Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 108
Filter
2.
Sci Rep ; 12(1): 3890, 2022 03 10.
Article in English | MEDLINE | ID: covidwho-1740469

ABSTRACT

The new outbreak of coronavirus disease 2019 (COVID-19) has infected and caused the death of millions of people worldwide. Intensive efforts are underway around the world to establish effective treatments. Immunoglobulin from immunized animals or plasma from convalescent patients might constitute a specific treatment to guarantee the neutralization of the virus in the early stages of infection, especially in patients with risk factors and a high probability of progressing to severe disease. Worldwide, a few clinical trials using anti-SARS-CoV-2 immunoglobulins from horses immunized with the entire spike protein or fragments of it in the treatment of patients with COVID-19 are underway. Here, we describe the development of an anti-SARS-CoV-2 equine F(ab')2 immunoglobulin using a newly developed SARS-CoV-2 viral antigen that was purified and inactivated by radiation. Cell-based and preclinical assays showed that the F(ab')2 immunoglobulin successfully neutralizes the virus, is safe in animal models, and reduces the severity of the disease in a hamster model of SARS-CoV-2 infection and disease.


Subject(s)
COVID-19/therapy , Immunoglobulins/therapeutic use , Receptors, Immunologic/therapeutic use , SARS-CoV-2/immunology , Animals , Enzyme-Linked Immunosorbent Assay , Female , Horses/immunology , Humans , Immunoglobulins/immunology , Immunoglobulins/isolation & purification , Male , Mesocricetus/immunology , Plasmapheresis/veterinary , Receptors, Immunologic/immunology
3.
J Glob Health ; 12: 05009, 2022.
Article in English | MEDLINE | ID: covidwho-1737332

ABSTRACT

Background: The COVID-19 pandemic caused by SARS-CoV-2 exposed a global problem, as highly effective vaccines are challenging to produce and distribute, particularly in regions with limited resources and funding. As an alternative, immunoglobulins produced in eggs of immunized hens (IgY) can be a simple and inexpensive source for a topical and temporary prophylaxis. Here, we developed a method to extract and purify IgY antibodies from egg yolks of hens immunized against viral pathogen-derived proteins using low-cost, readily available materials, for use in resource-limited settings. Methods: Existing protocols for IgY purification and equipment were modified, including extraction from yolks and separation of water-soluble IgY using common household reagents and tools. A replacement for a commercial centrifuge was developed, using a home food processor equipped with a 3D printed adapter to enable IgY precipitation. IgY purification was verified using standard gel electrophoresis and Western blot analyses. Results: We developed a step-by-step protocol for IgY purification for two settings in low- and middle-income countries (LMIC): a local laboratory, where commercial centrifuges are available, or a more rural setting, where an alternative for expensive centrifuges can be used. Gel electrophoresis and Western blot analyses confirmed that the method produced highly enriched IgY preparation; each commercial egg produced ~ 90 mg of IgY. We also designed a kit for IgY production in these two settings and provided a cost estimate of the kit. Conclusion: IgY purified from eggs of immunized local hens can offer a fast and affordable prophylaxis, provided that purification can be performed in a resource-limited setting. Here, we created a low-cost method that can be used anywhere where electricity is available using inexpensive, readily available materials in place of costly, specialized laboratory equipment and chemicals. This procedure can readily be used now to make an anti-SARS-CoV-2 prophylaxis in areas where vaccines are unavailable, and can be modified to combat future threats from viral epidemics and pandemics.


