Project Details
Description
PROJECT SUMMARY
COVID-19–related extra-pulmonary damage is common and may even be observed in patients with mild COVID-
19 symptoms. There is an urgent and immediate need to establish optimal post-infection health care strategies
for these patients, yet mechanisms underlying their appearance remain unexamined. For example, post-COVID-
19 chronic fatigue syndrome has been reported in 54% of COVID-19 survivors, including those without severe
symptoms during the acute infection; however, its cause has not been addressed. Post-COVID-19 chronic
fatigue syndrome’s symptoms mimic those experienced by patients with well-described pituitary hormone
deficiencies, supporting the concept that pituitary dysfunction in patients with COVID-19 may be implicated in
post–COVID-19 health complications. Several lines of evidence support the premise that SARS-CoV-2 infection
damages the pituitary, leading to disrupted pituitary function. First, we detected expression of the SARS-CoV-2
receptor ACE2 in the normal human pituitary by immunofluorescence, suggesting that SARS-CoV-2 may directly
damage pituitary endocrine cells. Second, it has been reported that the SARS pandemic in Southeast Asia in
2002, by SARS-CoV-1, caused post-infection pituitary function decline, although direct damage to the pituitary
was not investigated. Third, clinical observations suggest that patients with COVID-19 show aberrant immune
activity and may develop cytokine storm, with particularly acute elevations of IL-6 and TNFα. Cytokine storm,
which can occur as a consequence of with cancer immunotherapy treatment, for example, is frequently
associated with pituitary inflammation and dysfunction, although the detailed pathogenetic mechanisms are not
known. This suggests that aberrant activation of the immune system may also indirectly damage the pituitary in
patients with COVID-19. Elucidating the mechanisms underlying direct and indirect pituitary damage related to
SARS-CoV-2 infection is critical to establishing guidelines for timely diagnosis and management of pituitary
dysfunction in COVID-19 survivors. In Aim 1, we will determine whether SARS-CoV-2 directly invades the
pituitary and causes pituitary structural damage. We will study autopsy-derived pituitary tissues obtained from
COVID-19 deceased patients and normal control pituitary tissues. Moreover, using a novel spatial genomics
technology, we will determine changes in gene expression associated with COVID-19 in each of the five pituitary
endocrine lineages and stroma cells. In Aim 2, we will determine the association and the timeline of pituitary
dysfunction and symptoms in patients who were infected by SARS-CoV-2. By combining detailed and innovative
cellular and molecular analyses, and clinical studies, we will identify the mechanisms responsible for pituitary
dysfunction in COVID-19 patients and determine the course of pituitary dysfunction in COVID-19. These
innovative studies will, in turn, enable the development of an evidence-based clinical guide for evaluation and
management of hormone deficiencies in the vast COVID-19 population across the globe.
Status | Active |
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Effective start/end date | 9/1/21 → 7/31/24 |
Funding
- National Institute of Diabetes and Digestive and Kidney Diseases: $392,800.00
- National Institute of Diabetes and Digestive and Kidney Diseases: $391,475.00
- National Institute of Diabetes and Digestive and Kidney Diseases: $421,625.00
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