Post-Traumatic Stress in Children and Adolescents during the COVID-19 Pandemic: A Meta-Analysis and Intervention Approaches to Ensure Mental Health and Well-Being

Background: Since the World Health Organization (WHO) declared the COVID-19 pandemic in March 2020, many measures have been taken to prevent the spread of the virus. Consequently, many minors have been confined to their homes and have had to subsequently adapt to countless protocol changes. These factors appear to have contributed to post-traumatic stress disorder (PTSD) in many children. Materials and Methods: The authors searched Medline through PubMed and other databases for studies published from 1 December 2019 to 31 December 2021 on the prevalence of PTSD in schoolchildren. The authors used a random-effects model to calculate the pooled prevalence of PTSD. Results: A total of six studies were included in this review. Our results show a pooled prevalence of PTSD of 14% in children and adolescents. Subgroup analyses identify a significantly higher prevalence of PTSD for studies conducted in China and a higher prevalence in boys. The prevalence of PTSD appeared independent of child age or the methodological rigor of the study. Conclusions: Our results suggest that a large number of children may be suffering from PTSD (post-traumatic stress disorder). Public health measures are thus needed to improve children's mental health during and after the pandemic, so that the suffering is mitigated to prevent long-lasting effects.

Real-world effectiveness and factors associated with effectiveness of inactivated SARS-CoV-2 vaccines: a systematic review and meta-regression analysis.

BACKGROUND: The two inactivated SARS-CoV-2 vaccines, CoronaVac and BBIBP-CorV, have been widely used to control the COVID-19 pandemic. The influence of multiple factors on inactivated vaccine effectiveness (VE) during long-term use and against variants is not well understood. METHODS: We selected published or preprinted articles from PubMed, Embase, Scopus, Web of Science, medRxiv, BioRxiv, and the WHO COVID-19 database by 31 August 2022. We included observational studies that assessed the VE of completed primary series or homologous booster against SARS-CoV-2 infection or severe COVID-19. We used DerSimonian and Laird random-effects models to calculate pooled estimates and conducted multiple meta-regression with an information theoretic approach based on Akaike's Information Criterion to select the model and identify the factors associated with VE. RESULTS: Fifty-one eligible studies with 151 estimates were included. For prevention of infection, VE associated with study region, variants, and time since vaccination; VE was significantly decreased against Omicron compared to Alpha (P = 0.021), primary series VE was 52.8% (95% CI, 43.3 to 60.7%) against Delta and 16.4% (95% CI, 9.5 to 22.8%) against Omicron, and booster dose VE was 65.2% (95% CI, 48.3 to 76.6%) against Delta and 20.3% (95% CI, 10.5 to 28.0%) against Omicron; primary VE decreased significantly after 180 days (P = 0.022). For the prevention of severe COVID-19, VE associated with vaccine doses, age, study region, variants, study design, and study population type; booster VE increased significantly (P = 0.001) compared to primary; though VE decreased significantly against Gamma (P = 0.034), Delta (P = 0.001), and Omicron (P = 0.001) compared to Alpha, primary and booster VEs were all above 60% against each variant. CONCLUSIONS: Inactivated vaccine protection against SARS-CoV-2 infection was moderate, decreased significantly after 6 months following primary vaccination, and was restored by booster vaccination. VE against severe COVID-19 was greatest after boosting and did not decrease over time, sustained for over 6 months after the primary series, and more evidence is needed to assess the duration of booster VE. VE varied by variants, most notably against Omicron. It is necessary to ensure booster vaccination of everyone eligible for SARS-CoV-2 vaccines and continue monitoring virus evolution and VE. TRIAL REGISTRATION: PROSPERO, CRD42022353272.

Benefits of high-dose intravenous immunoglobulin on mortality in patients with severe COVID-19: An updated systematic review and meta-analysis.

