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

BackgroundAssessment of COVID-19 vaccines safety during pregnancy is urgently needed.MethodsWe 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).ResultsWe 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.ConclusionWe 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.     

Worldwide prevalence of fungal coinfections among COVID-19 patients: a comprehensive systematic review and meta-analysis

Microbial coinfections can increase the morbidity and mortality rates of viral respiratory diseases. Therefore, this study aimed to determine the pooled prevalence of fungal coinfections in coronavirus disease 2019 (COVID-19) patients. Web of Science, Medline, Scopus, and Embase were searched without language restrictions to identify the related research on COVID-19 patients with fungal coinfections from December 1, 2019, to December 30, 2020. A random-effects model was used for analysis. The sample size included 2,246 patients from 8 studies. The pooled prevalence of fungal coinfections was 12.60%. The frequency of fungal subtype coinfections was 3.71% for Aspergillus, 2.39% for Candida, and 0.39% for other. The World Health Organization’s Regional Office for Europe and Regional Office for Southeast Asia had the highest (23.28%) and lowest (4.53%) estimated prevalence of fungal coinfection, respectively. Our findings showed a high prevalence of fungal coinfections in COVID-19 cases, which is a likely contributor to mortality in COVID-19 patients. Early identification of fungal pathogens in the laboratory for COVID-19 patients can lead to timely treatment and prevention of further damage by this hidden infection.     

Dietary supplements and nutraceuticals in the recovery of COVID-19: A systematic review and meta-analysis

The outbreak of nSARS-CoV2 in December 2019 turned into a global pandemic and is still underway. Infection with nSARS-CoV2 resulted in severe acute respiratory distress syndrome and was named COVID-19. COVID-19 requires the intervention of a series of therapeutics, including antiviral, anti-inflammatory, and immune-modulating molecules. Additionally, studies have demonstrated that nutraceuticals offer a promising impact in fast recovery and boosting immunity. Here, the study aimed to provide a comprehensive synthesis of the scientific evidence examining the effectiveness of nutraceuticals. A detailed search of scientific literature was conducted utilizing the most relevant scientific studies published during 2019–2022 on the intervention of nutraceuticals in the management of COVID-19. PubMed, Cochrane Central Register of Controlled Trials and Scielo databases were explored for the most relevant studies. Meta-analysis was carried out using the MedCalC tool as per PRISMA guidelines for odds ratio among the studies along with risk factor analysis and relative risk. A total of 1,308 original records were identified, where 1,268 studies were collected from different databases, and 40 additional records were obtained from non-pre-defined sources. Odds ratio, risk analysis, and risk difference analysis showed nutraceuticals intervention reported effective (P < 0.001) in COVID-19 patient over control. Nutraceuticals-based interventions had improved immunity, short-term duration, and fast recovery of COVID-19 patients.     

Epidemiology of COVID-19 infection in young children under five years: A systematic review and meta-analysis

IntroductionEmerging evidence suggests young children are at greater risk of COVID-19 infection than initially predicted. However, a comprehensive understanding of epidemiology of COVID-19 infection in young children under five years, the most at-risk age-group for respiratory infections, remain unclear. We conducted a systematic review and meta-analysis of epidemiological and clinical characteristics of COVID-19 infection in children under five years.MethodFollowing the Preferred Reporting Items for Systematic Reviews and Meta-analyses , we searched several electronic databases (Pubmed, EMBASE, Web of Science, and Scopus) with no language restriction for published epidemiological studies and case-reports reporting laboratory-confirmed COVID-19 infection in children under five years until June 4, 2020. We assessed pooled prevalence for key demographics and clinical characteristics using Freeman-Tukey double arcsine random-effects model for studies except case-reports. We evaluated risk of bias separately for case-reports and other studies.ResultsWe identified 1,964 articles, of which, 65 articles were eligible for systematic review that represented 1,214 children younger than five years with laboratory-confirmed COVID-19 infection. The pooled estimates showed that 50% young COVID-19 cases were infants (95% CI: 36% ? 63%, 27 studies); 53% were male (95% CI: 41% ? 65%, 24 studies); 43% were asymptomatic (95% CI: 15% ? 73%, 9 studies) and 7% (95% CI: 0% ? 30%, 5 studies) had severe disease that required intensive-care-unit admission. Of 139 newborns from COVID-19 infected mothers, five (3.6%) were COVID-19 positive. There was only one death recorded.DiscussionThis systematic review reports the largest number of children younger than five years with COVID-19 infection till date. Our meta-analysis shows nearly half of young COVID-19 cases were asymptomatic and half were infants, highlighting the need for ongoing surveillance to better understand the epidemiology, clinical pattern, and transmission of COVID-19 to develop effective preventive strategies against COVID-19 disease in young paediatric population.     

