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BMJ (Clinical Research Ed.) May 2022To evaluate the effectiveness of heterologous and homologous covid-19 vaccine regimens with and without boosting in preventing covid-19 related infection, hospital... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the effectiveness of heterologous and homologous covid-19 vaccine regimens with and without boosting in preventing covid-19 related infection, hospital admission, and death.
DESIGN
Living systematic review and network meta-analysis.
DATA SOURCES
World Health Organization covid-19 databases, including 38 sources of published studies and preprints.
STUDY SELECTION
Randomised controlled trials, cohort studies, and case-control studies.
METHODS
38 WHO covid-19 databases were searched on a weekly basis from 8 March 2022 to 31 July 2022. Studies that assessed the effectiveness of heterologous and homologous covid-19 vaccine regimens with or without a booster were identified. Studies were eligible when they reported the number of documented, symptomatic, severe covid-19 infections, covid-19 related hospital admissions, or covid-19 related deaths among populations that were vaccinated and unvaccinated. The primary measure was vaccine effectiveness calculated as 1−odds ratio. Secondary measures were surface under the cumulative ranking curve (SUCRA) scores and the relative effects for pairwise comparisons. The risk of bias was evaluated by using the risk of bias in non-randomised studies of interventions (ROBINS-I) tool for all cohort and case-control studies. The Cochrane risk of bias tool (version 2; ROB-2) was used to assess randomised controlled trials.
RESULTS
The second iteration of the analysis comprised 63 studies. 25 combinations of covid-19 vaccine regimens were identified, of which three doses of mRNA vaccine were found to be 93% (95% credible interval 70% to 98%) effective against asymptomatic or symptomatic covid-19 infections for non-delta or non-omicron related infections. Heterologous boosting using two dose adenovirus vector vaccines with one dose mRNA vaccine showed a vaccine effectiveness of 94% (72% to 99%) against non-delta or non-omicron related asymptomatic or symptomatic infections. Three doses of mRNA vaccine were found to be the most effective in reducing non-delta or non-omicron related hospital admission (96%, 82% to 99%). The vaccine effectiveness against death in people who received three doses of mRNA vaccine remains uncertain owing to confounders. The estimate for a four dose mRNA vaccine regimen was of low certainty, as only one study on the effectiveness of four doses could be included in this update. More evidence on four dose regimens will be needed to accurately assess the effectiveness of a fourth vaccine dose. For people with delta or omicron related infection, a two dose regimen of an adenovirus vector vaccine with one dose of mRNA booster was 77% (42% to 91%) effective against asymptomatic or symptomatic covid-19 infections, and a three dose regimen of a mRNA vaccine was 93% (76% to 98%) effective against covid-19 related hospital admission.
CONCLUSION
An mRNA booster is recommended to supplement any primary vaccine course. Heterologous and homologous three dose regimens work comparably well in preventing covid-19 infections, even against different variants. The effectiveness of three dose vaccine regimens against covid-19 related death remains uncertain.
SYSTEMATIC REVIEW REGISTRATION
This review was not registered. The protocol is included in the supplementary document.
READERS' NOTE
This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication. This version is update 1 of the original article published on 31 May 2022 (BMJ 2022;377:e069989), and previous versions can be found as data supplements (https://www.bmj.com/content/377/bmj-2022-069989/related). When citing this paper please consider adding the version number and date of access for clarity.
Topics: Aged; COVID-19; COVID-19 Vaccines; Humans; Network Meta-Analysis; RNA, Messenger; SARS-CoV-2; Vaccines, Synthetic; mRNA Vaccines
PubMed: 35640925
DOI: 10.1136/bmj-2022-069989 -
Infectious Disorders Drug Targets 2022Many potential vaccines for COVID-19 are being studied and developed. Several studies have reported on the safety and efficacy of these vaccines. This systematic review...
INTRODUCTION
Many potential vaccines for COVID-19 are being studied and developed. Several studies have reported on the safety and efficacy of these vaccines. This systematic review aimed to report on the current evidence concerning the feasibility and effectiveness of vaccines for COVID-19.
METHODS
A systematic search was carried out utilizing the keywords in the online databases, including Scopus, Web of Science, PubMed, Embase, and Cochrane. We included both human and non-human studies because of the vaccine novelty, limiting our ability to include sufficient human studies.
