Evidence of Placental Villous Inflammation and Apoptosis in Third-Trimester Symptomatic SARS-CoV-2 Maternal Infection.

PURPOSE: In view of conflicting reports on the ability of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) to infect placental tissue, this study aimed to further evaluate the impact of inflammation and placental damage from symptomatic third-trimester maternal COVID-19 infection. MATERIALS AND METHODS: This case-control study included 32 placenta samples each from symptomatic COVID-19 pregnancy and normal non-COVID-19 pregnancy. The villous placental area's inflammatory expression [angiotensin converting enzyme-2 (ACE-2), transmembrane protease serine-2 (TMPRSS2), interferon-γ (IFN-γ), interleukin-6 (IL-6), and SARS-CoV-2 spike protein] and apoptotic rate were examined using immunohistochemistry and Terminal deoxynucleotidyl transferase dUTP Nick-End Labeling (TUNEL) assay. Comparison and correlation analysis were used based on COVID-19 infection, placental SARS-CoV-2 spike protein evidence, and maternal severity status. RESULTS: Higher expressions of TMPRSS2, IFN-γ, and trophoblast apoptotic rate were observed in the COVID-19 group (p<0.001), whereas ACE-2 and IL-6 expressions were not significantly different from the control group (p>0.05). Additionally, SARS-CoV-2 spike protein was detected in 8 (25%) placental samples of COVID-19 pregnancy. COVID-19 subgroup analysis revealed increased IFN-γ, trophoblast, and stromal apoptosis (p<0.01). Moreover, the results of the current study revealed no correlation between maternal COVID-19 severity and placental inflammation as well as the apoptotic process. CONCLUSION: The presence of SARS-CoV-2 spike protein as well as altered inflammatory and apoptotic processes may indicate the presence of placental disturbance in third-trimester maternal COVID-19 infection. The lack of correlation between placental disruption and maternal severity status suggests the need for more research to understand the infection process and any potential long-term impacts on all offsprings born to COVID-19-infected pregnant women.

The Efficacy and Safety of Monoclonal Antibody Treatments Against COVID-19: A Systematic Review and Meta-analysis of Randomized Clinical Trials.

BACKGROUND: The use of monoclonal antibody as the proposed treatment of COVID-19 showed different results in various prior studies, and Efficacy remains open in literature. This study aimed to comprehensively determine the effect of monoclonal antibodies on clinical, laboratory, and safety outcomes in COVID-19 patients. METHODS: Sixteen RCTs were analyzed in this meta-analysis using RevMan 5.4 to measure the pooled estimates of risk ratios (RRs) and standardized mean differences (SMDs) with 95% CIs. RESULTS: The pooled effect of Monoclonal antibodies demonstrated efficacy on mortality risk reduction (RR=0,89 (95%CI 0.82-0.96), I2=13%, fixed-effect), Tocilizumab also show efficacy on mortality risk reduction for severe-critical disease (RR=0.90 (95%CI 0.83-0.97), I2=12%, fixed-effect)), need for mechanical ventilation (RR=0.76 (95%CI 0.62-0.94), I2=42%, random-effects), and hospital discharge (RR=1.07 (95%CI 1.00-1.14), I2=60%, random-effects). Bamlanivimab monotherapy did not reduce viral load (SMD=-0.07 (95%CI -0.21-0.07), I2=44%, fixed-effect). Monoclonal antibodies did not differ from placebo/standard therapy for hospital discharge at day 28-30 (RR=1.05 (95%CI 0.99-1.12), I2=71%, random-effects) and safety (RR=1.04 (95%CI 0.76-1.43), I2=54%, random-effects). CONCLUSION: Tocilizumab should be used for severe to critical COVID-19 because it is not harmful and can improve mortality risk, mechanical ventilation, and hospital discharge. Bamlanivimab-Etesevimab and REGN-COV2 reduced viral load in mild-moderate outpatients.

Automated glycemic control with a bionic pancreas for type 1 diabetes mellitus: A systematic review and meta-analysis.

