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.

Maternal Secondhand Smoke Exposure Enhances Macrosomia Risk Among Pregnant Women Exposed to PM2.5: A New Interaction of Two Air Pollutants in a Nationwide Cohort.

Background: Fine particulate matter (PM2.5) is one of the most common outdoor air pollutants, and secondhand smoking (SHS) is an important source of inhalable indoor air pollution. Previous studies were controversial and inconsistent about PM2.5 and SHS air pollutants on neonatal birth weight outcomes, and no studies assessed the potential interactive effects between PM2.5 and SHS on birth weight outcomes. Purpose: To investigate the interaction between gestational PM2.5 and SHS air pollution exposure on the risk of macrosomia among pregnant women and examine the modifying effect of SHS exposure on the association of PM2.5 air pollution and birth weight outcomes during pregnancy. Methods: Research data were derived from the National Free Preconception Health Examination Project (NFPHEP), which lasted 3 years from January 1, 2010, to December 31, 2012. At least 240,000 Chinese women from 220 counties were enrolled in this project. PM2.5 exposure concentration was obtained using a hindcast model specific for historical PM2.5 estimation from satellite-retrieved aerosol optic depth. Different interaction models about air pollution exposure on birth weight outcomes were established, according to the adjustment of different confounding factors and different pregnancy stages. The establishment of interaction models was based on multivariable logistic regression, and the main confounding factors were maternal age at delivery and pre-pregnancy body mass index (BMI) of participants. SHS subgroups analysis was conducted to further confirm the results of interaction models. Results: In total, 197,877 participants were included in our study. In the full-adjusted interaction model, maternal exposure to PM2.5 was associated with an increased risk of macrosomia in whole, the first-, second-, and third trimesters of pregnancy (p < 0.001). The interactive effect was statistically significant between maternal exposure to PM2.5 and SHS on the risk of macrosomia in the whole (interaction p < 0.050) and the first-trimester pregnancy (interaction p < 0.050), not in the second (interaction p > 0.050) or third trimester (interaction p > 0.050) of pregnancy. The higher frequency of SHS exposure prompted the stronger interaction between the two air pollutants in the whole pregnancy and the first-trimester pregnancy. Conclusions: In the whole and first-trimester pregnancy, maternal exposure to SHS during pregnancy enhanced the risk of macrosomia among pregnant women exposed to PM2.5 air pollutants, and the interaction became stronger with the higher frequency of SHS exposure.

High-Dose Intravenous Immunoglobulin in Severe Coronavirus Disease 2019: A Multicenter Retrospective Study in China.

BACKGROUND: The effective treatment of coronavirus disease 2019 (COVID-19) remains unclear. We reported successful use of high-dose intravenous immunoglobulin (IVIg) in cases of severe COVID-19, but evidence from larger case series is still lacking. METHODS: A multi-center retrospective study was conducted to evaluate the effectiveness of IVIg administered within two weeks of disease onset at a total dose of 2 g/kg body weight, in addition to standard care. The primary endpoint was 28-day mortality. Efficacy of high-dose IVIg was assessed by using the Cox proportional hazards regression model and the Kaplan-Meier curve adjusted by inverse probability of treatment weighting (IPTW) analysis, and IPTW after multiple imputation (MI) analysis. RESULTS: Overall, 26 patients who received high-dose IVIg with standard therapy and 89 patients who received standard therapy only were enrolled in this study. The IVIg group was associated with a lower 28-day mortality rate and less time to normalization of inflammatory markers including IL-6, IL-10, and ferritin compared with the control. The adjusted HR of 28-day mortality in high-dose IVIg group was 0.24 (95% CI 0.06-0.99, p<0.001) in IPTW model, and 0.27 (95% CI 0.10-0.57, p=0.031) in IPTW-MI model. In subgroup analysis, patients with no comorbidities or treated in the first week of disease were associated with more benefit from high-dose IVIg. CONCLUSIONS: High-dose IVIg administered in severe COVID-19 patients within 14 days of onset was linked to reduced 28-day mortality, more prominent with those having no comorbidities or treated at earlier stage.

Corrigendum: High-Dose Intravenous Immunoglobulin in Severe Coronavirus Disease 2019: A Multicenter Retrospective Study in China.

[This corrects the article DOI: 10.3389/fimmu.2021.627844/full.].