Lineage-mosaic and mutation-patched spike proteins for broad-spectrum COVID-19 vaccine

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Use of convalescent serum reduces severity of COVID-19 in nonhuman primates

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Respiratory mucosal delivery of next-generation COVID-19 vaccine provides robust protection against both ancestral and variant strains of SARS-CoV-2

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mRNA vaccines for COVID-19: what,why and how

The Coronavirus disease-19 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus -2 (SARS-CoV-2), has impacted human lives in the most profound ways with millions of infections and deaths. Scientists and pharmaceutical companies have been in race to produce vaccines against SARS-CoV-2. Vaccine generation usually demands years of developing and testing for efficacy and safety. However, it only took less than one year to generate two mRNA vaccines from their development to deployment. The rapid production time, cost-effectiveness, versatility in vaccine design, and clinically proven ability to induce cellular and humoral immune response have crowned mRNA vaccines with spotlights as most promising vaccine candidates in the fight against the pandemic. In this review, we discuss the general principles of mRNA vaccine design and working mechanisms of the vaccines, and provide an up-to-date summary of pre-clinical and clinical trials on seven anti-COVID-19 mRNA candidate vaccines, with the focus on the two mRNA vaccines already licensed for vaccination. In addition, we highlight the key strategies in designing mRNA vaccines to maximize the expression of immunogens and avoid intrinsic innate immune response. We also provide some perspective for future vaccine development against COVID-19 and other pathogens.     

Absence of antibody responses to SARS-CoV-2 N protein in COVID-19 vaccine breakthrough cases

Understanding the risk factors for breakthrough coronavirus disease 2019 (COVID-19) (BC19) is critical to inform policy. Herein, we assessed Delta (Lineage B.1.617.2) variant-specific effectiveness of the BNT162b2 (Pfizer) vaccine and characterized Delta-driven BC19 cases (fully vaccinated individuals who get infected) with known-time-since-vaccination. In this longitudinal prospective study (January 21–October 30, 2021), 90 naïve and 15 convalescent individuals were enrolled at the initiation of vaccination. Samples from 27 unvaccinated individuals with previous laboratory-confirmed COVID-19 diagnosis were collected at a single time point. Longitudinal serology profile (antibodies against severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] S and N proteins) and live-virus-based neutralization capacities were assessed while controlling for age. Sex, age, history of reactions to the COVID-19 vaccine, and viral neutralization capacities were identified as significant risk factors for breakthrough COVID-19. At 8 months postvaccination, male sex, individuals ⩾65 years of age, and individuals who experienced noticeable side effects with the COVID-19 vaccine were at 5.47 (p-value = 0.0102), 4.33 (p-value = 0.0236), and 4.95 (p-value = 0.0159) fold greater risk of BC19 as compared to their peers, respectively. Importantly, every five-fold increase in viral neutralization capacities (by live-virus-based assays) was significantly associated with ~4-fold reduction in the risk occurrence of breakthrough COVID-19 (p-value = 0.045). Vaccine boosting remarkably increased these viral neutralization capacities by 16.22-fold (p- value = 0.0005), supporting the importance of the BNT162b2 booster in efforts to control the incursion of future variants into the population at large. Strikingly, BC19 cases exhibited a delayed/absent antibody response to the N protein, suggesting limited exposure to the virus. Since antibodies against N protein are widely used to evaluate the extent of virus spread in communities, our finding has important implications on the utility of existing serological diagnostic and surveillance for COVID-19.     

新型冠状病毒肺炎的诊断、治疗和预防

新型冠状病毒肺炎(coronavirus disease 2019,COVID-19)是一种由严重急性呼吸系统综合征冠状病毒2(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)引发的传染病.此种病毒传染性强,患者感染后会出现严重的急性呼吸道感染症状,...     

Seroprevalence of COVID-19 in Riyadh city during the early increase of COVID-19 infections in Saudi Arabia,June 2020

Severe acute respiratory syndrome coronavirus (SARS-CoV-2) emerged in December 2019 and caused a global pandemic of the Coronavirus Disease 2019 (COVID-19). More than 170 million cases have been reported worldwide with mortality rate of 1–3%. The detection of SARS-CoV-2 by molecular testing is limited to acute infections, therefore serological studies provide a better estimation of the virus spread in a population. This study aims to evaluate the seroprevalence of SARS-CoV-2 in the major city of Riyadh, Saudi Arabia during the sharp increase of the pandemic, in June 2020. Serum samples from non-COVID patients (n = 432), patients visiting hospitals for other complications and confirmed negative for COVID-19, and healthy blood donors (n = 350) were collected and evaluated using an in-house enzyme-linked immunosorbent assay (ELISA). The overall percentage of positive samples was 7.80% in the combined two populations (n = 782). The seroprevalence was lower in the blood donors (6%) than non-COVID-19 patients (9.25%), p = 0.0004. This seroprevalence rate is higher than the documented cases, indicating asymptomatic or mild unreported COVID-19 infections in these two populations. This warrants further national sero-surveys and highlights the importance of real-time serological surveillance during pandemics.     

