The TAK-003 dengue vaccine was licensed in Europe in December 2022, and the official recommendations from most EU countries are still under formulation. To support policymakers, we performed a meta-analysis to quantify TAK-003’s immunogenicity, efficacy and safety among seronegative and seropositive populations after the administration of one or two vaccine doses. We included trials retrieved from MEDLINE, Scopus and ClinicalTrials.gov. The outcomes were the rates of seroconversion, virologically confirmed dengue fever and serious adverse events after each vaccine dose. Data were combined using random-effect proportion or head-to-head meta-analyses. We retrieved a total of 19 datasets, including >20,000 participants. TAK-003 showed an excellent safety profile, and the immunogenicity after two doses against the four DENV serotypes was ≥90% among both adults and children/adolescents who were either seronegative or seropositive at baseline. A single dose was able to elicit a high immunogenic response among adults (≥70%) and children/adolescents (≥90%). The primary two-dose immunization course halved the risk of all types of virologically confirmed dengue fever among seropositive children/adolescents, but seronegative minors were only protected against the diseases caused by DENV-1 and DENV-2. Overall, the results support the use of TAK-003 for the prevention of dengue fever in the pediatric population of endemic countries. Uncertainties remain on the use of a single vaccine dose in non-endemic countries.

Several vaccines against chikungunya fever have been developed and tested, and one has been recently licensed. We performed a meta-analysis to estimate the immunogenicity and safety of all chikungunya vaccines that have been progressed to clinical trial evaluation (VLA1553; mRNA-1388/VAL-181388; PXVX0317/VRC-CHKVLP059-00-VP; ChAdOx1 Chik; MV-CHIK). We included trials retrieved from MedLine, Scopus, and ClinicalTrials.gov. The outcomes were the rates of seroconversion/seroresponse and serious adverse events (SAEs) after the primary immunization course. We retrieved a total of 14 datasets, including >4000 participants. All candidate chikungunya vaccines were able to elicit an immunogenic response in ≥96% of vaccinated subjects, regardless of the vaccination schedule and platform used, and the seroconversion/seroresponse rates remained high 6 to 12 months after vaccination for most vaccines. Four of the five candidate vaccines showed a good overall safety profile (no data were available for ChAdOx1 Chik), with no significant increase in the risk of SAEs among the vaccinated, and a low absolute risk of product-related SAEs. Overall, the present findings support the potential use of the candidate vaccines for the prevention of chikungunya and the current indication for use in adult travelers to endemic regions of the licensed VLA 1553 vaccine. In order to extend chikungunya vaccination to a wider audience, further studies are needed on individuals from endemic countries and frail populations.

Background: Despite the fact that thiocolchicoside has been widely used in the treatment of musculoskeletal pain, its efficacy has never been systematically evaluated. We carried out a systematic review and meta-analysis of randomized clinical trials (RCTs) to appraise the existing evidence on the efficacy of thiocolchicoside for musculoskeletal pain management. Methods: The literature search was performed on multiple databases, extracting reports of RCTs evaluating the efficacy of thiocolchicoside compared to placebo or no exposure. The reduction in pain intensity was evaluated through between-groups mean differences (MDs) in Visual Analogue Scale (VAS) scores after the intervention. The pooled effect estimates were compared to a minimally important difference (MID) of 1 point on a scale from 0 to 10. Results: We retrieved eight RCTs, including a total of 1397 patients. All the included studies were determined as being at high risk of bias. Seven trials evaluated patients with acute low back pain. After 2–3 days of treatment, the pooled MD in VAS score was −0.49 (95%CI = −0.90; −0.09) compared to controls. After 5–7 days of treatment, the summary MD was −0.82 (95%CI = −1.46; −0.18). Conclusions: Although thiocolchicoside was found to significantly reduce patient-reported low back pain, the clinical impact was very small, as the pooled effect estimates were below the MID, and the overall certainty of evidence was very low. In light of the safety concerns raised by the European Medicine Agency, an in-depth analysis on the risk–benefit balance of thiocolchicoside is required.