RESULTS
This review showed several SARS-CoV-2 vaccines to be currently under development using different platforms, including eight vaccines that are adenovirus-based vectors, six vaccines that are RNA-based formulations, one vaccine being DNA-based formulation, and other vaccines using other platforms, including lipid nanoparticles. Although the safety and efficacy profiles of these vaccines are still under debate, some countries have allowed for emergency use of some vaccines in at-risk populations, such as healthcare workers and the elderly.
CONCLUSION
It is crucial to gather as much clinically relevant evidence as possible regarding the immunogenicity, efficacy, and safety profiles of available vaccines and adhere wisely to CDC protocols and guidelines for vaccine production.
Topics: COVID-19; COVID-19 Vaccines; Feasibility Studies; Humans; Immunogenicity, Vaccine; Liposomes; Nanoparticles; SARS-CoV-2
PubMed: 34554905
DOI: 10.2174/1871526521666210923144837 -
Vaccines Mar 2020Optimal vaccine dosing is important to ensure the greatest protection and safety. Analysis of dose-response data, from previous studies, may inform future studies to... (Review)
Review
Immunologic Dose-Response to Adenovirus-Vectored Vaccines in Animals and Humans: A Systematic Review of Dose-Response Studies of Replication Incompetent Adenoviral Vaccine Vectors when Given via an Intramuscular or Subcutaneous Route.
Optimal vaccine dosing is important to ensure the greatest protection and safety. Analysis of dose-response data, from previous studies, may inform future studies to determine the optimal dose. Implementing more quantitative modelling approaches in vaccine dose finding have been recently suggested to accelerate vaccine development. Adenoviral vectored vaccines are in advanced stage of development for a variety of prophylactic and therapeutic indications, however dose-response has not yet been systematically determined. To further inform adenoviral vectored vaccines dose identification, historical dose-response data should be systematically reviewed. A systematic literature review was conducted to collate and describe the available dose-response studies for adenovirus vectored vaccines. Of 2787 papers identified by Medline search strategy, 35 were found to conform to pre-defined criteria. The majority of studies were in mice or humans and studied adenovirus serotype 5. Dose-response data were available for 12 different immunological responses. The majority of papers evaluated three dose levels, only two evaluated more than five dose levels. The most common dosing range was 10-10 viral particles in mouse studies and 10-10 viral particles in human studies. Data were available on adenovirus vaccine dose-response, primarily on adenovirus serotype 5 backbones and in mice and humans. These data could be used for quantitative adenoviral vectored vaccine dose optimisation analysis.
PubMed: 32192058
DOI: 10.3390/vaccines8010131 -
Vaccines Mar 2023Coronavirus disease 2019 (COVID-19) vaccine has effectively suppressed the spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and alleviated its... (Review)
Review
Coronavirus disease 2019 (COVID-19) vaccine has effectively suppressed the spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and alleviated its symptoms, but there are also many adverse events. Joint diseases caused by COVID-19 vaccine have been reported in many studies. Some are well-controlled arthritis patients who developed arthritis after COVID-19 vaccination, while others are new-onset joint pain and swelling problems after COVID-19 vaccination. The purpose of this systematic review is to examine the literature reports in existing databases and analyze the incidence of new-onset arthritis after COVID-19 vaccination. We included 31 eligible articles and described 45 patients, ranging in age from 17 to over 90, with more females than males. The majority (84.4%) of patients received the adenovirus vector vaccine (ChAdOx1) and the mRNA-based vaccine (BNT126b2 and mRNA-1273). Most (64.4%) patients developed joint-related symptoms after the first dose of vaccine, and 66.7% developed symptoms within the first week of vaccination. The joint symptoms involved were mainly joint swelling, joint pain, limited range of motion, and so on. A total of 71.1% of the patients involved multiple joints, both large and small; 28.9% of patients involved only a single joint. Some (33.3%) patients were confirmed by imaging, and the most common diagnoses were bursitis and synovitis. Two nonspecific inflammatory markers, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), were monitored in almost all cases, and all patients showed varying degrees of increase in these two markers. Most of the patients received the treatment of glucocorticoid drugs or nonsteroidal anti-inflammatory drugs (NSAIDs). Clinical symptoms markedly improved in most patients, with 26.7% making a full recovery and no relapse after a few months of follow-up. To determine whether there is a causal relationship between COVID-19 vaccination and the triggering of arthritis, large-scale and well-controlled research studies are needed in the future to verify this relationship and to further study its pathogenesis in detail. Clinicians should raise awareness of this complication with a view to early diagnosis and appropriate treatment.
