Document text
Principal Investigator: Fudong Liu
Organization: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
Fiscal Year: 2024
Award: $769,918
Funding agency: National Institute of Mental Health
PROJECT SUMMARY
To date over 16 million people in the US have been infected with the severe acute respiratory syndrome
coronavirus 2 virus (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19). While the vast
majority will survive the acute illness, many are at risk for experiencing long-term symptoms after the acute
illness. Acute neurologic symptoms including encephalitis, strokes and seizures have been reported in COVID-
19 patients. Increasingly, even survivors without acute neurologic conditions have reported neuropsychiatric
symptoms (NPS) months after their illness. The incidence and factors that influence the development of long-
term NPS is unknown. SARS-CoV-2 infection triggers a systemic pro-inflammatory response termed `cytokine
storm', characterized by an uncontrolled release of pro-inflammatory molecules. The consequences of
uncontrolled systemic inflammation on the brain and the link to long-term NPS after COVID-19 is unknown.
Sex differences in the outcome from COVID-19 are increasingly evident. Men have worse outcomes with
acute COVID-19 infection, with higher hospitalization rates and mortality, an effect seen globally. Sex
differences in the immune
literature
acute
inflammatory
circulating
immune
responses underlie the differences i n the acute disease course, as seen both in t he
and in our preliminary data. We have found that men have a more robust innate immune response to
COVID-19 infection, with increased circulating neutrophils and monocytes and higher serum levels of
cytokines and markers of brain injury (neuron specific enolase). In contrast, women have more
T and B cells in response to acute infection compared to men, hallmarks of an antigen-specific
response.Interestingly, our preliminary data suggest that women however, may be disproportionally
affected by the chronic effects of infection, including higher rates of NPS. To examine the mechanism of NPS,
we propose a longitudinal, prospective study to assess the impact of acute and chronic inflammation on
markers of brain injury, and long-term NPS for up to 2 years after COVID-19 infection. To accomplish this, we
will leverage our prospective clinical biorepository and long-term COVID-19 follow-up clinic. To date, over 400
hospitalized COVID-19 patients from three different hospitals have been enrolled into a prospective
biorepository and Houston is now at the verge of another surge. Identifying patients at risk for developing
chronic consequences of COVID-19 infection, and discovering potential underlying mechanisms leading to
NPS will be critical to the enhance the health of millions of COVID-19 survivors.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><Acquired brain injury><Active Follow-up><Acute><Acute Brain Injuries><Acute Disease><Affect><Age><Antigens><Anxiety><Apoplexy><B blood cells><B cell><B cells><B-Cells><B-Lymphocytes><B-cell><Blood><Blood Neutrophil><Blood Polymorphonuclear Neutrophil><Blood Reticuloendothelial System><Blood Serum><Blood leukocyte><Blood monocyte><Brain><Brain Inflammation><Brain Injuries><Brain Nervous System><Brain Vascular Accident><COVID infected patient><COVID patient><COVID positive patient><COVID survivors><COVID-19><COVID-19 affected><COVID-19 consequence><COVID-19 effect><COVID-19 impact><COVID-19 impacted><COVID-19 infected patient><COVID-19 infection><COVID-19 infection survivors><COVID-19 patient><COVID-19 positive patient><COVID-19 survivors><COVID-19 virus><COVID-19 virus infection><COVID19 infection><COVID19 patient><COVID19 positive patient><COVID19 virus><CV-19><Cardiology><Cell Body><Cells><Cerebral Stroke><Cerebrovascular Apoplexy><Cerebrovascular Stroke><Chronic><Clinic><Clinical><CoV-2><CoV2><Control Groups><Coronavirus Infectious Disease 2019><Data><Development><Differences between sexes><Differs between sexes><Disease><Disease Progression><Disorder><Disproportionate number of females><Disproportionate number of women><Disproportionately affects females><Disproportionately affects women><Disproportionately impacts females><Disproportionately impacts women><Disproportionately in females><Disproportionately in women><Drowsiness><Dysfunction><Encephalitis><Encephalon><Endothelium><Enrollment><Event><Fatigue><Flow Cytofluorometries><Flow Cytofluorometry><Flow Cytometry><Flow Microfluorimetry><Flow Microfluorometry><Functional disorder><Health><Hospital Admission><Hospitalization><Hospitals><Immune><Immune Cell Activation><Immune response><Immunes><Immunological response><Incidence><Infection><Inflammation><Inflammatory><Inflammatory Response><Injury><Innate Immune Response><Internal Medicine><Investigation><Lack of Energy><Length of Stay><Leukocytes><Leukocytes Reticuloendothelial System><Link><Literature><Long COVID><Long COVID-19><Long coronavirus disease><Long coronavirus disease 2019><Long-term prospective studies><Longitudinal Studies><Longterm prospective studies><Marrow Neutrophil><Marrow leukocyte><Marrow monocyte><Measures><Mechanical ventilation><Mental Depression><Modeling><Neurologic><Neurologic Manifestations><Neurologic Signs and Symptoms><Neurologic Symptoms><Neurologic outcome><Neurological><Neurological Manifestations><Neurological Signs and Symptoms><Neurological outcome><Neuron-Specific Enolase><Neuronal Injury><Neutrophilic Granulocyte><Neutrophilic Leukocyte><Number of Days in Hospital><Outcome><PTSD><Pain><Painful><Pathway