Background: The clinical benefits of high-dose intravenous immunoglobulin (IVIg) in treating COVID-19 remained controversial. Methods: We systematically searched databases up to February 17, 2022, for studies examining the efficacy of IVIg compared to routine care. Meta-analyses were conducted using the random-effects model. Subgroup analysis, meta-regression, and trial series analysis w ere performed to explore heterogeneity and statistical significance. Results: A total of 4,711 hospitalized COVID-19 patients (1,925 IVIg treated and 2786 control) were collected from 17 studies, including five randomized controlled trials (RCTs) and 12 cohort studies. The application of IVIg was not associated with all-cause mortality (RR= 0.89 [0.63, 1.26], P= 0.53; I2 = 75%), the length of hospital stays (MD= 0.29 [-3.40, 6.44] days, P= 0.88; I2 = 96%), the needs for mechanical ventilation (RR= 0.93 ([0.73, 1.19], P= 0.31; I2 = 56%), or the incidence of adverse events (RR= 1.15 [0.99, 1.33], P= 0.06; I2 = 20%). Subgroup analyses showed that overall mortality among patients with severe COVID-19 was reduced in the high-dose IVIg subgroup (RR= 0.33 [0.13, 0.86], P= 0.02, I2 = 68%; very low certainty). Conclusions: Results of this study suggest that severe hospitalized COVID-19 patients treated with high-dose IVIg would have a lower risk of death than patients with routine care. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021231040, identifier CRD42021231040.

Global influenza vaccination rates and factors associated with influenza vaccination.

OBJECTIVES: Influenza vaccination is an effective method for preventing influenza virus infection. Herein, we performed a meta-analysis to quantify global influenza vaccination rates (IVRs) and the factors influencing its uptake in the general population, individuals with chronic diseases, pregnant women, and healthcare workers. METHODS: Related articles were obtained from online databases and screened according to the inclusion criteria. The pooled IVRs were calculated using the random effects model. Subgroup analyses and multivariate meta-regression were performed to determine the factors associated with influenza vaccine uptake. RESULTS: e included 522 studies from 68 countries/regions. Most studies were conducted in the European region (247 studies), followed by the Western Pacific (135 studies) and American regions (100 studies). The IVRs with 95% confidence intervals (CIs) in the general population were lower (24.96%, 23.45%-26.50%) than in individuals with chronic diseases (41.65%, 40.08%-43.23%), healthcare workers (36.57%, 33.74%-39.44%), and pregnant women (25.92%, 23.18%-28.75%). The IVRs in high-income countries/regions were significantly higher than that in middle-income countries/regions. A free national or regional vaccination policy, perception of influenza vaccine efficacy and disease severity, a recommendation from healthcare workers, and having a history of influenza vaccination were positive factors for vaccine uptake (P <0.01). CONCLUSION: Overall, global IVRs were low, especially in the general population. The studies on the IVRs, especially for priority populations, should be strengthened in Eastern Mediterranean, South-East Asian, and African regions. Free vaccination policies and the dissemination of continuous awareness campaigns are effective measures to enhance vaccination uptake.

Association of Obesity With COVID-19 Severity and Mortality: An Updated Systemic Review, Meta-Analysis, and Meta-Regression.

Background: Obesity affects the course of critical illnesses. We aimed to estimate the association of obesity with the severity and mortality in coronavirus disease 2019 (COVID-19) patients. Data Sources: A systematic search was conducted from the inception of the COVID-19 pandemic through to 13 October 2021, on databases including Medline (PubMed), Embase, Science Web, and Cochrane Central Controlled Trials Registry. Preprint servers such as BioRxiv, MedRxiv, ChemRxiv, and SSRN were also scanned. Study Selection and Data Extraction: Full-length articles focusing on the association of obesity and outcome in COVID-19 patients were included. Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were used for study selection and data extraction. Our Population of interest were COVID-19 positive patients, obesity is our Intervention/Exposure point, Comparators are Non-obese vs obese patients The chief outcome of the study was the severity of the confirmed COVID-19 positive hospitalized patients in terms of admission to the intensive care unit (ICU) or the requirement of invasive mechanical ventilation/intubation with obesity. All-cause mortality in COVID-19 positive hospitalized patients with obesity was the secondary outcome of the study. Results: In total, 3,140,413 patients from 167 studies were included in the study. Obesity was associated with an increased risk of severe disease (RR=1.52, 95% CI 1.41-1.63, p<0.001, I2 = 97%). Similarly, high mortality was observed in obese patients (RR=1.09, 95% CI 1.02-1.16, p=0.006, I2 = 97%). In multivariate meta-regression on severity, the covariate of the female gender, pulmonary disease, diabetes, older age, cardiovascular diseases, and hypertension was found to be significant and explained R2 = 40% of the between-study heterogeneity for severity. The aforementioned covariates were found to be significant for mortality as well, and these covariates collectively explained R2 = 50% of the between-study variability for mortality. Conclusions: Our findings suggest that obesity is significantly associated with increased severity and higher mortality among COVID-19 patients. Therefore, the inclusion of obesity or its surrogate body mass index in prognostic scores and improvement of guidelines for patient care management is recommended.

