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BMJ Open Dec 2023The rapid spread of the SARS-CoV-2 Omicron variant has raised concerns regarding waning vaccine-induced immunity and durability. We evaluated protection of the... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
The rapid spread of the SARS-CoV-2 Omicron variant has raised concerns regarding waning vaccine-induced immunity and durability. We evaluated protection of the third-dose and fourth-dose mRNA vaccines against SARS-CoV-2 Omicron subvariant and its sublineages.
DESIGN
Systematic review and meta-analysis.
DATA SOURCES
Electronic databases and other resources (PubMed, Embase, CENTRAL, MEDLINE, CINAHL PLUS, APA PsycINFO, Web of Science, Scopus, ScienceDirect, MedRxiv and bioRxiv) were searched until December 2022.
STUDY ELIGIBILITY CRITERIA
We included studies that assessed the effectiveness of mRNA vaccine booster doses against SARS-CoV-2 infection and severe COVID-19 outcomes caused by the subvariant.
DATA EXTRACTION AND SYNTHESIS
Estimates of vaccine effectiveness (VE) at different time points after the third-dose and fourth-dose vaccination were extracted. Random-effects meta-analysis was used to compare VE of the third dose versus the primary series, no vaccination and the fourth dose at different time points. The certainty of the evidence was assessed by Grading of Recommendations, Assessments, Development and Evaluation approach.
RESULTS
This review included 50 studies. The third-dose VE, compared with the primary series, against SARS-CoV-2 infection was 48.86% (95% CI 44.90% to 52.82%, low certainty) at ≥14 days, and gradually decreased to 38.01% (95% CI 13.90% to 62.13%, very low certainty) at ≥90 days after the third-dose vaccination. The fourth-dose VE peaked at 14-30 days (56.70% (95% CI 50.36% to 63.04%), moderate certainty), then quickly declined at 61-90 days (22% (95% CI 6.40% to 37.60%), low certainty). Compared with no vaccination, the third-dose VE was 75.84% (95% CI 40.56% to 111.12%, low certainty) against BA.1 infection, and 70.41% (95% CI 49.94% to 90.88%, low certainty) against BA.2 infection at ≥7 days after the third-dose vaccination. The third-dose VE against hospitalisation remained stable over time and maintained 79.30% (95% CI 58.65% to 99.94%, moderate certainty) at 91-120 days. The fourth-dose VE up to 60 days was 67.54% (95% CI 59.76% to 75.33%, moderate certainty) for hospitalisation and 77.88% (95% CI 72.55% to 83.21%, moderate certainty) for death.
CONCLUSION
The boosters provided substantial protection against severe COVID-19 outcomes for at least 6 months, although the duration of protection remains uncertain, suggesting the need for a booster dose within 6 months of the third-dose or fourth-dose vaccination. However, the certainty of evidence in our VE estimates varied from very low to moderate, indicating significant heterogeneity among studies that should be considered when interpreting the findings for public health policies.
PROSPERO REGISTRATION NUMBER
CRD42023376698.
Topics: Humans; SARS-CoV-2; mRNA Vaccines; COVID-19; COVID-19 Vaccines
PubMed: 38128943
DOI: 10.1136/bmjopen-2023-076892 -
Medicine Dec 2023Immune system deregulation, including AAV, is a key event that may potentially evolve into ESRD. Abnormal activation of the cAP is also a cardinal feature of TMA,...
End stage renal disease in patient with microscopic polyangiitis and atypical hemolytic-uremic syndrome arose 3 weeks after the third dose of anti-SARS-CoV2 vaccine mRNA-1273: A case report with literature revision.
RATIONALE
Immune system deregulation, including AAV, is a key event that may potentially evolve into ESRD. Abnormal activation of the cAP is also a cardinal feature of TMA, particularly aHUS. The kidney is the most frequently involved organ, and renal-limited forms of TMA are often encountered in clinical practice. Isolated case reports described the occurrence of renal TMA in AAV patients. Some cases of both de novo and relapses of AAV and/or TMAs after anti-SARS-CoV2 vaccination have been reported. We reported, for the 1st time, a case of patients with new-onset MPA and aHUS occurring 3 weeks after the third dose of mRNA-1273 vaccine anti-SARS-CoV2.
PATIENT CONCERNS
We present a 67-year-old man, affected by arterial hypertension, reported, after mRNA-1273 vaccine anti-SARS-CoV2, anuria, fatigue, anorexia and nausea. Laboratory data revealed acute renal failure.