Tocilizumab therapy reduced intensive care unit admissions and/or mortality in COVID-19 patients

IntroductionNo therapy has yet proven effective in COVID-19. Tocilizumab (TCZ) in patients with severe COVID-19 could be an effective treatment.MethodWe conducted a retrospective case-control study in the Nord Franche-Comté Hospital, France. We compared the outcome of patients treated with TCZ and patients without TCZ considering a combined primary endpoint: death and/or ICU admissions.ResultsPatients with TCZ (n = 20) had a higher Charlson comorbidity index (5.3 [±2.4] vs 3.4 [±2.6], P = 0.014), presented with more severe forms (higher level of oxygen therapy at 13 L/min vs 6 L/min, P < 0.001), and had poorer biological findings (severe lymphopenia: 676/mm³ vs 914/mm³, P = 0.037 and higher CRP level: 158 mg/L vs 105 mg/L, P = 0.017) than patients without TCZ (n = 25). However, death and/or ICU admissions were higher in patients without TCZ than in the TCZ group (72% vs 25%, P = 0.002).ConclusionDespite the small sample size and retrospective nature of the work, this result strongly suggests that TCZ may reduce the number of ICU admissions and/or mortality in patients with severe SARS-CoV-2 pneumonia.     

A meta-analysis of influenza vaccination following correspondence: Considerations for COVID-19

BackgroundHigh vaccination rates are needed to protect against influenza and to end the COVID-19 pandemic. Health authorities need to know if supplementing mass communications with direct correspondence to the community would increase uptake.ObjectivesThe primary objective is to determine if sending a single written message directly to individuals increases influenza vaccine uptake, and a secondary objective is to identify any identified content shown to increase influenza vaccine uptake.MethodsMEDLINE, Embase, Cochrane CENTRAL, PsycINFO, and PubMed were searched for RCTs testing a single correspondence for members of the community in OECD countries to obtain influenza vaccination. A meta-analysis with inverse-variance, random-effects modelling was used to estimate a mean, weighted risk ratio effect size measure of vaccine uptake. Studies were quality assessed and analysis was undertaken to account for potential publication bias.ResultsTwenty-eight randomized controlled trials were included, covering 45 interventions. Of the 45 interventions, 37 (82.2%) report an increase in influenza vaccination rates. A formal meta-analysis shows that sending a single written message increased influenza vaccine uptake by 16%, relative to the no contact comparator group (RR = 1.16, 95% CI [1.13–1.20], Z = 9.25, p < .001). Analysis shows that the intervention is effective across correspondence type, age group, time, and location, and after allowing for risk of publication bias.LimitationsThe generalizability of results across the OECD may be questioned.Conclusions and implicationsThe implication for public health authorities organizing vaccination programs for influenza, and arguably also for COVID-19, is that sending written vaccination correspondence to members of the community is likely to increase uptake.This study is pre-registered on osf.io; details can be found at https://osf.io/98mr7.     

济南市现阶段新型冠状病毒肺炎的流行特征与思考

目的调查分析上海市一起新型冠状病毒肺炎(新冠肺炎)家庭聚集性疫情的流行病学特征,为完善诊断标准和密切接触者隔离医学观察标准提供参考。方法应用现场流行病学方法调查家庭新冠肺炎聚集性疫情中的病例及密切接触者,对流行病学调查资料和数据进行描述性分析。采用实时荧光定量RT-PCR法对呼吸道标本进行新型冠状病毒核酸检测。结果该起家庭聚集性疫情共涉及2例确诊病例,1例疑似病例。传染源为有湖北武汉居住史的病例1;病例2、病例3作为密切接触者接受了14 d集中隔离医学观察;病例2在病例1发病4 d后出现症状,2次核酸检测阴性后排除新冠肺炎诊断;隔离医学观察期满后,病例2再次就诊时被确诊,病例3先为疑似病例最后被排除。结论日常生活的密切接触是新型冠状病毒传播并造成聚集性疫情的重要原因。密接接触者出现症状后,要结合核酸检测、胸部CT检查、血清学检测等结果作出诊断;建议对密切接触者进行感染风险分级,对高感染风险的密切接触者强化医学观察解除标准。     

