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.

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.

Safety of COVID-19 vaccines, their components or their platforms for pregnant women: A rapid review.

BACKGROUND: Pregnant women with COVID-19 are at an increased risk of severe COVID-19 illness as well as adverse pregnancy and birth outcomes. Many countries are vaccinating or considering vaccinating pregnant women with limited available data about the safety of this strategy. Early identification of safety concerns of COVID-19 vaccines, including their components, or their technological platforms is therefore urgently needed. METHODS: We conducted a rapid systematic review, as the first phase of an ongoing full systematic review, to evaluate the safety of COVID-19 vaccines in pregnant women, including their components, and their technological platforms (whole virus, protein, viral vector or nucleic acid) used in other vaccines, following the Cochrane methods and the PRISMA statement for reporting (PROSPERO-CRD42021234185).We searched literature databases, COVID-19 and pregnancy registries from inception February 2021 without time or language restriction and explored the reference lists of relevant systematic reviews retrieved. We selected studies of any methodological design that included at least 50 pregnant women or pregnant animals exposed to the vaccines that were selected for review by the COVAX MIWG in August 2020 or their components or platforms included in the COVID-19 vaccines, and evaluated adverse events during pregnancy and the neonatal period.Pairs of reviewers independently selected studies through the COVIDENCE web software and performed the data extraction through a previously piloted online extraction form. Discrepancies were resolved by consensus. RESULTS: We identified 6768 records, 256 potentially eligible studies were assessed by full-text, and 37 clinical and non-clinical studies (38 reports, involving 2,397,715 pregnant women and 56 pregnant animals) and 12 pregnancy registries were included.Most studies (89%) were conducted in high-income countries. The most frequent study design was cohort studies (n=21), followed by surveillance studies, randomized controlled trials, and registry analyses. Most studies (76%) allowed comparisons between vaccinated and unvaccinated pregnant women (n=25) or animals (n=3) and reported exposures 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), followed by aluminum-based adjuvants (n=11). Aluminum phosphate was used in Respiratory Syncytial Virus Fusion candidate vaccines (n=3) and Tdap vaccines (n=3). Different aluminum-based adjuvants were used in hepatitis vaccines. The replication-deficient simian adenovirus ChAdOx1 was used for a Rift Valley fever vaccine. Only one study reported exposure to messenger RNA (mRNA) COVID-19 vaccines that also used lipid nanoparticles. 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 that were selected for review by the COVAX MIWG 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 women 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.

Cociente ganglionar como factor pronóstico de sobrevida. Recurrencia en carcinoma escamoso de cavidad oral / NODAL RATIO AS A PROGNOSTIC FACTOR OF SURVIVAL AND RECURRENCE IN ORAL SQUAMOUS CELL CARCINOMA

Antecedentes: El carcinoma escamoso de cavidad oral constituye una de las patologías de mayor frecuencia en cabeza y cuello. El tratamiento de elección es quirúrgico con altas tasas de control local. Sin embrago, se evidencian recidivas aún en etapas tempranas de la enfermedad, lo que lleva a la necesidad de identificar factores pronósticos confiables para mejorar la estadificación, tratamiento y seguimiento. El Cociente Ganglionar fue ratificado como herramienta pronóstica en otros tumores y validado en cavidad oral en un estudio multicéntrico dirigido por el Memorial Sloan Kettering Center de Nueva York. Objetivo: Validar en nuestro medio al Cociente ganglionar como factor pronóstico de sobrevida y recurrencia en carcinoma de cavidad oral. Lugar de aplicación: Hospital público de atención terciaria de tumores. Diseño: Cohorte Retrospectivo Institucional. Material y Métodos: Se recabó de manera retrospectiva información de historias clínicas, partes quirúrgicos e informes de anatomía patológica de un total de 92 pacientes. Se incluyeron aquellos con carcinoma escamoso de cavidad oral T 1-4 pN0-pN+ (pN1-2). Se calculó la sobrevida utilizando el método Kaplan-Meier y se realizó el análisis multivariado. Resultados: Un Cociente Ganglionar (CG.) mayor a 5% resultó estadísticamente significativo como factor pronóstico de sobrevida [HR 5,22(IC95% 1,86; 14;62) (p 0.002)] y recurrencia [HR 13.33 (IC95% 3.85; 46.16) No se evidenció diferencia pronóstica entre aquellos pacientes con vaciamientos pN0 y pN+ asociado a CG. menor a 5%. Pacientes pN1 y vaciamientos con recuento ganglionar total de 20 (1/20) podrían obtener un similar pronóstico al de pN0. Conclusiones: Fue posible ratificar al CG. como factor pronóstico y se plantea la posible utilidad del mismo en la indicación del tratamiento adyuvante

