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Principal Investigator: Savita Pahwa
Organization: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
Fiscal Year: 2021
Award: $153,500
Funding agency: National Institute on Drug Abuse
This Competitive Revision application for 2019 Novel Coronavirus research is related to the current grant
Immune Dysfunction in HIV+ Opioid Users (DA051202) which is investigating influenza vaccine responses in
people with HIV (PWH) who have opioid use disorder (OUD). The premise for the funded grant is that HIV
infection impairs immunity with evidence of persisting immune perturbations even after durable virologic
control. Opioids are immunosuppressive and abuse through prescription or injection can be damaging to the
immune system and prove to be specially harmful in PWH. Our central hypothesis in the parent grant is that
chronic opioid use by PWH (HIV+OP+) blunts the immune response and impairs the generation of influenza
vaccine induced immune response. Our plan is to investigate participants in 4 groups (HIV+OP+, HIV-OP+,
HIV+OP- and HIV-OP-) before and after influenza vaccine administered as a clinical trial. The project funding
started in the midst of the COVID-19 pandemic that has resulted in global morbidity and mortality. The
clinical course of SARS-CoV-2 infection is highly variable, ranging from asymptomatic to severe disease
resulting in full recovery, death, or persistent symptoms described as PASC (post acute sequalae of COVID-
19) which can affect one or more organs such as the brain, heart, lung, gut, kidneys, or musculosleletal
system. The immune response generated by SARs COV-2 is dynamic, involves innate and adaptive
immunity and evolves with the stage of the disease. Antibodies to the spike protein's receptor binding domain
corelate with neutralizing activity and form the basis of judging effectiveness of current vaccines as well as
monoclonal Ab therapy. Duration of Ab in the host following SARS CoV-2 infection or vaccination is unknown
and there are gaps in our knowledge about the role of T cells in Ab persistence or emergence of viral
variants. It is also unknown if COVID-19 causes detrimental effects on immunity and if this effect varies
depending on the host's immune competence, with the greatest impact in an immunocompromised host.
These issues are relevant for the HIV+OP+ population and need to be investigated. While Ab formation to
SARS CoV 2 is dependent upon infection or vaccination, T cell memory for SARS CoV2 has been shown to
pre-exist in approximately 50% of the general population due to cross reactive immunity induced by Common
Cold Corona viruses. Such SARS-CoV-2 specific memory T cells are considered to be beneficial to the host,
affording protection from infection, or reduction in disease severity, particularly in the face of absent or
waning humoral immunity. Despite the disruption in operations and regulatory delays due to COVID-19 our
project has been initiated, and we feel that a revision at this juncture to incorporate questions related to
SARS CoV-2 are timely and important. In this revision we are proposing to incorporate a pilot study of SARS-
CoV-2 seroprevalence and T cell memory in the context of original aims in the HIV+OP+ and the other 3
groups (HIV-OP+, HIV+OP- and HIV-OP-) being investigated for flu vaccine induced immune responses.
Terms: <19S Gamma Globulin><2019 novel corona virus><2019 novel coronavirus><2019-nCoV><2019-nCoV S protein><2019-nCoV spike glycoprotein><2019-nCoV spike protein><2019-nCoV vaccine><7S Gamma Globulin><AIDS Virus><Ab response><Acquired Immune Deficiency Syndrome Virus><Acquired Immunodeficiency Syndrome Virus><Active Follow-up><Acute><Acute Nasopharyngitis><Address><Affect><Antibodies><Antibody Formation><Antibody Production><Antigens><Applications Grants><Assay><Attention><B blood cells><B cell><B cells><B-Cells><B-Lymphocytes><B-cell><Bioassay><Biologic Assays><Biological Assay><Brain><Brain Nervous System><CD8 Cell><CD8 T cells><CD8 lymphocyte><CD8+ T cell><CD8+ T-Lymphocyte><CD8-Positive Lymphocytes><CD8-Positive T-Lymphocytes><COVID><COVID crisis><COVID disease severity><COVID epidemic><COVID pandemic><COVID severity><COVID-19><COVID-19 S protein><COVID-19 antibody><COVID-19 antigen><COVID-19 crisis><COVID-19 disease severity><COVID-19 epidemic><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 immunity><COVID-19 infection><COVID-19 pandemic><COVID-19 public health crisis><COVID-19 severity><COVID-19 spike glycoprotein><COVID-19 spike protein><COVID-19 vaccination><COVID-19 vaccine><COVID-19 virus><COVID19><COVID19 S protein><COVID19 crisis><COVID19 disease severity><COVID19 epidemic><COVID19 global health crisis><COVID19 global pandemic><COVID19 health crisis><COVID19 immunity><COVID19 infection><COVID19 pandemic><COVID19 public health crisis><COVID19 severity><COVID19 spike