Association of Lipid Levels With COVID-19 Infection, Disease Severity and Mortality: A Systematic Review and Meta-Analysis.

Background: Coronavirus disease 2019 (COVID-19) ranges from asymptomatic infection to severe illness. Cholesterol in the host cell plasma membrane plays an important role in the SARS-CoV-2 virus entry into cells. Serum lipids, especially low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), are in constant interaction with the lipid rafts in the host cell membranes and can modify the interaction of virus with host cells and the resultant disease severity. Recent studies on serum lipid levels and COVID-19 disease severity lack consistency. Objectives: Our systematic review and meta-analysis compared the serum levels of total cholesterol (TC), LDL-C, HDL-C, and triglycerides (TG) between (1) COVID-19 patients vs. healthy controls; (2) severe vs. non-severe COVID-19 disease; (3) deceased vs. surviving COVID-19 patients. Methods: PRISMA guidelines were followed. We included peer-reviewed articles on observational (case-control and cohort) studies from PubMed and Embase published from the database inception until September 1, 2021. We used random-effects meta-analysis for pooled mean-differences (pMD) in lipid levels (mg/dL) for the above groups. Results: Among 441 articles identified, 29 articles (26 retrospective and 3 prospective cohorts), with an aggregate of 256,721 participants, were included. COVID-19 patients had lower TC (pMD-14.9, 95%CI-21.6 to -8.3) and HDL-C (pMD-6.9, 95%CI -10.2 to -3.7) levels (mg/dL). Severe COVID-19 patients had lower TC (pMD-10.4, 95%CI -18.7 to -2.2), LDL-C (pMD-4.4, 95%CI -8.4 to -0.42), and HDL-C (pMD-4.4, 95%CI -6.9 to -1.8) at admission compared to patients with non-severe disease. Deceased patients had lower TC (pMD-14.9, 95%CI -21.6 to -8.3), LDL-C (pMD-10.6, 95%CI -16.5 to -4.6) and HDL-C (pMD-2.5, 95%CI -3.9 to -1.0) at admission. TG levels did not differ based on COVID-19 severity or mortality. No publication bias was noted. Conclusion: We demonstrated lower lipid levels in patients with COVID-19 infection and an association with disease severity and mortality. Their potential role in COVID-19 pathogenesis and their utility as prognostic factors require further investigation.

Meta-Regression on the Heterogenous Factors Contributing to the Prevalence of Mental Health Symptoms During the COVID-19 Crisis Among Healthcare Workers.

Objective: This paper used meta-regression to analyze the heterogenous factors contributing to the prevalence rate of mental health symptoms of the general and frontline healthcare workers (HCWs) in China under the COVID-19 crisis. Method: We systematically searched PubMed, Embase, Web of Science, and Medrxiv and pooled data using random-effects meta-analyses to estimate the prevalence rates, and ran meta-regression to tease out the key sources of the heterogeneity. Results: The meta-regression results uncovered several predictors of the heterogeneity in prevalence rates among published studies, including severity (e.g., above severe vs. above moderate, p < 0.01; above moderate vs. above mild, p < 0.01), type of mental symptoms (PTSD vs. anxiety, p = 0.04), population (frontline vs. general HCWs, p < 0.01), sampling location (Wuhan vs. Non-Wuhan, p = 0.04), and study quality (p = 0.04). Conclusion: The meta-regression findings provide evidence on the factors contributing to the prevalence rate of mental health symptoms of the general and frontline healthcare workers (HCWs) to guide future research and evidence-based medicine in several specific directions. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=220592, identifier: CRD42020220592.

The Comparative Efficacy of Treatments for Children and Young Adults with Internet Addiction/Internet Gaming Disorder: An Updated Meta-Analysis.