PubMed: 36992249
DOI: 10.3390/vaccines11030665 -
Bulletin of the National Research Centre 2021High effectiveness of COVID-19 vaccines is essential for the pandemic control. This study systematically reviewed available evidence on effectiveness of ChAdOx1 and... (Review)
Review
BACKGROUND
High effectiveness of COVID-19 vaccines is essential for the pandemic control. This study systematically reviewed available evidence on effectiveness of ChAdOx1 and BNT162b2 vaccines in the general population, for improved vaccine policies and strategies.
MAIN BODY OF THE ABSTRACT
Using several keywords, a search of Scopus, PubMed, Google scholar and Hinari databases was conducted from December 1, 2020 to June 9, 2021. Eligible studies comprising original studies reporting effectiveness of the vaccines, were included following PRISMA guidelines. Individual studies were assessed for quality using National Heart, Lung and Blood Institute quality assessment tool. A total of 1766 titles were retrieved and 11 were included, out of which only 5 were peer-reviewed. Although data availability was limited, studies suggest equivalent effectiveness of BNT162b2 and ChAdOx1 COVID-19 vaccine against SARS-CoV-2 infection and COVID-19 related morbidity and mortality. Vaccine effectiveness increased steadily to about 35 days, with an enhanced effectiveness following the second dose.
SHORT CONCLUSION
BNT162 and ChAdOx1 vaccines were associated with equivalent and high effectiveness which increased with time and a second dose in the general population. This encourages continued practice of other preventive measures, particularly during the first week of vaccination, and reinforces the need for a second dose.
PubMed: 34456555
DOI: 10.1186/s42269-021-00607-w -
Future Journal of Pharmaceutical... 2022Vaccination against Coronavirus disease 2019 (COVID-19) is an important means of controlling the pandemic, however they are expected to stimulate immune responses when... (Review)
Review
Immunogenicity and clinical features relating to BNT162b2 messenger RNA COVID-19 vaccine, Ad26.COV2.S and ChAdOx1 adenoviral vector COVID-19 vaccines: a systematic review of non-interventional studies.
BACKGROUND
Vaccination against Coronavirus disease 2019 (COVID-19) is an important means of controlling the pandemic, however they are expected to stimulate immune responses when administered to confer immunity. In this review, we evaluated the clinical and laboratory features associated with BNT162b2 messenger RNA COVID-19 vaccine, Ad26.COV2.S and ChAdOx1 adenoviral vector COVID-19 vaccines, to determine their immunogenicity. Demographic distribution of pathogenic autoimmune response and time interval between vaccination and onset of symptoms were also assessed. This was to identify; persons at risk of developing auto-immune reactions and markers to enhanced occurrence of this event.
MAIN BODY
Using relevant keywords, search was conducted in the databases of PubMed, Scopus, Web of Science and Google scholar from November 2020 to May 31, 2021. Additional article was also identified through hand-searching of reference lists, and the review was conducted in line with Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines 2009. Study outcome measures were presence of antibodies after vaccination and evidence of autoimmune reactions, therefore studies relating these measures were considered eligible for this review. Studies showed stimulation of immune response with administration of BNT162b2 mRNA vaccine, ChAdOx1 and Ad26.COV2-S adenovirus vector-based vaccines. Aside SARS-CoV-2 spike protein antibodies, elevated D-dimers, presence of PF4 and low fibrinogen were most commonly seen laboratory features in persons with autoimmune reactions following vaccination. In addition, thrombotic thrombocytopenia was the commonest clinical features observed with ChAdOx1 and Ad26.COV2-S adenovirus vector-based vaccines. Findings from this study also suggest higher susceptibility of women of 22-60 years to the pathogenic immunogenicity that may particular result from exposure to ChAdOx1 and Ad26.COV2-S adenovirus vector-based vaccines. Time interval of 4-37 days was mostly observed between vaccination and occurrence of a symptom.
CONCLUSION
Immune thrombotic thrombocytopenia and other PF4 dependent syndrome are likely associated with ChAdOx1 and Ad26.COV2.S adenovirus vector vaccines, mostly occurring in women usually within 4-37 days of first dose of vaccine. Enhanced knowledge about vaccine adverse effects and its distribution is crucial for effective vaccination strategies.
