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1.
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
2.
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
3.
Int Immunopharmacol ; 96: 107797, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1300822

ABSTRACT

Specific antibodies against SARS-CoV-2 structural protein have a wide range of effects in the diagnose, prevention and treatment of the COVID-19 epidemic. Among them, egg yolk immunoglobulin Y (IgY), which has high safety, high yield, and without inducing antibody-dependent enhancement, is an important biological candidate. In this study, specific IgY against the conservative nucleocapsid protein (NP) of SARS-CoV-2 was obtained by immunizing hens. Through a series of optimized precipitation and ultrafiltration extraction schemes, its purity was increased to 98%. The hyperimmune IgY against NP (N-IgY) at a titer of 1:50,000 showed strong NP binding ability, which laid the foundation of N-IgY's application targeting NP. In an in vitro immunoregulatory study, N-IgY (1 mg/mL) modulated NP-induced immune response by alleviating type II interferon secretion stimulated by NP (20 µg/mL). In summary, N-IgY can be mass produced by achievable method, which endows it with potential value against the current COVID-19 pandemic.


Subject(s)
Antibodies/immunology , Antiviral Agents/immunology , COVID-19/immunology , Immunoglobulins/immunology , Immunologic Factors/immunology , Interferon-gamma/metabolism , SARS-CoV-2/immunology , Animals , Antibodies/pharmacology , Antiviral Agents/pharmacology , COVID-19/therapy , Chickens , Drug Development , Egg Yolk/chemistry , Egg Yolk/metabolism , Humans , Immunity , Immunoglobulins/pharmacology , Immunologic Factors/pharmacology , Immunomodulation , In Vitro Techniques , Nucleocapsid Proteins/immunology , Nucleocapsid Proteins/metabolism , SARS-CoV-2/metabolism
4.
Cell Rep ; 35(6): 109109, 2021 05 11.
Article in English | MEDLINE | ID: covidwho-1201425

ABSTRACT

It is unclear whether individuals with enormous diversity in B cell receptor repertoires are consistently able to mount effective antibody responses against SARS-CoV-2. We analyzed antibody responses in a cohort of 55 convalescent patients and isolated 54 potent neutralizing monoclonal antibodies (mAbs). While most of the mAbs target the angiotensin-converting enzyme 2 (ACE2) binding surface on the receptor binding domain (RBD) of SARS-CoV-2 spike protein, mAb 47D1 binds only to one side of the receptor binding surface on the RBD. Neutralization by 47D1 is achieved independent of interfering RBD-ACE2 binding. A crystal structure of the mAb-RBD complex shows that the IF motif at the tip of 47D1 CDR H2 interacts with a hydrophobic pocket in the RBD. Diverse immunoglobulin gene usage and convergent epitope targeting characterize neutralizing antibody responses to SARS-CoV-2, suggesting that vaccines that effectively present the receptor binding site on the RBD will likely elicit neutralizing antibody responses in a large fraction of the population.


Subject(s)
Antibodies, Neutralizing/genetics , COVID-19/genetics , Immunoglobulins/genetics , Adult , Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Binding Sites/immunology , COVID-19/immunology , COVID-19/therapy , Epitopes/genetics , Epitopes/immunology , Female , Genes, Immunoglobulin/genetics , Genetic Variation/genetics , Humans , Immunization, Passive/methods , Immunoglobulins/immunology , Male , Middle Aged , Peptidyl-Dipeptidase A/metabolism , Protein Binding/immunology , Protein Domains/genetics , Receptors, Virus/immunology , Receptors, Virus/metabolism , SARS-CoV-2/genetics , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity
5.
Monoclon Antib Immunodiagn Immunother ; 40(2): 36-49, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1201076