Internet gaming disorder (IGD) is a formal mental disorder leading to bad outcomes for children and adolescents. This study comprehensively compared the estimated effect of various pharmacotherapy and psychosocial interventions for IGD from randomized controlled trials (RCT) through updated meta-analysis, using meta-regression. A search of PubMed/MEDLINE, Cochrane Library, and Airiti Library between 2000 and 2017 was conducted for various IA/IGD intervention modalities. A total of 124 studies from 29 selected papers involving 5601 children and young adults with IA/IGD were found. Meta-analyzing the pooled standardized mean difference (SMD) revealed a preliminary random effect of 1.399 with a 95% confidence interval of 1.272-1.527, suggesting highly effective treatment of IA/IGD. After adjusting for the confounding risks of age, publication year, type of subjects, and type of study, this study revealed that combining pharmacotherapy with cognitive behavioral therapy (CBT) or multi-level counseling (MLC) was the most effective treatment option. Using a scale of time spent online or a severity of IA symptoms scale was a more effective measurement, with p-values = 0.006 and 0.002, respectively. IA/IGD patients with comorbid depression showed worse outcomes than youth with another comorbidity. The corresponding model goodness-of-fit indices were τ2 = 1.188; I2-Residual = 89.74%; and Adjusted-R2 = 16.10%. This systematic review indicates that pharmacotherapy combined with CBT or MLC might be an effective therapeutic strategy for youth with gaming disorder.

Factors that Influence the Reported Sensitivity of Rapid Antigen Testing for SARS-CoV-2.

Tests that detect the presence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antigen in clinical specimens from the upper respiratory tract can provide a rapid means of coronavirus disease 2019 (COVID-19) diagnosis and help identify individuals who may be infectious and should isolate to prevent SARS-CoV-2 transmission. This systematic review assesses the diagnostic accuracy of SARS-CoV-2 antigen detection in COVID-19 symptomatic and asymptomatic individuals compared to quantitative reverse transcription polymerase chain reaction (RT-qPCR) and summarizes antigen test sensitivity using meta-regression. In total, 83 studies were included that compared SARS-CoV-2 rapid antigen-based lateral flow testing (RALFT) to RT-qPCR for SARS-CoV-2. Generally, the quality of the evaluated studies was inconsistent; nevertheless, the overall sensitivity for RALFT was determined to be 75.0% (95% confidence interval: 71.0-78.0). Additionally, RALFT sensitivity was found to be higher for symptomatic vs. asymptomatic individuals and was higher for a symptomatic population within 7 days from symptom onset compared to a population with extended days of symptoms. Viral load was found to be the most important factor for determining SARS-CoV-2 antigen test sensitivity. Other design factors, such as specimen storage and anatomical collection type, also affect the performance of RALFT. RALFT and RT-qPCR testing both achieve high sensitivity when compared to SARS-CoV-2 viral culture.

Global REnal Involvement of CORonavirus Disease 2019 (RECORD): A Systematic Review and Meta-Analysis of Incidence, Risk Factors, and Clinical Outcomes.

Introduction: The quantitative effect of underlying non-communicable diseases on acute kidney injury (AKI) incidence and the factors affecting the odds of death among coronavirus disease 2019 (COVID-19) AKI patients were unclear at population level. This study aimed to assess the association between AKI, mortality, underlying non-communicable diseases, and clinical risk factors. Methods: A systematic search of six databases was performed from January 1, 2020, until October 5, 2020. Peer-reviewed observational studies containing quantitative data on risk factors and incidence of renal manifestations of COVID-19 were included. Location, institution, and time period were matched to avoid duplicated data source. Incidence, prevalence, and odds ratio of outcomes were extracted and pooled by random-effects meta-analysis. History of renal replacement therapy (RRT) and age group were stratified for analysis. Univariable meta-regression models were built using AKI incidence as dependent variable, with underlying comorbidities and clinical presentations at admission as independent variables. Results: Global incidence rates of AKI and RRT in COVID-19 patients were 20.40% [95% confidence interval (CI) = 12.07-28.74] and 2.97% (95% CI = 1.91-4.04), respectively, among patients without RRT history. Patients who developed AKI during hospitalization were associated with 8 times (pooled OR = 9.03, 95% CI = 5.45-14.94) and 16.6 times (pooled OR = 17.58, 95% CI = 10.51-29.38) increased odds of death or being critical. At population level, each percentage increase in the underlying prevalence of diabetes, hypertension, chronic kidney disease, and tumor history was associated with 0.82% (95% CI = 0.40-1.24), 0.48% (95% CI = 0.18-0.78), 0.99% (95% CI = 0.18-1.79), and 2.85% (95% CI = 0.93-4.76) increased incidence of AKI across different settings, respectively. Although patients who had a kidney transplant presented with a higher incidence of AKI and RRT, their odds of mortality was lower. A positive trend of increased odds of death among AKI patients against the interval between symptom onset and hospital admission was observed. Conclusion: Underlying prevalence of non-communicable diseases partly explained the heterogeneity in the AKI incidence at population level. Delay in admission after symptom onset could be associated with higher mortality among patients who developed AKI and warrants further research.

