1.
COVID-19 convalescent plasma boosts early antibody titer and does not influence the adaptive immune response
McDyer JF, Azimpouran M, Durkalski-Mauldin VL, Clevenger RG, Yeatts SD, Deng X, Barsan W, Silbergleit R, El Kassar N, Popescu I, et al
JCI insight. 2023
Abstract
Multiple randomized, controlled clinical trials have yielded discordant results regarding the efficacy of convalescent plasma in outpatients, with some showing an approximate two-fold reduction in risk and others showing no effect. We quantified binding and neutralizing antibody levels in 492 of the 511 participants from the C3PO trial of a single unit of COVID-19 convalescent plasma (CCP) vs. saline infusion. In a subset of 70 participants, peripheral blood mononuclear cells were obtained to define the evolution of B and T cell responses through day 30. Binding and neutralizing antibody responses were measurably higher one hour post-infusion in recipients of CCP compared to saline plus multivitamin, but levels achieved by the native immune system by day 15 were much higher than seen immediately after CCP administration. Infusion of CCP did not block generation of the host antibody response or skew B or T cell phenotype or maturation. Activated CD4+ and CD8+ T cells were associated with more severe disease outcome. These data show that CCP leads to a measurable boost in anti-SARS-CoV-2 antibodies, but that the boost is modest and may not be sufficient to alter disease course.
2.
Potentially effective drugs for the treatment of COVID-19 or MIS-C in children: a systematic review
Wang Z, Zhao S, Tang Y, Wang Z, Shi Q, Dang X, Gan L, Peng S, Li W, Zhou Q, et al
European journal of pediatrics. 2022;:1-12
Abstract
The purpose of this systematic review is to evaluate the efficacy and safety of using potential drugs: remdesivir and glucocorticoid in treating children and adolescents with COVID-19 and intravenous immunoglobulin (IVIG) in treating MIS-C. We searched seven databases, three preprint platform, ClinicalTrials.gov, and Google from December 1, 2019, to August 5, 2021, to collect evidence of remdesivir, glucocorticoid, and IVIG which were used in children and adolescents with COVID-19 or MIS-C. A total of nine cohort studies and one case series study were included in this systematic review. In terms of remdesivir, the meta-analysis of single-arm cohort studies have shown that after the treatment, 54.7% (95%CI, 10.3 to 99.1%) experienced adverse events, 5.6% (95%CI, 1.2 to 10.1%) died, and 27.0% (95%CI, 0 to 73.0%) needed extracorporeal membrane oxygenation or invasive mechanical ventilation. As for glucocorticoids, the results of the meta-analysis showed that the fixed-effect summary odds ratio for the association with mortality was 2.79 (95%CI, 0.13 to 60.87), and the mechanical ventilation rate was 3.12 (95%CI, 0.80 to 12.08) for glucocorticoids compared with the control group. In terms of IVIG, most of the included cohort studies showed that for MIS-C patients with more severe clinical symptoms, IVIG combined with methylprednisolone could achieve better clinical efficacy than IVIG alone.Conclusions: Overall, the current evidence in the included studies is insignificant and of low quality. It is recommended to conduct high-quality randomized controlled trials of remdesivir, glucocorticoids, and IVIG in children and adolescents with COVID-19 or MIS-C to provide substantial evidence for the development of guidelines. What is Known: • The efficacy and safety of using potential drugs such as remdesivir, glucocorticoid, and intravenous immunoglobulin (IVIG) in treating children and adolescents with COVID-19/MIS-C are unclear. What is New: • Overall, the current evidence cannot adequately demonstrate the effectiveness and safety of using remdesivir, glucocorticoids, and IVIG in treating children and adolescents with COVID-19 or MIS-C. • We are calling for the publication of high-quality clinical trials and provide substantial evidence for the development of guidelines.
3.
Effectiveness of intravenous immunoglobulin for children with severe COVID-19: A rapid review
Zhang J, Yang Y, Yang N, Ma Y, Zhou Q, Li W, Wang X, Huang L, Luo X, Fukuoka T, et al
Annals of Translational Medicine. 2020
Abstract
Background: Intravenous immunoglobulin (IVIG) is usually used as supportive therapy, but the treatment of COVID-19 by IVIG is controversial This rapid review aims to explore the clinical effectiveness and safety of IVIG in the treatment of children with severe COVID-19 Methods: We systematically searched the literature on the use of IVIG in patients with COVID-19, severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS), including both adults and children We assessed the risk of bias and quality of evidence and reported the main findings descriptively Results: A total of 1,519 articles were identified by initial literature search, and finally six studies met our inclusion criteria, included one randomized controlled trial (RCT), four case series and one case report involving 198 patients One case series showed the survival of COVID-19 patients with acute respiratory distress syndrome (ARDS) was not improved by IVIG One case report showed high-dose IVIG could improve the outcome of COVID-19 adults Three observational studies showed inconsistent results of the effect of IVIG on SARS patients One RCT showed that IVIG did not reduce mortality or the incidence of nosocomial infection in adults with severe SARS The quality of evidence was between low and very low Conclusions: The existing evidence is insufficient to support the efficacy or safety of IVIG in the treatment of COVID-19
4.
Antiviral agents, glucocorticoids, antibiotics, and intravenous immunoglobulin usage in 1142 patients with coronavirus disease 2019: a systematic review and meta-analysis
Pei L, Zhang S, Huang L, Geng X, Ma L, Jiang W, Li W, Chen D
Pol Arch Intern Med. 2020
Abstract
INTRODUCTION Treatment effects of antiviral agents, glucocorticoids, antibiotics, and intravenous immunoglobulin are controversial in patients with Coronavirus disease 2019 (COVID-19). OBJECTIVES To evaluate the impact of drug therapy on the risk of death in patients with COVID-19. PATIENTS AND METHODS The PubMed, EMBASE, Web of Science, Cochrane Library, and major preprint platforms were searched to retrieve articles till 7 April 2020. The effects of specific drug interventions on mortality were assessed in COVID-19 patients. Odds ratios (ORs) and Risk Ratios (RRs) with corresponding 95% confidence intervals (CIs) were pooled using random-effects models. RESULTS Of 3421 references, six studies were included. Pooled results from retrospective studies revealed that antiviral agents may contribute to survival benefit (OR, 0.42, 95% CI, 0.17-0.99, p=0.048, I2=82.8%), while the RCT found no effects of antiviral agent on mortality (RR 0.77, 95% CI, 0.45-1.30, p=0.33). Glucocorticoids usage leads to an increased risk of death (OR 2.43, 95% CI, 1.44-4.10, p=0.001, I2=61.9%). Antibiotics intervention did not significantly affect mortality (OR 1.13, 95% CI, 0.67-1.89, p=0.64, I2=0%). Likewise, intravenous immunoglobulin had non-significant effects on mortality (OR 2.66, 95% CI, 0.72-9.89, p=0.14, I2=93.1%). CONCLUSIONS With the varied heterogeneities across interventions, the current evidence indicated a probable survival benefit of antiviral agent usage and a harmful effect of glucocorticoids in patients with COVID-19. None of antibiotics or intravenous immunoglobulin usage was associated with survival benefit in patients with COVID-19.