Safety of COVID-19 vaccines during pregnancy: A systematic review and meta-analysis.

BACKGROUND: Assessment of COVID-19 vaccines safety during pregnancy is urgently needed. METHODS: We conducted a systematic review and meta-analysis to evaluate the safety of COVID-19 vaccines, including their components and technological platforms used in other vaccines during pregnancy and animal studies to complement direct evidence. We searched literature databases from its inception to September 2021 without language restriction, COVID-19 vaccine websites, and reference lists of other systematic reviews and the included studies. Pairs of reviewers independently selected, data extracted, and assessed the risk of bias of the studies. Discrepancies were resolved by consensus. (PROSPERO CRD42021234185). RESULTS: We retrieved 8,837 records from the literature search; 71 studies were included, involving 17,719,495 pregnant persons and 389 pregnant animals. Most studies (94%) were conducted in high-income countries, were cohort studies (51%), and 15% were classified as high risk of bias. We identified nine COVID-19 vaccine studies, seven involving 309,164 pregnant persons, mostly exposed to mRNA vaccines. Among non-COVID-19 vaccines, the most frequent exposures were AS03 and aluminum-based adjuvants. A meta-analysis of studies that adjusted for potential confounders showed no association with adverse outcomes, regardless of the vaccine or the trimester of vaccination. Neither the reported rates of adverse pregnancy outcomes nor reactogenicity exceeded expected background rates, which was the case for ASO3- or aluminum-adjuvanted non-COVID-19 vaccines in the proportion meta-analyses of uncontrolled studies/arms. The only exception was postpartum hemorrhage after COVID-19 vaccination (10.40%; 95% CI: 6.49-15.10%), reported by two studies; however, the comparison with non-exposed pregnant persons, available for one study, found non-statistically significant differences (adjusted OR 1.09; 95% CI 0.56-2.12). Animal studies showed consistent results with studies in pregnant persons. CONCLUSION: We found no safety concerns for currently administered COVID-19 vaccines during pregnancy. Additional experimental and real-world evidence could enhance vaccination coverage. Robust safety data for non-mRNA-based COVID-19 vaccines are still needed.

Safety, immunogenicity, and effectiveness of COVID-19 vaccines for pregnant persons: A protocol for systematic review and meta analysis.

INTRODUCTION: Numerous vaccines have been evaluated and approved for coronavirus disease 2019 (COVID-19). Since pregnant persons have been excluded from most clinical trials of COVID-19 vaccines, sufficient data regarding the safety of these vaccines for the pregnant person and their fetus have rarely been available at the time of product licensure. However, as COVID-19 vaccines have been deployed, data on the safety, reactogenicity, immunogenicity, and efficacy of COVID-19 vaccines for pregnant persons and neonates are becoming increasingly available. A living systematic review and meta-analysis of the safety and effectiveness of COVID-19 vaccines for pregnant persons and newborns could provide the information necessary to help guide vaccine policy decisions. METHODS AND ANALYSIS: We aim to conduct a living systematic review and meta-analysis based on biweekly searches of medical databases (e.g., MEDLINE, EMBASE, CENTRAL) and clinical trial registries to systematically identify relevant studies of COVID-19 vaccines for pregnant persons. Pairs of reviewers will independently select, extract data, and conduct risk of bias assessments. We will include randomized clinical trials, quasi-experimental studies, cohort, case-control, cross-sectional studies, and case reports. Primary outcomes will be the safety, efficacy, and effectiveness of COVID-19 vaccines in pregnant persons, including neonatal outcomes. Secondary outcomes will be immunogenicity and reactogenicity. We will conduct paired meta-analyses, including prespecified subgroup and sensitivity analyses. We will use the grading of recommendations assessment, development, and evaluation approach to evaluate the certainty of evidence.

Bacterial co-infection and antibiotic stewardship in patients with COVID-19: a systematic review and meta-analysis.

