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High-dose intravenous immunoglobulins might modulate inflammation in COVID-19 patients.

ABSTRACT: The use of high-dose of intravenous immunoglobulins (IVIGs) as immunomodulators for the treatment of COVID-19-affected individuals has shown promising results. IVIG reduced inflammation in these patients, who progressively restored respiratory function. However, little is known about how they may modulate immune responses in COVID-19 individuals. Here, we have analyzed the levels of 41 inflammatory biomarkers in plasma samples obtained at day 0 (pretreatment initiation), 3, 7, and 14 from five hospitalized COVID-19 patients treated with a 5-d course of 400 mg/kg/d of IVIG. The plasmatic levels of several cytokines (Tumor Necrosis Factor, IL-10, IL-5, and IL-7), chemokines (macrophage inflammatory protein-1α), growth/tissue repairing factors (hepatic growth factor), complement activation (C5a), and intestinal damage such as Fatty acid-binding protein 2 and LPS-binding protein showed a progressive decreasing trend during the next 2 wk after treatment initiation. This trend was not observed in IVIG-untreated COVID-19 patients. Thus, the administration of high-dose IVIG to hospitalized COVID-19 patients may improve their clinical evolution by modulating their hyperinflammatory and immunosuppressive status.

SUBMITTER: Rodriguez de la Concepcion ML

PROVIDER: S-EPMC8321664 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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High-dose intravenous immunoglobulins might modulate inflammation in COVID-19 patients.

Rodríguez de la Concepción María Luisa ML Ainsua-Enrich Erola E Reynaga Esteban E Ávila-Nieto Carlos C Santos Jose Ramón JR Roure Silvia S Mateu Lourdes L Paredes Roger R Puig Jordi J Jimenez Juan Manuel JM Izquierdo-Useros Nuria N Clotet Bonaventura B Pedro-Botet María Luisa ML Carrillo Jorge J

Life science alliance 20210728 9

The use of high-dose of intravenous immunoglobulins (IVIGs) as immunomodulators for the treatment of COVID-19-affected individuals has shown promising results. IVIG reduced inflammation in these patients, who progressively restored respiratory function. However, little is known about how they may modulate immune responses in COVID-19 individuals. Here, we have analyzed the levels of 41 inflammatory biomarkers in plasma samples obtained at day 0 (pretreatment initiation), 3, 7, and 14 from five h ...[more]

PMID: 34321327

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Project description:BackgroundA profound inflammation-mediated lung injury with long-term acute respiratory distress and high mortality is one of the major complications of critical COVID-19. Immunoglobulin M (IgM)-enriched immunoglobulins seem especially capable of mitigating the inflicted inflammatory harm. However, the efficacy of intravenous IgM-enriched preparations in critically ill patients with COVID-19 is largely unclear.MethodsIn this retrospective multicentric cohort study, 316 patients with laboratory-confirmed critical COVID-19 were treated in ten German and Austrian ICUs between May 2020 and April 2021. The primary outcome was 30-day mortality. Analysis was performed by Cox regression models. Covariate adjustment was performed by propensity score weighting using machine learning-based SuperLearner to overcome the selection bias due to missing randomization. In addition, a subgroup analysis focusing on different treatment regimens and patient characteristics was performed.ResultsOf the 316 ICU patients, 146 received IgM-enriched immunoglobulins and 170 cases did not, which served as controls. There was no survival difference between the two groups in terms of mortality at 30 days in the overall cohort (HRadj: 0.83; 95% CI: 0.55 to 1.25; p = 0.374). An improved 30-day survival in patients without mechanical ventilation at the time of the immunoglobulin treatment did not reach statistical significance (HRadj: 0.23; 95% CI: 0.05 to 1.08; p = 0.063). Also, no statistically significant difference was observed in the subgroup when a daily dose of ≥ 15 g and a duration of ≥ 3 days of IgM-enriched immunoglobulins were applied (HRadj: 0.65; 95% CI: 0.41 to 1.03; p = 0.068).ConclusionsAlthough we cannot prove a statistically reliable effect of intravenous IgM-enriched immunoglobulins, the confidence intervals may suggest a clinically relevant effect in certain subgroups. Here, an early administration (i.e. in critically ill but not yet mechanically ventilated COVID-19 patients) and a dose of ≥ 15 g for at least 3 days may confer beneficial effects without concerning safety issues. However, these findings need to be validated in upcoming randomized clinical trials. Trial registration DRKS00025794 , German Clinical Trials Register, https://www.drks.de . Registered 6 July 2021.

