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1.
Transfusion ; 61(11): 3267-3271, 2021 11.
Article in English | MEDLINE | ID: covidwho-1434847

ABSTRACT

BACKGROUND: Large clinical trials have demonstrated the overall safety of vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, reports have emerged of autoimmune phenomena, including vaccine-associated myocarditis, immune thrombocytopenia, and immune thrombotic thrombocytopenia. CASE PRESENTATION: Here we present a novel case of a young woman who developed life-threatening autoimmune hemolytic anemia (AIHA) after her first dose of a SARS-CoV-2 mRNA vaccine. Notably, initial direct antiglobulin testing was negative using standard anti-IgG reagents, which are "blind" to certain immunoglobulin (IgG) isotypes. Further testing using an antiglobulin reagent that detects all IgG isotypes was strongly positive and confirmed the diagnosis of AIHA. The patient required transfusion with 13 units of red blood cells, as well as treatment with corticosteroids, rituximab, mycophenolate mofetil, and immune globulin. CONCLUSION: As efforts to administer SARS-CoV-2 vaccines continue globally, clinicians must be aware of potential autoimmune sequelae of these therapies.


Subject(s)
Anemia, Hemolytic, Autoimmune/chemically induced , Anemia, Hemolytic, Autoimmune/therapy , COVID-19 Vaccines/adverse effects , COVID-19/prevention & control , SARS-CoV-2 , Adrenal Cortex Hormones/administration & dosage , Adult , Anemia, Hemolytic, Autoimmune/blood , Autoantibodies/blood , COVID-19/blood , COVID-19 Vaccines/administration & dosage , Erythrocyte Transfusion , Female , Humans , Immunoglobulin G/blood , Immunoglobulins/administration & dosage , Mycophenolic Acid/administration & dosage , Rituximab/administration & dosage
2.
Viruses ; 13(3)2021 02 27.
Article in English | MEDLINE | ID: covidwho-1190473

ABSTRACT

The immunological findings from autopsies, biopsies, and various studies in COVID-19 patients show that the major cause of morbidity and mortality in COVID-19 is excess immune response resulting in hyper-inflammation. With the objective to review various mechanisms of excess immune response in adult COVID-19 patients, Pubmed was searched for free full articles not related to therapeutics or co-morbid sub-groups, published in English until 27.10.2020, irrespective of type of article, country, or region. Joanna Briggs Institute's design-specific checklists were used to assess the risk of bias. Out of 122 records screened for eligibility, 42 articles were included in the final review. The review found that eventually, most mechanisms result in cytokine excess and up-regulation of Nuclear Factor-κB (NF-κB) signaling as a common pathway of excess immune response. Molecules blocking NF-κB or targeting downstream effectors like Tumour Necrosis Factor α (TNFα) are either undergoing clinical trials or lack specificity and cause unwanted side effects. Neutralization of upstream histamine by histamine-conjugated normal human immunoglobulin has been demonstrated to inhibit the nuclear translocation of NF-κB, thereby preventing the release of pro-inflammatory cytokines Interleukin (IL) 1ß, TNF-α, and IL-6 and IL-10 in a safer manner. The authors recommend repositioning it in COVID-19.


Subject(s)
COVID-19/immunology , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/immunology , Histamine/administration & dosage , Immunoglobulins/administration & dosage , NF-kappa B/antagonists & inhibitors , NF-kappa B/immunology , Cytokine Release Syndrome/prevention & control , Cytokine Release Syndrome/virology , Databases, Factual , Down-Regulation/drug effects , Drug Repositioning , Humans , Immunity , Orphan Drug Production , SARS-CoV-2/drug effects , Signal Transduction/drug effects
3.
J Emerg Med ; 60(4): 531-535, 2021 04.
Article in English | MEDLINE | ID: covidwho-1139524

ABSTRACT

BACKGROUND: As the number of coronavirus disease 2019 (COVID-19) cases increases globally, more cases of a rare COVID-19-associated disease process are being identified in the pediatric population. This syndrome is referred to as multisystem inflammatory syndrome in children (MIS-C). Clinical manifestations of the syndrome vary and include one or a combination of the following: vasodilatory shock, cardiogenic shock, Kawasaki-like disease, cytokine storming, coronary artery dilatation, and aneurysms. CASE REPORT: This case report describes the presentation, findings, workup, and treatment for a 9-year-old boy diagnosed with MIS-C. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: It is important to recognize MIS-C, as it shares many of the same features as other disease processes, for example, Kawasaki disease and toxic shock syndrome, but has different complications if left untreated.