INTRODUCTION: Understanding the proportion of patients with COVID-19 who have respiratory bacterial co-infections and the responsible pathogens is important for managing COVID-19 effectively while ensuring responsible antibiotic use. OBJECTIVE: To estimate the frequency of bacterial co-infection in COVID-19 hospitalized patients and of antibiotic prescribing during the early pandemic period and to appraise the use of antibiotic stewardship criteria. METHODS: Systematic review and meta-analysis was performed using major databases up to May 5, 2021. We included studies that reported proportion/prevalence of bacterial co-infection in hospitalized COVID-19 patients and use of antibiotics. Where available, data on duration and type of antibiotics, adverse events, and any information about antibiotic stewardship policies were also collected. RESULTS: We retrieved 6,798 studies and included 85 studies with data from more than 30,000 patients. The overall prevalence of bacterial co-infection was 11% (95% CI 8% to 16%; 70 studies). When only confirmed bacterial co-infections were included the prevalence was 4% (95% CI 3% to 6%; 20 studies). Overall antibiotic use was 60% (95% CI 52% to 68%; 52 studies). Empirical antibiotic use rate was 62% (95% CI 55% to 69%; 11 studies). Few studies described criteria for stopping antibiotics. CONCLUSION: There is currently insufficient evidence to support widespread empirical use of antibiotics in most hospitalised patients with COVID-19, as the overall proportion of bacterial co-infection is low. Furthermore, as the use of antibiotics during the study period appears to have been largely empirical, clinical guidelines to promote and support more targeted administration of antibiotics in patients admitted to hospital with COVID-19 are required.

Prevalence and Factors Associated with Gaming Disorder in Latin America and the Caribbean: A Systematic Review.

We aimed to determine the prevalence and factors associated with gaming disorder (GD) in the population of Latin America and the Caribbean (LAC). A systematic review was performed (PROSPERO protocol registration: CRD42021230565). We included studies that identified participants with GD and/or factors associated with this condition, reported the prevalence of GD, or contained data that assisted in its estimation, were published after 2013 (the year of inclusion of GD in the Fifth Edition of the Diagnostic and Statistical Manual of Mental Disorders) and were carried out in a population residing in an LAC country. Evaluation of the quality of the studies was carried out using the Joanna Briggs Institute Critical appraisal checklist tool. A qualitative synthesis of the data was performed. Of the total of 1567 records identified, 25 passed the full-text review phase, and 6 met the selection criteria. These studies were published between 2018 and 2021 and had a cross-sectional design (three in Brazil, one in Ecuador, Mexico, and the other was multi-country, including a LAC country [Peru]). The prevalence of GD ranged from 1.1% to 38.2%. The three studies in Brazil had the highest figures of GD prevalence (20.4-38.2%). Four studies evaluated factors associated with GD. Characteristics regarding the game (type), pattern of use (hours played), as well as gender (higher in men), tobacco and alcohol consumption, poor interpersonal relationships, and the presence of mental disorders were found to be associated with GD in LAC. Evidence on the prevalence and factors associated with GD in LAC is limited. Studies on GD in LAC evaluate different population subgroups, describing a wide prevalence of this condition (present in up to 38 out of 100 evaluated). Characteristics such as the type and hours of use of the games, sociodemographic data, lifestyles, interpersonal relationships, and the presence of mental disorders increase the probability of presenting GD.

Remote non‐pharmacologic interventions for sleep problems in healthcare workers during the COVID‐19 pandemic

Objectives This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the effects of remote non‐pharmacologic interventions, compared with other specific intervention, non‐intervention or alternative intervention for sleep problems in in healthcare workers during the coronavirus disease 2019 outbreak.

Mouthrinses and SARS-CoV-2 viral load in saliva: a living systematic review.