Background: Oral cavity squamous cell carcinoma is one of the most common pathologies in head and neck surgery. Surgery is the treatment of choice with high rates of locoregional control. However, recurrences are seen even in early stages of the disease. This explains the need of new prognostic factors to provide a better staging, treatment and follow up. Nodal Ratio has been validated as a prognostic tool in other tumors and in oral cavity in a multicentric study by Memorial Sloan Kettering Center of Nueva York. Objective: To validate the Nodal Ratio as a prognostic factor in terms of survival and recurrence in oral cavity carcinoma in our medium. Design: Institutional retrospective cohort. Setting: Tertiary Public Hospital for treatment of tumours. Population and Methods: We retrospectively review 92 patient´s information from clinic histories, surgical protocols and pathologic informs. Inclusion criteria were squamous cell histopathology, T1-4 and pN0-N+ (pN1-2) stage. We calculate survival with Kaplan-Meier method and multivariate analysis was done to determinate the independence value. Results: A Nodal Ratio higher than 5% was statistically significant as a prognostic factor of survival [HR 5,22(IC95% 1,86; 14;62) (p 0.002)] and recurrence [HR 13.33 (IC95% 3.85; 46.16) There was no prognostic difference between patients with pN0 dissections and those with pN+ dissections plus NR less than 5%. pN1 patients with nodal yields of 20 (1/20) or more could have the same forecast as a pN0. Conclusions: We were able to validate NR as a prognostic factor. We postulate the potential use in the indication of adjuvant therapy.

Implicancias pronósticas de los márgenes quirúrgicos en el carcinoma oral / Prognostic implications of surgical margins in carcinoma of the oral cavity

Antecedentes: sobre la base de la bibliografía revisada y los resultados de supervivencia global y libre de enfermedad con diferentes márgenes de resección, se plantea la hipótesis de que márgenes < 5mm son suficientes para lograr una tasa de supervivencia global y comparables a las obtenidas con márgenes mayores. Objetivo: evaluar la supervivencia global y la supervivencia específica a 3 y 5 años de los pacientes con carcinomas escamosos de cavidad oral, en función de los márgenes quirúrgicos obtenidos. Material y métodos: se reclutaron entre enero de 2010 y diciembre de 2017 81 pacientes operados, 57,1%hombres, con una edad media de 60,49 años. Resultados: en el análisis multivariado en función de la supervivencia global y libre de enfermedad, resultaron variables pronósticas significativas el grado de diferenciación tumoral (p = 0,033), la invasión ganglionar extracapsular (p = 0,001) y la infiltración perineural (p = 0,000). Se pudo observar que no hay diferencias en la supervivencia libre de enfermedad de los diferentes grupos evaluados sobre la base de los márgenes quirúrgicos, pero se cree que la radioterapia posoperatoria estaría confundiendo la importancia real de los márgenes, debido a que la mayoría de los pacientes que presentaban márgenes cercanos fueron sometidos a radioterapia posoperatoria. Conclusiones: las variables analizadas concuerdan con la bibliografía en el sentido de que los únicos factores pronósticos resultan las características histológicas. Si bien existen muchos trabajos que analizan los márgenes en el carcinoma escamoso de cavidad oral, todavía no hay consenso en cuanto al valor pronóstico de los márgenes cercanos (1-5 mm).

