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Principal Investigator: Shyamasundaran Kottilil
Organization: UNIVERSITY OF MARYLAND BALTIMORE
Fiscal Year: 2020
Award: $154,500
Funding agency: National Institute on Drug Abuse
Risk factors for developing severe illness/acute respiratory distress syndrome from coronavirus
disease 2019 (COVID-19) include older age, male gender, and underlying conditions, currently
identified as smoking, chronic lung disease or moderate to severe asthma, heart disease with
complications, severe obesity, diabetes, renal failure or liver disease. Immune factors are likely
to contribute to disease progression. While immune activation is required for anti-viral response,
severely ill patients show an excessive and aberrant host immune response as evidenced by high
inflammatory markers and proinflammatory cytokines. On the other hand, factors associated
with less robust immune response against the virus, such as advanced age are associated with
severe disease. Opioid use disorder (OUD) is an important public heath condition associated with
dysregulated immunity. This may be related to higher prevalence of systemic comorbid
conditions and concomitant conditions like chronic HIV, hepatitis C or incident infections
related to injection drug use, which may further influence immune response to infections. An
especially vulnerable group is people living with HIV (PLWH) with OUD, which are expected to
have further immune dysregulations due to twin effect of HIV and opioids on immunity.
Additionally, people with OUD are at increased risk of COVID-19 due to social factors such
as homelessness, poor access to healthcare, housing insecurity, greater likelihood of
incarceration, which can make it more difficult to maintain social distancing and these
individuals may not seek medical care promptly due to lack of access to outpatient care. We are
asking whether OUD constitutes a risk factor for progressive (COVID-19), especially in PLWH.
We are investigating immune responses in individuals with OUD and HIV infection under our
NIDA funded R01; leveraging the clinical cohorts and IRB approved blood collection protocols
from COVID-19 patients, here we will investigate incidence and progression of COVID-19 in
these patient populations. First, we will document clinical course and outcomes of COVID-19 in
patients with or without OUD/HIV. To identify immune correlates of COVID-19 severity, we
will perform analysis of B and T cell responses and study impact of OUD and HIV on this
response. Our investigation of clinical and immunological features of the disease in PLWH and
OUD will expand on known correlates of progressive COVID-19 and will inform treatment and
prophylactic approaches for COVID-19 in vulnerable groups.
Terms: <19S Gamma Globulin><2019 novel coronavirus><2019-nCoV><7S Gamma Globulin><AIDS Virus><ARDS><Acquired Immune Deficiency Syndrome Virus><Acquired Immunodeficiency Syndrome Virus><Acute><Acute Respiratory Distress><Acute Respiratory Distress Syndrome><Adult ARDS><Adult RDS><Adult Respiratory Distress Syndrome><Affect><Age><Ambulatory Care><Anti-Viral Response><Antiviral Response><Area><Asthma><B blood cells><B cell><B cells><B-Cells><B-Lymphocytes><B-cell><Blood><Blood Reticuloendothelial System><Blood Serum><Bronchial Asthma><CD4 Cells><CD4 Positive T Lymphocytes><CD4 T cells><CD4 helper T cell><CD4 lymphocyte><CD4+ T-Lymphocyte><CD4-Positive Lymphocytes><CD8><CD8 Cell><CD8 T cells><CD8 lymphocyte><CD8+ T cell><CD8+ T-Lymphocyte><CD8-Positive Lymphocytes><CD8-Positive T-Lymphocytes><CD8B><CD8B1><CD8B1 gene><COVID-19><COVID19><Cancer Patient><Cardiac Diseases><Cardiac Disorders><Caring><Case Study><Chronic><Chronic lung disease><Classification><Clinical><Clinical Protocols><Collection><Da Nang Lung><Diabetes Mellitus><Disease><Disease Progression><Disorder><Elderly><Enrollment><Funding><Gender><Generations><Goals><HCV infection><HCV/HIV><HIV><HIV Infections><HIV and HCV><HIV and hepatitis C><HIV-HCV><HIV/HCV><HIV/Hepatitis