Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 13 de 13
Filter
1.
Neurotherapeutics ; 18(4): 2397-2418, 2021 10.
Article in English | MEDLINE | ID: covidwho-1509358

ABSTRACT

In the last 25 years, intravenous immunoglobulin (IVIg) has had a major impact in the successful treatment of previously untreatable or poorly controlled autoimmune neurological disorders. Derived from thousands of healthy donors, IVIg contains IgG1 isotypes of idiotypic antibodies that have the potential to bind pathogenic autoantibodies or cross-react with various antigenic peptides, including proteins conserved among the "common cold"-pre-pandemic coronaviruses; as a result, after IVIg infusions, some of the patients' sera may transiently become positive for various neuronal antibodies, even for anti-SARS-CoV-2, necessitating caution in separating antibodies derived from the infused IVIg or acquired humoral immunity. IVIg exerts multiple effects on the immunoregulatory network by variably affecting autoantibodies, complement activation, FcRn saturation, FcγRIIb receptors, cytokines, and inflammatory mediators. Based on randomized controlled trials, IVIg is approved for the treatment of GBS, CIDP, MMN and dermatomyositis; has been effective in, myasthenia gravis exacerbations, and stiff-person syndrome; and exhibits convincing efficacy in autoimmune epilepsy, neuromyelitis, and autoimmune encephalitis. Recent evidence suggests that polymorphisms in the genes encoding FcRn and FcγRIIB may influence the catabolism of infused IgG or its anti-inflammatory effects, impacting on individualized dosing or efficacy. For chronic maintenance therapy, IVIg and subcutaneous IgG are effective in controlled studies only in CIDP and MMN preventing relapses and axonal loss up to 48 weeks; in practice, however, IVIg is continuously used for years in all the aforementioned neurological conditions, like is a "forever necessary therapy" for maintaining stability, generating challenges on when and how to stop it. Because about 35-40% of patients on chronic therapy do not exhibit objective neurological signs of worsening after stopping IVIg but express subjective symptoms of fatigue, pains, spasms, or a feeling of generalized weakness, a conditioning effect combined with fear that discontinuing chronic therapy may destabilize a multi-year stability status is likely. The dilemmas of continuing chronic therapy, the importance of adjusting dosing and scheduling or periodically stopping IVIg to objectively assess necessity, and concerns in accurately interpreting IVIg-dependency are discussed. Finally, the merit of subcutaneous IgG, the ineffectiveness of IVIg in IgG4-neurological autoimmunities, and genetic factors affecting IVIg dosing and efficacy are addressed.


Subject(s)
Autoimmune Diseases of the Nervous System/immunology , Autoimmune Diseases of the Nervous System/therapy , Autoimmunity/immunology , Immunoglobulins, Intravenous/administration & dosage , Immunoglobulins, Intravenous/immunology , Withholding Treatment , Autoantibodies/drug effects , Autoantibodies/immunology , Autoimmunity/drug effects , COVID-19/immunology , COVID-19/therapy , Dose-Response Relationship, Immunologic , Humans , SARS-CoV-2/drug effects , SARS-CoV-2/immunology , Treatment Outcome
3.
Life Sci Alliance ; 4(9)2021 09.
Article in English | MEDLINE | ID: covidwho-1332524

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.


Subject(s)
COVID-19/therapy , Immunoglobulins, Intravenous/therapeutic use , Administration, Intravenous , Adult , Aged , Biomarkers/blood , COVID-19/blood , COVID-19/immunology , COVID-19/virology , Chemokines/blood , Cytokines/blood , Female , Humans , Immunity/immunology , Immunoglobulins/immunology , Immunoglobulins/therapeutic use , Immunoglobulins, Intravenous/immunology , Inflammation/blood , Inflammation/therapy , Inflammation/virology , Male , Middle Aged , SARS-CoV-2/isolation & purification
5.
J Med Virol ; 93(5): 2654-2661, 2021 05.
Article in English | MEDLINE | ID: covidwho-1196514

ABSTRACT

A novel coronavirus (SARS-CoV-2) is responsible for a severe acute respiratory syndrome called coronavirus disease 2019 (COVID-19). It is originated in Wuhan, China, in December 2019. Due to its extreme transmissibility with droplets and human contacts, in a few months, it has become a pandemic. Nowadays, no effective therapy is available, and the scientific community is moving to find a therapeutic choice to fight this silent enemy. Studies are ongoing on several therapeutic options, including antiviral agents, immunomodulant drugs, and immunotherapy. Due to viral features, including the ability to start an inflammatory response that seems to be the fulcrum of COVID-19 pathogenic action, immunotherapy could represent a promising alternative waiting for the vaccine. High-dose intravenous immunoglobulin (IVIg), already used in other infectious diseases, could represent an effective help. The aim of this narrative review is to reassemble the clinical experiences on the use of IVIg in COVID-19 and the rationale of its use.