BACKGROUND AND AIMS: The use of a bionic pancreas with automated insulin delivery systems to prevent complications of diabetes mellitus shows conflicting results. We aimed to comprehensively discuss the potential use of a bionic pancreas in patients with type 1 diabetes (T1D). METHODS: A systematic database search was conducted on October 24, 2022, for articles investigating the use of a bionic pancreas in patients with T1D. The hemoglobin A1c (HbA1c) level, mean glucose level, glucose coefficient of variability, time-in-range (TIR), and adverse events were investigated. RESULTS: Nine studies were included in this review. The data from these studies suggested that the use of a bionic pancreas could reduce the HbA1c (mean difference [MD] = -0.40% [95% confidence interval {CI} = -0.59 to -0.21], I2 = 0%, p < 0.0001) and mean glucose levels (MD = -21.06 [95% CI = -24.66 to -17.46], I2 = 45%, p < 0.00001) and improve the TIR (MD = 14.41% [95% CI = 10.99 to 17.83], I2 = 60%, p < 0.00001). The most common adverse events reported were nausea and vomiting. CONCLUSIONS: The use of a bionic pancreas shows potential in preventing complications of T1D by improving the TIR and decreasing the HbA1c and mean glucose levels. Furthermore, serious adverse events with the use of a bionic pancreas and standard of care show insignificant results, suggesting a good safety profile.

Importance of moderate-to-vigorous physical activity during the COVID-19 pandemic: a systematic review and meta-analysis.

Moderate-to-vigorous physical activity (MVPA) has been shown to have a favorable effect on many diseases as a complementary therapy and is a critical component of healthy living. During the pandemic era, physical activity has been promoted for resistance against coronavirus disease 2019 (COVID-19). However, there is scarce evidence on whether MVPA could reduce the infectivity and susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The objective of this meta-analysis was to determine the effect of MVPA on morbidity, mortality, and duration of hospitalization in COVID-19 patients. We performed a comprehensive search of five online databases for eligible studies up to September 9, 2021. Meta-analyses were conducted to determine the association between MVPA and COVID-19-related morbidity, hospitalization, and mortality. The odds ratio (OR) was applied as the summary statistic for the primary outcomes. Secondary analyses were conducted to evaluate the difference in the metabolic equivalent of tasks (METs) between the outcome and non-outcome groups with the mean difference as the pooled effect. This meta-analysis included eight observational studies. We found that MVPA significantly reduced the odds of contracting SARS-CoV-2 infection (OR=0.88; 95% confidence interval [CI] = 0.85-0.92), hospitalization (OR=0.56; 95% CI=0.35-0.92), and mortality (OR=0.42; 95% CI=0.21-0.81) due to COVID-19 compared to no physical activity. METs≥500 min/week were linked to decreased morbidity and mortality of COVID-19 (OR=0.94 [95% CI=0.90-0.98]; OR=0.56 [95% CI=0.38-0.83]). COVID-19 patients with MVPA demonstrated a lower risk of COVID-19-related morbidity, hospitalization, and mortality compared to those who were less active, highlighting the importance of an active lifestyle despite the pandemic situation where such activities are limited.

Effectiveness of COVID-19 Vaccines against SARS-CoV-2 Omicron Variant (B.1.1.529): A Systematic Review with Meta-Analysis and Meta-Regression.

Vaccine effectiveness (VE) and the urgency of booster vaccination against SARS-CoV-2 Omicron variant need evaluation. A systematic search was conducted from 1−6 April, 2022. VE difference (VED) estimates were assessed using random-effects and meta-regression analyses were performed for evaluating VE over time. Compared to full dose, booster dose of overall vaccines provided better protection against any and severe Omicron infections within 3 months (p < 0.001), and within 3 months or more in any, severe, and symptomatic infections (p < 0.001). From meta-regression analysis of overall vaccines, the full-dose VE against any and symptomatic Omicron infections reduced per month by 2.45% and 5.5%, respectively; whereas booster dose effectiveness against any and symptomatic Omicron infections reduced per month by 1.79% and 1.14%, respectively. The VE estimates of booster dose provide excellent protection against symptomatic infection compared to full dose. The VE estimates of Ad26.COV2.S, BNT162b2, ChAdOx1 nCov-19, and mRNA-1273 against Omicron infection are generally moderate, despite the VE estimates declining over time.

Clinical outcomes of opioid administration in acute and chronic heart failure: A meta-analysis.

