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Principal Investigator: Lawrence James Purpura
Organization: COLUMBIA UNIVERSITY HEALTH SCIENCES
Fiscal Year: 2024
Award: $192,260
Funding agency: National Institute of Allergy and Infectious Diseases
PROJECT SUMMARY/ABSTRACT: Rationale: The COVID-19 pandemic has affected over 42 million
individuals in the United States and long-term complications are frequently reported, referred to as post-acute
sequelae of SARS-CoV-2 (PASC). Even among survivors with mild acute illness, neurologic symptoms such
as chronic fatigue, dysautonomia, and cognitive impairment are frequently reported. To date, the etiology and
pathophysiology of neurologic PASC remain unclear; however, underlying autoantibodies and immune
activation are suspected. In our prospective COVID-19 ID Persistence Cohort (C-PIC), more than half of
COVID-19 survivors are reporting neurologic PASC at one year. We have identified an association between
neurologic PASC with both SARS-CoV-2 specific antibodies and ANA. Specifically, nucleocapsid (NP)
antibody levels are elevated compared to spike trimer (ST) antibody levels in participants with neurologic
PASC. Furthermore, our preliminary data has identified a potential signal linking neurologic PASC and
decreased gastrointestinal microbiota diversity. In this mentored career project, we hypothesize that
autoimmunity, immune activation, and microbiome dysbiosis are associated with neurologic PASC. Candidate:
As an Infectious Diseases physician with a master’s in public health and applied epidemiology and outbreak
training through the Center for Disease Control and Prevention’s Epidemic Intelligence Service, I am uniquely
positioned to study the epidemiology and determinants for neurologic PASC. My experience studying post-
Ebola syndrome in Liberia provided me with the foresight to contribute viral persistence and sequelae aims to
the C-PIC study, which includes longitudinal PASC survey data and biorepository specimens. Through the
guidance of my outstanding multidisciplinary team of mentors, I plan to fulfill my training objectives of (1)
developing expertise in advanced biostatistical analysis of survey data and (2) bridging translational research
and descriptive cohort data. Environment: My team of mentors at Columbia University Irving Medical Center
(CUIMC) are experts in epidemiology, biostatistics, immunology, and microbiome analysis. CUIMC also has a
long track record of enabling young physician-scientists to develop independent and successful careers in
academic medicine. Approach: We hypothesize that chronic fatigue, dysautonomia, and cognitive impairment
sub-phenotypes of neurologic PASC have different underlying pathophysiology, including autoimmunity,
immune activation, and microbiome dysbiosis. In Aim 1, we will characterize neurologic PASC epidemiology,
trajectory, and sub-phenotypes using longitudinal neurologic PASC surveys. In Aim 2, we will identify
associations between neurologic PASC with SARS-CoV-2 specific antibodies and autoantibodies. In Aim 3, we
will identify associations between neurologic PASC and immune activation and explore the role of gut
microbiota. This proposal provides an innovative approach to studying determinants for neurologic PASC, and
the proposed training will facilitate my transition into an independently funded clinician-scientist.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><2019-nCoV vaccine><ACE2><AIDS Virus><Acquired Immune Deficiency Syndrome Virus><Acquired Immunodeficiency Syndrome Virus><Acute><Acute Disease><Affect><Aldesleukin Gene><Antibiotic Agents><Antibiotic Drugs><Antibiotics><Antibodies><Antigens><Autoantibodies><Autoimmune Status><Autoimmunity><Biometrics><Biometry><Biostatistics><Burkitt Herpesvirus><Burkitt Lymphoma Virus><CD8 Cell><CD8 T cells><CD8 lymphocyte><CD8+ T cell><CD8+ T-Lymphocyte><CD8-Positive Lymphocytes><CD8-Positive T-Lymphocytes><COVID crisis><COVID epidemic><COVID pandemic><COVID survivors><COVID-19><COVID-19 crisis><COVID-19 epidemic><COVID-19 era><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 infection survivors><COVID-19 neural sequela><COVID-19 pandemic><COVID-19 period><COVID-19 public health crisis><COVID-19 survivors><COVID-19 vaccine><COVID-19 virus><COVID-19 years><COVID19 virus><CV-19><Causality><Cell Communication and Signaling><Cell Signaling><Centers for Disease Control><Centers for Disease Control and Prevention><Centers for Disease Control and Prevention (U.S.)