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Principal Investigator: Jeffrey Cohen
Organization: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
Fiscal Year: 2024
Award: $213,441
Funding agency: National Institute of Allergy and Infectious Diseases
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), is associated with respiratory-related disease and death. Assays to detect virus-specific antibodies are important to understand the prevalence of infection and the course of the immune response. Assays to detect virus-specific T cells are important to appreciate the role of T cell in controlling COVID-19, and HLA-matched virus-specific T cells might be used to treat immunocompromised persons with this disease and to accelerate virus clearance in these persons to reduce shedding and transmission. COVID-19 causes multi-organ dysfunction during acute infection and some patients have prolonged symptoms.
In FY2024 we collaborated with Dr. Robert Kreitman to study the immune response to COVID-19 in patients with hairy cell leukemia (HCL) and variant HCL (HCLv). Both leukemias are B-cell malignancies associated with decreased antibody responses. We prospectively monitored the largest cohort of patients with HCL/HCLv to date (n = 503) for COVID-19 by symptoms, antibody, and polymerase chain reaction (PCR) and/or antigen positivity. Fifty percent of the patients with HCL/HCLv had evidence of COVID-19, with 83% testing positive by PCR or rapid-antigen test. Of the 43 patients without positive tests, all had nucleocapsid antibodies indicating COVID-19 exposure; 7 recalled no symptoms, and 36 had mild symptoms. Of the 210 who tested positive, 175 began treatment for HCL/HCLv 0.4 to 429 (median, 66) months before, and 132 had their last dose of anti-CD20 monoclonal antibody 0.2 to 229 (median, 63) months before. Two patients died. Nearly all patients with HCL/HCLv recovered uneventfully from COVID-19 including those without vaccination or those with significant immunosuppression and recent treatment. However, decreased normal B cells from HCL or treatment was associated with lower spike antibody levels as a response to COVID-19 and longer recovery time. Thus, in a large cohort of patients with HCL/HCLv and in the first to determine relationships between COVID-19 outcome and immune markers, mortality was relatively low (∼1%), sequelae were uncommon, and recovery from COVID-19 was longer if normal B cells were low after recent treatment.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><Acceleration><Antibodies><Antibody Response><Antigenic Determinants><Antigens><Assay><B blood cells><B cell><B cell malignancy><B cells><B lymphoid malignancy><B-Cells><B-Lymphocytes><B-cell><Binding Determinants><Bioassay><Biological Assay><COVID-19><COVID-19 exposure><COVID-19 infection><COVID-19 virus><COVID-19 virus infection><COVID19 infection><COVID19 virus><CV-19><Cessation of life><CoV-2><CoV2><Collaborations><Coronavirus Infectious Disease 2019><Death><Disease><Disorder><Dose><Dysfunction><Epidemiologic Research><Epidemiologic Studies><Epidemiological Studies><Epidemiology Research><Epitopes><Functional disorder><Goals><Hairy Cell Leukemia><Hairy Cell Leukemia Variant><Human><Immune Markers><Immune response><Immunocompromised><Immunocompromised Host><Immunocompromised Patient><Immunologic Markers><Immunological response><Immunosuppressed Host><Immunosuppression><Immunosuppression Effect><Immunosuppressive Effect><Infection><Leukemic Reticuloendotheliosis><Measures><MoAb CD20><Modern Man><Monitor><Monoclonal Antibody CD20><Nucleocapsid><Organ><Outcome><Patients><Persons><Physiopathology><Polymerase Chain Reaction><Prevalence><Recovery><Role><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 exposure><SARS-CoV-2 infection><SARS-CoV2><SARS-CoV2 exposure><SARS-CoV2 infection><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Serology><Serology test><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-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 exposure><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome related corona virus 2><Symptoms><T cell response><T-Cells><T-Lymphocyte><Testing><Time><Transmission><Vaccination><Viral><Virus><Wuhan coronavirus><acute infection><anti-CD20><antigen based test><antigen test><cohort><coronavirus disease 2019><coronavirus disease 2019 exposure><coronavirus disease 2019 infection><coronavirus disease 2019 virus><coronavirus disease-19><coronavirus disease-19 virus><coronavirus infectious disease-19><epidemiologic investigation><epidemiology study><exposure to COVID-19><exposure to SARS-CoV-2><exposure to SARS-CoV2><exposure to Severe acute respiratory syndrome coronavirus 2><exposure to coronavirus disease 2019><hCoV19><hairy T cell leukemia><hairy cell leukemia cell><host response><immune suppression><immune suppressive activity><immune suppressive function><immune system response><immune-based biomarkers><immunogen><immunological biomarkers><immunological markers><immunoresponse><immunosuppressed patient><immunosuppressive activity><immunosuppressive function><immunosuppressive response><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><leukemia><mortality><nCoV2><pathophysiology><prospective><respiratory><response><serology assay><social role><thymus derived lymphocyte><transmission process><viral detection><virus detection>