The impact of COVID-19 vaccines on fertility-A systematic review and meta-analysis

BackgroundDespite literature’s evidence about COVID-19 vaccines' safety, concerns have arisen regarding adverse events, including the possible impact on fertility, accentuated by misinformation and anti-vaccine campaigns. The present study aims to answer the question: Is there any impact of COVID-19 vaccines on the fertility of men and women of reproductive age?MethodsPubMed, Scopus, Web of Science, Cochrane and Embase databases were searched for eligible studies until June 8th, 2022. The search was restricted to articles regarding humans, published in any languages, without additional restrictions. Studies’ quality was assessed by the Newcastle-Ottawa and the Before and After Quality Assessment scales for cohort and pre-post studies, respectively. Random-effect meta-analyses were performed for parameters considered in ≥ 2 studies, calculating means, p-values and 95 % Confidence Intervals (CIs).ResultsOut of 1406 studies screened, 29 were included in the systematic review. These studies, conducted in Israel (34.5 %), USA (24.1 %), Russia (20.7 %) China (10.3 %), Italy (3.5 %), North America (3.5%) and Turkey (3.5 %) were of poor (34.5 %), moderate (58.6 %) and good (6.9 %) quality. Meta-analyses were performed for pre- and post-vaccination sperm progressive motility (44 %, 95 % CI 42 %-62 % vs 43 %, 95 % CI 31 %-59 % p = 0.07) and concentration (50.6 mln/ml, 95 % CI 35.1–72.8 vs 55.4 mln/ml, 95 % CI 37.4–82.2p = 0.12). Biochemical (0.51, 95 % CI 0.40–0.66 vs 0.60, 95 % CI 0.53–0.68p = 0.45) and clinical (0.45, 95 % CI 0.37–0.54 vs 0.47, 95 % CI 0.40–0.55 p = 0.31) pregnancy rate did not differ among vaccinated and not vaccinated groups. Subgroup meta-analyses based on the type of vaccine showed no significant difference: between vaccinated with mRNA vaccines and non-vaccinated regarding biochemical pregnancy rates; pre- and post-vaccination with Gam-COVID-Vac regarding testosterone, FSH and LH levels; pre- and post-vaccination with BNT162b2 vaccines regarding sperm volumes.ConclusionBased on the studies published so far, there is no scientific proof of any association between COVID-19 vaccines and fertility impairment in men or women.     

COVID-19 prediction models: a systematic literature review

As the world grapples with the problem of the coronavirus disease 2019 (COVID-19) pandemic and its devastating effects, scientific groups are working towards solutions to mitigate the effects of the virus. This paper aimed to collate information on COVID-19 prediction models. A systematic literature review is reported, based on a manual search of 1,196 papers published from January to December 2020. Various databases such as Google Scholar, Web of Science, and Scopus were searched. The search strategy was formulated and refined in terms of subject keywords, geographical purview, and time period according to a predefined protocol. Visualizations were created to present the data trends according to different parameters. The results of this systematic literature review show that the study findings are critically relevant for both healthcare managers and prediction model developers. Healthcare managers can choose the best prediction model output for their organization or process management. Meanwhile, prediction model developers and managers can identify the lacunae in their models and improve their data-driven approaches.     

