# Maternal obesity and inflammation as drivers of maternal morbidity in COVID-19

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $175,254

## Abstract

PROJECT SUMMARY
While substantial attention on COVID-19 in pregnancy has been focused on whether vertical
transmission occurs, COVID-19 is also associated with severe maternal morbidity and maternal
mortality. How pregnancy-specific immune changes impact the response to SARS-CoV-2 and the
trajectory of COVID-19 illness remains unknown. Similarly, it is not understood how maternal obesity,
one of the most widespread maternal comorbidities, influences risk for severe disease. Recent work
suggests that the cytokine storm pathophysiology of severe COVID-19 may be mediated by monocytes
and macrophages. Our laboratory’s focus on maternal obesity and its impact on pro-inflammatory
macrophage priming in pregnancy therefore positions us well to answer these pressing scientific
questions. In light of the recent projection that millions of pregnant women will be exposed to COVID-
19, understanding mechanisms underlying severe disease in pregnancy is an urgent public health
concern.
“Fetal Brain-Placental Immune Activation in Maternal Obesity” is a pre-clinical R01 that tests the
hypothesis that maternal obesity-associated inflammatory priming of fetal brain microglia and resident
placental macrophages or Hofbauer cells is a targetable mechanism underlying offspring cognitive
deficits. A key translational aspect of the funded project is to determine whether Hofbauer cells
represent a novel biologic surrogate for fetal brain microglial reactivity in the setting of maternal obesity.
This administrative supplement proposal aims to test a maternally-focused hypothesis based on the
same premise: that maternal obesity will potentiate maternal inflammatory response to SARS-CoV-2
infection by priming maternal monocytes and placental macrophages to overrespond to the virus, and
that maternal peripheral monocyte and placental Hofbauer cell reactivity can be used as a risk
assessment or biomarker for COVID-19 disease severity. Here we propose to expand the ex vivo cell
stimulation experiments in Aim 1a to include stimulation of SARS-CoV-2-exposed and unexposed
human maternal peripheral monocytes with toll-like receptor ligands, and to examine the impact of
obesity on maternal monocyte response to SARS-CoV-2. We also propose to expand the single-cell
RNA-sequencing experiments in Aim 1b to include human Hofbauer cells exposed and unexposed to
SARS-CoV-2 and maternal obesity, to determine whether these exposures induce pro-inflammatory
alterations in Hofbauer cell programs. Together, these experiments will generate key insights into how
maternal obesity and associated priming of maternal monocytes and placental macrophages may drive
maternal morbidity in the setting of COVID-19. Monocyte-macrophage priming can be used not only to
identify women at risk for morbidity, but are targetable mechanisms that can inform novel therapies.

## Key facts

- **NIH application ID:** 10200505
- **Project number:** 3R01HD100022-02S2
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Andrea Goldberg Edlow
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $175,254
- **Award type:** 3
- **Project period:** 2019-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10200505

## Citation

> US National Institutes of Health, RePORTER application 10200505, Maternal obesity and inflammation as drivers of maternal morbidity in COVID-19 (3R01HD100022-02S2). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10200505. Licensed CC0.

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