# Factors Responsible for the Development of Post-Acute Sequelae of Acute COVID Infection (PASC) In Hawaii

> **NIH NIH U54** · UNIVERSITY OF HAWAII AT MANOA · 2023 · $462,752

## Abstract

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.

## Key facts

- **NIH application ID:** 10707356
- **Project number:** 5U54MD007601-37
- **Recipient organization:** UNIVERSITY OF HAWAII AT MANOA
- **Principal Investigator:** Gehan Devendra
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $462,752
- **Award type:** 5
- **Project period:** 1997-09-23 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10707356

## Citation

> US National Institutes of Health, RePORTER application 10707356, Factors Responsible for the Development of Post-Acute Sequelae of Acute COVID Infection (PASC) In Hawaii (5U54MD007601-37). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10707356. Licensed CC0.

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