COVID-19: Pathogenesis,cytokine storm and therapeutic potential of interferons

The outbreak of the novel SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) responsible for coronavirus disease 2019 (COVID-19) has developed into an unprecedented global pandemic. Clinical investigations in patients with COVID-19 has shown a strong upregulation of cytokine and interferon production in SARS-CoV2- induced pneumonia, with an associated cytokine storm syndrome. Thus, the identification of existing approved therapies with proven safety profiles to treat hyperinflammation is a critical unmet need in order to reduce COVI-19 associated mortality. To date, no specific therapeutic drugs or vaccines are available to treat COVID-19 patients. This review evaluates several options that have been proposed to control SARS-CoV2 hyperinflammation and cytokine storm, eincluding antiviral drugs, vaccines, small-molecules, monoclonal antibodies, oligonucleotides, peptides, and interferons (IFNs).     

广西1例本地新冠肺炎病例感染的溯源调查

描述2021年1月广西1例本地新冠肺炎病例发现和感染的溯源过程,旨在为今后类似疫情溯源调查工作提供经验参考。按照《新型冠状病毒感染的肺炎病例流行病学调查方案(第七版)》对病例开展流行病学调查,收集病例的流行病学史、发病诊疗情况等,对病例、密接者标本采用荧光实时定量RT-PCR法检测新冠病毒核酸和胶体金法检测血清特异性抗体。同时对重点场所环境采样进行核酸检测,对核酸阳性标本开展全基因组测序和系统进化分析。全基因组序列比对发现本地病例A和印度尼西亚入境的无症状感染者C同属L基因型欧洲家系分支2.3,共享25个核苷酸变异位点;结合流行病学调查,推测本次疫情的感染来源与印度尼西亚入境的无症状感染者密切相关,可能的传播途径为无症状感染者污染入住隔离酒店环境,本地病例在对酒店消毒作业中因防护不规范暴露于病毒污染环境而导致感染。境外输入病例导致的本土疫情是我国新冠肺炎常态化防控的重点。     

新型冠状病毒感染相关嗅觉障碍的流行现状、机制和康复

新型冠状病毒感染（coronavirus disease 2019,COVID-19）,下简称“新冠”,是由严重急性呼吸系统综合征冠状病毒2（severe acute respiratory syndrome coronavirus 2,SARS-CoV-2）引发的全球流行传染病。鉴于嗅觉障碍是其主要神经症状,明确相关流行现状、机制和康复对促进公共健康非常重要。文献报道的新冠相关嗅觉障碍的发生率存在差异,与评估工具、人群以及变异毒株3个因素有关。其中,不同毒株之间嗅觉障碍发生率的差异可能源于刺突糖蛋白和侵入方式的变异。在外周嗅觉系统,SARS-CoV-2主要引发嗅裂炎症、支持细胞死亡和宿主免疫反应,而关于SARS-CoV-2入侵中枢的途径和机制仍存争议。部分“长新冠”患者存在持续的嗅觉障碍,SARS-CoV-2诱发慢性炎症反应和对嗅上皮再生的破坏是其潜在的病理基础。根据嗅觉媒介假说,SARS-CoV-2可能借由嗅觉系统影响中枢功能并最终诱发神经退行性变。嗅觉训练、药物等方法可帮助新冠相关嗅觉障碍的康复。     

Covaxin: An overview of its immunogenicity and safety trials in India

The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to a global coronavirus disease-19 (COVID-19) pandemic. Several vaccine types, such as inactivated, viral vector-, or mRNA-based, have received approval against SARS-CoV-2. The ability to induceT-helper-1 cell (Th1) responses is desirable from an effective vaccine against this virus. Covaxin (BBV152) is a wholevirion inactivated SARS-CoV-2 vaccine adjuvanted with Algel-Imidazoquinoline (IMDG) molecule, a toll-like receptor (TLR) 7/8 agonist. The mRNA-based vaccine use is hindered because of cold storage requirement, whereas covaxin is stored between 2°C and 8°C, making it suitable for countries with limited resources. The Drug Controller General of India (DCGI) has approved the BBV152 vaccine. Therefore, it is of interest to document known data on BBV152 vaccine phase I, phase II and phase III human clinical trials to evaluate the safety, reactogenicity, tolerance, and immunogenicity of the whole-virion inactivated SARS-CoV-2 vaccine (BBV152).     