Subject(s)
COVID-19 , Pandemics , Animals , Antibodies , Antiviral Agents , COVID-19/prevention & control , Chickens , Female , Humans , Immunoglobulins , SARS-CoV-2
4.
Molecules ; 27(5)2022 Mar 03.
Article in English | MEDLINE | ID: covidwho-1732129

ABSTRACT

Quality control of human immunoglobulin formulations produced by caprylic acid precipitation necessitates a simple, rapid, and accurate method for determination of residual caprylic acid. A high-performance liquid chromatography method for that purpose was developed and validated. The method involves depletion of immunoglobulins, the major interfering components that produce high background noise, by precipitation with acetonitrile (1:1, v/v). Chromatographic analysis of caprylic acid, preserved in supernatant with no loss, was performed using a reverse-phase C18 column (2.1 × 150 mm, 3 µm) as a stationary phase and water with 0.05% TFA-acetonitrile (50:50, v/v) as a mobile phase at a flow rate of 0.2 mL/min and run time of 10 min. The developed method was successfully validated according to the ICH guidelines. The validation parameters confirmed that method was linear, accurate, precise, specific, and able to provide excellent separation of peaks corresponding to caprylic acid and the fraction of remaining immunoglobulins. Furthermore, a 24-1 fractional factorial design was applied in order to test the robustness of developed method. As such, the method is highly suitable for the quantification of residual caprylic acid in formulations of human immunoglobulins for therapeutic use, as demonstrated on samples produced by fractionation of convalescent anti-SARS-CoV-2 human plasma at a laboratory scale. The obtained results confirmed that the method is convenient for routine quality control.


Subject(s)
Caprylates/analysis , Chromatography, High Pressure Liquid/methods , Drug Compounding , Immunoglobulins/chemistry , COVID-19/therapy , COVID-19/virology , Caprylates/chemistry , Humans , Immunization, Passive/methods , Immunoglobulins/therapeutic use , Limit of Detection , Reproducibility of Results , SARS-CoV-2/isolation & purification
5.
Clin Infect Dis ; 74(7): 1208-1219, 2022 Apr 09.
Article in English | MEDLINE | ID: covidwho-1704072

ABSTRACT

BACKGROUND: Natural and vaccine-induced immunity will play a key role in controlling the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. SARS-CoV-2 variants have the potential to evade natural and vaccine-induced immunity. METHODS: In a longitudinal cohort study of healthcare workers (HCWs) in Oxfordshire, United Kingdom, we investigated the protection from symptomatic and asymptomatic polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection conferred by vaccination (Pfizer-BioNTech BNT162b2, Oxford-AstraZeneca ChAdOx1 nCOV-19) and prior infection (determined using anti-spike antibody status), using Poisson regression adjusted for age, sex, temporal changes in incidence and role. We estimated protection conferred after 1 versus 2 vaccinations and from infections with the B.1.1.7 variant identified using whole genome sequencing. RESULTS: In total, 13 109 HCWs participated; 8285 received the Pfizer-BioNTech vaccine (1407 two doses), and 2738 the Oxford-AstraZeneca vaccine (49 two doses). Compared to unvaccinated seronegative HCWs, natural immunity and 2 vaccination doses provided similar protection against symptomatic infection: no HCW vaccinated twice had symptomatic infection, and incidence was 98% lower in seropositive HCWs (adjusted incidence rate ratio 0.02 [95% confidence interval {CI} < .01-.18]). Two vaccine doses or seropositivity reduced the incidence of any PCR-positive result with or without symptoms by 90% (0.10 [95% CI .02-.38]) and 85% (0.15 [95% CI .08-.26]), respectively. Single-dose vaccination reduced the incidence of symptomatic infection by 67% (0.33 [95% CI .21-.52]) and any PCR-positive result by 64% (0.36 [95% CI .26-.50]). There was no evidence of differences in immunity induced by natural infection and vaccination for infections with S-gene target failure and B.1.1.7. CONCLUSIONS: Natural infection resulting in detectable anti-spike antibodies and 2 vaccine doses both provide robust protection against SARS-CoV-2 infection, including against the B.1.1.7 variant.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines , Cohort Studies , Health Personnel , Humans , Immunoglobulins , Incidence , Longitudinal Studies , Vaccination
6.
Int J Biol Sci ; 18(2): 617-636, 2022.
Article in English | MEDLINE | ID: covidwho-1689841

