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Frontiers in Immunology 2021There is a significant research gap in meta-analysis on the efficacy and safety of coronavirus disease 2019 (COVID-19) vaccines. This study analyzed the efficacy of... (Meta-Analysis)
Meta-Analysis
There is a significant research gap in meta-analysis on the efficacy and safety of coronavirus disease 2019 (COVID-19) vaccines. This study analyzed the efficacy of COVID-19 vaccines. Published phase I, phase II, and phase III trials analyzing safety and immunogenicity and phase III randomized clinical trials evaluating the efficacy of COVID-19 vaccines were included. We searched MEDLINE, Scopus, and The Lancet for published articles evaluating the relative reduction in COVID-19 risk after vaccination. Selected literatures were published between December 15, 2019 and May 15, 2021 on the safety, efficacy, and immunogenicity of COVID-19 vaccines. This meta-analysis included studies that confirmed cases of COVID-19 using reverse transcriptase polymerase chain reaction. This study detected 8,926 eligible research articles published on COVID-19 vaccines. Of these, 25 studies fulfilled the inclusion criteria. Among the selected articles, 19 randomized clinical trials, 2 non-randomized clinical trials, and 3 observational studies were analyzed. Seven (28%) studies were included in the meta-analysis. The efficacy of the adenovirus vector vaccine was 73% (95% CI = 69-77) and that of the messenger RNA (mRNA) vaccine was 85% (95% CI = 82-88) in participants aged ≥18 years. There are no reports of clinical trials in participants aged under 16 years. The production of neutralizing antibodies against receptor-binding domains (RBDs) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in >90% of the vaccinated samples was reported within 0-30 days of the first or the second dose of the vaccine. Pain at the injection site was the most common local symptom in people receiving mRNA vaccines (29%-85% of participants). Fever (0.2%-95%) was the most prevalent in people receiving adenovirus vector vaccines, and fatigue (8.4%-55%) was the most common side effect in people receiving the mRNA vaccines. Studies suggest that mRNA vaccines and adenovirus vector vaccines can provide moderate to high protection against COVID-19 infection in people over 18 years. Evidence of the long-term protection of the vaccines in people aged under 16 years against the multiple variants of COVID-19 are limited. This study will provide an integrated evaluation on the efficacy, safety, and immunogenicity of the COVID-19 vaccines.
Topics: Adolescent; Adult; Aged; Antibodies, Neutralizing; COVID-19; COVID-19 Vaccines; Humans; Immunogenicity, Vaccine; Injections, Intramuscular; Middle Aged; Pain; Randomized Controlled Trials as Topic; SARS-CoV-2; Young Adult
PubMed: 34707602
DOI: 10.3389/fimmu.2021.714170 -
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 -
Journal of Advanced Pharmaceutical... 2021Search for an effective and safe vaccine to prevent transmission of current pandemic is an unmet need. This study reviews and compares the available early phase clinical... (Review)
Review
Search for an effective and safe vaccine to prevent transmission of current pandemic is an unmet need. This study reviews and compares the available early phase clinical data of vaccine candidates which have reached phase 3 of clinical development. The latest update of "DRAFT landscape of coronavirus (CoV) disease 2019 candidate vaccines (October 2, 2020)" released by the World Health Organization was accessed to identify the potential vaccine candidates. The full text articles (published and/or preprint) of data of early clinical trials of the selected vaccines were accessed from the links provided in the same document, PubMed and/or medRxiv.com. After extraction and synthesis, the data were critically evaluated for the study efficacy and safety outcomes. Of the total 193 candidate vaccines 10 were found to reach phase 3 of the clinical development. Nine of these were included in the evaluation process. In all of the included studies, immunogenicity and serious adverse events/local or systemic adverse events/laboratory parameters abnormality was considered as efficacy and safety outcomes respectively. Immunogenicity response with most of the vaccines was either higher than or similar to the respective controls except one (recombinant adenovirus type 26 COV2 [Ad26.COV2.S]) for which it was less than that in control. Overall adverse events (related and/or unrelated) were more with vaccines than those with respective control(s) in three studies, in other two, these were similar whereas in one study, the events were less in the vaccine group than in control group and in the rest, data described were descriptive only without any mention for the same for the control. In conclusion all studies showed immunogenic response to target protein of severe acute respiratory syndrome CoV-2 and which was higher than the respective control except for Ad26.CoV2.S. Many of the vaccines caused more adverse events than the controls, however most were mild and transient and/or manageable.
PubMed: 34345597
DOI: 10.4103/japtr.JAPTR_229_20 -
Journal of Medical Virology Dec 2021To systematically evaluate the effectiveness and safety of the SARS-CoV-2 vaccines currently undergoing clinical trials. (Review)
Review Meta-Analysis
OBJECTIVE
To systematically evaluate the effectiveness and safety of the SARS-CoV-2 vaccines currently undergoing clinical trials.