Associations of D-Dimer on Admission and Clinical Features of COVID-19 Patients: A Systematic Review, Meta-Analysis, and Meta-Regression.

Background: Dynamic D-dimer level is a key biomarker for the severity and mortality of COVID-19 (coronavirus disease 2019). How aberrant fibrinolysis influences the clinical progression of COVID-19 presents a clinicopathological dilemma challenging intensivists. Methods: We performed meta-analysis and meta regression to analyze the associations of plasma D-dimer with 106 clinical variables to identify a panoramic view of the derangements of fibrinolysis in 14,862 patients of 42 studies. There were no limitations of age, gender, race, and country. Raw data of each group were extracted separately by two investigators. Individual data of case series, median and interquartile range, and ranges of median or mean were converted to SDM (standard deviation of mean). Findings: The weighted mean difference of D-dimer was 0.97 µg/mL (95% CI 0.65, 1.29) between mild and severe groups, as shown by meta-analysis. Publication bias was significant. Meta-regression identified 58 of 106 clinical variables were associated with plasma D-dimer levels. Of these, 11 readouts were negatively related to the level of plasma D-dimer. Further, age and gender were confounding factors. There were 22 variables independently correlated with the D-dimer level, including respiratory rate, dyspnea plasma K+, glucose, SpO2, BUN (blood urea nitrogen), bilirubin, ALT (alanine aminotransferase), AST (aspartate aminotransferase), systolic blood pressure, and CK (creatine kinase). Interpretation: These findings support elevated D-dimer as an independent predictor for both mortality and complications. The identified D-dimer-associated clinical variables draw a landscape integrating the aggregate effects of systemically suppressive and pulmonary hyperactive derangements of fibrinolysis, and the D-dimer-associated clinical biomarkers, and conceptually parameters could be combined for risk stratification, potentially for tracking thrombolytic therapy or alternative interventions.

Association between markers of immune response at hospital admission and COVID-19 disease severity and mortality: A meta-analysis and meta-regression.

BACKGROUND: To determine the utility of admission laboratory markers in the assessment and prognostication of coronavirus disease-2019 (COVID-19), a systematic review and meta-analysis were conducted on the association between admission laboratory values in hospitalized COVID-19 patients and subsequent disease severity and mortality. MATERIAL AND METHODS: Searches were conducted in MEDLINE, Pubmed, Embase, and the WHO Global Research Database from December 1,2019 to May 1, 2020 for relevant articles. A random effects meta-analysis was used to calculate the weighted mean difference (WMD) and 95% confidence interval (95% CI) for each of 27 laboratory markers. The impact of age and sex on WMDs was estimated using meta-regression techniques for 11 markers. RESULTS: In total, 64 studies met the inclusion criteria. The most marked WMDs were for neutrophils (ANC) at 3.82 × 109 /L (2.76, 4.87), lymphocytes (ALC) at -0.34 × 109 /L (-0.45, -0.23), interleukin-6 (IL-6) at 32.59 pg/mL (23.99, 41.19), ferritin at 814.14 ng/mL (551.48, 1076.81), C-reactive protein (CRP) at 66.11 mg/L (52.16, 80.06), D-dimer at 5.74 mg/L (3.91, 7.58), LDH at 232.41 U/L (178.31, 286.52), and high sensitivity troponin I at 90.47 pg/mL (47.79, 133.14) when comparing fatal to nonfatal cases. Similar trends were observed comparing severe to non-severe groups. There were no statistically significant associations between age or sex and WMD for any of the markers included in the meta-regression. CONCLUSION: The results highlight that hyper inflammation, blunted adaptive immune response, and intravascular coagulation play key roles in the pathogenesis of COVID-19. Markers of these processes are good candidates to identify patients for early intervention and, importantly, are likely reliable regardless of age or sex in adult patients.

