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Cureus Aug 2022The coronavirus disease 2019 (COVID-19) pandemic has claimed nearly 5.5 million lives worldwide. Adenovirus-based vaccines are safe and effective, but they are rarely...
The coronavirus disease 2019 (COVID-19) pandemic has claimed nearly 5.5 million lives worldwide. Adenovirus-based vaccines are safe and effective, but they are rarely associated with vaccine-induced thrombosis and thrombocytopenia (VITT) as well as cerebral venous sinus thrombosis (CVST). We conducted a systematic literature search of intracerebral hemorrhage (ICH) secondary to CVST associated with VITT from the Ad26.COV2.S vaccine, and we present the first case of this pathology in the reviewed literature of a patient who required neurosurgical decompression. The systematic literature review was completed on December 19, 2021, by searching PubMed and Ovid for articles with primary data on CVST associated with VITT following the Ad26.COV2.S vaccine. We also specifically searched for cases that required neurosurgical intervention. Articles were independently screened by two authors, and both secondary and tertiary searches were done as well. Descriptive statistics were collected and presented in table form. Nine studies were identified that met inclusion criteria. There were no cases identified of patients who underwent neurosurgical decompression after developing this pathology. We thus present the first case in the reviewed literature of a patient who developed ICH after receiving the Ad26.COV2.S vaccine and underwent decompressive hemicraniectomy. Despite severe thrombocytopenia and prolonged intensive care, the patient was discharged to neurorehabilitation. There is a much greater risk of CVST and ICH during COVID-19 infections than from the vaccines. However, as booster vaccines are approved and widely distributed, it is critical to make prompt, accurate diagnoses of this vaccine-related complication and consider neurosurgical decompression.
PubMed: 36127984
DOI: 10.7759/cureus.28083 -
Neurology Oct 2022Acute arterial ischemic stroke (AIS) has been reported as a rare adverse event following coronavirus disease 2019 (COVID-19) vaccination with messenger RNA (mRNA) or... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVES
Acute arterial ischemic stroke (AIS) has been reported as a rare adverse event following coronavirus disease 2019 (COVID-19) vaccination with messenger RNA (mRNA) or viral vector vaccines. However, data are sparse regarding the risk of postvaccination AIS and its potential association with thrombotic-thrombocytopenia syndrome (TTS).
METHODS
A systematic review and meta-analysis of randomized controlled clinical trials (RCTs), pharmacovigilance registries, registry-based studies, observational cohorts, and case-series was performed with the aim to calculate the following: (1) the pooled proportion of patients presenting with AIS following COVID-19 vaccination; (2) the prevalence of AIS after mRNA and vector-based vaccination; and (3) the proportion of TTS among postvaccination AIS cases. Patient characteristics were assessed as secondary outcomes.
RESULTS
Two RCTs, 3 cohort studies, and 11 registry-based studies comprising 17,481 AIS cases among 782,989,363 COVID-19 vaccinations were included in the meta-analysis. The pooled proportion of AIS following exposure to any COVID-19 vaccine type was 4.7 cases per 100,000 vaccinations (95% CI 2.2-8.1; = 99.9%). The pooled proportion of AIS following mRNA vaccination (9.2 cases per 100,000 vaccinations; 95% CI 2.5-19.3; = 99.9%) did not differ compared with adenovirus-based vaccination (2.9 cases per 100,000 vaccinations; 95% CI 0.3-7.8; = 99.9%). No differences regarding demographics were disclosed between patients with AIS following mRNA-based or vector-based vaccination. The pooled proportion of TTS among postvaccination AIS cases was 3.1% (95% CI 0.7%-7.2%; = 78.8%).
DISCUSSION
The pooled proportion of AIS following COVID-19 vaccination is comparable with the prevalence of AIS in the general population and much lower than the AIS prevalence among severe acute respiratory syndrome coronavirus 2-infected patients. TTS is very uncommonly reported in patients with AIS following COVID-19 vaccination.