Subject(s)
COVID-19/complications , Systemic Inflammatory Response Syndrome/diagnosis , Aspirin/administration & dosage , Aspirin/therapeutic use , COVID-19/diagnosis , COVID-19/drug therapy , Child , Humans , Immunoglobulins/administration & dosage , Immunoglobulins/therapeutic use , Male , SARS-CoV-2 , Systemic Inflammatory Response Syndrome/drug therapy
4.
Viruses ; 13(3)2021 02 27.
Article in English | MEDLINE | ID: covidwho-1125711

ABSTRACT

The immunological findings from autopsies, biopsies, and various studies in COVID-19 patients show that the major cause of morbidity and mortality in COVID-19 is excess immune response resulting in hyper-inflammation. With the objective to review various mechanisms of excess immune response in adult COVID-19 patients, Pubmed was searched for free full articles not related to therapeutics or co-morbid sub-groups, published in English until 27.10.2020, irrespective of type of article, country, or region. Joanna Briggs Institute's design-specific checklists were used to assess the risk of bias. Out of 122 records screened for eligibility, 42 articles were included in the final review. The review found that eventually, most mechanisms result in cytokine excess and up-regulation of Nuclear Factor-κB (NF-κB) signaling as a common pathway of excess immune response. Molecules blocking NF-κB or targeting downstream effectors like Tumour Necrosis Factor α (TNFα) are either undergoing clinical trials or lack specificity and cause unwanted side effects. Neutralization of upstream histamine by histamine-conjugated normal human immunoglobulin has been demonstrated to inhibit the nuclear translocation of NF-κB, thereby preventing the release of pro-inflammatory cytokines Interleukin (IL) 1ß, TNF-α, and IL-6 and IL-10 in a safer manner. The authors recommend repositioning it in COVID-19.


Subject(s)
COVID-19/immunology , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/immunology , Histamine/administration & dosage , Immunoglobulins/administration & dosage , NF-kappa B/antagonists & inhibitors , NF-kappa B/immunology , Cytokine Release Syndrome/prevention & control , Cytokine Release Syndrome/virology , Databases, Factual , Down-Regulation/drug effects , Drug Repositioning , Humans , Immunity , Orphan Drug Production , SARS-CoV-2/drug effects , Signal Transduction/drug effects
5.
Viruses ; 13(3)2021 02 27.
Article in English | MEDLINE | ID: covidwho-1120708

ABSTRACT

The immunological findings from autopsies, biopsies, and various studies in COVID-19 patients show that the major cause of morbidity and mortality in COVID-19 is excess immune response resulting in hyper-inflammation. With the objective to review various mechanisms of excess immune response in adult COVID-19 patients, Pubmed was searched for free full articles not related to therapeutics or co-morbid sub-groups, published in English until 27.10.2020, irrespective of type of article, country, or region. Joanna Briggs Institute's design-specific checklists were used to assess the risk of bias. Out of 122 records screened for eligibility, 42 articles were included in the final review. The review found that eventually, most mechanisms result in cytokine excess and up-regulation of Nuclear Factor-κB (NF-κB) signaling as a common pathway of excess immune response. Molecules blocking NF-κB or targeting downstream effectors like Tumour Necrosis Factor α (TNFα) are either undergoing clinical trials or lack specificity and cause unwanted side effects. Neutralization of upstream histamine by histamine-conjugated normal human immunoglobulin has been demonstrated to inhibit the nuclear translocation of NF-κB, thereby preventing the release of pro-inflammatory cytokines Interleukin (IL) 1ß, TNF-α, and IL-6 and IL-10 in a safer manner. The authors recommend repositioning it in COVID-19.


Subject(s)
COVID-19/immunology , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/immunology , Histamine/administration & dosage , Immunoglobulins/administration & dosage , NF-kappa B/antagonists & inhibitors , NF-kappa B/immunology , Cytokine Release Syndrome/prevention & control , Cytokine Release Syndrome/virology , Databases, Factual , Down-Regulation/drug effects , Drug Repositioning , Humans , Immunity , Orphan Drug Production , SARS-CoV-2/drug effects , Signal Transduction/drug effects
6.
J Korean Med Sci ; 36(2): e17, 2021 Jan 11.
Article in English | MEDLINE | ID: covidwho-1021881

ABSTRACT

In April 2020, a pediatric report of an unusual inflammatory illness associated with coronavirus disease 2019 (COVID-19) led to similar cases in Europe and North America, which was referred to as multisystem inflammatory syndrome in children (MIS-C). Herein, we describe the case of a 12-year-old boy who had a history of polymerase chain reaction-confirmed COVID-19 and developed MIS-C approximately three weeks after an initial diagnosis of COVID-19. High fever with abdominal pain mimicking appendicitis was the initial manifestation of MIS-C, which could have been easily missed if the patient's history of COVID-19 was ignored. Intravenous immunoglobulin was administered twice, 24 hours apart, five days after the onset of MIS-C, and the patient fully recovered without any obvious sequelae. Early recognition by disease awareness and prompt management are the keys to saving the lives of children affected by MIS-C.