Subject(s)
COVID-19/drug therapy , COVID-19/immunology , Immunoglobulins, Intravenous/immunology , Immunoglobulins, Intravenous/therapeutic use , Inflammation/immunology , Antiviral Agents/therapeutic use , China , Cross Reactions , Humans , Immunotherapy , Pandemics , SARS-CoV-2
6.
Front Immunol ; 12: 627285, 2021.
Article in English | MEDLINE | ID: covidwho-1120044

ABSTRACT

Introduction: Cross-reactivity to SARS-CoV-2 antigenic peptides has been detected on T-cells from pre-pandemic donors due to recognition of conserved protein fragments within members of the coronavirus's family. Further, preexisting antibodies recognizing SARS-CoV-2 with conserved epitopes in the spike region have been now seen in uninfected individuals. High-dose Intravenous Immunoglobulin (IVIg), derived from thousands of healthy donors, contains natural IgG antibodies against various antigens which can be detected both within the IVIg preparations and in the serum of IVIg-receiving patients. Whether IVIg preparations from pre-pandemic donors also contain antibodies against pre-pandemic coronaviruses or autoreactive antibodies that cross-react with SARS-CoV-2 antigenic epitopes, is unknown. Methods: 13 samples from 5 commercial IVIg preparations from pre-pandemic donors (HyQvia (Baxalta Innovations GmbH); Privigen (CSL Behring); Intratect (Biotest AG); IgVena (Kedrion S.p.A); and Flebogamma (Grifols S.A.) were blindly screened using a semi-quantitative FDA-approved and validated enzyme-linked immunosorbent assay (ELISA) (Euroimmun, Lubeck, Germany). Results: Nine of thirteen preparations (69.2%), all from two different manufactures, were antibody-positive based on the defined cut-off positivity (index of sample OD to calibrator OD > 1.1). From one manufacturer, 7/7 lots (100%) and from another 2/3 lots (67%), tested positive for cross-reacting antibodies. 7/9 of the positive preparations (77%) had titers as seen in asymptomatically infected individuals or recent COVID19-recovered patients, while 2/9 (23%) had higher titers, comparable to those seen in patients with active symptomatic COVID-19 infection (index > 2.2). Conclusion: Pre-pandemic IVIg donors have either natural autoantibodies or pre-pandemic cross-reactive antibodies against antigenic protein fragments conserved among the "common cold" - related coronaviruses. The findings are important in: (a) assessing true anti-SARS-CoV-2-IgG seroprevalence avoiding false positivity in IVIg-receiving patients; (b) exploring potential protective benefits in patients with immune-mediated conditions and immunodeficiencies receiving acute or chronic maintenance IVIg therapy, and (c) validating data from a recent controlled study that showed significantly lower in-hospital mortality in the IVIg- treated group.


Subject(s)
Antibodies, Viral/immunology , Autoimmunity , COVID-19/immunology , Immunoglobulins, Intravenous/immunology , SARS-CoV-2/immunology , Seasons , COVID-19/epidemiology , Cross Reactions , Epitopes/immunology , Humans , Spike Glycoprotein, Coronavirus/immunology
7.
Immunotherapy ; 13(5): 397-407, 2021 04.
Article in English | MEDLINE | ID: covidwho-1073248

ABSTRACT

Background: This study assesses the feasibility of producing hyperimmune anti-COVID-19 intravenously administrable immunoglobulin (C-IVIG) from pooled convalescent plasma (PCP) to provide a safe and effective passive immunization treatment option for COVID-19. Materials & methods: PCP was fractionated by modified caprylic acid precipitation followed by ultrafiltration/diafiltration to produce hyperimmune C-IVIG. Results: In C-IVIG, the mean SARS-CoV-2 antibody level was found to be threefold (104 ± 30 cut-off index) that of the PCP (36 ± 8.5 cut-off index) and mean protein concentration was found to be 46 ± 3.7 g/l, comprised of 89.5% immunoglobulins. Conclusion: The current method of producing C-IVIG is feasible as it uses locally available PCP and simpler technology and yields a high titer of SARS-CoV-2 antibody. The safety and efficacy of C-IVIG will be evaluated in a registered clinical trial (NCT04521309).