Objective To conduct a living systematic review of the clinical evidence about the effect of different mouthrinses on the viral load of SARS-CoV-2 in the saliva of infected patients.Methods This study was reported using the PRISMA guidelines. An electronic search was conducted in seven databases and preprint repositories. We included human clinical trials that evaluated the effect of mouthrinses with antiseptic substances on the viral load of SARS-CoV-2 in the saliva of children or adults, who tested positive for SARS-CoV-2 by reverse transcriptase-polymerase chain reaction (RT-PCR). The risk of bias was assessed using the ROBINS-I tool. PROSPERO registration number: CRD42021240561.Results Five studies were included (n = 66 participants). Study participants underwent oral rinses with hydrogen peroxide (H2O2) at 1%, povidone-iodine (PI) at 0.5% or 1%, chlorhexidine gluconate (CHX) at 0.2% or 0.12%, cetylpyridinium chloride (CPC) at 0.075%, and Linolasept. Only one study included a control group with sterile water. Three of the studies identified a reduction in viral load in saliva after the use of mouthrinses with PI (up to three hours), CHX (up to four hours), or Linolasept mouthwash (up to six hours). One study reported a statistically significant reduction after the use of mouthrinses with CPC or PI vs water (up to six hours) and one study reported a non-significant reduction in viral load after the use of H2O2 rinses.Conclusions According to the present systematic review, the effect of mouthrinses on SARS-CoV-2 viral load in the saliva of COVID-19 patients remains uncertain. Evidence from well-designed randomised clinical trials is required for further and more objective evaluation of this effect.

Seroprevalence and lethality by SARS-CoV-2 in indigenous populations of Latin America and the Caribbean: a systematic review.

BACKGROUND: Latin America and the Caribbean (LAC) has presented some of the highest numbers of cases and deaths due to COVID-19 in the world. Even though indigenous communities represent 8% of the total population in this region, the impact of COVID-19 on this historically vulnerable population has only been briefly explored. Thus, this study aimed to estimate the seroprevalence and lethality attributable to SARS-CoV-2 in the indigenous population of LAC. METHODS: A systematic review was conducted utilizing multiple databases (registry PROSPERO: CRD42020207862). Studies published in English, Spanish or Portuguese were selected between December 1st, 2019, and April 14th, 2021. The evaluation of the quality of the study was carried out utilizing the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. A qualitative synthesis of the data analyzed was conducted following the MOOSE and PRISMA declarations. RESULTS: Fifteen studies met the inclusion criteria. Eleven studies were carried out in a Brazilian population, three in a Mexican population, and one in a Colombian population. Four studies reported data about the seroprevalence of SARS-CoV-2 in indigenous populations of Brazil (range: 4.2-81.65%). Twelve studies reported lethality in indigenous people (eight in Brazil, three in Mexico, and one in Colombia). In Brazil, a lethality of 53.30% was described in a hospital setting and between 1.83% and 4.03% in community studies. In Mexico, the lethality of COVID-19 ranged between 16.5% and 19.9%. Meanwhile, in Colombia, a lethality of 3.41% was reported. Most studies were deemed to be of good quality. CONCLUSIONS: Despite COVID-19 affecting indigenous populations of LAC, there is limited evidence of the seroprevalence and lethality of the infection by SARS-CoV-2 in this population. Future investigations should ensure standardized methods that allow comparability among studies and ensure the precision of the results obtained.

Remote non‐pharmacologic interventions for sleep problems in adults during the COVID‐19 pandemic

Objectives This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the effects of remote non‐pharmacologic interventions, compared with other specific intervention, non‐intervention or alternative intervention for sleep problems in adults during the coronavirus disease 2019 outbreak.

Bacterial coinfection and antibiotic stewardship in patients with COVID-19: a systematic review and meta-analysis