Probiotics,prebiotics, and COVID-19 infection: A review article

The beneficial live microbes of humans and animals are termed probiotics, and the chemical compounds that improve the growth of probiotics are known as prebiotics. Paraprobiotics and postbiotics refer to dead or inactivated living cells of probiotics and healthful metabolic products that are produced by the living cells of probiotics, respectively. Although the healthful, functional, nutritional, and immune benefits of probiotics and prebiotics are scientifically well established beyond a reasonable doubt, their potential biological roles against COVID-19 infection still warrant further clinical and laboratory investigation.     

SARS-CoV-2 breakthrough infections elicit potent,broad, and durable neutralizing antibody responses

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The NLRP3 inflammasome and COVID-19: Activation,pathogenesis and therapeutic strategies

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), exhibits a wide spectrum of clinical presentations, ranging from asymptomatic cases to severe pneumonia or even death. In severe COVID-19 cases, an increased level of proinflammatory cytokines has been observed in the bloodstream, forming the so-called “cytokine storm”. Generally, nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome activation intensely induces cytokine production as an inflammatory response to viral infection. Therefore, the NLRP3 inflammasome can be a potential target for the treatment of COVID-19. Hence, this review first introduces the canonical NLRP3 inflammasome activation pathway. Second, we review the cellular/molecular mechanisms of NLRP3 inflammasome activation by SARS-CoV-2 infection (e.g., viroporins, ion flux and the complement cascade). Furthermore, we describe the involvement of the NLRP3 inflammasome in the pathogenesis of COVID-19 (e.g., cytokine storm, respiratory manifestations, cardiovascular comorbidity and neurological symptoms). Finally, we also propose several promising inhibitors targeting the NLRP3 inflammasome, cytokine products and neutrophils to provide novel therapeutic strategies for COVID-19.     

Obesity,a major risk factor for immunity and severe outcomes of COVID-19

An influenza-like virus named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for COVID-19 disease and spread worldwide within a short time. COVID-19 has now become a significant concern for public health. Obesity is highly prevalent worldwide and is considered a risk factor for impairing the adaptive immune system. Although diabetes, hypertension, cardiovascular disease (CVD), and renal failure are considered the risk factors for COVID-19, obesity is not yet well-considered. The present study approaches establishing a systemic association between the prevalence of obesity and its impact on immunity concerning the severe outcomes of COVID-19 utilizing existing knowledge. Overall study outcomes documented the worldwide prevalence of obesity, its effects on immunity, and a possible underlying mechanism covering obesity-related risk pathways for the severe outcomes of COVID-19. Overall understanding from the present study is that being an immune system impairing factor, the role of obesity in the severe outcomes of COVID-19 is worthy.     

Stopping the COVID-19 pandemic in dental offices: A review of SARS-CoV-2 transmission and cross-infection prevention

Due to the essential role of dentists in stopping the COVID-19 pandemic, the purpose of this review is to help dentists to detect any weaknesses in their disinfection and cross-contamination prevention protocols, and to triage dental treatments to meet the needs of patients during the pandemic. We used PRISMA to identify peer-reviewed publications which supplemented guidance from the center for disease control about infection control and guidelines for dentists. Dentists must triage dental treatments to meet the needs of patients during the pandemic. The ongoing pandemic has changed the practice of dentistry forever, the changes make it more cumbersome, time-consuming, and costly due to the possible pathways of transmission and mitigation steps needed to prevent the spread of COVID-19. Dental chairside rapid tests for SARS-CoV-2 are urgently needed. Until then, dentists need to screen patients for COVID-19 even though 75% of people with COVID-19 have no symptoms. Despite the widespread anxiety and fear of the devastating health effects of COVID-19, only 61% of dentists have implemented a change to their treatment protocols. As an urgent matter of public health, all dentists must identify the additional steps they can take to prevent the spread of COVID-19. The most effective steps to stop the pandemic in dental offices are to; vaccinate all dentists, staff, and patients; triage dental treatments for patients, separate vulnerable patients, separate COVID-19 patients, prevent cross-contamination, disinfect areas touched by patients, maintain social distancing, and change personal protective equipment between patients.     

COVID-19: comparative clinical features and outcome in 114 patients with or without pneumonia (Nord Franche-Comte Hospital,France)

COVID-19 patients (n = 114) were included (55 patients with pneumonia (group P) and 59 without pneumonia (group NP). Patients in group P were older (69 (±17) years vs 46 (±16); p < 0.001) with a male predominance (58.2% vs 27.1%; p < 0.001). The symptoms which were statistically more frequents in patients with pneumonia were fever ≥ 38 °C (93% vs 70%; p = 0.002) and dyspnea (73% vs 22%; p < 0.001). Symptoms such as facial headache (42% vs 15%; p = 0.001), sore throat (39% vs 16%; p = 0.007), dysgeusia (61% vs 33%; p = 0.003), anosmia (63% vs 31%; p = 0.001) were statistically more frequents in patients without pneumonia.     