Background: Based on the literature reviewed and the results of overall and disease-free survival with different surgical margins, we hypothesized that margins < 5mm are sufficient to achieve and overall survival rate and are comparable to those obtained with larger margins. Objective: The primary outcome of the present study was to evaluate overall survival and specific survival at 3 and 5 years of patients with squamous cell carcinoma of the oral cavity according to the surgical margins obtained. Material and methods: Between January 2010 and December 2017, 81 patients underwent surgery; 57.1% were men and mean age was 60.49 years. Results: At multivariate analysis, tumor differentiation (p = 0.033), extracapsular lymph node invasion (p = 0.001) and perineural invasion (p = 0.000) were identified as significant predictors of overall survival and disease-free survival. There were no differences in disease-free survival in the different groups evaluated based on the surgical margins. Yet, postoperative radiotherapy may actually obscure the importance of margins since most patients with close margins underwent postoperative radiotherapy. Conclusions: The variables analyzed in this paper are consistent with the literature in that only histological characteristics are prognostic factors. Although there are many studies analyzing the surgical margins in squamous carcinoma of the oral cavity, there is still no consensus regarding the prognostic value of close margins (1-5 mm).

Un caso inusual de quiste sebáceo infectado por Dermabacter hominis / Unusually infected sebaceous cyst by Dermabacter hominis

La especie Dermabacter hominis está constituida por bacilos gram positivos corineformes, anaerobios facultativos, que forman parte de la microbiota residente de la piel. Excepcionalmente se ha asociado a estos microorganismos con infecciones en pacientes inmunocomprometidos o muy debilitados. Se describe el caso de una mujer adulta joven, inmunocompetente, con un quiste sebáceo en el cuello, infectado por D. hominis como único agente etiológico. Se logró la identificación fenotípica del agente causal mediante pruebas simples basadas en el esquema originalmente propuesto por Funke y Bernard, factibles de ser realizadas en un laboratorio hospitalario de microbiología. Características fenotípicas como la morfología cocoide, el olor acre/espermático, la hidrólisis de la esculina, la producción de pirrolidonil arilamidasa y de lisina y ornitina descarboxilasas son pruebas claves en la identificación de D. hominis. La espectrometría de masas (MALDI-TOF MS) confirmó la identificación fenotípica.

Dermabacter hominis species is constituted by Gram positive facultative anaerobic coryneform rods being part of the resident microbiota human skin, and exceptionally associated to infections in immunocompromised or severely debilitated patients. An immunocompetent young adult woman with a neck sebaceous cyst infected by D. hominis as unique etiologic agent is presented. Phenotypic identification of the causative agent was achieved through simple tests, based on the originally scheme proposed by Funke and Bernard, and feasible to be performed in a hospital Microbiology Laboratory. Phenotypic characteristics as coccoid morphology, the acrid/spermatic odor, esculin hydrolysis, the production of pyrrolidonyl-arylamidase, lysine and ornithine decarboxylase, are key tests to identify D. hominis. The matrix-asisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) confirmed the phenotypic identification.

[Unusually infected sebaceous cyst by Dermabacter hominis]. / Un caso inusual de quiste sebáceo infectado por Dermabacter hominis.

Dermabacter hominis species is constituted by Gram positive facultative anaerobic coryneform rods being part of the resident microbiota human skin, and exceptionally associated to infections in immunocompromised or severely debilitated patients. An immunocompetent young adult woman with a neck sebaceous cyst infected by D. hominis as unique etiologic agent is presented. Phenotypic identification of the causative agent was achieved through simple tests, based on the originally scheme proposed by Funke and Bernard, and feasible to be performed in a hospital Microbiology Laboratory. Phenotypic characteristics as coccoid morphology, the acrid/spermatic odor, esculin hydrolysis, the production of pyrrolidonyl-arylamidase, lysine and ornithine decarboxylase, are key tests to identify D. hominis. The matrix-asisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) confirmed the phenotypic identification.