METHODS
PubMed, EMBASE, and Cochrane Library databases were searched to collect open human COVID-19 vaccines randomized controlled trials, without limiting the search time and language. The research papers collected in the above-mentioned databases were initially screened according to the title and abstract content and merged, and the repeated ones were removed. After reading the full text of the remaining research, the studies that did not meet the inclusion criteria were excluded, and finally, nine studies were obtained. After extracting the statistical data of adverse events in the study, load them into Review Manager for heterogeneity analysis.
RESULTS
The incidence of adverse reactions of inactivated virus vaccines, RNA vaccines, and adenovirus vector vaccines was higher than that of placebo. Common adverse reactions included pain, swelling, and fever at the injection site.
CONCLUSION
From the perspective of effectiveness, RNA vaccine > adenovirus vector vaccine > inactivated virus vaccine. From the perspective of safety, the incidence of adverse reactions of the three vaccines is higher than that of a placebo, and the incidence of adverse reactions of the adenovirus vector vaccine is higher.
Topics: Adenovirus Vaccines; COVID-19; COVID-19 Vaccines; Humans; SARS-CoV-2; Spike Glycoprotein, Coronavirus; Vaccination; Vaccines, Inactivated; Vaccines, Synthetic
PubMed: 34264528
DOI: 10.1002/jmv.27203 -
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 -
Vaccines May 2021The current study systematically reviewed, summarized and meta-analyzed the clinical features of the vaccines in clinical trials to provide a better estimate of their... (Review)
Review
The current study systematically reviewed, summarized and meta-analyzed the clinical features of the vaccines in clinical trials to provide a better estimate of their efficacy, side effects and immunogenicity. All relevant publications were systematically searched and collected from major databases up to 12 March 2021. A total of 25 RCTs (123 datasets), 58,889 cases that received the COVID-19 vaccine and 46,638 controls who received placebo were included in the meta-analysis. In total, mRNA-based and adenovirus-vectored COVID-19 vaccines had 94.6% (95% CI 0.936-0.954) and 80.2% (95% CI 0.56-0.93) efficacy in phase II/III RCTs, respectively. Efficacy of the adenovirus-vectored vaccine after the first (97.6%; 95% CI 0.939-0.997) and second (98.2%; 95% CI 0.980-0.984) doses was the highest against receptor-binding domain (RBD) antigen after 3 weeks of injections. The mRNA-based vaccines had the highest level of side effects reported except for diarrhea and arthralgia. Aluminum-adjuvanted vaccines had the lowest systemic and local side effects between vaccines' adjuvant or without adjuvant, except for injection site redness. The adenovirus-vectored and mRNA-based vaccines for COVID-19 showed the highest efficacy after first and second doses, respectively. The mRNA-based vaccines had higher side effects. Remarkably few experienced extreme adverse effects and all stimulated robust immune responses.
PubMed: 34066475
DOI: 10.3390/vaccines9050467 -
Frontiers in Immunology 2021Although acute transverse myelitis (ATM) is a rare neurological condition (1.34-4.6 cases per million/year) COVID-19-associated ATM cases have occurred during the...
Acute Transverse Myelitis (ATM):Clinical Review of 43 Patients With COVID-19-Associated ATM and 3 Post-Vaccination ATM Serious Adverse Events With the ChAdOx1 nCoV-19 Vaccine (AZD1222).
INTRODUCTION
Although acute transverse myelitis (ATM) is a rare neurological condition (1.34-4.6 cases per million/year) COVID-19-associated ATM cases have occurred during the pandemic.
CASE-FINDING METHODS
We report a patient from Panama with SARS-CoV-2 infection complicated by ATM and present a comprehensive clinical review of 43 patients with COVID-19-associated ATM from 21 countries published from March 2020 to January 2021. In addition, 3 cases of ATM were reported as serious adverse events during the clinical trials of the COVID-19 vaccine ChAdOx1 nCoV-19 (AZD1222).
RESULTS
All patients had typical features of ATM with acute onset of paralysis, sensory level and sphincter deficits due to spinal cord lesions demonstrated by imaging. There were 23 males (53%) and 20 females (47%) ranging from ages 21- to 73- years-old (mean age, 49 years), with two peaks at 29 and 58 years, excluding 3 pediatric cases. The main clinical manifestations were quadriplegia (58%) and paraplegia (42%). MRI reports were available in 40 patients; localized ATM lesions affected ≤3 cord segments (12 cases, 30%) at cervical (5 cases) and thoracic cord levels (7 cases); 28 cases (70%) had longitudinally-extensive ATM (LEATM) involving ≥4 spinal cord segments (cervicothoracic in 18 cases and thoracolumbar-sacral in 10 patients). Acute disseminated encephalomyelitis (ADEM) occurred in 8 patients, mainly women (67%) ranging from 27- to 64-years-old. Three ATM patients also had blindness from myeloneuritis optica (MNO) and two more also had acute motor axonal neuropathy (AMAN).