Introduction Understanding the proportion of patients with COVID-19 who have respiratory bacterial coinfections and the responsible pathogens is important to managing COVID-19 effectively while ensuring responsible antibiotic use. Objectives To estimate the frequency of bacterial coinfection in COVID-19 patients and of antibiotic prescribing and to appraise the use of antibiotic stewardship criteria. Methods Systematic review and meta-analysis was performed using major databases up to May 15, 2020. We included studies that reported a) proportion/prevalence of bacterial coinfection in COVID-19 patients and b) use of antibiotics. Where available, data on duration and type of antibiotics, adverse events, and any information about antibiotic stewardship policies were also collected. Results We included 39 studies with a total of 10 815 patients. The overall prevalence of bacterial coinfection was 10.6% (95% CI 6.8%–14.3%). When only confirmed bacterial coinfections were included the prevalence was 4.6% (95% CI 2.9%–7%). Thirty-five bacterial species were identified, the most frequent being Mycoplasma pneumoniae (n = 12 [34%]), Pseudomonas aeruginosa (n = 4 [11.4%]) and Legionella pneumophila (n = 2 [6%]). The overall antibiotic use was 71.3% (95% CI 63.1%–79.5%). Only one study described criteria for stopping them. All included studies had a moderate to high risk of bias. Conclusions There is currently insufficient evidence to support widespread empirical use of antibiotics in most hospitalized patients with COVID-19, as the overall proportion of bacterial coinfection is low. Furthermore, as the use of antibiotics appears currently to be largely empirical, it is necessary to formulate clinical guidelines to promote and support more targeted administration of antibiotics in patients admitted to hospital with COVID-19.

Safety of components and platforms of COVID-19 vaccines considered for use in pregnancy: A rapid review.

BACKGROUND: Rapid assessment of COVID-19 vaccine safety during pregnancy is urgently needed. METHODS: We conducted a rapid systematic review, to evaluate the safety of COVID-19 vaccines selected by the COVID-19 Vaccines Global Access-Maternal Immunization Working Group in August 2020, including their components and their technological platforms used in other vaccines for pregnant persons. We searched literature databases, COVID-19 vaccine pregnancy registries, and explored reference lists from the inception date to February 2021 without language restriction. Pairs of reviewers independently selected studies through COVIDENCE, and performed the data extraction and the risk of bias assessment. Discrepancies were resolved by consensus. Registered on PROSPERO (CRD42021234185). RESULTS: We retrieved 6757 records and 12 COVID-19 pregnancy registries from the search strategy; 38 clinical and non-clinical studies (involving 2,398,855 pregnant persons and 56 pregnant animals) were included. Most studies (89%) were conducted in high-income countries and were cohort studies (57%). Most studies (76%) compared vaccine exposures with no exposure during the three trimesters of pregnancy. The most frequent exposure was to AS03 adjuvant, in the context of A/H1N1 pandemic influenza vaccines, (n = 24) and aluminum-based adjuvants (n = 11). Only one study reported exposure to messenger RNA in lipid nanoparticles COVID-19 vaccines. Except for one preliminary report about A/H1N1 influenza vaccination (adjuvant AS03), corrected by the authors in a more thorough analysis, all studies concluded that there were no safety concerns. CONCLUSION: This rapid review found no evidence of pregnancy-associated safety concerns of COVID-19 vaccines or of their components or platforms when used in other vaccines. However, the need for further data on several vaccine platforms and components is warranted, given their novelty. Our findings support current WHO guidelines recommending that pregnant persons may consider receiving COVID-19 vaccines, particularly if they are at high risk of exposure or have comorbidities that enhance the risk of severe disease.

COVID-19 and pregnancy: An umbrella review of clinical presentation, vertical transmission, and maternal and perinatal outcomes.