DIAGNOSIS
Positivity of MPO-ANCA was observed. 7 days after admission, we observed a worsening of anemia and thrombocytopenia with haptoglobin reduction, LDH increase and presence of schistocytes. Plasma levels of ADAMTS-13 were normal. A renal biopsy was performed, and findings were consistent with microscopic polyangiitis, with features of micro-thrombotic glomerulopathy. Genetic tests revealed absence of hybrid genes associated with the increased risk of aHUS.
INTERVENTIONS AND OUTCOMES
We started renal replacement treatment, including hemodialysis, and pulsed methylprednisolone, with no improvement of laboratory parameters. Then, plasma exchange was performed leading to partial haematological response. Only with Eculizumab, a human C5 inhibitor, we observed a normalization of haptoglobin levels and platelets' count. However, three months after discharge, the patient still required hemodialysis.
LESSONS
To our knowledge we observed the first case aHUS, without genetic predisposition, associated with MPA occurring after the third dose of anti-SARS-CoV2 vaccine. This case report highlights the potential link between anti-SARS-CoV2 vaccine as a trigger of MPA and aHUS. This systematic review offers additional perspectives. It is plausible to hypothesize that the vaccine was the trigger for the development of these 2 diseases.Solid evidence on the mechanisms of interaction between vaccine and immune system, the role of genetic predisposition, and other variables, will shed additional light on the controversial link between anti-SARS-CoV2 vaccine and autoimmunity.
Topics: Male; Humans; Aged; Atypical Hemolytic Uremic Syndrome; 2019-nCoV Vaccine mRNA-1273; Microscopic Polyangiitis; Haptoglobins; COVID-19; Kidney Failure, Chronic; Genetic Predisposition to Disease
PubMed: 38115241
DOI: 10.1097/MD.0000000000036560 -
The Lancet. Global Health Jan 2024Tuberculosis is a leading cause of infectious disease mortality worldwide, but diagnosis of pulmonary tuberculosis remains challenging. Oral swabs are a promising...
BACKGROUND
Tuberculosis is a leading cause of infectious disease mortality worldwide, but diagnosis of pulmonary tuberculosis remains challenging. Oral swabs are a promising non-sputum alternative sample type for the diagnosis of pulmonary tuberculosis. We aimed to assess the diagnostic accuracy of oral swabs to detect pulmonary tuberculosis in adults and children and suggest research implications.
METHODS
In this systematic review, we searched published and preprint studies from Jan 1, 2000, to July 5, 2022, from eight databases (MEDLINE, Embase, Scopus, Science Citation Index, medRxiv, bioRxiv, Global Index Medicus, and Google Scholar). We included diagnostic accuracy studies including cross-sectional, cohort, and case-control studies in adults and children from which we could extract or derive sensitivity and specificity of oral swabs as a sample type for the diagnosis of pulmonary tuberculosis against a sputum microbiological (nucleic acid amplification test [NAAT] on sputum or culture) or composite reference standard.
FINDINGS
Of 550 reports identified by the search, we included 16 eligible reports (including 20 studies and 3083 participants) that reported diagnostic accuracy estimates on oral swabs for pulmonary tuberculosis. Sensitivity on oral swabs ranged from 36% (95% CI 26-48) to 91% (80-98) in adults and 5% (1-14) to 42% (23-63) in children. Across all studies, specificity ranged from 66% (95% CI 52-78) to 100% (97-100), with most studies reporting specificity of more than 90%. Meta-analysis was not performed because of sampling and testing heterogeneity.
INTERPRETATION
Sensitivity varies in both adults and children when diverse methods are used. Variability in sampling location, swab type, and type of NAAT used in accuracy studies limits comparison. Although data are suggestive that high accuracy is achievable using oral swabs with molecular testing, more research is needed to define optimal methods for using oral swabs as a specimen for tuberculosis detection. The current data suggest that tongue swabs and swab types that collect increased biomass might have increased sensitivity. We would recommend that future studies use these established methods to continue to refine sample processing to maximise sensitivity.
FUNDING
Bill and Melinda Gates foundation (INV-045721) and FIND (Netherlands Enterprise Agency on behalf of the Minister for Foreign Trade and Development Cooperation [NL-GRNT05] and KfW Development Bank, German Federal Ministry of Education and Research [KFW-TBBU01/02]).
Topics: Adult; Child; Humans; Mycobacterium tuberculosis; Cross-Sectional Studies; Pathology, Molecular; Tuberculosis, Pulmonary; Tuberculosis; Sensitivity and Specificity; Molecular Diagnostic Techniques
PubMed: 38097297
DOI: 10.1016/S2214-109X(23)00469-2 -
Qatar Medical Journal 2023As part of the COVID-19 control strategy, a growing number of vaccine portfolios evolved and got fast-tracked through regulatory agencies, with a limited examination of...
