Document text
Principal Investigator: Gehan Devendra
Organization: UNIVERSITY OF HAWAII AT MANOA
Fiscal Year: 2023
Award: $462,752
Funding agency: National Institute on Minority Health and Health Disparities
PROJECT SUMMARY/ABSTRACT
Nearly one third of individuals who recover from acute COVID-19 will have chronic symptoms, so called ‘Post-
Acute Sequelae of SARS-CoV-2’ infection (PASC). Among individuals with PASC, pulmonary complications
such as persistent dyspnea and chronic cough are common. Although Native Hawaiians and Pacific Islanders
(NHOPI) and Filipinos have been disproportionately affected by COVID-19, the prevalence and severity of
pulmonary PASC (PPASC) among race/ethnicity is not known. As the number of individuals recovering from
COVID-19 grows, PPASC is increasing with a devastating impact on patients, families and the healthcare
system.
Monocytes and monocyte-derived macrophages have been considered as key determinants of COVID-19
severity and respiratory failure. However, much less is known about their contribution to PPASC development,
resolution, and disease persistence. The objective of the proposed project is to understand the
pathophysiologic mechanisms of PPASC and how macro-social and psychological determinants are
associated with these biological mechanisms. Our preliminary data showed that monocyte counts and CD169+
monocytes were significantly higher in PPASC compared to healthy individuals. Also, CD169+ non-classical
monocytes were positively correlated with D-dimer levels in PPASC, suggesting that a specific monocyte
subset and their activation may contribute to the disease severity. Our central hypothesis is that the
development and persistence of PPASC is related to the influx of bone marrow-derived monocytes with
proinflammatory phenotype into the lungs and is associated with macro-social and psychological determinants.
To test this hypothesis, we propose the following Aims: (1) To understand monocyte dysregulation associated
with the development and persistence of PPASC, particularly focusing on dynamic changes in the monocyte
number, subpopulation, activation, and cytokines during the disease progression and resolution. (2) In a subset
of the study cohort, to characterize the pathologic changes in respiratory system response to COVID-19. A
detailed characterization of cell composition and cytokines in bronchoalveolar lavage (BAL) fluid will give an
insight into monocyte activation and differentiation that is responsible for inflammatory dysregulation and
fibrosis. (3) To examine the association of macro-social determinants (e.g., income and housing condition),
and psychosocial factors (e.g., social isolation) with development of PPASC and changes in monocyte
alteration. In summary, this is the first study to investigate the impact of macro-social and psychological
determinants on clinical outcome in PPASC and the relationship between monocyte alteration in individuals
with PPASC. Elucidating mechanisms in the role of monocytes in the pulmonary immunopathology of COVID-
19 will provide information for potential therapeutic interventions to ameliorate PPASC particularly among
NHOPI and Filipinos.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><Acute><Airway failure><Anxiety><Biological><Blood monocyte><Bone Marrow><Bone Marrow Reticuloendothelial System><Breathlessness><Bronchoalveolar Lavage Fluid><Bronchoscopy><COVID crisis><COVID disease severity><COVID epidemic><COVID pandemic><COVID severity><COVID-19><COVID-19 affected><COVID-19 consequence><COVID-19 crisis><COVID-19 disease severity><COVID-19 effect><COVID-19 epidemic><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 impact><COVID-19 impacted><COVID-19 pandemic><COVID-19 public health crisis><COVID-19 severity><COVID-19 virus><COVID19><COVID19 crisis><COVID19 disease severity><COVID19 epidemic><COVID19 global health crisis><COVID19 global pandemic><COVID19 health crisis><COVID19 pandemic><COVID19 public health crisis><COVID19 severity><COVID19 virus><CV-19><CV19><Case Fatality Rates><Cell Body><Cells><Chemotactic Cytokines><Chronic><Clinical><CoV-2><CoV2><Cohort Studies><Concurrent Studies><Coughing><D-dimer><D-dimer fibrin><D-dimer fragments><Data><Development><Disease><Disease Progression><Disorder><Dyspnea><Economic Income><Economical Income><Ethnic Origin><Ethnicity><Family><Fatigue><Fibrin fragment D><Fibrosis><Filipino><Frequencies><Hawaii><Health Care Systems><Health Disparities Research><Health disparities related research><Healthcare Systems><History><Homologous Chemotactic Cytokines><Housing><Immune><Immunes><Immunochemical Immunologic><Immunologic><Immunological><Immunologically><Immunologics><Income><Individual><Infection><Inflammation Mediators><Inflammatory><Intercrines><Lack of Energy><Long-term cohort study><Longitudinal cohort study><Longterm cohort study><Low income><Lung><Lung Function Tests><Lung Respiratory System><Lung Tissue Fibrosis><Lung symptom><Macrophage><Marrow monocyte><Memory Loss><Modeling><Mφ><NCMHD><NIMHD><National Center on Minority Health and Health Disparities><National Institute of Minority Health and Health Disparities><National Institute on Minority Health and Health Disparities><Native Hawaiian and Other Pacific Islander><Native Hawaiian and Pacific Islander><Native Hawaiian or Other Pacific Islander><Native Hawaiian or Pacific Islander><Natural regeneration><Nature><Outcome><PASC><Participant><Pathologic><Patients><Phenotype><Play><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><Prevalence><Preventive><Process><Psychological Factors><Psychosocial Factor><Pulmonary Body System><Pulmonary Fibrosis><Pulmonary Organ System><Pulmonary function tests><Race><Races><Recording of previous events><Regeneration><Resolution><Respiratory Failure><Respiratory System><Respiratory Tracts><Respiratory tract structure><Role><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 disease severity><SARS-CoV-2 epidemic><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 pandemic><SARS-CoV-2 severity><SARS-CoV2><SARS-CoV2 epidemic><SARS-CoV2 pandemic><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><SIS cytokines><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 CoV 2 epidemic><Severe Acute Respiratory Syndrome CoV 2 pandemic><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 epidemic><Severe acute respiratory syndrome coronavirus 2 pandemic><Severe acute respiratory syndrome related corona virus 2><Severities><Severity of illness><Sleep Disorders><Social isolation><Source><Symptoms><Syndrome><Testing><Therapeutic><Therapeutic Intervention><Wuhan coronavirus><adverse sequelae of COVID><adverse sequelae of COVID-19><adverse sequelae of coronavirus disease><adverse sequelae of coronavirus disease 2019><biologic><chemoattractant cytokine><chemokine><chronic COVID-19 sequelae><chronic symptom><co-morbid><co-morbidity><comorbidity><corona virus disease 2019><corona virus disease 2019 epidemic><corona virus disease 2019 pandemic><coronavirus disease 2019><coronavirus disease 2019 consequence><coronavirus disease 2019 crisis><coronavirus disease 2019 disease severity><coronavirus disease 2019 effect><coronavirus disease 2019 epidemic><coronavirus disease 2019 global health 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2019><long-term sequelae of COVID-19><long-term sequelae of SARS-CoV-2><long-term sequelae of coronavirus disease 2019><long-term sequelae of severe acute respiratory syndrome coronavirus 2><longitudinal design><lung fibrosis><lung repair><lung tissue repair><memory decline><minority health><minority health disparity><monocyte><nCoV2><persistent symptom><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><prospective><psychologic><psychological><psychosocial variables><pulmonary><pulmonary repair><pulmonary symptom><racial><racial background><racial origin><regenerate><resolutions><response><severe acute respiratory syndrome coronavirus 2 disease severity><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><severe acute respiratory syndrome coronavirus 2 severity><sleep diseases><sleep dysfunction><sleep illness><sleep problem><social><social determinants><social factors><social role><sociodeterminant>