ABSTRACT

Among numerous studies on coronavirus 2019 (COVID-19), we noted that the infection and mortality rates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) increased with age and that fetuses known to be particularly susceptible to infection were better protected despite various mutations. Hence, we established the hypothesis that a new immune system exists that forms before birth and decreases with aging. Methods: To prove this hypothesis, we established new ex-vivo culture conditions simulating the critical environmental factors of fetal stem cells (FSCs) in early pregnancy. Then, we analyzed the components from FSCs cultivated newly developed ex-vivo culture conditions and compared them from FSCs cultured in a normal condition. Results: We demonstrated that immunoglobulin M (IgM), a natural antibody (NAb) produced only in early B-1 cells, immunoglobulins (Igs) including IgG3, which has a wide range of antigen-binding capacity and affinity, complement proteins, and antiviral proteins are induced in FSCs only cultured in newly developed ex-vivo culture conditions. Particularly we confirmed that their extracellular vesicles (EVs) contained NAbs, Igs, various complement proteins, and antiviral proteins, as well as human leukocyte antigen G (HLA-G), responsible for immune tolerance. Conclusion: Our results suggest that FSCs in early pregnancy can form an independent immune system responding to unlearned antigens as a self-defense mechanism before establishing mature immune systems. Moreover, we propose the possibility of new solutions to cope with various infectious diseases based on the factors in NAbs-containing EVs, especially not causing unnecessary immune reaction due to HLA-G.


Subject(s)
Aging/immunology , COVID-19/immunology , Fetal Stem Cells/physiology , Immunity/physiology , SARS-CoV-2 , Antibody Affinity , Antigens, Viral , Complement System Proteins , Female , Fetal Stem Cells/virology , Gene Expression Regulation, Developmental/immunology , Humans , Immunoglobulins/metabolism , Pregnancy
8.
Bull Cancer ; 108(12S): S90-S97, 2021 Dec.
Article in French | MEDLINE | ID: covidwho-1559003

ABSTRACT

Infections occurring after CAR T-cells are a common complication. At the acute phase of treatment following CAR T-cell infusion, the exact incidence of infections is unknown given the overlapping symptoms with cytokine release syndrome. The risk factors for infection include the malignant underlying disease and its multiple treatments, and an immunosuppressive state induced by CAR-T cells themselves and the treatment of their complications. During the twelfth edition of practice harmonization workshops of the Francophone society of bone marrow transplantation and cellular therapy (SFGM-TC), a working group focused its work on the management of post-CAR infectious complications. In this review we discuss anti-infection prophylaxis and vaccination of patients undergoing CAR T-cell therapy as well as a special chapter for the specific case of COVID-19. These recommendations apply to commercial CAR-T cells, in order to guide strategies for the management and prevention of infectious complications associated with this new therapeutic approach.


Subject(s)
Bacterial Infections/prevention & control , Immunotherapy, Adoptive , Mycoses/prevention & control , Receptors, Chimeric Antigen/therapeutic use , Virus Diseases/prevention & control , Bone Marrow Transplantation , COVID-19/prevention & control , Cell Transplantation , Cytokine Release Syndrome , Humans , Immunization , Immunocompromised Host , Immunoglobulins/therapeutic use , Immunotherapy, Adoptive/adverse effects , Neoplasms/complications , Neoplasms/therapy , Pneumocystis , Risk Factors
10.
Cell Mol Immunol ; 19(3): 352-369, 2022 03.
Article in English | MEDLINE | ID: covidwho-1517622

ABSTRACT

The COVID pandemic has refreshed and expanded recognition of the vital role that sustained antibody (Ab) secretion plays in our immune defenses against microbes and of the importance of vaccines that elicit Ab protection against infection. With this backdrop, it is especially timely to review aspects of the molecular programming that govern how the cells that secrete Abs arise, persist, and meet the challenge of secreting vast amounts of these glycoproteins. Whereas plasmablasts and plasma cells (PCs) are the primary sources of secreted Abs, the process leading to the existence of these cell types starts with naive B lymphocytes that proliferate and differentiate toward several potential fates. At each step, cells reside in specific microenvironments in which they not only receive signals from cytokines and other cell surface receptors but also draw on the interstitium for nutrients. Nutrients in turn influence flux through intermediary metabolism and sensor enzymes that regulate gene transcription, translation, and metabolism. This review will focus on nutrient supply and how sensor mechanisms influence distinct cellular stages that lead to PCs and their adaptations as factories dedicated to Ab secretion. Salient findings of this group and others, sometimes exhibiting differences, will be summarized with regard to the journey to a distinctive metabolic program in PCs.