interactions><Patients><Peripheral><Persons><Physiopathology><Polymorphonuclear Cell><Polymorphonuclear Leukocytes><Polymorphonuclear Neutrophils><Population><Post-Traumatic Neuroses><Post-Traumatic Stress Disorders><Posttraumatic Neuroses><Prevalence><Public Health><Reaction><Reporting><Research><Risk><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 infected patient><SARS-CoV-2 infection><SARS-CoV-2 patient><SARS-CoV-2 positive patient><SARS-CoV-2 survivors><SARS-CoV2><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><Sampling><Seizures><Serum><Serum Markers><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 infection><Severe acute respiratory syndrome related corona virus 2><Sex Differences><Sexual differences><Somnolence><Stroke><Survivors><Symptoms><T-Cells><T-Lymphocyte><Time><Virus><White Blood Cells><White Cell><Woman><Wuhan coronavirus><access to vaccination><access to vaccines><active followup><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><after COVID-19 infection><after SARS-CoV-2 infection><after SARS-CoV2 infection><after infection by SARS-CoV-2><after severe acute respiratory distress syndrome CoV-2 infection><ages><bio-informatics tool><biobank><bioinformatics tool><biorepository><brain attack><brain damage><brain-injured><cerebral vascular accident><cerebrovascular accident><chronic COVID><chronic COVID-19><chronic novel coronavirus disease 2019><cognitive function><computer based prediction><coronavirus disease 2019><coronavirus disease 2019 consequence><coronavirus disease 2019 effect><coronavirus disease 2019 impact><coronavirus disease 2019 infected patient><coronavirus disease 2019 infection><coronavirus disease 2019 patient><coronavirus disease 2019 positive patient><coronavirus disease 2019 virus><coronavirus disease infected patient><coronavirus disease patient><coronavirus disease positive patient><coronavirus disease-19><coronavirus disease-19 impact><coronavirus disease-19 patient><coronavirus disease-19 virus><coronavirus infectious disease-19><coronavirus patient><cytokine><cytokine release syndrome><cytokine storm><death risk><depression><developmental><enroll><experience><female bias><female preponderance><flow cytophotometry><follow up><follow-up><followed up><following COVID-19 infection><following SARS-CoV-2 infection><following SARS-CoV2 infection><following infection by SARS-CoV-2><following severe acute respiratory distress syndrome CoV-2 infection><followup><functional status><hCoV19><hospital days><hospital length of stay><hospital stay><hospitalization rates><host response><immune activation><immune system response><immunogen><immunoresponse><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><inflammation marker><inflammatory marker><injuries><long haul COVID><long haul COVID-19><long haul coronavirus disease><long haul coronavirus disease 2019><long-hauler COVID><long-hauler COVID-19><long-hauler coronavirus disease 2019><long-hauler syndrome><long-term COVID><long-term COVID-19><long-term coronavirus disease><long-term coronavirus disease 2019><long-term sequelae><long-term study><longitudinal outcome studies><longitudinal, prospective study><longterm COVID><longterm COVID-19><longterm coronavirus disease><longterm coronavirus disease 2019><longterm study><mechanical respiratory assist><mechanically ventilated><men><monocyte><mortality><mortality risk><nCoV2><neural manifestation><neuron injury><neuropsychiatric symptom><neutrophil><pandemic><pandemic disease><pathophysiology><pathway><patient infected with COVID><patient infected with COVID-19><patient infected with SARS-CoV-2><patient infected with coronavirus disease><patient infected with coronavirus disease 2019><patient infected with severe acute respiratory syndrome coronavirus 2><patient with COVID><patient with COVID-19><patient with COVID19><patient with SARS-CoV-2><patient with coronavirus disease><patient with coronavirus disease 2019><patient with severe acute respiratory distress syndrome coronavirus 2><persistent COVID-19><post COVID syndrome><post COVID-19 syndrome><post SARS-CoV-2 infection><post acute COVID syndrome><post acute COVID-19><post acute COVID-19 syndrome><post acute SARS-CoV-2><post acute coronavirus disease 2019><post acute coronavirus disease 2019 syndrome><post acute coronavirus disease syndrome><post acute severe acute respiratory syndrome coronavirus 2><post coronavirus disease 2019 syndrome><post coronavirus disease syndrome><post-acute phases of COVID-19><post-trauma stress disorder><posttrauma stress disorder><predictive modeling><previous COVID-19 infection><previous SARS-CoV-2 infection><previous SARS-CoV2 infection><previous severe acute respiratory distress syndrome CoV-2 infection><prior COVID-19 infection><prior SARS-CoV-2 infection><prior SARS-CoV2 infection><prior severe acute respiratory distress syndrome CoV-2 infection><prolonged COVID-19 symptoms><prospective><response><severe acute respiratory syndrome coronavirus 2 infected patient><severe acute respiratory syndrome coronavirus 2 patient><severe acute respiratory syndrome coronavirus 2 positive patient><sex><sex based differences><sex-dependent differences><sex-related differences><sex-specific differences><sleepiness><stroked><strokes><survive COVID-19><survive SARS-CoV-2><systemic inflammation><systemic inflammatory response><thymus derived lymphocyte><traumatic neurosis><vaccination access><vaccination availability><vaccine access><vaccine availability><white blood cell><white blood corpuscle><women's preponderance>