treated with the inactivated vaccine remain largely unknown. We performed single-cell V(D)J sequencing of B cells from six healthy donors with three shots of inactivated SARS-CoV-2 vaccine (BBIBP-CorV), five people who received the BBIBP-CorV vaccine after having recovered from COVID-19, five unvaccinated COVID-19 recovered patients and then integrated with public data of B cells from four SARS-CoV-2-infected subjects. We discovered that BCR variable (V) genes were more prominently used in the SARS-CoV-2 exposed groups (both in the group with active infection and in the group that had recovered) than in the vaccinated groups. The VH gene that expanded the most after SARS-CoV-2 infection was IGHV3-33, while IGHV3-23 in the vaccinated groups. SARS-CoV-2-infected group enhanced more BCR clonal expansion and somatic hypermutation than the vaccinated healthy group. A small proportion of public clonotypes were shared between the SARS-CoV-2 infected, vaccinated healthy, and recovered groups. Moreover, several public antibodies had been identified against SARS-CoV-2 spike protein. We comprehensively characterize the paired heavy and light chain BCR repertoire from SARS-CoV-2 infection to vaccination, providing further guidance for the development of the next-generation precision vaccine.