Exploring the Effect of Collective Cultural Attributes on Covid-19-Related Public Health Outcomes.

Infections and deaths associated with COVID-19 show a high degree of heterogeneity across different populations. A thorough understanding of population-level predictors of such outcomes is crucial for devising better-targeted and more appropriate public health preparedness measures. While demographic, economic, and health-system capacity have featured prominently in recent work, cultural, and behavioral characteristics have largely been overlooked. However, cultural differences shape both the public policy response and individuals' behavioral responses to the crisis in ways that can impact infection dynamics and key health outcomes. To address this gap, we used meta-analytic methods to explore the global variability of three public health outcomes (i.e., crude test positivity, case/infection fatality, and mortality risk) during the first wave of the pandemic. This set of analyses identified several cultural/behavioral attributes (e.g., uncertainty avoidance and long-term vs. short-term normative orientation) as independent predictors of public health outcomes after adjusting for key demographic, political, economic, and health-system-related predictors; which were robust in sensitivity analyses. In conclusion, this study clearly demonstrates that cultural attributes do in fact account for some of the global disparities in COVID-19-attributed health outcomes. As a consequence, policymakers should more explicitly consider a society's cultural attributes alongside other important parameters such as demographic characteristics and health system constraints in order to develop better tailored and more effective policy responses.

Risk factors and predictors associated with the severity of COVID-19 in China: a systematic review, meta-analysis, and meta-regression.

Since December 2019, the pneumonia cases infected with 2019 novel coronavirus have appeared, posing a critical threat to global health. In this study, we performed a meta-analysis to discover the different clinical characteristics between severe and non-severe patients with COVID-19 to find the potential risk factors and predictors of this disease's severity, as well as to serve as a guidance for subsequent epidemic prevention and control work. PubMed, Cochrane Library, Medline, Embase and other databases were searched to collect studies on the difference of clinical characteristics of severe and non-severe patients. Meta-analysis was performed using RevMan 5.3 software, and the funnel plots could be made to evaluate the publication bias. P>0.05 means no statistical significance. Furthermore, a meta-regression analysis was performed by using Stata 15.0 to find the potential factors of the high degree of heterogeneity (I2>50%). Sixteen studies have been included, with 1,172 severe patients and 2,803 non-severe patients. Compared with non-severe patients, severe patients were more likely to have the symptoms of dyspnea, hemoptysis, and the complications of ARDS, shock, secondary infection, acute kidney injury, and acute cardiac injury. Interestingly, the former smokers were more prevalent in severe cases as compared to non-severe cases, but there was no difference between the two groups of 'current smokers'. Except for chronic liver disease and chronic kidney disease, the underlying comorbidities of hypertension, diabetes, cardiovascular disease, chronic obstructive pulmonary disease (COPD), malignancy, cerebrovascular disease, and HIV can make the disease worse. In terms of laboratory indicators, the decreased lymphocyte and platelet count, and the increased levels of white blood cell (WBC), D-dimer, creatine kinase, lactate dehydrogenase, procalcitonin, alanine aminotransferase, aspartate aminotransferase, and C-reactive protein were more prevalent in severe patients. Meta-regression analysis showed that patient age, gender, and proportion of severe cases did not significantly impact on the outcomes of any clinical indexes that showed high degree of heterogeneity in the meta-analysis. In conclusion, the severity of COVID-19 could be evaluated by, radiologic finding, some symptoms like dyspnea and hemoptysis, some laboratory indicators, and smoking history, especially the ex-smokers. Compared with non-severe patients, severe patients were more likely to have complications and comorbidities including hypertension, cardiovascular disease etc., which were the risk factors for the disease to be severer, but the chronic liver disease and chronic kidney disease were not associated the severity of COVID-19 in China.

