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.

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.].

Prolonged presence of viral nucleic acid in clinically recovered COVID-19 patients was not associated with effective infectiousness.

Prolonged presence of viral nucleic acid was reported in certain patients with coronavirus disease 2019 (COVID-19), with unclear clinical and epidemiological significance. We here described the clinical and epidemiological characteristics of 37 recovered COVID-19 patients with prolonged presence of viral RNA in Wuhan, China. For those who had been discharged and re-admitted, their close contacts outside the hospital were traced and evaluated. The median age of the 37 patients was 62 years (IQR 50, 68), and 24 (64.9%) were men. They had common or severe COVID-19. With prolonged positive RT-PCR, most patients were clinically stable, 29 (78.4%) denied any symptoms. A total of 431 PCR tests were carried out, with each patient at a median of 8 time points. The median time of PCR positivity to April 18 was 78 days (IQR 67.7, 84.5), and the longest 120 days. 22 of 37 patients had been discharged at a median of 44 days (IQR 22.3, 50) from disease onset, and 9 had lived with their families without personal protections for a total of 258 person-days and no secondary infection was identified through epidemiological investigation, nucleic acid and antibody screening. Infectiousness in COVID-19 patients with prolonged presence of viral nucleic acid should not solely be evaluated by RT-PCR. Those patients who have clinically recovered and whose disease course has exceeded four weeks were associated with very limited infectiousness. Reconsideration of disease control in such patients is needed.

High-Dose Intravenous Immunoglobulins in the Treatment of Severe Acute Viral Pneumonia: The Known Mechanisms and Clinical Effects.

The current outbreak of viral pneumonia, caused by novel coronavirus SARS-CoV-2, is the focus of worldwide attention. The WHO declared the COVID-19 outbreak a pandemic event on Mar 12, 2020, and the number of confirmed cases is still on the rise worldwide. While most infected individuals only experience mild symptoms or may even be asymptomatic, some patients rapidly progress to severe acute respiratory failure with substantial mortality, making it imperative to develop an efficient treatment for severe SARS-CoV-2 pneumonia alongside supportive care. So far, the optimal treatment strategy for severe COVID-19 remains unknown. Intravenous immunoglobulin (IVIg) is a blood product pooled from healthy donors with high concentrations of immunoglobulin G (IgG) and has been used in patients with autoimmune and inflammatory diseases for more than 30 years. In this review, we aim to highlight the known mechanisms of immunomodulatory effects of high-dose IVIg therapy, the immunopathological hypothesis of viral pneumonia, and the clinical evidence of IVIg therapy in viral pneumonia. We then make cautious therapeutic inferences about high-dose IVIg therapy in treating severe COVID-19. These inferences may provide relevant and useful insights in order to aid treatment for COVID-19.

High-Dose Intravenous Immunoglobulin as a Therapeutic Option for Deteriorating Patients With Coronavirus Disease 2019.

The outbreak of coronavirus disease 2019 (COVID-19) has spread rapidly in China. Until now, no definite effective treatment has been identified. We reported on 3 patients with severe COVID-19 who received high-dose intravenous immunoglobulin (IVIg) with satisfactory recovery. Based on these observations, randomized studies of high-dose IVIg should be considered in deteriorating patients infected with COVID-19.