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Principal Investigator: Lawrence James Purpura
Organization: COLUMBIA UNIVERSITY HEALTH SCIENCES
Fiscal Year: 2022
Award: $192,102
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><CDC><COVID crisis><COVID epidemic><COVID pandemic><COVID survivors><COVID-19><COVID-19 crisis><COVID-19 epidemic><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 public health crisis><COVID-19 survivors><COVID-19 vaccine><COVID-19 virus><COVID19><COVID19 crisis><COVID19 epidemic><COVID19 global health crisis><COVID19 global pandemic><COVID19 health crisis><COVID19 pandemic><COVID19 public health crisis><COVID19 vaccine><COVID19 virus><CV-19><CV19><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 Fatigue-Fibromyalgia 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><Communicable Diseases><Complication><Cytotoxic cell><Data><Diagnostic><Disease Outbreaks><Disturbance in cognition><Dysautonomias><Dysfunction><E-B Virus><EB virus><EBV><Ebola><Environment><Epidemic><Epidemiology><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><Gamma interferon><Gastrointestinal microbiota><Goals><Gut Epithelial Permeability><Gut Hyperpermeability><Gut permeability><HHV-4><HHV4><HIV><HIV 1 associated neurocognitive disorder><HIV Infections><HIV-1 associated neurocognitive disorder><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><Interferon-gamma><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><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 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pandemic><SARS-coronavirus-2 vaccine><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Scientist><Services><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><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 CoV disease><Severe Acute Respiratory Syndrome coronavirus disease><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 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><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><Virus Diseases><Virus-HIV><Wuhan coronavirus><activin B><acute disease/disorder><acute disorder><acute 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><corona virus disease 2019><corona virus disease 2019 epidemic><corona virus disease 2019 pandemic><corona virus disease 2019 vaccine><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 pandemic><coronavirus disease-19 pandemic><coronavirus disease-19 vaccine><coronavirus disease-19 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design><microbial><microbial consortia><microbial flora><microbial imbalance><microbiome><microbiome analysis><microbiota><microflora><multidisciplinary><multispecies consortia><nCoV2><neural manifestation><neural sequela in COVID-19><neuro post-acute sequelae of SARS-CoV-2><neurocognitive outcomes of coronavirus disease-19><neurocognitive symptoms and sequelae during COVID-19><neurologic sequelae of COVID-19><neurological post-acute sequelae of SARS-CoV-2><neurological sequelae associated with SARS-CoV-2><neurological sequelae caused by SARS-CoV-2><novel><pathogen><pathophysiology><post-acute CNS symptoms of SARS-CoV-2 infection><post-acute sequelae following SARS-CoV-2 infection><post-acute sequelae of COVID-19><post-acute sequelae of acute COVID infection><post-acute sequelae of coronavirus disease 2019><post-orthostatic tachycardia><postural orthostatic tachycardia><prospective><self reactive antibody><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><skills><social role><stool><stress protein><survive COVID-19><survive SARS-CoV-2><transcriptome sequencing><translation research><trend><trial regimen><trial treatment><vaccine against 2019-nCov><vaccine against SARS-CoV-2><vaccine against SARS-CoV2><vaccine against SARS-coronavirus-2><vaccine against Severe Acute Respiratory Syndrome CoV 2><vaccine against Severe acute respiratory syndrome coronavirus 2><vaccine for novel coronavirus><viral infection><virus infection><virus-induced disease>