Subject(s)
Antibody Formation , COVID-19 , Humans , Immunoglobulins/metabolism , Nutrients , Plasma Cells , Signal Transduction
12.
J Appl Microbiol ; 132(3): 2421-2430, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1488216

ABSTRACT

AIMS: COVID-19 pandemic caused by SARS-CoV-2 has become a public health crisis worldwide. In this study, we aimed at demonstrating the neutralizing potential of the IgY produced after immunizing chicken with a recombinant SARS-CoV-2 spike protein S1 subunit. METHODS AND RESULTS: E. coli BL21 carrying plasmid pET28a-S1 was induced with IPTG for the expression of SARS-CoV-2 S1 protein. The recombinant His-tagged S1 was purified and verified by SDS-PAGE, Western blot and biolayer interferometry (BLI) assay. Then S1 protein emulsified with Freund's adjuvant was used to immunize layer chickens. Specific IgY against S1 (S1-IgY) produced from egg yolks of these chickens exhibited a high titer (1:25,600) and a strong binding affinity to S1 (KD  = 318 nmol L-1 ). The neutralizing ability of S1-IgY was quantified by a SARS-CoV-2 pseudotyped virus-based neutralization assay with an IC50  value of 0.99 mg ml-1 . In addition, S1-IgY exhibited a strong ability in blocking the binding of SARS-CoV-2 S1 to hACE2, and it could partially compete with hACE2 for the binding sites on S1 by BLI assays. CONCLUSIONS: We demonstrated here that after immunization of chickens with our recombinant S1 protein, IgY neutralizing antibodies were generated against the SARS-CoV-2 spike protein S1 subunit; therefore, showing the potential use of IgY to block the entry of this virus. SIGNIFICANCE AND IMPACT OF THE STUDY: IgY targeting S1 subunit of SARS-CoV-2 could be a promising candidate for pre- and post-exposure prophylaxis or treatment of COVID-19. Administration of IgY-based oral preparation, oral or nasal spray may have profound implications for blocking SARS-CoV-2.


Subject(s)
Antibodies, Neutralizing/pharmacology , Immunoglobulins/pharmacology , SARS-CoV-2/drug effects , Spike Glycoprotein, Coronavirus/antagonists & inhibitors , Virus Internalization/drug effects , Animals , COVID-19 , Chickens , Egg Yolk/immunology , Humans , Pandemics
13.
Crit Care Med ; 49(11): 1974-1982, 2021 11 01.
Article in English | MEDLINE | ID: covidwho-1475880
14.
Crit Care Med ; 49(11): e1151-e1156, 2021 11 01.
Article in English | MEDLINE | ID: covidwho-1467423