Focus: Vaccines: Sufficient Sleep,Time of Vaccination,and Vaccine Efficacy: A Systematic Review of the Current Evidence and a Proposal for COVID-19 Vaccination

Introduction: The emergence of the novel Coronavirus Disease 2019 (COVID-19) sparked an unprecedented effort to develop effective vaccines against the disease. Some factors may boost the vaccine efficacy, including sufficient sleep and morning vaccination. We aimed to conduct a rapid systematic review to summarize data regarding the association between sleep and time of vaccination with immunity after vaccination. Materials and Methods: The systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol, and three databases (PubMed, Web of Science, and Scopus) were searched up to March 12, 2022. Results: Eight studies were included regarding the sleep and immune response after vaccination, of them, five studies were on influenza, two studies on hepatitis A (HAV), and one study on hepatitis B. Accordingly, six out of eight studies found a positive correlation between sleep and immune response after vaccination. Regarding the time of vaccination, seven studies were eligible to be included (two studies on influenza, one study on HAV and influenza, one study on BCG, one study on hexavalent vaccine, and two studies on SARS-CoV-2 vaccine). Among them, four out of seven studies (including a study on SARS-CoV-2 inactivated vaccine) reported the priorities of morning versus afternoon vaccination regarding antibody production and immune response after vaccination. Conclusion: Taken together, cumulative evidence suggests that sufficient sleep and vaccination in the morning could enhance the immune response after vaccination. Hence, modulating the time of vaccination and sufficient sleep could a be simple and applicable strategy for increasing vaccine efficacy. Future studies could be performed with SARS-CoV-2 vaccines to investigate the effects of time of vaccination and sufficient sleep on COVID-19 vaccine efficacy.     

Mortality and pre-hospitalization use of low-dose aspirin in COVID-19 patients with coronary artery disease

To determine whether pre-hospitalization use of aspirin is associated with all-cause mortality in coronavirus disease 2019 (COVID-19) patients with coronary artery disease (CAD). We recruited 183 adult patients with CAD diagnosed with COVID-19, including 52 taking low-dose aspirin (mean [SD] age, 69.7 [1.1] years; 59.6% men) and 131 without using aspirin (mean [SD] age, 71.8 [0.9] years; 51.9% men), who were admitted in the Tongji hospital in Wuhan, China from January 10, 2020 to March 30, 2020. There was no difference on in-hospital mortality between aspirin group and non-aspirin group (21.2% vs. 22.1%, P = .885). Similarly, for critically severe COVID-19 patients, the mortality in aspirin group was close to that in non-aspirin group (44% vs. 45.9%, P = .872). Moreover, the percentage of patients with CAD taking low-dose aspirin did not differ between those survivors and non-survivors (28.7% vs. 27.5%, P = .885). Meanwhile, the usage of aspirin was not correlated with all-cause mortality in multivariate analysis (OR = 0.944, 95% CI: 0.411-2.172, P = .893). Collectively, our study suggested that the pre-hospitalization use of low-dose aspirin was not associated with the clinical outcome of patients with CAD hospitalized with COVID-19 infections.     

An update comprehensive review on the status of COVID-19: vaccines,drugs, variants and neurological symptoms

Various recently reported mutant variants, candidate and urgently approved current vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), many current situations with severe neurological damage and symptoms as well as respiratory tract disorders have begun to be reported. In particular, drug, vaccine, and neutralizing monoclonal antibodies (mAbs) have been developed and are currently being evaluated in clinical trials. Here, we review lessons learned from the use of novel mutant variants of the COVID-19 virus, immunization, new drug solutions, and antibody therapies for infections. Next, we focus on the B 1.1.7, B 1.351, P.1, and B.1.617 lineages or variants of concern that have been reported worldwide, the new manifestations of neurological manifestations, the current therapeutic drug targets for its treatment, vaccine candidates and their efficacy, implantation of convalescent plasma, and neutralization of mAbs. We review specific clinical questions, including many emerging neurological effects and respiratory tract injuries, as well as new potential biomarkers, new studies in addition to known therapeutics, and chronic diseases of vaccines that have received immediate approval. To answer these questions, further understanding of the burden kinetics of COVID-19 and its correlation with neurological clinical outcomes, endogenous antibody responses to vaccines, pharmacokinetics of neutralizing mAbs, and action against emerging viral mutant variants is needed.