ABSTRACT

The dawn of the 20th century saw the formative years of developments in immunology. In particular, immunochemistry, specifically pertaining to antibodies, was extensively studied. These studies laid the foundations for employing antibodies in a variety of ways. Not surprisingly, antibodies have been used for applications ranging from biomedical research to disease diagnostics and therapeutics to evaluation of immune responses during natural infection and those elicited by vaccines. Despite recent advancements in cellular immunology and the excitement of T cell therapy, use of antibodies represents a large proportion of immunotherapeutic approaches as well as clinical interventions. Polyclonal antibodies in the form of plasma or sera continue to be used to treat a number of diseases, including autoimmune disorders, cancers, and infectious diseases. Historically, antisera to toxins have been the longest serving biotherapeutics. In addition, intravenous immunoglobulins (IVIg) have been extensively used to treat not only immunodeficiency conditions but also autoimmune disorders. Beyond the simplistic suppositions of their action, the IVIg have also unraveled the immune regulatory and homeostatic ramifications of their use. The advent of monoclonal antibodies (MAbs), on the other hand, has provided a clear pathway for their development as drug molecules. MAbs have found a clear place in the treatment of cancers and extending lives and have been used in a variety of other conditions. In this review, we capture the important developments in the therapeutic applications of antibodies to alleviate disease, with a focus on some of the recent developments.


Subject(s)
Antibodies, Monoclonal/therapeutic use , COVID-19/therapy , Diphtheria/therapy , Neoplasms/therapy , Animals , Antibodies, Monoclonal/immunology , COVID-19/immunology , COVID-19/virology , Cell- and Tissue-Based Therapy , Diphtheria/immunology , Humans , Immunoglobulins/immunology , Immunoglobulins/therapeutic use , Neoplasms/immunology , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , T-Lymphocytes/immunology
6.
Isr Med Assoc J ; 23(4): 208-211, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1200569

ABSTRACT

BACKGROUND: This mini review includes two case descriptions. It introduces the use of chicken egg yolk antibody (IgY) solutions in the prevention and cure of viral and bacterial infections. Application for the protection against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), rotavirus, and influenza viruses, as well as for the eradication of Pseudomonas aeruginosa, caries, various enteric bacteria and other pathogens, and toxins have been developed. This approach is a fast, reliable, safe, and tested method for producing molecular shield and protection against emerging pathogens and epidemics. In the current pandemic situation caused by coronavirus disease-2019 (COVID-19), this method of passive immunization could be applied for rapid protection against modifiable agents. The specific IgY antibodies start to accumulate into egg yolks about 3 weeks after the immunization of the chicken. The product can be collected safely, as the antigen is not found in the eggs. This method for microbial safety uses natural means and commonly used food substances, which have been tested and could be produced for both blocking epidemics and applying personalized medicine.


Subject(s)
Antibodies/therapeutic use , COVID-19/prevention & control , Egg Yolk/immunology , Immunization, Passive/methods , Immunoglobulins/immunology , Animals , Bacterial Infections/prevention & control , Chickens , Humans , Immunity, Mucosal/immunology , Infant, Newborn , Virus Diseases/prevention & control
7.
Eur Rev Med Pharmacol Sci ; 24(24): 13049-13055, 2020 12.
Article in English | MEDLINE | ID: covidwho-1000850