ABSTRACT

TRIAL REGISTRATION: NCT04420468. OBJECTIVES: Severe acute respiratory syndrome coronavirus 2-related multisystem inflammatory syndrome in children is frequently associated with shock; endothelial involvement may be one of the underlying mechanisms. We sought to describe endothelial dysfunction during multisystem inflammatory syndrome in children with shock and then assess the relationship between the degree of endothelial involvement and the severity of shock. DESIGN: Observational study. SETTING: A PICU in a tertiary hospital. PATIENTS: Patients aged under 18 (n = 28) with severe acute respiratory syndrome coronavirus 2-related multisystem inflammatory syndrome in children and shock, according to the Centers for Disease Control and Prevention criteria. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Correlations between endothelial marker levels and shock severity were assessed using Spearman coefficient. The median (interquartile range) age was 9 years (7.5-11.2 yr). Sixteen children presented with cardiogenic and distributive shock, 10 presented with cardiogenic shock only, and two presented with distributive shock only. The median left ventricular ejection fraction, troponin level, and lactate level were, respectively, 40% (35-45%), 261 ng/mL (131-390 ng/mL), and 3.2 mmol/L (2-4.2 mmol/L). Twenty-five children received inotropes and/or vasopressors; the median Vasoactive and Inotropic Score was 8 (5-28). Plasma levels of angiopoietin-2 (6,426 pg/mL [2,814-11,836 pg/mL]), sE-selectin (130,405 pg/mL [92,987-192,499 pg/mL]), von Willebrand factor antigen (344% [288-378%]), and the angiopoietin-2/angiopoietin-1 ratio (1.111 [0.472-1.524]) were elevated and significantly correlated with the Vasoactive and Inotropic Score (r = 0.45, p = 0.016; r = 0.53, p = 0.04; r = 0.46, p = 0.013; and r = 0.46, p = 0.012, respectively). CONCLUSIONS: Endothelial dysfunction is associated with severe acute respiratory syndrome coronavirus 2-related multisystem inflammatory syndrome in children with shock and may constitute one of the underlying mechanisms.


Subject(s)
COVID-19/complications , Shock/pathology , Systemic Inflammatory Response Syndrome/pathology , Adrenal Cortex Hormones/therapeutic use , Angiopoietin-2/blood , Biomarkers , C-Reactive Protein/analysis , COVID-19/drug therapy , COVID-19/pathology , Cardiotonic Agents/therapeutic use , Child , Female , Humans , Immunoglobulins/therapeutic use , Intensive Care Units, Pediatric , Interleukin-6/blood , Lactic Acid/blood , Male , Respiration, Artificial , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index , Shock, Cardiogenic/pathology , Systemic Inflammatory Response Syndrome/drug therapy , Troponin/blood , Vasoconstrictor Agents/therapeutic use , Ventricular Function, Left
15.
Sci Rep ; 11(1): 19980, 2021 10 07.
Article in English | MEDLINE | ID: covidwho-1462034

ABSTRACT

The coronavirus disease 2019 (COVID-19) is the latest biological hazard for the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Even though numerous diagnostic tests for SARS-CoV-2 have been proposed, new diagnosis strategies are being developed, looking for less expensive methods to be used as screening. This study aimed to establish salivary vibrational modes analyzed by attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy to detect COVID-19 biological fingerprints that allow the discrimination between COVID-19 and healthy patients. Clinical dates, laboratories, and saliva samples of COVID-19 patients (N = 255) and healthy persons (N = 1209) were obtained and analyzed through ATR-FTIR spectroscopy. Then, a multivariate linear regression model (MLRM) was developed. The COVID-19 patients showed low SaO2, cough, dyspnea, headache, and fever principally. C-reactive protein, lactate dehydrogenase, fibrinogen, D-dimer, and ferritin were the most important altered laboratory blood tests, which were increased. In addition, changes in amide I and immunoglobulin regions were evidenced in the FTIR spectra analysis, and the MLRM showed clear discrimination between both groups. Specific salivary vibrational modes employing ATR-FTIR spectroscopy were established; moreover, the COVID-19 biological fingerprint in saliva was characterized, allowing the COVID-19 detection using an MLRM, which could be helpful for the development of new diagnostic devices.


Subject(s)
COVID-19 Testing/methods , COVID-19/diagnosis , Saliva/chemistry , Spectroscopy, Fourier Transform Infrared/methods , Adult , Aged , Female , Humans , Immunoglobulins/analysis , Male , Middle Aged , Oxygen/analysis , SARS-CoV-2/isolation & purification
16.
Can Respir J ; 2021: 6590528, 2021.
Article in English | MEDLINE | ID: covidwho-1450631