C><HTLV-III Infections><HTLV-III-LAV Infections><Heart Diseases><Helper Cells><Helper T-Cells><Helper T-Lymphocytes><Helper-Inducer T-Cells><Helper-Inducer T-Lymphocyte><Hepatic Disorder><Hepatitis C><Hepatitis C virus infection><Hepatitis, Viral, Non-A, Non-B, Parenterally-Transmitted><Hepatitus C><High Prevalence><Homelessness><Housing><Human><Human Immunodeficiency Viruses><Human T-Lymphotropic Virus Type III Infections><IRB><IRBs><IgG><IgM><Immune><Immune Cell Activation><Immune response><Immune system><Immunes><Immunity><Immunochemical Immunologic><Immunoglobulin G><Immunoglobulin M><Immunologic><Immunologic Factors><Immunological><Immunological Factors><Immunological response><Immunologically><Immunologics><Immunosuppression><Immunosuppression Effect><Immunosuppressive Effect><Impairment><Imprisonment><Incidence><Individual><Inducer Cells><Inducer T-Lymphocytes><Infection><Injecting drug user><Injection Drug User><Institutes><Institutional Review Boards><Investigation><Kidney Failure><Kidney Insufficiency><LAV-HTLV-III><LYT3><Laboratories><Liver diseases><Lymphadenopathy-Associated Virus><Mediator><Mediator of Activation><Mediator of activation protein><Medical><Modern Man><Monitor><Morbid Obesity><NIAID><NIDA><NIH><National Institute of Allergy and Infectious Disease><National Institute of Drug Abuse><National Institute on Drug Abuse><National Institutes of Health><Opiates><Opioid><Outcome><Outpatient Care><PBMC><PWID><Patients><Peripheral Blood Mononuclear Cell><Persons><Pneumonia><Production><Progressive Disease><Protocol><Protocols documentation><Recovery><Renal Failure><Renal Insufficiency><Research><Resolution><Risk><Risk Factors><SARS-CoV-2><SARS-CoV2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related coronavirus 2><Sampling><Serum><Severe acute respiratory syndrome coronavirus 2><Severe obesity><Severities><Severity of illness><Shock Lung><Smoker><Smoking><Social Distance><Stiff lung><Substance abuse problem><Syndrome><Systematics><T cell response><T-Cell Activation><T4 Cells><T4 Lymphocytes><T8 Cells><T8 Lymphocytes><Twin Multiple Birth><Twins><United States National Institutes of Health><Viral Diseases><Virus><Virus Diseases><Virus-HIV><Vulnerable Populations><Wuhan coronavirus><abuse of substances><access to health care><access to healthcare><accessibility of health care><accessibility to health care><accessibility to healthcare><adaptive immunity><advanced age><ages><allergic/immunologic body system><allergic/immunologic organ system><arm><base><case report><clinical investigation><co-morbid><co-morbidity><cohort><comorbidity><corona virus disease 2019><coronavirus disease 2019><cytokine><cytokine release syndrome><cytokine storm><diabetes><disease severity><elders><enroll><exhaustion><extreme obesity><geriatric><health care access><health care availability><health care service access><health care service availability><healthcare access><healthcare accessibility><healthcare availability><healthcare service access><healthcare service availability><heart disorder><hep C><hepatic disease><hepatitis non A non B><hepatopathy><high risk><homeless><host response><immune activation><immune suppression><immunologic substance><immunological substance><immunoresponse><incarcerated><incarceration><inflammation marker><inflammatory marker><injection drug use><interest><late life><later life><liver disorder><male><non A, non B hepatitis><non-A, non-B hepatitis><older adult><older person><opiate abuse><opiate drug abuse><opiate use disorder><opioid abuse><opioid drug abuse><opioid use disorder><outpatient treatment><patient population><patient subgroups><patient subpopulations><patient subsets><patient subtypes><people who inject drugs><people who inject illicit drugs><persons who inject drugs><primary outcome><prophylactic><response><sample collection><senior citizen><social factors><specimen collection><substance abuse><success><unhoused><viral infection><virology><virus infection><virus-induced disease><vulnerable group><wet lung>