ABSTRACT

OBJECTIVE: This review was conducted to systematically analyze the effects of aerobic exercise on immunological biomarkers to provide safe aerobic exercise recommendations and specifications for patients with COVID-19. MATERIALS AND METHODS: A systematic search was conducted through MEDLINE (PubMed), Science Direct, Web of Science, Scopus, Cochrane Library, and SciELO databases. The search included the following keywords "immune system", "immune cell", or "immune function"; "aerobic training", "aerobic exercise", or "physical activity"; "human" or "adult"; and "cytokine", "killer cell", "T cell", "interleukin", "lymphocyte", "leukocyte" or "adhesion molecule". RESULTS: Eleven studies met the inclusion and exclusion criteria of this search. The most used exercise prescriptions included walking, cycling, or running. The duration of exercise ranged from 18 to 60 min with an intensity of 55% to 80% of VO2max or 60%-80% of maximum heart rate. The frequency range was 1 to 3 times/week. The mainly increased immunological biomarkers included leukocytes, lymphocytes, neutrophils, monocytes, eosinophils, IL-6, CD16-56, CD16, CD4, CD3, CD8, and CD19. CONCLUSIONS: This review demonstrated that patients with COVID-19 should follow a regular program of aerobic exercise for 20-60 min. This program should be in the form of cycling or walking with an intensity of 55%-80% VO2max or 60%-80% of maximum heart rate. This program should be repeated 2-3 sessions/week. These previous parameters could safely enhance immune functions without producing any exhaustion.


Subject(s)
COVID-19/rehabilitation , Exercise Therapy/methods , Exercise/physiology , Bicycling , COVID-19/immunology , Cytokines/immunology , Humans , Immunoglobulins/immunology , Leukocyte Count , Lymphocyte Count , Neutrophils , Oxygen Consumption , Running , SARS-CoV-2 , Walking
8.
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
9.
Cell ; 183(2): 308-314, 2020 10 15.
Article in English | MEDLINE | ID: covidwho-866494

ABSTRACT

The 2020 Lasker Awards, a celebration of one of the most prestigious international prizes given to individuals for extraordinary contributions to Basic and Clinical Medical Research, Pubic Health, and Special Achievement, was cancelled because of the COVID-19 pandemic. Typically, essays on the awardees and their scientific and medical contributions are solicited and published in Cell in collaboration with the Lasker Committee. This year, the Lasker Committee commissioned an essay to reflect on the historic contributions that scientists and physicians have made to our understanding of immunology and virology, and future directions in medical and basic research that have been highlighted by COVID-19 pandemic.


Subject(s)
Allergy and Immunology , Betacoronavirus/immunology , Coronavirus Infections/immunology , Immunity , Pneumonia, Viral/immunology , Allergy and Immunology/history , Animals , Awards and Prizes , COVID-19 , Cytokines/immunology , History, 19th Century , History, 20th Century , History, 21st Century , Humans , Immune System/cytology , Immunoglobulins/genetics , Immunoglobulins/immunology , Lymphocytes/cytology , Pandemics , SARS-CoV-2 , Vaccination/history
10.
Pediatr Infect Dis J ; 39(11): e366-e367, 2020 11.
Article in English | MEDLINE | ID: covidwho-835206

ABSTRACT

With recent reports showing clinical and laboratory overlap of multisystem inflammatory syndrome in children and Kawasaki disease (KD), we addressed the hypothesis that cross coronavirus humoral immunity leads to a parallel postinfectious phenomenon explaining similar pathologic findings in KD and multisystem inflammatory syndrome in children. We demonstrated no cross-reactivity in children with KD but observed some nonspecific interactions postintravenous immunoglobulin infusion.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/immunology , Immunoglobulins/immunology , Mucocutaneous Lymph Node Syndrome/immunology , Pneumonia, Viral/immunology , Viral Proteins/immunology , COVID-19 , Child , Coronavirus Infections/blood , Coronavirus Infections/virology , Cross Reactions/immunology , Humans , Immunity, Humoral , Immunoglobulins/blood , Mucocutaneous Lymph Node Syndrome/blood , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/virology , SARS-CoV-2
11.
Science ; 369(6508): 1210-1220, 2020 09 04.
Article in English | MEDLINE | ID: covidwho-704393

