# Leveraging genomic data to dissect the association of internalizing disorders with the risk, onset, and vulnerability of COVID-19

> **NIH NIH RF1** · YALE UNIVERSITY · 2022 · $3,694,722

## Abstract

Abstract. Although our understanding of the COVID-19 and its infectious agent, SARS-Cov-2,
is greatly improved and effective vaccines have been developed, there are many uncertainties
regarding how and when the pandemic is going to end. Additionally, there are many
consequences due to the pervasive impact of COVID-19 on individuals and societies that we
will continue to face in the post-pandemic world. An aspect that is strongly contributing to the
ongoing crisis is the systematic lack of reliable information to guide healthcare professionals
and policymakers. To apply a network approach to COVID-19 research, we should prioritize the
“hubs” connecting the different domains of COVID-19 consequences. Mental health is surely
one of the health domains that are being more strongly affected by COVID-19 outcomes.
Isolation, psychological stress, and “free-time” boredom induced by COVID-19 restrictions have
been consistently associated with increased internalizing symptoms, including anxiety and
depression. Additionally, traumatic experiences related to COVID-19 (e.g., severe symptoms,
hospitalization, and death of a loved one) have been also linked to posttraumatic stress
disorder. In a vicious circle, internalizing disorders have been associated with an increased risk
of SARS-Cov-2 infection and COVID-19 severe symptoms, hospitalization, and mortality. For
instance, SARS-Cov-2 infection and COVID-19 severity can be due to the effect of a weakened
immune system associated with internalizing disorders. In recent years, genetic research has
demonstrated to be an invaluable tool to dissect the underlying dynamics related to internalizing
disorders and traits. Indeed, genetic information can be used as an anchor for causal inference
to test the relationships linking human traits and diseases and to investigate the effect of
genomic regulatory mechanisms on disease risk. Based on our expertise and the supporting
findings generated by our studies, we propose a multivariate investigation to identify the latent
factors linking the internalizing spectrum (anxiety, major depressive disorder, and posttraumatic
stress disorder) and COVID-19 outcomes (infection, hospitalization, and critical illness). Then,
we will investigate the regulatory mechanisms of these latent factors across multiple omics
domains, tissues, and cell types. In parallel, we will also test the interaction of the internalizing
spectrum with blood-based transcriptomic and epigenomic changes associated with COVID-19
morbidity and psychological stress. Our findings will provide a multi-dimensional perspective on
the processes underlying the associations between COVID-19 outcomes and internalizing
disorders.

## Key facts

- **NIH application ID:** 10612299
- **Project number:** 1RF1MH132337-01
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** RENATO POLIMANTI
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $3,694,722
- **Award type:** 1
- **Project period:** 2022-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10612299

## Citation

> US National Institutes of Health, RePORTER application 10612299, Leveraging genomic data to dissect the association of internalizing disorders with the risk, onset, and vulnerability of COVID-19 (1RF1MH132337-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10612299. Licensed CC0.

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