Topics: Humans; COVID-19; Ischemic Stroke; Vaccination; Arteries; RNA, Messenger; Syndrome
PubMed: 36002319
DOI: 10.1212/WNL.0000000000200996 -
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 -
Expert Review of Vaccines Sep 2022A number of vaccines have now been developed against COVID-19. Differences in reactogenicity and safety profiles according to the vaccine technologies employed are... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
A number of vaccines have now been developed against COVID-19. Differences in reactogenicity and safety profiles according to the vaccine technologies employed are becoming apparent from clinical trials.
METHODS
Five databases (Medline, EMBASE, Science Citation Index, Cochrane Central Register of Controlled Trials, London School of Hygiene and Tropical Medicine COVID-19 vaccine tracker) were searched for relevant randomized controlled trials between 1 January 2020 and 12 January 2022 according to predetermined criteria with no language limitations.
RESULTS
Forty-two datasets were identified, with 20 vaccines using four different technologies (viral vector, inactivated, mRNA and protein sub-unit). Adults and adolescents over 12 years were included. Control groups used saline placebos, adjuvants, and comparator vaccines. The most consistently reported solicited adverse events were fever, fatigue, headache, pain at injection site, redness, and swelling. Both doses of mRNA vaccines, the second dose of protein subunit and the first dose of adenovirus vectored vaccines were the most reactogenic, while the inactivated vaccines were the least reactogenic.
CONCLUSIONS
The different COVID-19 vaccines currently available appear to have distinct reactogenicity profiles, dependent on the vaccine technology employed. Awareness of these differences may allow targeted recommendations for specific populations. Greater standardization of methods for adverse event reporting will aid future research in this field.
Topics: Adjuvants, Immunologic; Adolescent; Adult; COVID-19; COVID-19 Vaccines; Humans; Vaccines, Inactivated
PubMed: 35796029
DOI: 10.1080/14760584.2022.2098719 -
Journal of Clinical Virology : the... Aug 2022Children and adolescents form a large proportion of societies and play an important role in the transmission of COVID-19. On the other hand, their education, mental and... (Meta-Analysis)
Meta-Analysis
Immunologic response, Efficacy, and Safety of Vaccines against COVID-19 Infection in Healthy and immunosuppressed Children and Adolescents Aged 2 - 21 years old: A Systematic Review and Meta-analysis.
Children and adolescents form a large proportion of societies and play an important role in the transmission of COVID-19. On the other hand, their education, mental and physical wellness, and safety are compromised which makes vaccination a crucial step to return to normal life. In the current systematic review, the COVID-19 vaccination was evaluated in a total of 50,148 children and adolescents in 22 published studies and 5,279 participants in two ongoing clinical trials. The study was registered in the PROSPERO with the ID# CRD42022303615. Data were collected about multiple vaccines including BNT162b2 (Pfizer), mRNA-1273 (Moderna), JNJ-78436735 (Johnson and Johnson), CoronaVac (Sinovac), BBIBP-CorV (Sinopharm), adenovirus type-5-vectored vaccine, ZyCov-D, and BBV152 (COVAXIN). The immune response and efficacy of such vaccines were 96% - 100% in healthy children and adolescents and were also acceptable in those with underlying diseases and suppressed immune systems. The current systematic review revealed favorable safety profiles of employed vaccines in children and adolescents; however, adverse reactions such as myocarditis and myopericarditis were reported which were transient and resolved entirely. Consequently, vaccinating children and adolescents aged 2 - 21 years old is beneficial to abort the COVID-19 pandemic. Moreover, the risk-benefit assessments revealed favorable results for vaccinating children and adolescents, especially those with underlying diseases and immunosuppressed conditions, alongside adults to prevent transmission, severe infection, negative outcomes, and new variants formation. Also, according to the meta-analysis, the efficacy and immune response of vaccines after the first and second doses were 91% and 92%, respectively. Meanwhile, overall immune response for all vaccines was 95% and 91% for Pfizer vaccine.