><Chronic><Chronic Fatigue Disorder><Chronic Fatigue Syndrome><Chronic Fatigue and Immune Dysfunction Syndrome><Chronic Infectious Mononucleosis-Like Syndrome><Clinical><Clinical Management><Clinical Research><Clinical Study><Clinical Treatment><CoV-2><CoV2><Cognitive Disturbance><Cognitive Impairment><Cognitive decline><Cognitive function abnormal><Cohort Studies><Communicable Diseases><Complication><Concurrent Studies><Coronavirus Infectious Disease 2019><Cytotoxic cell><Data><Diagnostic><Disease Outbreaks><Disturbance in cognition><Dysautonomias><Dysfunction><EB virus><EBV><Ebola><Environment><Epidemiologic Research><Epidemiologic Studies><Epidemiological Studies><Epidemiology><Epidemiology Research><Epstein Barr Virus><Etiology><Fatigue><Feces><Functional disorder><Funding><G Protein-Complex Receptor><G Protein-Coupled Receptor Genes><G-Protein-Coupled Receptors><GI microbiota><GPCR><Gastrointestinal microbiota><Generalized Growth><Goals><Growth><Gut Epithelial Permeability><Gut Hyperpermeability><Gut permeability><HHV-4><HHV4><HIV><HIV 1 associated neurocognitive disorder><HIV Infections><HIV associated neurocognitive deficit><HIV associated neurocognitive impairment><HIV induced neurocognitive deficit><HIV induced neurocognitive impairment><HIV neurocognitive impairment><HIV-1 associated neurocognitive deficit><HIV-1 associated neurocognitive disorder><HIV-1 associated neurocognitive impairment><HIV-associated neurocognitive disorder><HTLV-III Infections><HTLV-III-LAV Infections><Heat shock proteins><Host Factor><Host Factor Protein><Human Herpesvirus 4><Human Immunodeficiency Viruses><Human T-Lymphotropic Virus Type III Infections><IFN><IFN-Gamma><IFN-g><IFN-γ><IFNG><IFNγ><IL-2 Gene><IL2><IL2 gene><Immune><Immune Cell Activation><Immune Interferon><Immunes><Immunology><Impaired cognition><Individual><Infection><Infectious Disease Pathway><Infectious Diseases><Infectious Disorder><Infectious Mononucleosis Virus><Inflammation><Integration Host Factors><Intelligence><Interferon Gamma><Interferon Type II><Interferons><Interleukin 2 Precursor Gene><Interleukin-2 Gene><Intestinal Epithelial Permeability><Intestinal Hyperpermeability><Intestinal permeability><Intracellular Communication and Signaling><K lymphocyte><K23 Award><K23 Mechanism><K23 Program><Knowledge><LAV-HTLV-III><Lack of Energy><Liberia><Link><Long-term cohort><Longitudinal cohort><Longterm cohort><Lymphadenopathy-Associated Virus><ME/CFS><Medical center><Medicine><Memory><Mentored Patient-Oriented Research Career Development Award><Mentored Patient-Oriented Research Career Development Award (K23)><Mentors><Miscellaneous Antibiotic><Myalgic Encephalomyelitis><NK Cells><Natural Killer Cells><Neurocognitive Impairment in HIV><Neurocognitive Impairment in HIV-1><Neurologic><Neurologic Manifestations><Neurologic Signs and Symptoms><Neurologic Symptoms><Neurological><Neurological Manifestations><Neurological Signs and Symptoms><Nucleocapsid><Outbreaks><Outcome><PASC><Participant><Peripheral><Phase><Phenotype><Physicians><Physiopathology><Position><Positioning Attribute><Post Acute Sequelae of COVID19><Post Acute Sequelae of SARS-CoV-2><Post Acute Sequelae of SARS-CoV2><Post Acute Sequelae of severe acute respiratory syndrome coronavirus 2><Post-Acute Sequelae of SARS-CoV-2 Infection><Postural Orthostatic Tachycardia Syndrome><Postural Tachycardia Syndrome><Postviral Fatigue Syndrome><Predisposing Factor><Public Health><RNA Seq><RNA sequencing><RNAseq><Relapse><Reporting><Research Specimen><Role><Royal Free Disease><SARS><SARS corona virus 2><SARS coronavirus disease><SARS-CO-V2><SARS-COVID-2><SARS-CoV disease><SARS-CoV-2><SARS-CoV-2 epidemic><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 neurological sequelae><SARS-CoV-2 pandemic><SARS-CoV-2 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corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 epidemic><Severe acute respiratory syndrome coronavirus 2 pandemic><Severe acute respiratory syndrome coronavirus 2 vaccine><Severe acute respiratory syndrome related corona virus 2><Severities><Severity of illness><Signal Transduction><Signal Transduction Systems><Signaling><Specimen><Survey Instrument><Surveys><Survivors><Syndrome><T-Cell Growth Factor Gene><T8 Cells><T8 Lymphocytes><TCGF Gene><Testing><Time><Tissue Growth><Training><Translational Research><Translational Science><United States><United States Centers for Disease Control><United States Centers for Disease Control and Prevention><Universities><Vaccination><Variant><Variation><Viral><Viral Diseases><Virus Diseases><Virus-HIV><Wuhan coronavirus><activin B><acute COVID-19><acute SARS-CoV-2 infection><acute disease/disorder><acute disorder><acute infection><acute phase of COVID-19><acute phase of SARS-CoV-2 infection><adverse sequelae of COVID><adverse sequelae of COVID-19><adverse sequelae of coronavirus disease><adverse sequelae of coronavirus disease 2019><analyze microbiome><angiotensin converting enzyme 2><angiotensin converting enzyme II><autoimmune antibody><autoreactive antibody><biobank><biological signal transduction><biorepository><career><causation><chronic COVID-19 sequelae><co-morbid><co-morbidity><cognitive dysfunction><cognitive loss><cohort><comorbidity><coronavirus disease 2019><coronavirus disease 2019 crisis><coronavirus disease 2019 epidemic><coronavirus disease 2019 global health crisis><coronavirus disease 2019 global pandemic><coronavirus disease 2019 health crisis><coronavirus disease 2019 pandemic><coronavirus disease 2019 public health crisis><coronavirus disease 2019 vaccine><coronavirus disease 2019 virus><coronavirus disease crisis><coronavirus disease epidemic><coronavirus disease pandemic><coronavirus disease-19><coronavirus disease-19 global 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infection><virus-induced disease>