Subject(s)
Antibodies, Viral/isolation & purification , COVID-19/blood , Immunoglobulins, Intravenous/isolation & purification , SARS-CoV-2/immunology , Antibodies, Viral/immunology , Antibodies, Viral/therapeutic use , COVID-19/therapy , Caprylates/chemistry , Chemical Fractionation , Humans , Immunization, Passive , Immunoglobulins, Intravenous/immunology , Immunoglobulins, Intravenous/therapeutic use
8.
Transfusion ; 61(2): 356-360, 2021 02.
Article in English | MEDLINE | ID: covidwho-889820

ABSTRACT

BACKGROUND: There are several types of coronaviruses that infect humans and cause disease. The latest is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is an emerging global threat with no current effective treatment. Normal intravenous immunoglobulin (N-IVIG) has been administered to coronavirus disease 2019 (COVID-19) patients to control severe inflammation and the cellular immune response. However, the neutralizing activity of N-IVIG against SARS-CoV-2 has not yet been fully evaluated. The aim of this study was to determine whether N-IVIG manufactured before the start of the COVID-19 pandemic contained IgG antibodies against the circulating human coronaviruses (HCoVs) that cross-react with the highly pathogenic coronaviruses SARS-CoV-1, Middle East respiratory syndrome coronavirus (MERS-CoV), and SARS-CoV-2. No cases of SARS-CoV-1 or MERS-CoV have been reported in Japan. STUDY DESIGN AND METHODS: The neutralizing and binding activities of N-IVIG against SARS-CoV-1, MERS-CoV, SARS-CoV-2, HCoV 229E, and HCoV OC43 were evaluated. Nine N-IVIG lots manufactured between 2000 and 2018, derived from donors in Japan, were tested. Binding activity was evaluated by indirect immunofluorescence assay. RESULTS: None of the N-IVIG lots tested displayed neutralizing or binding activity against SARS-CoV-1, MERS-CoV, or SARS-CoV-2. However, they displayed substantial neutralizing and binding activity against HCoV OC43 and weak neutralizing and substantial binding activity against HCoV 229E. CONCLUSION: N-IVIG derived from healthy donors in Japan before the start of the COVID-19 pandemic had no direct effect against SARS-CoV-2. Further studies are warranted to determine the effects of N-IVIG manufactured after the start of the COVID-19 pandemic against SARS-CoV-2.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/metabolism , Coronavirus 229E, Human/immunology , Coronavirus OC43, Human/immunology , Immunoglobulins, Intravenous/immunology , Immunoglobulins, Intravenous/metabolism , Humans , Immunity, Cellular/physiology , Immunoglobulin G/immunology , Immunoglobulin G/metabolism , Japan , Middle East Respiratory Syndrome Coronavirus/immunology , Pandemics , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology
9.
J Infect Dis ; 222(12): 1960-1964, 2020 Nov 13.
Article in English | MEDLINE | ID: covidwho-780405

ABSTRACT

The 2020 SARS-CoV-2 pandemic is caused by a zoonotic coronavirus transmitted to humans, similar to earlier events. Whether the other, seasonally circulating coronaviruses induce cross-reactive, potentially even cross-neutralizing, antibodies to the new species in humans is unclear. The question is particularly relevant for people with immune deficiencies, as their health depends on treatment with immunoglobulin preparations that need to contain neutralizing antibodies against the pathogens in their environment. Testing 54 intravenous immunoglobulin preparations, produced from plasma collected in Europe and the United States, confirmed highly potent neutralization of a seasonal coronavirus; however, no cross-neutralization of the new SARS-CoV-2 was seen.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Immunoglobulins, Intravenous/immunology , SARS-CoV-2/immunology , COVID-19/virology , Cross Reactions , Europe , Humans , Neutralization Tests , Plasma/immunology , United States
10.
Immunotherapy ; 12(17): 1247-1255, 2020 12.
Article in English | MEDLINE | ID: covidwho-750790

ABSTRACT

Background: Cross-reactivity against human coronaviruses with Flebogamma® DIF and Gamunex®-C, two available intravenous immunoglobulins (IVIG), has been reported. In this study, these IVIG were tested for neutralization activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), SARS-CoV and Middle East respiratory syndrome CoV (MERS-CoV). Materials & methods: Neutralization capacity of lots of IVIG manufactured prior to COVID-19 pandemic was assessed against these viruses in cell culture. Infectivity neutralization was quantified by percent reduction in plaque-forming units and/or cytopathic/cytotoxic methods. Results: All IVIG preparations showed neutralization of SARS-CoV-2 isolates. All IVIG lots produced neutralization of SARS-CoV. No IVIG preparation showed significant neutralizing activity against MERS-CoV. Conclusion: The tested IVIG contain antibodies with significant in vitro cross-neutralization capacity against SARS-CoV-2 and SARS-CoV, but not MERS-CoV. These preparations are currently under evaluation as potential therapies for COVID-19.