ABSTRACT

Background: The direct effect of SARS-CoV-2 on the lungs results in increased hospitalization rates of patients with pneumonia. Severe COVID-19 patients often develop ARDS which is associated with poor prognosis. Assessing risk factors for COVID-19 severity is indispensable for implementing and evaluating therapeutic interventions. We investigated the temporal associations between the SARS-CoV-2 antigen (Ag), total Immunoglobulin (Ig) levels, and several laboratory parameters in hospitalized patients with varying degrees of COVID-19 severity. Methods: The SARS-CoV-2 nucleocapsid protein (NP) and total Ig Spike (S) protein-specific antibodies were determined for each patient with lateral flow assays through repeated sampling every two days. Hematological and biochemical parameters were evaluated at the same time points. Results: 40 Greek COVID-19 patients (31 males, 9 females) with a median age of 59.50 ± 16.21 years were enrolled in the study. The median time from symptom onset to hospitalization was 8.0 ± 4.19 days. A significant negative correlation was observed between the SARS-CoV-2 Ag and total Ig levels. The temporal correlation patterns of the SARS-CoV-2 NP Ag and anti-S total Ig levels with laboratory markers varied among patients with differing degrees of COVID-19 severity. Severe-critical cases had lower SARS-CoV-2 Ag and increased total Ig levels as compared to mild-moderate cases. Conclusions: Distinct temporal profiles of the SARS-CoV-2 NP Ag and anti-S total Ig levels may distinguish different groups of COVID-19 severity.


Subject(s)
Antigens, Viral/immunology , COVID-19/virology , Coronavirus Nucleocapsid Proteins/immunology , Immunoglobulins/immunology , Pandemics , SARS-CoV-2/immunology , Adult , Aged , Aged, 80 and over , COVID-19/epidemiology , COVID-19/immunology , Enzyme-Linked Immunosorbent Assay , Female , Follow-Up Studies , Greece/epidemiology , Humans , Male , Middle Aged , Prospective Studies
17.
Postgrad Med ; 133(8): 994-1000, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1450321

ABSTRACT

OBJECTIVES: Multisystem inflammatory syndrome in children (MIS-C) is a rare but severe condition resulting in excessive response of the immune system after SARS-CoV-2 infection. We report a single-center cohort of children with MIS-C, describing the spectrum of presentation, therapies, clinical course, and short-term outcomes. METHODS: This is a prospective observational study from to a tertiary pediatric rheumatology center including patients (aged 1 month to 21 years) diagnosed with MIS-C between April 2020-April 2021. Demographic, clinical, laboratory results and follow-up data were collected through the electronic patient record system and analyzed. RESULTS: A total of 67 patients with MIS-C were included in the study. Fever was detected in all patients; gastrointestinal system symptoms were found in 67.2% of the patients, rash in 38.8%, conjunctivitis in 31.3%, hypotension in 26.9% myocarditis, and/or pericarditis in 22.4%, respectively. Respiratory symptoms were only in five patients (7.5%). Kawasaki Disease like presentation was found 37.3% of the patients. The mean duration of hospitalization was 11.8 7.07 days. Fifty-seven patients (85%) received intravenous immunoglobulin (IVIG), 45 (67%) received corticosteroids, 17 (25.3%) received anakinra, and one (1.5%) received tocilizumab. Seven of the patients (10.4%) underwent therapeutic plasma exchange (TPE). In 21 (31.3%) patients, a pediatric intensive care unit (PICU) was required in a median of 2 days. The first finding to improve was fever, while the first parameter to decrease was ferritin (median 6.5 days (IQR, 4-11.2 days)). Sixty-five patients were discharged home with a median duration of hospital stay of 10 days (IQR, 7-15 days). CONCLUSION: Patients with MIS-C may have severe cardiac findings and intensive care requirements in admission and hospital follow-up. The vast majority of these findings improve with effective treatment without any sequelae until discharge and in a short time in follow-up. Although the pathogenesis and treatment plan of the disease are partially elucidated, follow-up studies are needed in terms of long-term prognosis and relapse probabilities.


