Document text
Principal Investigator: Emily Ricotta
Organization: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
Fiscal Year: 2024
Award: $294,282
Funding agency: National Institute of Allergy and Infectious Diseases
COVID-19 is caused by the novel SARS-CoV-2 and is associated with a hyper-inflammatory immune response which leads to severe and potentially life-threatening symptoms. Little is known about how and the extent to which COVID-19 presents in people with immunodeficiencies, but because of the known severity of the illness in the general population, vaccination against SARS-CoV-2 is critical. Understanding whether immunodeficient individuals produce an adequate immune response to the COVID-19 vaccine, as well as the number and type of AEs experienced in these people is necessary.
Since the initiation of the study in April 2021, 308 study participants have been enrolled: 235 people with immune disorders, 73 healthy volunteers. Participant enrollment ended in January 2023 and sample collection ended July 2023 due to the ending of the COVID-19 emergency declaration and subsequent re-obligation of COVID-19 funds.
We have collected samples from 1166 timepoints ranging from baseline through post-vaccination 5. Samples include microsamplers (dried whole blood), serum, plasma, PBMCs, and DNA extracted from buffy coat, although not all samples are available for every timepoint. We also collected 3173 saliva samples, RNA is available on 67 of 84 positives that were identified in the Department of Laboratory Medicine (11 pending RNA extraction).
Analysis for the study is ongoing. From the first-round analytic cohort of 195 immune deficient people (IDP) and 35 healthy volunteers, anti-spike IgG was detected in 88% of IDP post-dose 2, increasing to 93% by six months post-dose 3. Despite high seroconversion, median IgG levels for IDP never surpassed 1/3 that of healthy volunteers. IgG binding to Omicron BA.1 was lower than all other variants. Angiotensin-converting enzyme 2 pseudo-neutralization (% inhibition) was only modestly correlated with anti-spike IgG concentration. IgG levels were not significantly altered by participants use of different mRNA-based vaccines, immunomodulating treatments, and prior SARS-CoV-2 infections. While our data show that three doses of COVID-19 vaccinations induce anti-spike IgG in most IDP, additional doses are needed to achieve the levels of protection in healthy volunteers. Due to the strikingly reduced IgG response to Omicron BA.1, the efficacy of additional vaccinations, including bivalent vaccines, should be studied in this population.
Continued analysis will focus on T and B cell receptor repertoire of the post-vaccine samples, as well as a detailed analysis of breakthrough COVID-19 infections, including individuals with repeat and persistent infection. We will also be doing a second-round update to report on IgG response through the remainder of the sampling timepoints.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><2019-nCoV vaccine><7S Gamma Globulin><ACE2><APECED><APRF protein><Acquired Agammaglobulinemia><Acute-Phase Response Factor><Aldrich Syndrome><Anaphylactic Reaction><Anaphylactic Shock><Anaphylaxis><Antibodies><Attenuated Vaccines><Authorization><Authorization documentation><Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal-Dystrophy><Autoimmune polyendocrine syndrome type 1><Autoimmune polyglandular syndrome type 1><B blood cells><B cell><B cell receptor><B cells><B-Cell Antigen Receptor><B-Cells><B-Lymphocytes><B-cell><BA.1 variant><Binding><Blood Neutrophil><Blood Plasma><Blood Polymorphonuclear Neutrophil><Blood Serum><Bruton agammaglobulinemia><Bruton's Sex-Linked Agammaglobulinemia><Bruton's X-Linked Agammaglobulinemia><COVID prevalence><COVID-19><COVID-19 disease prevalence><COVID-19 infection><COVID-19 prevalence><COVID-19 vaccination><COVID-19 vaccine><COVID-19 virus><COVID-19 virus infection><COVID19 infection><COVID19 