ABSTRACT

Coronavirus disease 2019 (COVID-19) represents a global crisis, yet major knowledge gaps remain about human immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We analyzed immune responses in 76 COVID-19 patients and 69 healthy individuals from Hong Kong and Atlanta, Georgia, United States. In the peripheral blood mononuclear cells (PBMCs) of COVID-19 patients, we observed reduced expression of human leukocyte antigen class DR (HLA-DR) and proinflammatory cytokines by myeloid cells as well as impaired mammalian target of rapamycin (mTOR) signaling and interferon-α (IFN-α) production by plasmacytoid dendritic cells. By contrast, we detected enhanced plasma levels of inflammatory mediators-including EN-RAGE, TNFSF14, and oncostatin M-which correlated with disease severity and increased bacterial products in plasma. Single-cell transcriptomics revealed a lack of type I IFNs, reduced HLA-DR in the myeloid cells of patients with severe COVID-19, and transient expression of IFN-stimulated genes. This was consistent with bulk PBMC transcriptomics and transient, low IFN-α levels in plasma during infection. These results reveal mechanisms and potential therapeutic targets for COVID-19.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/immunology , Pneumonia, Viral/immunology , COVID-19 , Cytokines/blood , DNA, Bacterial/blood , Dendritic Cells/immunology , Dendritic Cells/metabolism , Female , Flow Cytometry , HLA-DR Antigens/analysis , Humans , Immunity , Immunity, Innate , Immunoglobulins/blood , Immunoglobulins/immunology , Inflammation Mediators/blood , Interferon Type I/metabolism , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/metabolism , Lipopolysaccharides/blood , Male , Myeloid Cells/immunology , Myeloid Cells/metabolism , Pandemics , SARS-CoV-2 , Signal Transduction , Single-Cell Analysis , Systems Biology , TOR Serine-Threonine Kinases/metabolism , Transcription, Genetic , Transcriptome
12.
Int Immunopharmacol ; 85: 106654, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-505643

ABSTRACT

The present state of diagnostic and therapeutic developmental race for vaccines against the SARS CoV-2 (nCOVID-19) focuses on prevention and control of this global pandemic which also represents a critical challenge to the global health community. Although development of novel vaccines can prevent the SARS CoV-2 infections, it is still impeded by several other factors and therefore novel approaches towards treatment and management of this disease is the urgent need. Passive immunotherapy plays a vital role as a possible alternative to meet this challenge and among various antibody sources, chicken egg yolk antibodies (IgY) can be used as an alternative to mammalian antibodies which have been previously studied against SARS CoV outbreak in China. In this review, we discuss the strategies for the use of chicken egg yolk (IgY) antibodies in the development of rapid diagnosis and immunotherapy against SARS CoV-2. Also, IgY antibodies have previously been used against various respiratory bacterial and viral infections in humans and animals. Compared to mammalian antibodies (IgG), chicken egg yolk antibodies (IgY) have greater binding affinity to specific antigens, ease of extraction and lower production costs, hence possessing remarkable pathogen-neutralizing activity of pathogens in respiratory and lungs. We provide an overall importance for the use of monoclonal chicken egg yolk antibodies (IgY) using phage display method describing their potential passive immunotherapeutic application for the treatment and prevention of SARS CoV-2 infection which is simple, fast and safe way of approach for treating patients effectively.


Subject(s)
Antibodies, Monoclonal/immunology , Antibodies, Viral/immunology , Betacoronavirus/immunology , Cell Surface Display Techniques , Clinical Laboratory Techniques , Coronavirus Infections , Immunoglobulins/immunology , Pandemics , Pneumonia, Viral , Spike Glycoprotein, Coronavirus/immunology , Animals , Antibody Affinity , Antibody Specificity , Betacoronavirus/genetics , COVID-19 , COVID-19 Testing , Chickens , Coronavirus Infections/diagnosis , Coronavirus Infections/therapy , Egg Yolk , Forecasting , Humans , Immunization, Passive , Mammals/immunology , Models, Molecular , Pneumonia, Viral/diagnosis , Pneumonia, Viral/therapy , RNA, Viral/genetics , SARS-CoV-2 , Single-Chain Antibodies/immunology , Species Specificity , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/metabolism
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