BACKGROUND AND AIMS
As part of the COVID-19 control strategy, a growing number of vaccine portfolios evolved and got fast-tracked through regulatory agencies, with a limited examination of their efficacy and safety in vulnerable populations, such as patients with chronic conditions and immunocompromised states. Patients with chronic liver disease (CLD), and cohorts post liver transplant (LT) in particular, were underrepresented in the determinant trials of vaccine development, hence the paucity of data on their efficacy and safety in published literature. This systematic review aims to examine the available evidence and ascertain the effectiveness and safety of Covid-19 vaccination in patients with CLD and those with LT.
METHODS
A systematic review of PubMed (Medline), Google Scholar, Cochrane Library, and ScienceDirect from inception until 1 March 2022 was conducted. We included observational studies and assessed vaccine efficacy regarding seroconversion or immunological rate, whereas serious or significant adverse effects have been considered safety outcomes when reported.
RESULTS
Studies comprised 45275 patients, performed in 11 different countries. Seroconversion or immunological rate after Covid-19 vaccination was mostly the primary endpoint, whereas other endpoints like covid-19 related adverse effects were also reported. Twenty-four of the final analyzed studies are prospective cohort studies, while four are retrospective cohort studies. Twenty-one studies included patients who underwent LT and received the Covid vaccine; nine included patients who had CLD due to various etiologies. The median age range of all included patients varied from 43-69 years. All patients with LT who received at least two doses of Covid vaccine had a seroconversion rate of around 60%. Patients with CLD had a seroconversion rate of about 92% post two doses of Covid vaccination. The average seroconversion rate in post-transplant recipients was around 45% after two doses of the significant Covid vaccines: Pfizer, AstraZeneca, Moderna, and Jansen. Only two studies have reported a higher seroconversion rate of 75% and 73% after the third dose of Covid vaccine. No significant adverse effects were reported in all studies; the most commonly reported negative effect was local injection site pain.
CONCLUSION
The present systematic review, comprising real-world observational data studies, concludes that Covid-19 vaccination was associated with 92% and 60% seroconversion rates in patients with CLD and LT, respectively. No significant side effects were reported in all studies. This finding helps to resolve the uncertainty associated with Covid-19 vaccination in this cohort of patients.
PubMed: 38089670
DOI: 10.5339/qmj.2023.21 -
Vaccine Jan 2024To systematically review immunogenicity and safety data of maternal group B streptococcal (GBS) vaccines in published clinical trials until July 2023. (Review)
Review
PURPOSE
To systematically review immunogenicity and safety data of maternal group B streptococcal (GBS) vaccines in published clinical trials until July 2023.
METHODS
EMBASE, MEDLINE, Cochrane Library and clinicaltrial.gov. databases were searched for clinical studies that reported immunogenicity and/or safety of GBS vaccine in non-pregnant adults, pregnant women and infants between 1st of January 1996 to 31st of July 2023. Pairs of reviewers independently selected, data extracted, and assessed the risk of bias of the studies. Discrepancies were resolved by consensus. (PROSPERO CRD42020185213).
RESULTS
We retrieved 1472 records from the literature search; 20 studies and 6 sub-studies were included, involving 4440 non-pregnant participants and 1325 pregnant women with their newborns. There was a significantly higher IgG Geometric Mean Concentration (GMC) and IgG placental transfer ratios in vaccinated compared to placebo groups, with peak response 4-8 weeks after vaccination. Placental transfer ratio varied from 0.4 to 1.4 across five studies. The different clinical trials used different assays that limited direct comparison. There were no significant differences in the risk of serious adverse events (adjusted OR 0.73; 95 % CI 0.49-1.07), serious adverse events leading to withdrawal (adjusted OR 0.44; 95 % CI 0.13-1.51), and systemic illness or fever (adjusted OR 1.05; 95 % CI 0.26-4.19) between the vaccine and placebo groups.
CONCLUSIONS
The published clinical trials show significant IgG GMC response in subjects receiving the conjugated capsular polysaccharide and surface subunit protein vaccines compared to placebo. In current clinical trials of experimental GBS maternal vaccines, there have been no observed serious adverse events of special interest directly linked to vaccination.