BACKGROUND: We conducted an overview of systematic reviews (SRs) summarizing the best evidence regarding the effect of COVID-19 on maternal and child health following Cochrane methods and PRISMA statement for reporting (PROSPERO-CRD42020208783). METHODS: We searched literature databases and COVID-19 research websites from January to October 2020. We selected relevant SRs reporting adequate search strategy, data synthesis, risk of bias assessment, and/or individual description of included studies describing COVID-19 and pregnancy outcomes. Pair of reviewers independently selected studies through COVIDENCE web-software, performed the data extraction, and assessed its quality through the AMSTAR-2 tool. Discrepancies were resolved by consensus. Each SR's results were synthesized and for the most recent, relevant, comprehensive, and with the highest quality, by predefined criteria, we presented GRADE evidence tables. RESULTS: We included 66 SRs of observational studies out of 608 references retrieved and most (61/66) had "critically low" overall quality. We found a relatively low degree of primary study overlap across SRs. The most frequent COVID-19 clinical findings during pregnancy were fever (28-100%), mild respiratory symptoms (20-79%), raised C-reactive protein (28-96%), lymphopenia (34-80%), and pneumonia signs in diagnostic imaging (7-99%). The most frequent maternal outcomes were C-section (23-96%) and preterm delivery (14-64%). Most of their babies were asymptomatic (16-93%) or presented fever (0-50%), low birth weight (5-43%) or preterm delivery (2-69%). The odds ratio (OR) of receiving invasive ventilation for COVID-19 versus non-COVID-19 pregnant women was 1.88 (95% Confidence Interval [CI] 1.36-2.60) and the OR that their babies were admitted to neonatal intensive care unit was 3.13 (95%CI 2.05-4.78). The risk of congenital transmission or via breast milk was estimated to be low, but close contacts may carry risks. CONCLUSION: This comprehensive overview supports that pregnant women with COVID-19 may be at increased risk of adverse pregnancy and birth outcomes and low risk of congenital transmission.

Chlorine dioxide and chlorine derivatives for the prevention or treatment of COVID-19: a systematic review. / Dióxido de cloro y derivados del cloro para prevenir o tratar la COVID-19: revisión sistemática.

OBJECTIVES: To systematically review the effectiveness and safety of chlorine dioxide solution and chlorine derivatives used in the prevention or treatment of COVID-19. METHODS: This review adheres to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) and follows the guidelines provided in the Cochrane Handbook for Systematic Reviews of Interventions. A librarian developed and executed the search strategy; it was further reviewed by two of the authors and complemented by manual search. Randomized clinical trials, quasi-experimental studies, cohort studies, case-control studies, cross-sectional studies, and case reports were included; in vitro or animal studies were excluded. Abstract and full-text screening according to pre-defined eligibility criteria were performed by two reviewers independently using web application Rayyan QCRI. Disagreements on study selection were resolved by a third reviewer. The systematic review protocol was registered in PROSPERO (CRD42020200641). RESULTS: Neither published nor pre-print studies evaluating the use of chlorine dioxide or derivatives on SARS-CoV-2 infection were identified. The only finding was an unpublished observational study registry which has no results released yet. CONCLUSIONS: To date, there are no scientific evidence to uphold the use of chlorine dioxide or derivatives as preventive or therapeutic agents against COVID-19.

OBJETIVOS: Realizar una revisión sistemática acerca de la efectividad y seguridad del uso de dióxido de cloro y derivados del cloro, en la prevención o el tratamiento de la COVID-19. MATERIALES Y MÉTODOS: Se siguieron las pautas internacionales de elaboración de revisiones sistemáticas de PRISMA y el Manual Cochrane para revisiones sistemáticas de intervenciones. La estrategia de búsqueda la desarrolló un bibliotecario y la revisaron dos de los autores. Se complementó la búsqueda electrónica con una búsqueda manual. Se incluyeron ensayos clínicos aleatorizados, estudios cuasiexperimentales, estudios de cohorte, estudios de casos y controles, estudios de corte transversal y reportes de casos; y se excluyeron estudios in vitro o realizados en animales. Dos revisores, de forma independiente, seleccionaron los estudios según los criterios de elegibilidad definidos, usando el aplicativo web Rayyan, en caso de discordancia se hizo partícipe a un tercer revisor. El protocolo de la revisión sistemática se registró en PROSPERO (CRD42020200641). RESULTADOS: No se identificó ningún estudio publicado ni en proceso de publicación que haya evaluado el uso del dióxido de cloro o derivados del cloro, administrado por vía inhalatoria, oral o parenteral en humanos, como agente preventivo o terapéutico de la COVID-19 o en infecciones por otros coronavirus. Solo se identificó el registro de un único estudio catalogado como observacional que hasta ahora no tiene resultados. CONCLUSIONES: A la fecha, no existe evidencia científica que apoye el uso del dióxido de cloro o derivados del cloro para prevenir o tratar la COVID-19.