Associations of pre-existing cardiovascular morbidity with severity and the fatality rate in COVID-19 patients: a systematic review and meta-analysis

ObjectivesThe aim of this study was to evaluate the association of pre-existing cardiovascular comorbidities, including hypertension and coronary heart disease, with coronavirus disease 2019 (COVID-19) severity and mortality.MethodsPubMed, ScienceDirect, and Scopus were searched between January 1, 2020, and July 18, 2020, to identify eligible studies. Random-effect models were used to estimate the pooled event rates of pre-existing cardiovascular disease comorbidities and odds ratio (OR) with 95% confidence intervals (95% CIs) of disease severity and mortality associated with the exposures of interest.ResultsA total of 34 studies involving 19,156 patients with COVID-19 infection met the inclusion criteria. The prevalence of pre-existing cardiovascular disease in the included studies was 14.0%. Pre-existing cardiovascular disease in COVID-19 patients was associated with severe outcomes (OR, 4.1; 95% CI, 2.9 to 5.7) and mortality (OR, 6.1; 95% CI, 2.9 to 12.7). Hypertension and coronary heart disease increased the risk of severe outcomes by 3 times (OR, 3.2; 95% CI, 2.0 to 3.6) and 2.5 times (OR, 2.5; 95% CI, 1.7 to 3.8), respectively. No significant publication bias was indicated.ConclusionCOVID-19 patients with pre-existing cardiovascular comorbidities have a higher risk of severe outcomes and mortality. Awareness of pre-existing cardiovascular comorbidity is important for the early management of COVID-19.     

COVID-19 transmission: a rapid systematic review of current knowledge

ObjectivesThe objective of this study was to identify the potential and definite sources of transmission of coronavirus disease 2019 (COVID-19).MethodsDue to time constraints and the acute nature of the pandemic, we searched only PubMed/MEDLINE from inception until January 28, 2021. We analyzed the level of evidence and risk of bias in each category and made suggestions accordingly.ResultsThe virus was traced from its potential origin via possible ways of transmission to the last host. Symptomatic human-to-human transmission remains the driver of the epidemic, but asymptomatic transmission can potentially contribute in a substantial manner. Feces and fomites have both been found to contain viable virus; even though transmission through these routes has not been documented, their contribution cannot be ruled out. Finally, transmission from pregnant women to their children has been found to be low (up to 3%).ConclusionEven though robust outcomes cannot be easily assessed, medical personnel must maintain awareness of the main routes of transmission (via droplets and aerosols from even asymptomatic patients). This is the first attempt to systematically review the existing knowledge to produce a paper with a potentially significant clinical impact.     

Obesity pandemic during COVID-19 outbreak: Narrative review and future considerations

Factors associated with increased severity and risk of death for COVID-19 in obesity.

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Impact of obesity on hospitalizations and mortality,due to COVID-19: A systematic review

The aim of the current review was to assess whether there was an association between obesity and higher levels of hospitalization, poor outcomes and mortality due to the disease of novel coronavirus (COVID-19). Methodology: A systematic review of articles on the novel coronavirus, containing information on obesity and its association with COVID-19 morbidity and mortality. In the bibliographic research, four databases were used, with the terms ['COVID-19′] AND ['hospitalization'] AND ['obesity'] AND ['mortality']. Studies published from 12/01/2019 until 05/01/2020 were included. The research contains inclusive criteria targeting studies of humans adults infected by Sars-Cov-2, with or without comorbidities. This research was selected from publications in Spanish and English languages. Results: 96 articles were identified, 15 being presented in two databases. Twenty articles were included, with a population total estimated from 1 to 7671 patients, with a prevalence of obesity ranging from 13.3% to 68.6%. The association of obesity and mortality has been observed in at least 4 studies, that 85.3% of the population was hospitalized. Among 19 of the 20 studies, more severe forms of the disease were observed and in 14 of them, higher rates of complications among obese people infected with the new coronavirus. Limitation differences in the definition of obesity was observed among publications, of which obesity was considered from a body mass index >25 kg/m². Conclusions: In the current review, obesity and overweight were represented an unfavorable factor for infection of novel coronavirus, where the higher the BMI the worse the outcomes. This occurred by worsening the infection itself, as well as increasing the prevalence of hospitalizations, worst outcomes and greater lethality; especially when co-occurring with other chronic conditions and in the elderly as well. Given this evidence, greater attention is suggested to the obese and overweight population in the face of the current pandemic.     