Subject(s)
COVID-19/complications , Intensive Care Units, Pediatric/statistics & numerical data , Rheumatology/statistics & numerical data , Systemic Inflammatory Response Syndrome/drug therapy , Systemic Inflammatory Response Syndrome/etiology , Systemic Inflammatory Response Syndrome/physiopathology , Administration, Intravesical , Adolescent , Adrenal Cortex Hormones/administration & dosage , Adrenal Cortex Hormones/therapeutic use , Child , Child, Preschool , Cohort Studies , Female , Humans , Immunoglobulins/administration & dosage , Immunoglobulins/therapeutic use , Infant , Infant, Newborn , Interleukin 1 Receptor Antagonist Protein/administration & dosage , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Male , Oxytocin/administration & dosage , Oxytocin/analogs & derivatives , Oxytocin/therapeutic use , Plasma Exchange , Prospective Studies
18.
Gigascience ; 10(9)2021 09 28.
Article in English | MEDLINE | ID: covidwho-1443047

ABSTRACT

BACKGROUND: B-cell immunoglobulin repertoires with paired heavy and light chain can be determined by means of 10X single-cell V(D)J sequencing. Precise and quick analysis of 10X single-cell immunoglobulin repertoires remains a challenge owing to the high diversity of immunoglobulin repertoires and a lack of specialized software that can analyze such diverse data. FINDINGS: In this study, specialized software for 10X single-cell immunoglobulin repertoire analysis was developed. SCIGA (Single-Cell Immunoglobulin Repertoire Analysis) is an easy-to-use pipeline that performs read trimming, immunoglobulin sequence assembly and annotation, heavy and light chain pairing, statistical analysis, visualization, and multiple sample integration analysis, which is all achieved by using a 1-line command. Then SCIGA was used to profile the single-cell immunoglobulin repertoires of 9 patients with coronavirus disease 2019 (COVID-19). Four neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were identified from these repertoires. CONCLUSIONS: SCIGA provides a complete and quick analysis for 10X single-cell V(D)J sequencing datasets. It can help researchers to interpret B-cell immunoglobulin repertoires with paired heavy and light chain.


Subject(s)
Immunoglobulins/metabolism , Single-Cell Analysis/methods , Software , Antibodies, Monoclonal/chemistry , Antibodies, Monoclonal/genetics , Antibodies, Monoclonal/metabolism , COVID-19/pathology , COVID-19/virology , Humans , Immunoglobulins/chemistry , Immunoglobulins/genetics , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification
19.
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
20.
Viruses ; 13(9)2021 09 14.
Article in English | MEDLINE | ID: covidwho-1411074

ABSTRACT

Presently, the use of convalescent plasma and hyperimmunoglobulin obtained from individuals who have recovered from coronavirus disease 2019 (COVID-19) has proved to potentially provide passive antibody-based immunity, thereby leading to several clinical trials to develop an immune-based COVID-19 treatment. However, the therapeutic efficacy of hyperimmunoglobulin in critically ill patients with COVID-19 remains unknown. On 23 October 2020, we first administered GC5131 in a compassionate-use program to critically ill patients at the Kyungpook National University, Chilgok Hospital, Korea. Since then, five more critically ill patients were treated with GC5131 in this compassionate-use program in our hospital up until 17 December 2020. We retrospectively reviewed the clinical responses of six critically ill patients diagnosed with COVID-19 who received the hyperimmunoglobulin concentrate, GC5131, which was produced by the Green Cross Corporation. After the administration of GC5131, five patients died due to an exacerbation of COVID-19 pneumonia. GC5131 was ineffective when administered to critically ill patients with COVID-19. Nevertheless, we propose that to expect a therapeutic effect from GC5131, it should be administered as early as possible to avoid the excessive inflammatory response phase in patients with severe and advanced COVID-19 infection. This step was difficult to achieve in the real world due to the time required for decision making and the process of the compassionate-use program.


Subject(s)
COVID-19/drug therapy , COVID-19/therapy , COVID-19/virology , Critical Illness , Immunoglobulins/therapeutic use , SARS-CoV-2/drug effects , Aged , COVID-19/diagnosis , Compassionate Use Trials , Female , Humans , Immunization, Passive , Male , Republic of Korea , Treatment Outcome
SELECTION OF CITATIONS
SEARCH DETAIL