Subject(s)
COVID-19/pathology , COVID-19/therapy , Immunoglobulins, Intravenous/therapeutic use , Systemic Inflammatory Response Syndrome , Antibodies, Viral/therapeutic use , COVID-19/diagnosis , Child , Humans , Immunization, Passive/methods , Immunoglobulins/administration & dosage , Immunoglobulins/therapeutic use , Male , Republic of Korea , SARS-CoV-2/immunology , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/pathology , Systemic Inflammatory Response Syndrome/therapy , Treatment Outcome
7.
Drugs R D ; 21(1): 1-8, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-951645

ABSTRACT

At present, no cure is available for COVID-19 but vaccines, antiviral drugs, immunoglobulins, or the combination of immunoglobulins with antiviral drugs have been suggested and are in clinical trials. The purpose of this paper is to discuss the role of a pharmacokinetic and viral load analysis as a basis for adjusting immunoglobulin dosing to treat COVID-19. We reviewed the pre-clinical and clinical literature that describes the impact of a high antigen load on pharmacokinetic data following antibody treatment. Representative examples are provided to illustrate the effect of high viral and tumor loads on antibody clearance. We then highlight the implications of these factors for facilitating the development and dosing of hyperimmune anti-SARS CoV2 immunoglobulin. Both nonclinical and clinical examples indicate that high antigen loads, whether they be viral, bacterial, or tumoral in origin, result in increased clearance and decreased area under the curve and half-life of antibodies. A dosing strategy that matches the antigen load can be achieved by giving initially high doses and adjusting the frequency of dosing intervals based on pharmacokinetic parameters. We suggest that study design and dose selection for immunoglobulin products for the treatment of COVID-19 require special considerations such as viral load, antibody-virus interaction, and dosing adjustment based on the pharmacokinetics of the antibody.


Subject(s)
Antibodies, Viral/blood , Antiviral Agents/administration & dosage , COVID-19/blood , COVID-19/drug therapy , Immunoglobulins/administration & dosage , Viral Load/drug effects , Antigens, Viral/blood , Antiviral Agents/pharmacokinetics , Dose-Response Relationship, Drug , Humans , Immunoglobulins/blood , Viral Load/physiology
9.
J Immunol Res ; 2020: 9465398, 2020.
Article in English | MEDLINE | ID: covidwho-879699

ABSTRACT

This new decade has started with a global pandemic of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), precipitating a worldwide health crisis and economic downturn. Scientists and clinicians have been racing against time to find therapies for COVID-19. Repurposing approved drugs, developing vaccines and employing passive immunization are three major therapeutic approaches to fighting COVID-19. Chicken immunoglobulin Y (IgY) has the potential to be used as neutralizing antibody against respiratory infections, and its advantages include high avidity, low risk of adverse immune responses, and easy local delivery by intranasal administration. In this study, we raised antibody against the spike (S) protein of SARS-CoV-2 in chickens and extracted IgY (called IgY-S) from egg yolk. IgY-S exhibited high immunoreactivity against SARS-CoV-2 S, and by epitope mapping, we found five linear epitopes of IgY-S in SARS-CoV-2 S, two of which are cross-reactive with SARS-CoV S. Notably, epitope SIIAYTMSL, one of the identified epitopes, partially overlaps the S1/S2 cleavage region in SARS-CoV-2 S and is located on the surface of S trimer in 3D structure, close to the S1/S2 cleavage site. Thus, antibody binding at this location could physically block the access of proteolytic enzymes to S1/S2 cleavage site and thereby impede S1/S2 proteolytic cleavage, which is crucial to subsequent virus-cell membrane fusion and viral cell entry. Therefore, the feasibility of using IgY-S or epitope SIIAYTMS-specific IgY as neutralizing antibody for preventing or treating SARS-CoV-2 infection is worth exploring.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/therapy , Epitope Mapping , Immunoglobulins/isolation & purification , Pneumonia, Viral/therapy , Administration, Intranasal , Animals , Antibodies, Neutralizing/administration & dosage , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/isolation & purification , Antibodies, Viral/administration & dosage , Antibodies, Viral/immunology , Antibodies, Viral/isolation & purification , COVID-19 , Chickens , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Coronavirus Infections/virology , Cross Reactions , Feasibility Studies , Humans , Immunization, Passive/methods , Immunoglobulins/administration & dosage , Immunoglobulins/immunology , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/immunology
11.
Iran J Kidney Dis ; 14(3): 239-242, 2020 05.
Article in English | MEDLINE | ID: covidwho-170320