PubMed: 35368622
DOI: 10.1186/s43094-022-00409-5 -
Frontiers in Immunology 2022Tuberculosis (TB), caused by respiratory infection with , remains a major global health threat. The only licensed TB vaccine, the one-hundred-year-old Bacille... (Review)
Review
Tuberculosis (TB), caused by respiratory infection with , remains a major global health threat. The only licensed TB vaccine, the one-hundred-year-old Bacille Calmette-Guérin has variable efficacy and often provides poor protection against adult pulmonary TB, the transmissible form of the disease. Thus, the lack of an optimal TB vaccine is one of the key barriers to TB control. Recently, the development of highly efficacious COVID-19 vaccines within one year accelerated the vaccine development process in human use, with the notable example of mRNA vaccines and adenovirus-vectored vaccines, and increased the public acceptance of the concept of the controlled human challenge model. In the TB vaccine field, recent progress also facilitated the deployment of an effective TB vaccine. In this review, we provide an update on the current virus-vectored TB vaccine pipeline and summarize the latest findings that might facilitate TB vaccine development. In detail, on the one hand, we provide a systematic literature review of the virus-vectored TB vaccines are in clinical trials, and other promising candidate vaccines at an earlier stage of development are being evaluated in preclinical animal models. These research sharply increase the likelihood of finding a more effective TB vaccine in the near future. On the other hand, we provide an update on the latest tools and concept that facilitating TB vaccine research development. We propose that a pre-requisite for successful development may be a better understanding of both the lung-resident memory T cell-mediated mucosal immunity and the trained immunity of phagocytic cells. Such knowledge could reveal novel targets and result in the innovative vaccine designs that may be needed for a quantum leap forward in vaccine efficacy. We also summarized the research on controlled human infection and ultra-low-dose aerosol infection murine models, which may provide more realistic assessments of vaccine utility at earlier stages. In addition, we believe that the success in the ongoing efforts to identify correlates of protection would be a game-changer for streamlining the triage of multiple next-generation TB vaccine candidates. Thus, with more advanced knowledge of TB vaccine research, we remain hopeful that a more effective TB vaccine will eventually be developed in the near future.
Topics: Animals; COVID-19; COVID-19 Vaccines; Humans; Mice; Tuberculosis; Tuberculosis Vaccines; Vaccine Development
PubMed: 35812383
DOI: 10.3389/fimmu.2022.895020 -
Vaccines Dec 2022Vaccination is one of the most effective measures for children as the epidemic progresses. However, there is a significant research gap in the meta-analysis of the... (Review)
Review
Vaccination is one of the most effective measures for children as the epidemic progresses. However, there is a significant research gap in the meta-analysis of the COVID-19 vaccines for children younger than 18 years. This study is a comprehensive review of different COVID-19 vaccines. Published articles were retrieved from PubMed, Embase, and the Cochrane Library. Twelve randomized controlled trials (RCTs) of COVID-19 vaccines were included in the review until 21 October 2022. Most local and systemic adverse reactions were predominantly mild to moderate in severity and disappeared quickly after different types of vaccines. The subunit vaccine had the highest safety. The significant risk was lower in the subunit vaccine group after the initial (RR 1.66, 95% CI 1.26-2.17, = 0.0003) and booster vaccination (RR 1.40, 95% CI 1.02-1.92, = 0.04). Younger children had a more outstanding safety profile in the mRNA and inactivated vaccine groups. The humoral immune response was proportional to the number of doses in the inactivated and the adenovirus vaccine groups, and the strength of immunogenicity was negatively correlated with age in the inactivated vaccine. The mRNA and the subunit vaccines provided satisfactory prevention against COVID-19, especially seven days after the booster dose. However, more research and longer-term follow-up are needed to assess the duration of immune responses, efficacy, and safety.
PubMed: 36679932
DOI: 10.3390/vaccines11010087 -
Frontiers in Public Health 2022As the epidemic progresses, universal vaccination against COVID-19 has been the trend, but there are still some doubts about the efficacy and safety of COVID-19 vaccines... (Meta-Analysis)
Meta-Analysis
BACKGROUND
As the epidemic progresses, universal vaccination against COVID-19 has been the trend, but there are still some doubts about the efficacy and safety of COVID-19 vaccines in adolescents, children, and even infants.
PURPOSE
To evaluate the safety, immunogenicity, and efficacy of COVID-19 vaccines in the population aged 0-17 years.