virus><CV-19><Chickenpox Vaccine><Chronic Granulomatous Disease><CoV-2><CoV2><Common Variable Immunodeficiency><Complement><Complement Proteins><Coronavirus Infectious Disease 2019><Cytokinesis><Cytoplasmic Division><DNA><DNA Recombination><Data><Defect><Deoxyribonucleic Acid><Disease><Disorder><Dose><Dryness><Dysfunction><EBV Infections><Edodekin Alfa><Emberger syndrome><Emergencies><Emergency Situation><Enrollment><Epstein-Barr Virus Infections><Epstein-Barr viral infections><Exclusion><Functional disorder><Funding><GATA2 deficiency><GATA2 haploinsufficiency><General Population><General Public><Genes><Genetic Recombination><Grippe><H influenzae type b><H. influenzae type b><Haemophilus influenzae type b><Herd Immunity><Hib><Hyper-IgE Syndrome><Hyperimmunoglobulin E Syndrome><Hyperimmunoglobulin E-Recurrent Infection Syndrome><IFN-Gamma><IFN-g><IFN-γ><IFNG><IFNγ><IL-12><IL12><IL6-response factor><IgG><Immune><Immune Cell Activation><Immune Diseases><Immune Disorders><Immune Dysfunction><Immune Interferon><Immune Modulation Therapy><Immune System Diseases><Immune System Disorder><Immune System Dysfunction><Immune System and Related Disorders><Immune response><Immunes><Immunochemical Immunologic><Immunodeficiency and Immunosuppression Disorders><Immunoglobulin G><Immunologic><Immunologic Diseases><Immunological><Immunological Diseases><Immunological Dysfunction><Immunological System Dysfunction><Immunological response><Immunologically><Immunologics><Impairment><Individual><Individuals from minority><Individuals of minority><Inflammasome><Inflammatory><Influenza><Inositide Phospholipids><Inositol Phosphoglycerides><Inositol Phospholipids><Interferon Gamma><Interferon Type II><Interleukin-12><Kinases><LIF-response factor><Laboratories><Leukocyte Adhesion Deficiency><Life><Light><Link><Literature><Live-attenuated Vaccine><MMR Vaccine><Magnesium><Marrow Neutrophil><Measles-Mumps-Rubella Vaccine><Measures><Medicine><Mg element><Minority Groups><Minority People><Minority Population><Minority individual><Molecular Interaction><MonoMAC><NIAID><NKSF><NOMID><National Institute of Allergy and Infectious Disease><Natural Killer Cell Stimulatory Factor><Neonatal Onset Multisystem Inflammatory Disease><Neoplasms><Neutrophilic Granulocyte><Neutrophilic Leukocyte><Non-Polyadenylated RNA><Oka Varicella Vaccine><Omicron BA.1><PBMC><Participant><Pathway interactions><Peripheral Blood Mononuclear Cell><Permission><Persons><Phosphatidyl Inositol><Phosphatidylinositols><Phosphoinositides><Phosphotransferase Gene><Phosphotransferases><Photoradiation><Physiopathology><Plasma><Plasma Serum><Polyglandular Autoimmune Syndrome Type I><Polymorphonuclear Cell><Polymorphonuclear Leukocytes><Polymorphonuclear Neutrophils><Population><Primary Immunodeficiency><PtdIns><RNA><RNA Gene Products><RNA vaccine><RNA-based vaccine><Recombination><Reporting><Reticuloendothelial System, Serum, Plasma><Ribonucleic Acid><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 BA.1><SARS-CoV-2 infection><SARS-CoV-2 infection prevalence><SARS-CoV-2 prevalence><SARS-CoV-2 vaccination><SARS-CoV-2 vaccine><SARS-CoV2><SARS-CoV2 infection><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-coronavirus-2 vaccine><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><STAT1><STAT1 gene><STAT91><Safety><Sampling><Serum><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome CoV 2 vaccine><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe Combined Immunodeficiency><Severe Combined Immunodeficiency Syndrome><Severe Combined Immunologic Deficiency><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome coronavirus 2 vaccination><Severe acute respiratory syndrome coronavirus 2 vaccine><Severe acute respiratory syndrome related corona virus 2><Severities><Severity of illness><Signal Transducer and Activator of Transcription 3><Stat3 protein><Symptoms><T cell response><T-Cells><T-Lymphocyte><Transphosphorylases><United States><Update><Vaccination><Vaccines><Variant><Variation><Varicella