CONCLUSIONS
We found ATM to be an unexpectedly frequent neurological complication of COVID-19. Most cases (68%) had a latency of 10 days to 6 weeks that may indicate post-infectious neurological complications mediated by the host's response to the virus. In 32% a brief latency (15 hours to 5 days) suggested a direct neurotropic effect of SARS-CoV-2. The occurrence of 3 reported ATM adverse effects among 11,636 participants in the AZD1222 vaccine trials is extremely high considering a worldwide incidence of 0.5/million COVID-19-associated ATM cases found in this report. The pathogenesis of ATM remains unknown, but it is conceivable that SARS-CoV-2 antigens -perhaps also present in the AZD1222 COVID-19 vaccine or its chimpanzee adenovirus adjuvant- may induce immune mechanisms leading to the myelitis.
Topics: Adolescent; Adult; Aged; COVID-19; COVID-19 Vaccines; ChAdOx1 nCoV-19; Child; Child, Preschool; Female; Humans; Male; Middle Aged; Myelitis, Transverse; Nervous System Diseases; SARS-CoV-2; Spinal Cord; Viral Tropism; Young Adult
PubMed: 33981305
DOI: 10.3389/fimmu.2021.653786 -
BMJ Open Jul 2020The aetiology and burden of viral-induced acute liver failure remains unclear globally. It is important to understand the epidemiology of viral-induced ALF to plan for...
OBJECTIVES
The aetiology and burden of viral-induced acute liver failure remains unclear globally. It is important to understand the epidemiology of viral-induced ALF to plan for clinical case management and case prevention.
PARTICIPANTS
This systematic review was conducted to synthesize data on the relative contribution of different viruses to the aetiology of viral-induced acute liver failure in an attempt to compile evidence that is currently missing in the field. EBSCOhost, PubMed, ScienceDirect, Scopus and Web of Science were searched for relevant literature published from 2009 to 2019. The initial search was run on 9 April 2019 and updated via PubMed on 30 September 2019 with no new eligible studies to include. Twenty-five eligible studies were included in the results of this review.
RESULTS
This systematic review estimated the burden of acute liver failure after infection with hepatitis B virus, hepatitis A virus, hepatitis C virus, hepatitis E virus, herpes simplex virus/human herpesvirus, cytomegalovirus, Epstein-Barr virus and parvovirus B19. Data were largely missing for acute liver failure after infection with varicella-zostervirus, human parainfluenza viruses, yellow fever virus, coxsackievirus and/or adenovirus. The prevalence of hepatitis A-induced acute liver failur was markedly lower in countries with routine hepatitis A immunisation versus no routine hepatitis A immunisation. Hepatitis E virus was the most common aetiological cause of viral-induced acute liver failure reported in this review. In addition, viral-induced acute liver failure had poor outcomes as indicated by high fatality rates, which appear to increase with poor economic status of the studied countries.
CONCLUSIONS
Immunisation against hepatitis A and hepatitis B should be prioritised in low-income and middle-income countries to prevent high viral-induced acute liver failure mortality rates, especially in settings where resources for managing acute liver failure are lacking. The expanded use of hepatitis E immunisation should be explored as hepatitis E virus was the most common cause of acute liver failure.
REGISTRATION
PROSPERO registration number: CRD42017079730.
Topics: Cytomegalovirus; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; Liver Failure, Acute; Virus Diseases
PubMed: 32690747
DOI: 10.1136/bmjopen-2020-037473 -
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 -
Epidemiology and Infection Mar 2020Gastroenteritis remains a serious health condition among children under 5 years especially in Africa. We conducted a systematic review and meta-analysis to investigate... (Meta-Analysis)
Meta-Analysis
Gastroenteritis remains a serious health condition among children under 5 years especially in Africa. We conducted a systematic review and meta-analysis to investigate the aetiologic pathogens of gastroenteritis in the region. We did a systematic search for articles with original data on the aetiology of gastroenteritis and acute diarrhoea among children younger than 5 years. Pooled results were extracted and analysed in STATA version 12.0 using random-effects for statistical test for homogeneity following the guidelines provided in the Cochrane Collaboration and Preferred reporting items for systematic reviews and meta-analyses. Overall, viruses accounted for 50.2% of the cases followed by bacteria with 31.6% of the cases. Parasites accounted for 12.1% of the case. Rotavirus was the most common cause of acute diarrhoea in all regions resulting in 29.2% of the cases followed by E. coli (15.6%) of diarrhoeal cases and Adenovirus (10.8%). The most prevalent parasite detected was Giardia lamblia (7.3%). Acute diarrhoea remains rampant with Rotavirus still being the major pathogen responsible for the disease in children less than 5 years old despite the introduction of vaccine. It is recommended that the vaccine should be promoted much more widely in the region.
Topics: Adenoviridae; Adenovirus Infections, Human; Africa South of the Sahara; Child, Preschool; Diarrhea; Escherichia coli; Escherichia coli Infections; Gastroenteritis; Giardia lamblia; Giardiasis; Humans; Infant; Infant, Newborn; Rotavirus; Rotavirus Infections
PubMed: 32115003
DOI: 10.1017/S0950268820000618