Topics: Infant; Adult; Humans; Infant, Newborn; Female; Pregnancy; Placenta; Vaccines; Vaccination; Streptococcus agalactiae; Immunoglobulin G; Immunogenicity, Vaccine
PubMed: 38072754
DOI: 10.1016/j.vaccine.2023.11.056 -
The Lancet. Microbe Feb 2024The high strain diversity of Streptococcus pyogenes serves as a major obstacle to vaccine development against this leading global pathogen. We did a systematic review of... (Review)
Review
The high strain diversity of Streptococcus pyogenes serves as a major obstacle to vaccine development against this leading global pathogen. We did a systematic review of studies in PubMed, MEDLINE, and Embase that reported the global distribution of S pyogenes emm-types and emm-clusters from Jan 1, 1990, to Feb 23, 2023. 212 datasets were included from 55 countries, encompassing 74 468 bacterial isolates belonging to 211 emm-types. Globally, an inverse correlation was observed between strain diversity and the UNDP Human Development Index (HDI; r=-0·72; p<0·0001), which remained consistent upon subanalysis by global region and site of infection. Greater strain diversity was associated with a lower HDI, suggesting the role of social determinants in diseases caused by S pyogenes. We used a population-weighted analysis to adjust for the disproportionate number of epidemiological studies from high-income countries and identified 15 key representative isolates as vaccine targets. Strong strain type associations were observed between the site of infection (invasive, skin, and throat) and several streptococcal lineages. In conclusion, the development of a truly global vaccine to reduce the immense burden of diseases caused by S pyogenes should consider the multidimensional diversity of the pathogen, including its social and environmental context, and not merely its geographical distribution.
Topics: Humans; Streptococcus pyogenes; Streptococcal Infections; Antigens, Bacterial; Bacterial Outer Membrane Proteins; Vaccines
PubMed: 38070538
DOI: 10.1016/S2666-5247(23)00318-X -
Journal of Clinical Medicine Nov 2023Antiviral treatment reduces the severity and mortality of SARS-CoV-2 infection; however, its effectiveness against long COVID-19 is unclear. This study aimed to evaluate... (Review)
Review
Antiviral treatment reduces the severity and mortality of SARS-CoV-2 infection; however, its effectiveness against long COVID-19 is unclear. This study aimed to evaluate the effectiveness of antiviral drugs in preventing long COVID and related hospitalizations/deaths. Scientific and medical databases were searched from 1 January 2020 to 30 June 2023. We included observational cohort studies comparing individuals receiving early antiviral therapy for COVID-19 and those receiving supportive treatment. A fixed-effects model was used to merge the effects reported in two or more studies. The risk of post-acute sequelae of COVID-19 (PASC) was combined as an odds ratio (OR). Six studies were selected, including a total of 3,352,235 participants. The occurrence of PASC was 27.5% lower in patients who received antiviral drugs during the early stages of SARS-CoV-2 infection (OR = 0.725; 95% confidence interval [CI] = 0.409-0.747) than in the supportive treatment group. Moreover, the risk of PASC-associated hospitalization and mortality was 29.7% lower in patients receiving early antiviral therapy than in the supportive treatment group (OR = 0.721; 95% CI = 0.697-0.794). Early antiviral therapy was associated with a reduced risk of PASC and related hospitalization or death. Thus, early antiviral therapy is recommended for at-risk individuals.
PubMed: 38068427
DOI: 10.3390/jcm12237375 -
Anais Da Academia Brasileira de Ciencias 2023Sexually Transmitted Infections (STIs) are a public health burden rising in developed and developing nations. The World Health Organization estimates nearly 374 million...
Sexually Transmitted Infections (STIs) are a public health burden rising in developed and developing nations. The World Health Organization estimates nearly 374 million new cases of curable STIs yearly. Global efforts to control their spread have been insufficient in fulfilling their objective. As there is no vaccine for many of these infections, these efforts are focused on education and condom distribution. The development of vaccines for STIs is vital for successfully halting their spread. The field of immunoinformatics is a powerful new tool for vaccine development, allowing for the identification of vaccine candidates within a bacterium's genome and allowing for the design of new genome-based vaccine peptides. The goal of this review was to evaluate the usage of immunoinformatics in research focused on non-viral STIs, identifying fields where research efforts are concentrated. Here we describe gaps in applying these techniques, as in the case of Treponema pallidum and Trichomonas vaginalis.
Topics: Humans; Vaccinology; Sexually Transmitted Diseases; Trichomonas vaginalis; Vaccines
PubMed: 38055447
DOI: 10.1590/0001-3765202320230617 -
Open Forum Infectious Diseases Nov 2023Identification of risk factors for severe respiratory syncytial virus (RSV) disease in adults could facilitate their appropriate vaccine recommendations. We conducted a...