Vaccine><Whole Blood><Wiskott syndrome><Wiskott-Aldrich Syndrome><Wuhan coronavirus><X-Linked Agammaglobulinemia><after COVID-19 infection><after SARS-CoV-2 infection><after SARS-CoV2 infection><after infection by SARS-CoV-2><after severe acute respiratory distress syndrome CoV-2 infection><angiotensin converting enzyme 2><angiotensin converting enzyme II><autoimmune polyendocrinopathy syndrome type 1><chronic infection><cohort><combined T and B cell inborn immunodeficiency><common variable immune deficiency><complementation><congenital immune deficiency><congenital immunodeficiency><coronavirus disease 2019><coronavirus disease 2019 infection><coronavirus disease 2019 vaccination><coronavirus disease 2019 vaccine><coronavirus disease 2019 virus><coronavirus disease-19><coronavirus disease-19 vaccine><coronavirus disease-19 virus><coronavirus infectious disease-19><disease severity><eczema thromocytopenia diarrhea syndrome><eczema thromocytopenia immunodeficiency syndrome><eczema thromocytopenia syndrome><enroll><experience><following COVID-19 infection><following SARS-CoV-2 infection><following SARS-CoV2 infection><following infection by SARS-CoV-2><following severe acute respiratory distress syndrome CoV-2 infection><genetic immune defect><genetic immune deficiency><genetic immunodeficiency><hCoV19><healthy volunteer><host response><hypoimmunity><immune activation><immune deficiency><immune modulating therapies><immune modulatory therapies><immune response to vaccination><immune response to vaccines><immune system response><immune-modulation treatment><immunodeficiency><immunogenicity><immunomodulation therapy><immunomodulation treatment><immunomodulator therapies><immunomodulator treatment><immunomodulator-based therapies><immunomodulatory therapies><immunomodulatory therapy><immunomodulatory treatment><immunoresponse><inborn errors in immunity><inborn errors of immunity><inborn immunodeficiency><infected with COVID-19><infected with COVID19><infected with SARS-CoV-2><infected with SARS-CoV2><infected with coronavirus disease 2019><infected with severe acute respiratory syndrome coronavirus 2><inherited immune defect><inherited immune deficiency><inherited immunodeficiency><interest><lFN-Gamma><live vaccine><live vaccines><mRNA vaccine><mRNA-based vaccine><nCoV vaccine><nCoV-19 vaccine><nCoV19 vaccine><nCoV2><neoplasia><neoplastic growth><neutrophil><novel><participant enrollment><pathophysiology><pathway><patient enrollment><persistent infection><post SARS-CoV-2 infection><previous COVID-19 infection><previous SARS-CoV-2 infection><previous SARS-CoV2 infection><previous severe acute respiratory distress syndrome CoV-2 infection><primary immune defect><primary immune deficiency><prior COVID-19 infection><prior SARS-CoV-2 infection><prior SARS-CoV2 infection><prior severe acute respiratory distress syndrome CoV-2 infection><response><saliva sample><salivary sample><sample collection><seroconversion><severe acute respiratory syndrome coronavirus 2 BA.1><specimen collection><thymus derived lymphocyte><vaccinate against COVID-19><vaccinate against SARS-CoV-2><vaccinate against coronavirus disease 2019><vaccinate against severe acute respiratory syndrome coronavirus 2><vaccination against COVID-19><vaccination against SARS-CoV-2><vaccination against Severe acute respiratory syndrome coronavirus 2><vaccination against coronavirus disease 2019><vaccination study><vaccination trial><vaccine against 2019-nCov><vaccine against COVID-19><vaccine against SARS-CoV-2><vaccine against SARS-coronavirus-2><vaccine against Severe Acute Respiratory Syndrome CoV 2><vaccine against Severe acute respiratory syndrome coronavirus 2><vaccine associated immune response><vaccine candidates against SARS-CoV-2><vaccine for novel coronavirus><vaccine immune response><vaccine immunogenicity><vaccine induced immune response><vaccine study><vaccine trial><vaccines preventing COVID><vaccines to prevent COVID>