Project description:Oxidative stress is a pivotal point in the pathophysiology of COVID-19 and presumably also in Long-COVID. Inflammation and oxidative stress are mutually reinforcing each other, thus contributing to the systemic hyperinflammatory state and coagulopathy which are cardinal pathological mechanisms of severe stages. COVID-19 patients, like other critically ill patients e.g. with pneumonia, very often show severe deficiency of the antioxidant vitamin C. So far, it has not been investigated how long this deficiency lasts or whether patients with long COVID symptoms also suffer from deficiencies. A vitamin C deficit has serious pathological consequences because vitamin C is one of the most effective antioxidants, but also co-factor of many enzymatic processes that affect the immune and nervous system, blood circulation and energy metabolism. Because of its anti-oxidative, anti-inflammatory, endothelial-restoring, and immunomodulatory effects the supportive intravenous (iv) use of supraphysiological doses has been investigated so far in 12 controlled or observational studies with altogether 1578 inpatients with COVID-19. In these studies an improved oxygenation, a decrease in inflammatory markers and a faster recovery were observed. In addition, early treatment with iv high dose vitamin C seems to reduce the risks of severe courses of the disease such as pneumonia and also mortality. Persistent inflammation, thrombosis and a dysregulated immune response (auto-immune phenomena and/or persistent viral load) seem to be major contributors to Long-COVID. Oxidative stress and inflammation are involved in the development and progression of fatigue and neuro-psychiatric symptoms in various diseases by disrupting tissue (e.g. autoantibodies), blood flow (e.g. immune thrombosis) and neurotransmitter metabolism (e.g. excitotoxicity). In oncological diseases, other viral infections and autoimmune diseases, which are often associated with fatigue, cognitive disorders, pain and depression similar to Long-COVID, iv high dose vitamin C was shown to significantly relieve these symptoms. Supportive iv vitamin C in acute COVID-19 might therefore reduce the risk of severe courses and also the development of Long-COVID.

Project description:BackgroundThe development of specific immunoglobulins to COVID-19 after natural infection or vaccination has been proposed. The efficacy and dynamics of this response are not clear yet.AimThis study aims to analyze the immunoglobulins response among COVID-19 patients, COVID-19 vaccine recipients and random individuals.MethodsA total of 665 participants including 233 COVID-19 patients, 288 COVID-19 vaccine recipients, and 144 random individuals were investigated for anti-COVID-19 immunoglobulins (IgA, IgG, IgM).ResultsAmong COVID-19 patients, 22.7% had detectable IgA antibodies with a mean of 27.3±57.1 ng/ml, 29.6% had IgM antibodies with a mean of 188.4±666.0 BAU/ml, while 59.2% had IgG antibodies with a mean of 101.7±139.7 BAU/ml. Pfizer-BioNTech vaccine recipients had positive IgG in 99.3% with a mean of 515.5±1143.5 BAU/ml while 85.7% of Sinopharm vaccine recipients had positive IgG with a mean of 170.0±230.0 BAU/ml. Regarding random individuals, 54.9% had positive IgG with a mean of 164.3±214 BAU/ml. The peak IgM response in COVID-19 patients was detected early at 15-22 days, followed by IgG peak at 16-30 days, and IgA peak at 0-60 days. IgM antibodies disappeared at 61-90 days, while IgG and IgA antibodies decreased slowly after the peak and remained detectable up to 300 days. The frequency of IgG positivity among patients was significantly affected by increased age, admission department (inpatient or outpatient), symptoms, need for oxygen therapy, and increased duration between positive COVID-19 RT PCR test and serum sampling (p˂0.05). Positive correlations were noted between different types of immunoglobulins (IgG, IgM, and IgA) among patients.ConclusionsNatural infection and COIVD-19 vaccines provide IgG-mediated immunity. The class, positivity, mean, efficacy, and duration of immunoglobulins response are affected by the mechanism of immunity and host related variables. Random community individuals had detectable COVID-19 IgG at ~55%, far from reaching herd immunity levels.

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High-dose intravenous immunoglobulins might modulate inflammation in COVID-19 patients.

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High-dose intravenous immunoglobulins might modulate inflammation in COVID-19 patients.

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