glycoprotein><COVID19 spike protein><COVID19 vaccination><COVID19 vaccine><COVID19 virus><CV-19><CV19><Caring><Cell Body><Cell Communication><Cell Interaction><Cell-to-Cell Interaction><Cells><Cessation of life><Chronic><Clinical><Clinical Trials><CoV disease><CoV-2><CoV2><Common Cold><Coronaviridae><Coronavirus><Death><Diagnostic><Disease><Disorder><ELISA><Effectiveness><Encephalon><Enzyme-Linked Immunosorbent Assay><Evaluation><Flow Cytofluorometries><Flow Cytofluorometry><Flow Cytometry><Flow Microfluorimetry><Flow Microfluorometry><Flu vaccination><Frequencies><Funding><General Population><General Public><Generations><Germinal Center><Goals><Grant><Grant Proposals><HIV><HIV Infections><HTLV-III Infections><HTLV-III-LAV Infections><Heart><Helper Cells><Helper T-Cells><Helper T-Lymphocytes><Helper-Inducer T-Cells><Helper-Inducer T-Lymphocyte><Hospital Admission><Hospitalization><Human Immunodeficiency Viruses><Human T-Lymphotropic Virus Type III Infections><Humoral Immunities><IgA><IgG><IgM><Immune><Immune Cell Activation><Immune Diseases><Immune Disorders><Immune Dysfunction><Immune System Diseases><Immune System Disorder><Immune System Dysfunction><Immune System and Related Disorders><Immune response><Immune system><Immunes><Immunity><Immunocompetence><Immunocompromised><Immunocompromised Host><Immunocompromised Patient><Immunodeficiency and Immunosuppression Disorders><Immunoglobulin A><Immunoglobulin G><Immunoglobulin M><Immunologic Competence><Immunologic Diseases><Immunological Competence><Immunological Diseases><Immunological Dysfunction><Immunological System Dysfunction><Immunological response><Immunosuppressed Host><Impairment><Incidence><Individual><Inducer Cells><Inducer T-Lymphocytes><Infection><Inflammation><Influenza Vaccines><Influenza immunization><Influenza vaccination><Injections><Innate Immunity><Intensive Care Units><Interview><Kidney><Kidney Urinary System><Knowledge><LAV-HTLV-III><Lung><Lung Respiratory System><Lymphadenopathy-Associated Virus><Measures><Mediating><Memory><Morbidity><Morbidity - disease rate><Native Immunity><Natural Immunity><Needle-Exchange Programs><Non-Specific Immunity><Nonspecific Immunity><Nucleocapsid><Nucleocapsid Proteins><Opiate user><Opiates><Opioid><Opioid drug user><Organ><PWUO><Participant><Persons><Pilot Projects><Population><Population Sizes><Prevalence><Prevalence Study><Prophylactic vaccination against influenza><Proteins><Questionnaires><Reaction><Receptor Protein><Recovery><Research><Role><SARS corona virus 2><SARS-CoV-2><SARS-CoV-2 S protein><SARS-CoV-2 antibody><SARS-CoV-2 antigen><SARS-CoV-2 disease severity><SARS-CoV-2 epidemic><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 immunity><SARS-CoV-2 infection><SARS-CoV-2 pandemic><SARS-CoV-2 severity><SARS-CoV-2 spike glycoprotein><SARS-CoV-2 spike protein><SARS-CoV-2 vaccination><SARS-CoV-2 vaccine><SARS-CoV2><SARS-CoV2 S protein><SARS-CoV2 antibody><SARS-CoV2 antigen><SARS-CoV2 epidemic><SARS-CoV2 infection><SARS-CoV2 pandemic><SARS-CoV2 spike glycoprotein><SARS-CoV2 spike protein><SARS-CoV2 vaccine><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><SARS-coronavirus-2 vaccine><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Seroprevalences><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 epidemic><Severe Acute Respiratory Syndrome CoV 2 pandemic><Severe Acute Respiratory Syndrome CoV 2 vaccine><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 corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 S protein><Severe acute respiratory syndrome coronavirus 2 epidemic><Severe acute respiratory syndrome coronavirus 2 immunity><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome coronavirus 2 pandemic><Severe acute respiratory syndrome coronavirus 2 spike glycoprotein><Severe acute respiratory syndrome coronavirus 2 spike protein><Severe acute respiratory syndrome coronavirus 2 vaccination><Severe acute respiratory syndrome coronavirus 2 vaccine><Severe acute respiratory syndrome related corona virus 2><Severity of illness><Structure of germinal center of lymph node><Substance Use Disorder><Swab><Symptoms><Syringe-Exchange Programs><System><T memory cell><T-Cells><T-Lymphocyte><T8 Cells><T8 Lymphocytes><Testing><Time><Universities><Vaccination><Vaccines><Variant><Variation><Viral><Viral Activity><Viral Function><Viral Physiology><Virus-HIV><Vulnerable Populations><Wuhan coronavirus><active followup><adaptive immunity><allergic/immunologic body system><allergic/immunologic organ system><antibody against COVID-19><antibody against SARS-CoV-2><antibody against SARS-CoV2><antibody against coronavirus disease 2019><antibody against severe acute respiratory syndrome coronavirus 2><antibody biosynthesis><antibody to COVID-19><antibody to SARS-CoV-2><antibody to SARS-CoV2><antibody to coronavirus disease 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detection><vulnerable group>