METHOD
A comprehensive search for relevant randomized controlled trials (RCTs) was conducted in PubMed, Embase, and the Cochrane Library from inception to November 9, 2021. All data were pooled by RevMan 5.3 statistical software, with risk ratio (RR) and its 95% confidence interval as the effect measure. This study protocol was registered on PROSPERO (CRD42021290205).
RESULTS
There was a total of six randomized controlled trials included in this systematic review and meta-analysis, enrolling participants in the age range of 3-17 years, and containing three types of COVID-19 vaccines. Compared with mRNA vaccines and adenovirus vector vaccines, inactivated vaccines have a more satisfactory safety profile, both after initial (RR 1.40, 95% CI 1.04-1.90, = 0.03) and booster (RR 1.84, 95% CI 1.20-2.81, = 0.005) vaccination. The risk of adverse reactions was significantly increased after the first and second doses, but there was no significant difference between the first two doses (RR 1.00, 95%CI 0.99-1.02, = 0.60). Nevertheless, the two-dose regimen is obviously superior to the single-dose schedule for immunogenicity and efficacy. After booster vaccination, both neutralizing antibodies (RR 144.80, 95%CI 44.97-466.24, < 0.00001) and RBD-binding antibodies (RR 101.50, 95%CI 6.44-1,600.76, = 0.001) reach optimal levels, but the cellular immune response seemed not to be further enhanced. In addition, compared with younger children, older children and adolescents were at significantly increased risk of adverse reactions after vaccination, with either mRNA or inactivated vaccines, accompanied by a stronger immune response.
CONCLUSION
The available evidence suggests that the safety, immunogenicity and efficacy of COVID-19 vaccines are acceptable in people aged 3-17 years. However, there is an urgent need for additional multicenter, large-sample studies, especially in younger children under 3 years of age and even in infants, with long-term follow-up data.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021290205, identifier: CRD42021290205.
Topics: Adolescent; COVID-19; COVID-19 Vaccines; Child; Child, Preschool; Humans; Multicenter Studies as Topic; Vaccination; Vaccines
PubMed: 35493393
DOI: 10.3389/fpubh.2022.829176 -
The Journal of Allergy and Clinical... Oct 2021Concerns for anaphylaxis may hamper severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunization efforts. We convened a multidisciplinary group of... (Meta-Analysis)
Meta-Analysis Review
The Risk of Allergic Reaction to SARS-CoV-2 Vaccines and Recommended Evaluation and Management: A Systematic Review, Meta-Analysis, GRADE Assessment, and International Consensus Approach.
Concerns for anaphylaxis may hamper severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunization efforts. We convened a multidisciplinary group of international experts in anaphylaxis composed of allergy, infectious disease, emergency medicine, and front-line clinicians to systematically develop recommendations regarding SARS-CoV-2 vaccine immediate allergic reactions. Medline, EMBASE, Web of Science, the World Health Organizstion (WHO) global coronavirus database, and the gray literature (inception, March 19, 2021) were systematically searched. Paired reviewers independently selected studies addressing anaphylaxis after SARS-CoV-2 vaccination, polyethylene glycol (PEG) and polysorbate allergy, and accuracy of allergy testing for SARS-CoV-2 vaccine allergy. Random effects models synthesized the data to inform recommendations based on the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) approach, agreed upon using a modified Delphi panel. The incidence of SARS-CoV-2 vaccine anaphylaxis is 7.91 cases per million (n = 41,000,000 vaccinations; 95% confidence interval [95% CI] 4.02-15.59; 26 studies, moderate certainty), the incidence of 0.15 cases per million patient-years (95% CI 0.11-0.2), and the sensitivity for PEG skin testing is poor, although specificity is high (15 studies, very low certainty). We recommend vaccination over either no vaccination or performing SARS-CoV-2 vaccine/excipient screening allergy testing for individuals without history of a severe allergic reaction to the SARS-CoV-2 vaccine/excipient, and a shared decision-making paradigm in consultation with an allergy specialist for individuals with a history of a severe allergic reaction to the SARS-CoV-2 vaccine/excipient. We recommend further research to clarify SARS-CoV-2 vaccine/vaccine excipient testing utility in individuals potentially allergic to SARS-CoV2 vaccines or their excipients.
Topics: Anaphylaxis; COVID-19; COVID-19 Vaccines; Consensus; GRADE Approach; Humans; RNA, Viral; SARS-CoV-2
PubMed: 34153517
DOI: 10.1016/j.jaip.2021.06.006