Subject(s)
Antibodies, Neutralizing/immunology , Betacoronavirus/immunology , Coronavirus Infections/immunology , Immunoglobulins, Intravenous/immunology , Pneumonia, Viral/immunology , Antibodies, Viral/immunology , Antibodies, Viral/pharmacology , Betacoronavirus/drug effects , COVID-19 , Cross Reactions/immunology , Humans , Immunoglobulins, Intravenous/pharmacology , Middle East Respiratory Syndrome Coronavirus/drug effects , Middle East Respiratory Syndrome Coronavirus/immunology , Pandemics , SARS-CoV-2
12.
Expert Opin Biol Ther ; 20(9): 1033-1046, 2020 09.
Article in English | MEDLINE | ID: covidwho-692644

ABSTRACT

INTRODUCTION: Coronavirus disease 2019 (COVID-19) has spread to several countries globally. Currently, there is no specific drug or vaccine available for managing COVID-19. Antibody-based immunotherapeutic strategies using convalescent plasma, monoclonal antibodies (mAbs), neutralizing antibodies (NAbs), and intravenous immunoglobulins have therapeutic potential. AREAS COVERED: This review provides the current status of the development of various antibody-based immunotherapeutics such as convalescent plasma, mAbs, NAbs, and intravenous immunoglobulins against COVID-19. The review also highlights their advantages, disadvantages, and clinical utility for the treatment of COVID-19 patients. EXPERT OPINION: In a pandemic situation such as COVID-19, the development of new drugs should focus on and expedite the strategies where safety and efficacy are proven. Antibody-based immunotherapeutic approaches such as convalescent plasma, intravenous immunoglobulins, and mAbs have a proven record of safety and efficacy and are in use for decades. Some of them are already being used to manage COVID-19 patients and found to be useful. However, the mAbs with virus neutralization potential is the need of the hour during this COVID-19 pandemic to be more specific and virus targeted. The research and investment need to be accelerated to bring them into clinical use for prophylactic and therapeutic purposes against COVID-19.


Subject(s)
Betacoronavirus , Immunoglobulins, Intravenous/therapeutic use , Immunotherapy/methods , Antibodies, Neutralizing/therapeutic use , COVID-19 , Coronavirus Infections/blood , Coronavirus Infections/immunology , Coronavirus Infections/therapy , Humans , Immunization, Passive , Immunoglobulins, Intravenous/immunology , Immunotherapy/trends , Pandemics/prevention & control , Pneumonia, Viral/blood , Pneumonia, Viral/immunology , Pneumonia, Viral/therapy , SARS-CoV-2
13.
Immunotherapy ; 12(8): 571-576, 2020 06.
Article in English | MEDLINE | ID: covidwho-245635

ABSTRACT

Aim: There is a critical need for effective therapies that are immediately available to control the spread of COVID-19 disease. Material & methods: Gamunex®-C and Flebogamma® DIF (Grifols) intravenous immunoglobulin (IVIG) products were tested using ELISA techniques for antibodies against several antigens of human common betacoronaviruses that may crossreact with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Results: Both IVIGs showed consistent reactivity to components of the tested viruses. Positive crossreactivity was seen in SARS-CoV, middle east respiratory syndrome-CoV and SARS-CoV-2. For SARS-CoV-2, positive reactivity was observed at IVIG concentrations ranging from 100 µg/ml with Gamunex-C to 1 mg/ml with Flebogamma 5% DIF. Conclusion: Gamunex-C and Flebogamma DIF contain antibodies reacting against SARS-CoV-2 antigens. Studies to confirm the utility of IVIG preparations for COVID-19 management may be warranted.


Subject(s)
Antigens, Viral/immunology , Betacoronavirus/immunology , Coronavirus Infections/therapy , Immunoglobulins, Intravenous/immunology , Immunoglobulins, Intravenous/therapeutic use , Pneumonia, Viral/therapy , SARS Virus/immunology , Antibodies, Viral/immunology , COVID-19 , Cross Reactions/immunology , Enzyme-Linked Immunosorbent Assay , Humans , Immunoglobulins, Intravenous/blood , Middle East Respiratory Syndrome Coronavirus/immunology , Pandemics , SARS-CoV-2
SELECTION OF CITATIONS
SEARCH DETAIL