COVID-19 and Routine Childhood and Adolescent Immunizations: Evidence from Louisiana Medicaid

The COVID-19 pandemic disrupted routine vaccinations for children and adolescents. However, it remains unclear whether the impact has been different for children and adolescents from low-income families. To address this, we compared monthly routine vaccination use per 1000 vaccine-eligible children and adolescents enrolled in Louisiana Medicaid in the years before (2017–2019) and during the COVID-19 pandemic (2020). Compared to the 2017–2019 average vaccination rates, we found a 28% reduction in measles, mumps, and rubella (MMR), a 35% reduction in human papillomavirus (HPV), and a 30% reduction in tetanus, diphtheria, pertussis (Tdap) vaccinations in 2020. Vaccine uptake was lower in April 2020 after the declaration of a state of emergency and in late summer when back-to-school vaccinations ordinarily occur. We found little evidence of recovery in later months. Our findings suggest that a substantial number of disadvantaged children may experience longer periods of vulnerability to preventable infections because of missed vaccinations.     

新型冠状病毒肺炎诊疗方案（试行第九版）

为进一步做好新型冠状病毒肺炎（COVID-19）诊疗工作,我们组织专家对《新型冠状病毒肺炎诊疗方案（试行第八版修订版）》相关内容进行修订,形成《新型冠状病毒肺炎诊疗方案（试行第九版）》。     

Safety and immunogenicity of heterologous ChAdOx1-nCoV19 and BNT162b2 vaccination: A meta-analysis of the heterologous COVID-19 vaccination outcomes

IntroductionHere, we systematically assessed the safety and immunogenicity of the heterologous ChAd/BNT vaccination regimens.Materials and methodsWe evaluated the immunogenicity by the geometric mean titers ratio (GMTR) of the neutralizing antibody and anti-spike IgG. The safety of heterologous ChAd/BNT vaccination was evaluated using the pooled risk ratios (RRs) calculated by the random-effects model about the adverse events. Our study was registered with PROSPERO, CRD42021265165.ResultsEleven studies were included in the analyses. Compared to the homologous ChAd/ChAd vaccination, the heterologous ChAd/BNT vaccination showed significantly higher immunogenicity in terms of the neutralizing antibody and GMTR of anti-spike IgG, but at the same time displayed higher incidence of total adverse reactions, especially for the local adverse reactions. Moreover, heterologous ChAd/BNT vaccination showed similar immunogenicity to the homologous BNT/BNT vaccination (GMTR of neutralizing antibody and anti-spike IgG) and similar safety.DiscussionHeterologous ChAd/BNT vaccination showed robust immunogenicity and tolerable safety.     

International estimates of intended uptake and refusal of COVID-19 vaccines: A rapid systematic review and meta-analysis of large nationally representative samples

BackgroundWidespread uptake of COVID-19 vaccines will be essential to controlling the COVID-19 pandemic. Vaccines have been developed in unprecedented time and quantifying levels of hesitancy towards vaccination among the general population is of importance.MethodsSystematic review and meta-analysis of studies using large nationally representative samples (n ≥ 1000) to examine the percentage of the population intending to vaccinate, unsure, or intending to refuse a COVID-19 vaccine when available. Generic inverse meta-analysis and meta-regression were used to pool estimates and examine time trends. PubMed, Scopus and pre-printer servers were searched from January-November 2020. Registered on PROSPERO (CRD42020223132).FindingsTwenty-eight nationally representative samples (n = 58,656) from 13 countries indicate that as the pandemic has progressed, the percentage of people intending to vaccinate decreased and the percentage of people intending to refuse vaccination increased. Pooled data from surveys conducted during June-October suggest that 60% (95% CI: 49% to 69%) intend to vaccinate and 20% (95% CI: 13% to 29%) intend to refuse vaccination, although intentions vary substantially between samples and countries (I² > 90%). Being female, younger, of lower income or education level and belonging to an ethnic minority group were consistently associated with being less likely to intend to vaccinate. Findings were consistent across higher vs. lower quality studies.InterpretationIntentions to be vaccinated when a COVID-19 vaccine becomes available have been declining across countries and there is an urgent need to address social inequalities in vaccine hesitancy and promote widespread uptake of vaccines as they become available.FundingN/A.