# Identification of the Initial Targets of Transmission

> **NIH NIH R37** · NORTHWESTERN UNIVERSITY · 2020 · $786,043

## Abstract

Summary: The current pandemic of COVID-19 has rapidly spread around the world infecting millions and killing
more than 200,000 people in just months. The first wave of the pandemic is currently peaking in the United
States causing almost 60,000 deaths in the past 6 weeks. This highly contagious virus with the unique features
of a high percentage of asymptomatic infected and delayed severe symptoms has wreaked havoc on the
population of the US. Without any other options, the US population is flattening the curve by social distancing
and self-isolation. To return to normality we need an effective vaccine or therapy to protect populations around
the world. Although the SARS-CoV-2 (CoV2) virus is known as a respiratory virus, it clearly has an impact
beyond lung infection with increasing evidence of infection influencing multiple organ systems. Unanticipated
pathologies associated with CoV2 infection such as heart attacks, loss of taste and smell, kidney failure, stroke,
and COVID toe suggest possible virus dissemination beyond the respiratory tract. Such dispersed anatomical
infection is possible because the CoV2 receptor ACE2 is expressed in a variety of tissues, tightly regulated by
innate and adaptive immunity, and plays a key role in vascular homeostasis. High levels of ACE2 expression in
the respiratory tract, liver, kidney, pancreas and cardiovascular tissues correlates with co-morbidities associated
with death after extended infection. But to better define COVID-19 pathogenesis, it is essential to determine if
these multiple end organ diseases leading to death are an indirect consequence of CoV2 induced inflammation
and hypoxia or a consequence of direct CoV2 infection of various tissues and organs. Through the parent project
and other work, we have developed the concepts of signal guided necropsies and multiscale imaging to identify
and study small foci of SIV replication in the early days after mucosal transmission or rebound after cessation of
antiretroviral drug treatment. The best of these methods utilizes radiolabeled and fluorescently tagged antibody-
based probes to identify and in vivo fluorescently label SIVmac239 infected cells. In this emergency competitive
revision application, we will adapt these novel and innovative techniques to study CoV2 infection. Critically,
these state-of-the-art methods to identify active sites of CoV2 at the whole live animal method in an unbiased
manner. Knowing the active anatomical sites of virus replication and inflammation will synergize with modern
pathology approaches to provide an increased understanding of the natural history and pathogenesis of CoV2
infection. Based on the conceptual and technical innovation described above, combined with the more than 50
years of combined virology research expertise of Drs. Veazey and Hope, we believe the application has great
potential to impact and advance the new field of COVID-19 research. This critical basic understanding will
inform the field and advanc...

## Key facts

- **NIH application ID:** 10157877
- **Project number:** 3R37AI094595-09S1
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Thomas Hope
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $786,043
- **Award type:** 3
- **Project period:** 2020-08-10 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10157877

## Citation

> US National Institutes of Health, RePORTER application 10157877, Identification of the Initial Targets of Transmission (3R37AI094595-09S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10157877. Licensed CC0.

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