Background: During the COVID-19 pandemic, paracetamol was widely recommended in different clinical settings, and sometimes advised over non-steroidal anti-inflammatory drugs (NSAIDs). These recommendations sparked a strong debate, with reports suggesting either potential benefits or harms for the individuals infected with SARS-CoV-2. As no systematic review is available, we performed a meta-analysis to estimate the impact of paracetamol on COVID-19 clinical outcomes compared to a placebo, no use, or NSAIDs. Methods: We searched PubMed, Scopus, Web of Science, and ClinicalTrials.gov for randomized trials or observational studies evaluating any COVID-19 clinical outcome. Data were combined using a generic inverse-variance approach. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach was used to determine the certainty of evidence for each outcome. Results: One randomized trial and five observational studies, enrolling over 34,000 patients, were included. Overall, as compared to the patients using NSAIDs or receiving no treatment, the individuals who received paracetamol showed no significant differences in the risk of death (summary relative risks 0.93 and 0.91, respectively: both p > 0.05), need to transfer to the intensive care unit, need for respiratory support, or cardiovascular or renal complications. All studies showed a high risk of bias, with a low overall quality of evidence. Conclusions: This meta-analysis found no evidence of harmful or beneficial effects of paracetamol on main COVID-19-related outcomes. Also, the current literature does not provide sufficient data to support a preferential choice between paracetamol and NSAIDs for COVID-19 symptoms management. Further research is needed to confirm the present findings and provide critical insights on the policies to adopt in the case of future pandemics.

Background/Objectives: Hantaviruses infections are responsible for a hemorrhagic fever with renal and cardiopulmonary syndrome with case-fatality rates up to 50%. While inactivated vaccines are already available in China and South Korea, several additional candidate vaccines are under development. This systematic review summarizes the current clinical evidence on immunogenicity and short-term safety of vaccines targeting different hantavirus strains. Methods: Following PRISMA 2020 guidelines, a systematic literature search was carried out to identify randomized and nonrandomized trials of any phase. Data were synthesized narratively within strata defined by vaccine platform, target virus, assay, immunogenicity and safety. Results: Ten trials on 961 adults were included: four single-arm trials on the inactivated vaccine and six early-phase DNA-vaccine trials. One month after last dose, the inactivated vaccine achieved neutralizing seropositivity by PRNT₅₀ in 45.1% of the tested subjects after two priming doses and 55.7% after three, while the corresponding binding-antibody values measured by IFA were 87.3% and 95.7%. Among DNA vaccines, homologous responses reached 100% against HTNV and 83.3% against PUUV with monovalent constructs, whereas dual responses to the bivalent construct were registered in 33.3% and 77.8% of the subjects, when measured through PRNT₅₀ and PsVNA₅₀, respectively. One serious adverse event occurred, most likely unrelated to vaccination. Conclusions: No serious safety signal was identified, although safety remains insufficiently characterized. Measured immunogenicity depends as much on the assay as on the vaccine, and, in the absence of a validated correlate of protection, it cannot be read as a clinical benefit. Future research should prioritize validated correlates of protection and innovative trial designs adapted to low-incidence diseases.

Background/Objectives: There is wide variability in the available estimates on the burden of Long-COVID (LC), both among adults and children. Preliminary evidence suggests that this inconsistency may be due, at least in part, to the adoption of uneven diagnostic criteria, proposed by several international entities during the course of the pandemic, but no comprehensive evaluation has been performed so far to quantify the extent of variation among children. This systematic review and meta-analysis aims to update the available epidemiological estimates of LC among pediatric subjects, and to systematically appraise the degree of variability that can be attributed to the diagnostic criteria adopted. Methods: A systematic literature search identified cohort studies providing data on LC among children and adolescents with a previous SARS-CoV-2 infection. We computed (a) proportion and (b) head-to-head meta-analyses (a) to quantify the pooled rates of LC and LC-related symptoms, and (b) to assess the likelihood of developing LC based upon selected demographic and/or clinical characteristics, respectively. Results: In total, 52 cohort studies and 960,089 subjects were included. The pooled rate of LC was 18.1% (95% CI: 13.1–23.6), ranging from 16.2% to 21.6%, according to NIH or WHO diagnostic criteria, respectively. Fatigue, respiratory and neurological symptoms were most commonly reported by LC patients. Stratified analyses showed that females, adolescents (vs. children), subjects with comorbidities, and those with a previous severe COVID-19 (as compared to asymptomatic primary infections) were more likely to develop LC (all p < 0.05). In contrast, the likelihood of LC onset did not significantly vary between individuals with ≥1 anti-SARS-CoV-2 vaccine dose, versus the unvaccinated (pooled OR: 0.92; 95% CI: 0.61–1.41). Conclusions: Although the available estimates may largely vary depending on the adopted definition, LC affects a meaningful proportion of the pediatric population; as such, common clinical criteria and diagnostic approaches are urgently needed. Moreover, given the relevant methodological heterogeneity and the generally poor-to-fair quality of a large part of the available literature, high-quality studies adopting standardized methodologies are warranted to identify at-risk populations and guide the implementation of targeted follow-up strategies.