High-dose intravenous immunoglobulins might modulate inflammation in COVID-19 patients.
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ABSTRACT:
SUBMITTER: Rodriguez de la Concepcion ML
PROVIDER: S-EPMC8321664 | biostudies-literature |
REPOSITORIES: biostudies-literature
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| S-EPMC8797024 | biostudies-literature
Project description:Although several therapeutic strategies have been investigated, the optimal treatment approach for patients with coronavirus disease (COVID-19) remains to be elucidated. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of polyclonal intravenous immunoglobulin (IVIG) therapy in COVID-19. A systematic literature search using appropriate medical subject heading (MeSH) terms was performed through Medline (PubMed), EMBASE, SCOPUS, OVID and Cochrane Library electronic databases. The main outcomes considered were mortality and safety of IVIG versus placebo/standard of care. This review was carried out in accordance with Cochrane methodology including the risk bias assessment and grading of the quality of evidence. Measures of treatment effect were mean differences (MD) together with 95% confidence intervals (CIs) for continuous outcome measures and risk ratio (RR) or MD for binary outcomes. Two reviewers independently extracted data from individual studies, and disagreements were resolved by a third reviewer. A total of 2401 COVID-19 patients from 10 studies (four randomized controlled trials (RCT) and six non-randomized controlled trials (non-RCTs)) were included in the analysis. Participants received IVIG or placebo/standard of care. The use of IVIG was not associated with a significantly reduced risk of death (RR 0.50, 95% CIs 0.18-1.36, p = 0.17 for RCTs; RR 0.95, 95% CIs 0.61-1.58, p = 0.94 for non-RCTs; low certainty of evidence). IVIG significantly reduced the length of hospital stay (MD -2.24, 95% CIs -3.20/-1.27; p = 0.00001; low certainty of evidence), although this difference was significant only for studies evaluating moderate COVID-19 patients. No significant difference was observed in the incidence of overall and serious adverse events between IVIG recipients and controls (very low certainty of evidence). The current evidence from the literature does not support the use of IVIG in COVID-19 patients.
| S-EPMC8779789 | biostudies-literature
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.
| S-EPMC9260992 | biostudies-literature
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.
| S-EPMC9100929 | biostudies-literature
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.
| S-EPMC9928079 | biostudies-literature
Project description: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.
| S-EPMC7372093 | biostudies-literature
Project description:Intravascular neutrophil recruitment and activation are key pathogenic factors that contribute to vascular injury. Intravenous immunoglobulin (IVIG) has been shown to have a beneficial effect in systemic inflammatory disorders; however, the mechanisms underlying IVIG's inhibitory effect on neutrophil recruitment and activation are not understood.We studied the mechanisms by which IVIG exerts protection from neutrophil-mediated acute vascular injury.We examined neutrophil behavior in response to IVIG in vivo, using real-time intravital microscopy. We found that an antibody that blocks both Fc?RIII and its inhibitory receptor counterpart, Fc?RIIB, abrogated the inhibitory effect of IVIG on leukocyte recruitment and heterotypic red blood cell (RBC) interactions with adherent leukocytes in wild-type mice. In the context of sickle cell disease, the blockade of both Fc?RIIB and III abrogated the protective effect of IVIG on acute vaso-occlusive crisis caused by neutrophil recruitment and activation. Analysis of Fc?RIIB- and Fc?RIII-deficient mice revealed the predominant expression of Fc?RIII on circulating neutrophils. Fc?RIII mediated IVIG-triggered inhibition of leukocyte recruitment, circulating RBC capture, and enhanced Mac-1 activity, whereas Fc?RIIB was dispensable. In addition, Fc?RIII-induced IVIG anti-inflammatory activity in neutrophils was mediated by recruitment of Src homology 2 (SH2)-containing tyrosine phosphatase-1 (SHP-1). Indeed, the protective effect of IVIG on leukocyte recruitment and activation was abrogated in SHP-1-mutant mice.Fc?RIII, a classic activating receptor, has an unexpected inhibitory role on neutrophil adhesion and activation via recruitment of SHP-1 in response to IVIG. Our results identify SHP-1 as a therapeutic target in neutrophil-mediated vascular injury.
| S-EPMC3351009 | biostudies-literature
Project description:Hepatotoxicity is a rare adverse event of methylprednisolone that should be considered in clinical practice. In patients at risk, we propose liver function surveillance, by measuring hepatic enzymes concentration 15-30 days after methylprednisolone administration. Additionally, we propose ACTH, dexamethasone, or plasma exchange as alternate treatment options for these patients.
| S-EPMC5538224 | biostudies-other
Project description:PurposeTocilizumab has been shown to decrease mortality when used concomitantly with steroids in COVID-19 with 8 mg/kg (max 800 mg) being the standard dose. Our study sought to assess whether a low dose (400 mg) shows similar benefit compared to a high dose for COVID patients concurrently on the same median dose of steroids.Materials/methodsA retrospective, multihospital observational study of COVID-19 patients who received tocilizumab in conjunction with steroids between March 2020 and August 2021 was conducted.ResultsA total of 407 patients were analyzed with low dose group being significantly more ill at baseline as a higher percentage of patients received vasopressors, were admitted to the ICU and on mechanical ventilation. In the propensity-matched analysis, both groups receiving a median dexamethasone equivalent dose of 10 mg showed no difference in 28-day mortality (p = 0.613). The high dose group had a higher rate of fungal and viral infections.ConclusionCompared to low dose tocilizumab, the high dose did not provide additional efficacy and mortality benefit but resulted in higher fungal and viral infections. This study illustrates that low dose tocilizumab can be an alternative to high dose during a drug shortage of tocilizumab without compensating for efficacy and safety, conserving resources for more patients.
| S-EPMC10084735 | biostudies-literature
Project description:AIM:Patients on parenteral nutrition (PN) are prone to inflammation. This may aggravate an existing proinflammatory state and become a critical factor in the development of liver dysfunction (LD). Intravenous fish oil may attenuate this inflammatory state, but data on its use in adults are scarce. The aim of this study was to investigate the effects of adding a pure fish oil intravenous lipid emulsion (ILE) into short- and long-term PN in patients either at risk of, or with existing, inflammation. METHODS:A retrospective analysis of 61 patients (32 female, 29 male, mean age 51.5 ± 12.6 years) who received all-in-one PN, including amino acids, glucose, and lipids supplemented with pure fish oil ILE, was performed. Pure fish oil ILE (Omegaven®, Fresenius Kabi, Bad Homburg, Germany) was used along with the standard ILE to reach a fish oil dose of 0.4-0.5 g fish oil/kg/d. Diagnoses were chronic intestinal failure (CIF, n = 20), Crohn's disease (CD, n = 22), and ulcerative colitis (UC, n = 19). The observation period was 12 months for CIF and 21 days for UC and CD. RESULTS:A reduction in inflammation was noticeable in all patients and became statistically significant in CD (hsCRP p < 0.0001, ESR p = 0.0034, procalcitonin p = 0.0014, Il-6 p = 0.001) and UC groups (hsCRP and ESR p < 0.0001, Il-6 p = 0.0001, TNF-? p = 0.0113). In the CIF group, the total bilirubin concentration (p = 0.2157) and aspartate transaminase SGOT (p = 0.1785) did not vary over time. CONCLUSIONS:PN with pure fish oil ILE reduces some inflammatory parameters in IBD and maintains liver function parameters in CIF patients. Fish oil might become a valuable ingredient in both short- and long-term PN in patients at risk of liver dysfunction.
| S-EPMC7551918 | biostudies-literature