BACKGROUND AND AIMS: Opioid use in heart failure (HF) management is controversial, and whether rapid symptomatic relief outweighs the risks of opioid use in HF remains unknown. This study aimed to explore the clinical outcomes of opioid administration in patients with acute or chronic HF. METHODS: A systematic search for eligible studies was conducted in databases (MEDLINE, Scopus, Web of Science, EBSCO) and registries (ClinicalTrials.gov, WHO Clinical Trial Registry) until June 8, 2022. Odds ratios (ORs) or adjusted OR (aORs) and mean difference (MD) or standardized MD were quantified for binary and continuous outcomes, respectively. Meta-regression was performed using the restricted maximum likelihood method. RESULTS: A total of 20 studies (154,736 participants) were included. In acute HF, opioid use presented a high risk for in-hospital mortality (OR = 2.35; 95% confidence interval (CI): 1.03-5.38; I2 = 97%), invasive (OR = 2.78; 95%CI: 1.17-6.61; I2 = 93%) and noninvasive (OR = 2.97; 95%CI: 1.06-8.28; I2 = 95%) ventilations, intensive care unit admission (OR = 3.62; 95%CI: 3.11-4.21; I2 = 6%), and inotrope use (OR = 2.54; 95%CI: 1.94-3.32; I2 = 63%). In chronic HF New York Heart Association (NYHA) Class II/III, opioid use improved ventilatory efficiency (MD = -3.16; 95%CI: (-4.78)-(-1.54); I2 = 0%), and exercise test duration (MD = 69.24; 95%CI: 10.11-128.37; I2 = 89%). CONCLUSIONS: Opioids are not recommended for acute HF management; however, they showed an advantage in exercise testing by improving ventilatory efficiency, chemosensitivity, and exercise test duration in stable patients with chronic HF NYHA Class II/III. Nonetheless, larger randomized controlled trials and individual patient-level data meta-analyses are warranted.

The Effect of Angiotensin Converting Enzyme (ACE) I/D Polymorphism on Atherosclerotic Cardiovascular Disease and Cardiovascular Mortality Risk in Non-Hemodialyzed Chronic Kidney Disease: The Mediating Role of Plasma ACE Level.

The association between angiotensin-converting enzyme insertion/deletion (ACE I/D) polymorphisms and plasma ACE levels may allow for the optimization of a preventive intervention to reduce cardiovascular morbidity and mortality in the chronic kidney disease (CKD) population. In this study, we aimed to analyze the association between ACE I/D polymorphism and cardiovascular mortality risk among non-hemodialyzed chronic kidney disease patients. This cross-sectional study examined 70 patients of Javanese ethnic origin with stable CKD who did not receive hemodialysis. ACE I/D polymorphisms, plasma ACE levels, atherosclerotic cardiovascular disease (ASCVD) risk, and cardiovascular mortality risk were investigated. As per our findings, the I allele was found to be more frequent (78.6) than the D allele (21.4), and the DD genotype was less frequent than the II genotype (4.3 vs. 61.4). The ACE I/D polymorphism had a significant direct positive effect on plasma ACE levels (path coefficient = 0.302, p = 0.021). Similarly, plasma ACE levels had a direct and significant positive effect on the risk of atherosclerotic cardiovascular disease (path coefficient = 0.410, p = 0.000). Moreover, atherosclerotic cardiovascular disease risk had a significant positive effect on cardiovascular mortality risk (path coefficient = 0.918, p = 0.000). The ACE I/D polymorphism had no direct effect on ASCVD and cardiovascular mortality risk. However, our findings show that the indirect effects of high plasma ACE levels may be a factor in the increased risk of ASCVD and cardiovascular mortality in Javanese CKD patients.

Impact of COVID-19 Lockdown on the Metabolic Control Parameters in Patients with Diabetes Mellitus: A Systematic Review and Meta-Analysis.