Topics: Ad26COVS1; Adolescent; BNT162 Vaccine; COVID-19; COVID-19 Vaccines; Child; Child, Preschool; Humans; Myocarditis; Pandemics; Young Adult
PubMed: 35716417
DOI: 10.1016/j.jcv.2022.105196 -
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 -
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 -
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 -
Stroke Jun 2022Cerebral venous thrombosis (CVT) has recently been reported as a common thrombotic manifestation in association with vaccine-induced thrombotic thrombocytopenia, a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cerebral venous thrombosis (CVT) has recently been reported as a common thrombotic manifestation in association with vaccine-induced thrombotic thrombocytopenia, a syndrome that mimics heparin-induced thrombocytopenia (HIT) and occurs after vaccination with adenovirus-based SARS-CoV-2 vaccines. We aimed to systematically review the incidence, clinical features, and prognosis of CVT occurring in patients with HIT.
METHODS
The study protocol was registered with PROSPERO (CRD42021249652). MEDLINE, EMBASE and Cochrane CENTRAL were searched up to June 1, 2021 for HIT case series including >20 patients, or any report of HIT-related CVT. Demographic, neuroradiological, clinical, and mortality data were retrieved. Meta-analysis of proportions with random-effect modeling was used to derive rate of CVT in HIT and in-hospital mortality. Pooled estimates were compared with those for CVT without HIT and HIT without CVT, to determine differences in mortality.
RESULTS
From 19073 results, we selected 23 case series of HIT (n=1220) and 27 cases of HIT-related CVT (n=27, 71% female). CVT developed in 1.6% of 1220 patients with HIT (95% CI,1.0%-2.5%, =0%). Hemorrhagic brain lesions occurred in 81.8% of cases of HIT-related CVT and other concomitant thrombosis affecting other vascular territory was reported in 47.8% of cases. In-hospital mortality was 33.3%. HIT-related CVT carried a 29% absolute increase in mortality rate compared with historical CVT controls (33.3% versus 4.3%, <0.001) and a 17.4% excess mortality compared with HIT without CVT (33.3% versus 15.9%, =0.046).
CONCLUSIONS
CVT is a rare thrombotic manifestation in patients with HIT. HIT-related CVT has higher rates of intracerebral hemorrhage and a higher mortality risk, when compared with CVT in historical controls. The recently reported high frequency of CVT in patients with vaccine-induced thrombotic thrombocytopenia was not observed in HIT, suggesting that additional pathophysiological mechanisms besides anti-platelet factor-4 antibodies might be involved in vaccine-induced thrombotic thrombocytopenia-related CVT.
Topics: COVID-19; COVID-19 Vaccines; Female; Humans; Intracranial Thrombosis; Male; SARS-CoV-2; Thrombocytopenia; Thrombosis; Vaccines; Venous Thrombosis
PubMed: 35240862
DOI: 10.1161/STROKEAHA.121.036824 -
Frontiers in Pediatrics 2021Haematopoietic stem cell transplantation (HSCT) in paediatric patients with acute lymphoblastic leukaemia (ALL) is associated with a variety of infectious complications...
Haematopoietic stem cell transplantation (HSCT) in paediatric patients with acute lymphoblastic leukaemia (ALL) is associated with a variety of infectious complications which result in significant morbidity and mortality. These patients are profoundly immunocompromised, and immune reconstitution after HSCT generally occurs in astrictly defined order. During the early phase after HSCT until engraftment, patients are at risk of infections due to presence of neutropenia and mucosal damage, with Gramme-positive and Gramme-negative bacteria and fungi being the predominant pathogens. After neutrophil recovery, the profound impairment of cell-mediated immunity and use of glucocorticosteroids for control of graft-vs.-host disease (GvHD) increases the risk of invasive mould infection and infection or reactivation of various viruses, such as cytomegalovirus, varicella zoster virus, Epstein-Barr virus and human adenovirus. In the late phase, characterised by impaired cellular and humoral immunity, particularly in conjunction with chronic GvHD, invasive infections with encapsulated bacterial infections are observed in addition to fungal and viral infections. HSCT also causes a loss of pretransplant naturally acquired and vaccine-acquired immunity; therefore, complete reimmunization is necessary to maintain long-term health in these patients. During the last two decades, major advances have been made in our understanding of and in the control of infectious complications associated with HSCT. In this article, we review current recommendations for the diagnosis, prophylaxis and treatment of infectious complications following HSCT for ALL in childhood.
PubMed: 35223707
DOI: 10.3389/fped.2021.782530