UNLABELLED
Identification of risk factors for severe respiratory syncytial virus (RSV) disease in adults could facilitate their appropriate vaccine recommendations. We conducted a systematic literature review (last 10 years in PubMed/Embase) to identify quantitative estimates of risk factors for severe RSV infection outcomes in high-income countries. Severe outcomes from RSV infection included hospitalization, excess mortality, lower respiratory tract infection, or a composite measure: severe RSV, which included these outcomes and others, such as mechanical ventilation and extended hospital stay. Among 1494 articles screened, 26 met eligibility criteria. We found strong evidence that the following increased the risk of severe outcomes: age, preexisting comorbid conditions (eg, cardiac, pulmonary, and immunocompromising diseases, as well as diabetes and kidney disease), and living conditions (socioeconomic status and nursing home residence). The frequency of severe outcomes among younger adults with comorbidities was generally similar to that experienced by older adults, suggesting that immunosenescence and chronic conditions are both contributing factors for elevated risk.
TRIAL REGISTRATION
PROSPERO (CRD42022315239).
PubMed: 38033988
DOI: 10.1093/ofid/ofad513 -
PloS One 2023Streptoccocal A (Strep A, GAS) infections in Australia are responsible for significant morbidity and mortality through both invasive (iGAS) and post-streptococcal...
BACKGROUND
Streptoccocal A (Strep A, GAS) infections in Australia are responsible for significant morbidity and mortality through both invasive (iGAS) and post-streptococcal (postGAS) diseases as well as preceding superficial (sGAS) skin and throat infection. The burden of iGAS and postGAS are addressed in some jurisdictions by mandatory notification systems; in contrast, the burden of preceding sGAS has no reporting structure, and is less well defined. This review provides valuable, contemporaneous evidence on the epidemiology of sGAS presentations in Australia, informing preventative health projects such as a Streptococcal A vaccine and standardisation of primary care notification.
METHODS AND FINDINGS
MEDLINE, Scopus, EMBASE, Web of Science, Global Health, Cochrane, CINAHL databases and the grey literature were searched for studies from an Australian setting relating to the epidemiology of sGAS infections between 1970 and 2020 inclusive. Extracted data were pooled for relevant population and subgroup analysis. From 5157 titles in the databases combined with 186 grey literature reports and following removal of duplicates, 4889 articles underwent preliminary title screening. The abstract of 519 articles were reviewed with 162 articles identified for full text review, and 38 articles identified for inclusion. The majority of data was collected for impetigo in Aboriginal and Torres Strait Islander populations, remote communities, and in the Northern Territory, Australia. A paucity of data was noted for Aboriginal and Torres Strait Islander people living in urban centres or with pharyngitis. Prevalence estimates have not significantly changed over time. Community estimates of impetigo point prevalence ranged from 5.5-66.1%, with a pooled prevalence of 27.9% [95% CI: 20.0-36.5%]. All studies excepting one included >80% Aboriginal and Torres Strait Islander people and all excepting two were in remote or very remote settings. Observed prevalence of impetigo as diagnosed in healthcare encounters was lower, with a pooled estimate of 10.6% [95% CI: 3.1-21.8%], and a range of 0.1-50.0%. Community prevalence estimates for pharyngitis ranged from 0.2-39.4%, with a pooled estimate of 12.5% [95% CI: 3.5-25.9%], higher than the prevalence of pharyngitis in healthcare encounters; ranging from 1.0-5.0%, and a pooled estimate of 2.0% [95% CI: 1.3-2.8%]. The review was limited by heterogeneity in study design and lack of comparator studies for some populations.
CONCLUSIONS
Superficial Streptococcal A infections contribute to an inequitable burden of disease in Australia and persists despite public health interventions. The burden in community studies is generally higher than in health-services settings, suggesting under-recognition, possible normalisation and missed opportunities for treatment to prevent postGAS. The available, reported epidemiology is heterogeneous. Standardised nation-wide notification for sGAS disease surveillance must be considered in combination with the development of a Communicable Diseases Network of Australia (CDNA) Series of National Guideline (SoNG), to accurately define and address disease burden across populations in Australia.
TRIAL REGISTRATION
This review is registered with PROSPERO. Registration number: CRD42019140440.
Topics: Humans; Australian Aboriginal and Torres Strait Islander Peoples; Health Services, Indigenous; Impetigo; Northern Territory; Pharyngitis; Streptococcus
PubMed: 38033025
DOI: 10.1371/journal.pone.0288016