BACKGROUND: Abrupt implementation of lockdowns during the coronavirus disease 2019 (COVID-19) pandemic affected the management of diabetes mellitus in patients worldwide. Limited access to health facilities and lifestyle changes potentially affected metabolic parameters in patients at risk. We conducted a meta-analysis to determine any differences in the control of metabolic parameters in patients with diabetes, before and during lockdown. METHODS: We performed searches of five databases. Meta-analyses were carried out using random- or fixed-effect approaches to glycaemic control parameters as the primary outcome: glycosylated hemoglobin (HbA1c), random blood glucose (RBG), fasting blood glucose (FBG), time-in-range (TIR), time-above-range (TAR), time-below-range (TBR). Mean difference (MD), confidence interval (CI), and P value were calculated. Lipid profile was a secondary outcome and is presented as a descriptive analysis. RESULTS: Twenty-one studies enrolling a total of 3,992 patients with type 1 or type 2 diabetes mellitus (T1DM or T2DM) were included in the study. Patients with T1DM showed a significant improvement of TIR and TAR (MD=3.52% [95% CI, 0.29 to 6.74], I2=76%, P=0.03; MD=-3.36% [95% CI, -6.48 to -0.25], I2=75%, P=0.03), while FBG among patients with T2DM significantly worsened (MD=3.47 mg/dL [95% CI, 1.22 to 5.73], I2=0%, P<0.01). No significant difference was found in HbA1c, RBG, and TBR. Use of continuous glucose monitoring in T1DM facilitated good glycaemic control. Significant deterioration of lipid parameters during lockdown, particularly triglyceride, was observed. CONCLUSION: Implementation of lockdowns during the COVID-19 pandemic did not worsen glycaemic control in patients with diabetes. Other metabolic parameters improved during lockdown, though lipid parameters, particularly triglyceride, worsened.

mRNA Covid-19 vaccines in pregnancy: A systematic review.

OBJECTIVE: Pregnancy is a known risk factor for severe Coronavirus disease 2019. It is important to develop safe vaccines that elicit strong maternal and fetal antibody responses. METHODS: Registries (ClinicalTrials.gov, the WHO Clinical Trial Registry, and the European Union Clinical Trial Registry) and databases (MEDLINE, ScienceDirect, Cochrane Library, Proquest, Springer, medRxiv, and bioRxiv) were systematically searched in June 20-22, 2021, for research articles pertaining to Covid-19 and pregnancy. Manual searches of bioRxiv and medRxiv were also conducted. Inclusion criteria were studies that focused on Covid-19 vaccination among pregnant women, while review articles and non-human studies were excluded. Infection rate, maternal antibody response, transplacental antibody transfer, and adverse events were described. RESULTS: There were 13 observational studies with a total of 48,039 pregnant women who received mRNA vaccines. Of those, three studies investigated infection rate, six studies investigated maternal antibody response, seven studies investigated antibody transfer, three studies reported local adverse events, and five studies reported systemic adverse events. The available data suggested that the mRNA-based vaccines (Pfizer-BioNTech and Moderna) can prevent future SARS-CoV-2 infection. These vaccines did not show clear harm in pregnancy. The most commonly encountered adverse reactions were pain at the injection site, fatigue, and headache, but these were transient. Antibody responses were rapid after the first vaccine dose. After the booster, antibody responses were stronger and associated with better transplacental antibody transfer. Longer intervals between first vaccination dose and delivery were also associated with higher antibody fetal IgG and a better antibody transfer ratio. CONCLUSIONS: The SARS-CoV-2 mRNA vaccines are encouraged for pregnancy. These vaccines can be a safe option for pregnant women and their fetuses. Two vaccine doses are recommended for more robust maternal and fetal antibody responses. Longer latency is associated with higher fetal antibody responses. Further research about its long-term effect on pregnancy is needed. SYSTEMATIC REVIEW REGISTRATION: PROSPERO (CRD42021261684).

Remdesivir for pregnancy: A systematic review of antiviral therapy for COVID-19.

OBJECTIVE: The use of remdesivir for pregnant patients with coronavirus disease 2019 (COVID-19) showed conflicting results in prior studies. We aimed to systematically review its efficacy and safety for this population from the existing literature. METHODS: On July 26, 2021, registries (ClinicalTrials.gov) and databases (MEDLINE, ScienceDirect, Cochrane Library, JSTOR, DOAJ, and medRxiv) were systematically searched for research articles investigating remdesivir use in pregnant people with COVID-19. Clinical outcome, hospitalization duration, laboratory outcome, mortality, and adverse events were investigated. RESULTS: We obtained 13 observation studies with 113 pregnant people. In these studies, remdesivir improved the clinical condition of pregnant patients with COVID-19, especially those who had a better clinical status at baseline and received earlier remdesivir treatment. Most fetuses were delivered via cesarean section, primarily because of emergency causes. No vertical transmissions were noted. The most reported adverse event was transaminitis, in which 10-day remdesivir treatment yielded more incidence than the 5-day treatment. CONCLUSIONS: In pregnancy, the use of Remdesivir in combination with other COVID-19 treatments is inconclusive but its use should be followed with careful monitoring of adverse reactions and transaminase enzyme levels. Further studies are required to confirm its finding.