ABSTRACT

During the COVID-19 pandemic, we had a 25 years old male case without any underlying disease or history of autoimmune disease in COVID-19 Clinic, Isfahan, Iran. He presented with arthralgia and weakness so we started COVID-19 therapeutic regimen. In his hospitalization, creatinine increases and abnormalities in random urine sediment was seen. Methylprednisolone and cyclophosphamide were prescribed due to suspected glomerulonephritis. After renal biopsy the diagnose was confirmed as crescentic proliferative glomerulonephritis. The patient also, underwent plasmapheresis and intravenous immunoglobulin injection. He was discharged healthy without development of new pulmonary symptoms despite immunosuppressive treatment.


Subject(s)
Coronavirus Infections/complications , Glomerulonephritis/complications , Glomerulonephritis/diagnosis , Pneumonia, Viral/complications , Administration, Intravenous , Adult , Biopsy , COVID-19 , Coronavirus Infections/diagnosis , Cyclophosphamide/therapeutic use , Glomerulonephritis/drug therapy , Glomerulonephritis/surgery , Humans , Immunoglobulins/administration & dosage , Male , Methylprednisolone/therapeutic use , Pandemics , Pneumonia, Viral/diagnosis , Treatment Outcome
12.
J Allergy Clin Immunol Pract ; 8(6): 1894-1899.e2, 2020 06.
Article in English | MEDLINE | ID: covidwho-46747

ABSTRACT

BACKGROUND: A rapidly expanding pandemic of the new coronavirus has become the focus of global scientific attention. Data are lacking on the impact of the pandemic caused by the severe acute respiratory syndrome coronavirus 2 on health-related quality of life among patients affected by primary antibody deficiencies (PADs). OBJECTIVE: To identify factors impacting the health-related-quality of life (HRQOL) among Italian patients affected by PADs switched to remote assistance at the time of the coronavirus disease 2019 pandemic. METHODS: The quality of life was surveyed in 158 patients with PADs by the Common Variable Immune Deficiency Quality of Life questionnaire, a disease-specific tool, and by the 12-item General Health Questionnaire, a generic tool to assess the risk of anxiety/depression. Since the beginning of the coronavirus disease 2019 epidemic, we shifted all patients with PADs to home therapy, and activated remote visits. Questionnaires were sent by email 4 weeks later. Common Variable Immune Deficiency Quality of Life questionnaire and 12-item General Health Questionnaire data scores were compared with the same set of data from a survey done in 2017. RESULTS: Of 210 patients, 158 (75%) agreed to participate. The quality of life was worse in the group of patients who were at risk of anxiety/depression at the study time. HRQOL was similar in patients forced to shift from hospital-based to home-based immunoglobulin treatment and in patients who continued their usual home-based replacement. The risk of anxiety/depression is associated with pandemia caused by the severe acute respiratory syndrome coronavirus 2 and with patients' fragility, and not with related clinical conditions associated with common variable immune deficiencies. Anxiety about running out of medications is a major new issue. CONCLUSIONS: The coronavirus disease 2019 epidemic impacted HRQOL and the risk of anxiety/depression of patients with PADs. The remote assistance program was a useful possibility to limit personal contacts without influencing the HRQOL.


Subject(s)
Anxiety/psychology , Common Variable Immunodeficiency/psychology , Common Variable Immunodeficiency/therapy , Coronavirus Infections/prevention & control , Depression/psychology , Immunoglobulins/administration & dosage , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Quality of Life/psychology , Adolescent , Adult , Aged , COVID-19 , Coronavirus Infections/epidemiology , Female , Home Infusion Therapy/psychology , Humans , Infusions, Subcutaneous , Italy/epidemiology , Male , Middle Aged , Pneumonia, Viral/epidemiology , Surveys and Questionnaires , Telemedicine , Young Adult
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