Random effects meta-analysis of COVID-19/S. aureus partnership in co-infection.

Aim: To assess the hypothesis that coinfection with SARS-CoV-2 and S. aureus exacerbates morbidity and mortality among patients, the study aims to report the pooled burden of S. aureus co-infections in patients hospitalized with COVID-19. Methods: We searched electronic databases and the bibliographies of pertinent papers for articles. We considered studies in which the core result was the number of patients with bacterial (S. aureus) co-infection. We performed random effects meta-analysis (REM) because the studies included were sampled from a universe of different populations and high heterogeneity was anticipated. Using the Cochran's Q statistic, the observed dispersion (heterogeneity) among effect sizes was assessed. The percentage of total variability in the estimates of the effect size was calculated with the I2 index. To check for publication bias, the Egger weighted regression, Begg rank correlation and meta-funnel plot were used. We conducted meta-regression analysis to evaluate the variability between our outcomes and the covariates using computational options such as "methods of moments" and then "maximum likelihood" ratio. Results: We included 18 studies and retrieved data for 63,370 patients hospitalized with influenza-like illness, of which about 14,369 (22.67%) tested positive for COVID-19 by rRT-PCR. Of this number, 8,249 (57.4%) patient samples were analyzed. Bacterial, fungal and viral agents were detected in 3,038 (36.8%); S. aureus in 1,192 (39.2%). Five studies reported MRSA co-infection. Study quality ranged from 6 to 9 (median 7.1) on a JBI scale. From the meta-analysis, 33.1% patients were found to be coinfected (95%, CI 18.0 to 52.6%, Q=3473: df=17, I2=99·48%, p=0.00). The rate of S. aureus /COVID-19 co-infection was 25.6% (95% CI: 15.6 to 39.0, Q=783.4, df=17, I2=97.702%, p=0.003).The proportion of COVID-19/S. aureus co-infected patients with MRSA was 53.9% (95% CI, 24.5 to 80.9, n=66, 5 studies, Q=29.32, df=4, I2=86.369%, p=0.000). With the multivariate meta-regression model, study type (p=0.029), quality (p=0.000) and country (p=0.000) were significantly associated with heterogeneity. Conclusions: The pooled rates of S. aureus among COVID-19 patients documented in this study support the concern of clinicians about the presence of S. aureus in co-infections. Improved antibiotic stewardship can be accomplished through rapid diagnosis by longitudinal sampling of patients.

Assessing the age specificity of infection fatality rates for COVID-19: systematic review, meta-analysis, and public policy implications.

Determine age-specific infection fatality rates for COVID-19 to inform public health policies and communications that help protect vulnerable age groups. Studies of COVID-19 prevalence were collected by conducting an online search of published articles, preprints, and government reports that were publicly disseminated prior to 18 September 2020. The systematic review encompassed 113 studies, of which 27 studies (covering 34 geographical locations) satisfied the inclusion criteria and were included in the meta-analysis. Age-specific IFRs were computed using the prevalence data in conjunction with reported fatalities 4 weeks after the midpoint date of the study, reflecting typical lags in fatalities and reporting. Meta-regression procedures in Stata were used to analyze the infection fatality rate (IFR) by age. Our analysis finds a exponential relationship between age and IFR for COVID-19. The estimated age-specific IFR is very low for children and younger adults (e.g., 0.002% at age 10 and 0.01% at age 25) but increases progressively to 0.4% at age 55, 1.4% at age 65, 4.6% at age 75, and 15% at age 85. Moreover, our results indicate that about 90% of the variation in population IFR across geographical locations reflects differences in the age composition of the population and the extent to which relatively vulnerable age groups were exposed to the virus. These results indicate that COVID-19 is hazardous not only for the elderly but also for middle-aged adults, for whom the infection fatality rate is two orders of magnitude greater than the annualized risk of a fatal automobile accident and far more dangerous than seasonal influenza. Moreover, the overall IFR for COVID-19 should not be viewed as a fixed parameter but as intrinsically linked to the age-specific pattern of infections. Consequently, public health measures to mitigate infections in older adults could substantially decrease total deaths.

Effect of convalescent blood products for patients with severe acute respiratory infections of viral etiology: A systematic review and meta-analysis.

OBJECTIVES: The aim of this study was to determine whether convalescent blood products (CBPs) offer a survival advantage for patients with severe acute respiratory infections of viral etiology. METHODS: Up-to-date trials were identified by the authors through searches of the MEDLINE, Embase, Cochrane Library, Web of Science, ClinicalTrials.gov, and medRxiv databases from inception up to September 14, 2020. Meta-analyses were performed using a random-effects model. RESULTS: According to the observational studies, patients who received CBPs showed a decline in all-cause mortality compared with patients who did not receive CBPs (odds ratio (OR) 0.36, 95% confidence interval (CI) 0.23-0.56; p < 0.00001). However, the randomized controlled trials (RCTs) showed no difference between the intervention group and the control group regarding all-cause mortality (OR 0.82, 95% CI 0.57-1.19; p = 0.30). The use of CBPs did not increase the risk of adverse events (OR 0.88, 95% CI 0.60-1.29; p = 0.51). Using CBPs earlier compared with using CBPs later was associated with a significant reduction in all-cause mortality (OR 0.18, 95% CI 0.08-0.40; p < 0.0001). CONCLUSIONS: Based on the outcomes of RCTs, CBPs may not decrease all-cause mortality. Furthermore, compared with later initiation of CBP therapy, earlier initiation of this therapy may decrease the rate of mortality.

Is BCG associated with reduced incidence of COVID-19? A meta-regression of global data from 160 countries.

BACKGROUND: Global research is running towards to find a vaccine to stop the threat of the COVID-19. The Bacillus Calmette-Guérin (BCG) vaccine that prevents severe forms of tuberculosis is getting more attention in this scenario. The objective of our study was to determine the association between BCG vaccine coverage and incidence of COVID-19 at a national-level across the Globe. METHODS: The data of 160 countries were included in the study. Meta-regression was done to estimate the difference in the incidence of COVID-19 cases between countries with BCG vaccination coverage. BCG coverage was categorized as ≤70%, >70% and no vaccination. The analyses were carried out by adjusting for factors such as population density, income group, latitude, and percentage of the total population under age groups 15-64 and above 65 years of each country. RESULTS: The countries that had ≤70% coverage of BCG vaccine reported 6.5 (95% CI: -8.4 to -4.5) less COVID-19 infections per 10,000 population as compared to countries that reported no coverage. Those that had >70% coverage reported 10.1 (95% CI: -11.4 to -8.7) less infections per 10,000 population compared to those with no BCG countries. CONCLUSION: Our analysis suggests that BCG is associated with reduced COVID-19 infections if the BCG vaccine coverage is over 70%. The region-wise analyses also suggested similar findings, except the Middle East and North African region.

A Systematic Review and Meta-Analysis of Hypothermia in Experimental Traumatic Brain Injury: Why Have Promising Animal Studies Not Been Replicated in Pragmatic Clinical Trials?

Therapeutic hypothermia was a mainstay of severe traumatic brain injury (TBI) management for half a century. Recent trials have suggested that its effect on long-term functional outcome is neutral or negative, despite apparently promising pre-clinical data. Systematic review and meta-analysis is a useful tool to collate experimental data and investigate the basis of its conclusions. We searched three online databases to identify studies testing systemic hypothermia as monotherapy for treatment of animals subjected to a TBI. Data pertaining to TBI paradigm, animal subjects, and hypothermia management were extracted as well as those relating to risk of bias. We pooled outcome data where sufficient numbers allowed and investigated heterogeneity in neurobehavioral outcomes using multi-variate meta-regression. We identified 90 publications reporting 272 experiments testing hypothermia in animals subject to TBI. The subjects were mostly small animals, with well-established models predominating. Target temperature was comparable to clinical trial data but treatment was initiated very early. Study quality was low and there was some evidence of publication bias. Delay to treatment, comorbidity, and blinded outcome assessment appeared to predict neurobehavioral outcome on multi-variate meta-regression. Therapeutic hypothermia appears to be an efficacious treatment in experimental TBI, which differs from the clinical evidence. The pre-clinical literature showed limitations in quality and design and these both appeared to affect neurobehavioral experiment outcome. These should be acknowledged when designing and interpreting pre-clinical TBI studies in the future.