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Principal Investigator: Amal O Amer
Organization: OHIO STATE UNIVERSITY
Fiscal Year: 2020
Award: $460,500
Funding agency: National Institute of Allergy and Infectious Diseases
Summary
This administrative supplement (under NIH PA-18-591 Administrative Supplements to Existing NIH Grants and
Cooperative Agreements) seeks funding for research responsive to the SARS-CoV-2/COVID-19 outbreak that
falls within the scope of the ongoing grant 5R01AI124121-05.
The original grant (5R01AI124121-05) is focused on understanding the role of the ion channel Cystic Fibrosis
Transmembrane conductance Regulator (CFTR) on exacerbated inflammation in the airways. Patients with
mutations in this ion channel leading to its malfunction develop Cystic Fibrosis (CF), a disease associated with
impaired bacterial clearance and increased lung inflammation, which ultimately results in lung failure. As an ion
channel, CFTR regulates fluid homeostasis in the lung. In addition, our published studies demonstrated for the
first time that macrophages lacking functional CFTR had impaired autophagy resulting in excessive inflammatory
profile. In addition to inflammation, the CFTR ion channel plays also a role in fluid homeostasis in the lung such
as edema. Relevant to this Supplement, findings from our group show that mice with reduced CFTR
(heterozygous) have increased expression of the severe acute respiratory syndrome coronavirus (SARS-CoV)
and SARS-CoV-2 receptor ACE2. The novel emergent pathogen responsible for COVID-19, SARS-CoV-2, is a
global threat responsible for over 420,000 deaths worldwide as of today and is projected to cause >130,000
deaths in the US alone by the end of June 2020. In Aim 1, we will identify mutations and polymorphisms in the
CFTR gene in SARS-CoV-2 positive patients. Aim 2 will determine whether there is a genetic association
between CFTR mutations and polymorphisms and severity of respiratory disease. Findings from this study will
reveal whether CFTR is a modifier gene to COVID-19. This study will help in the identification of patients prone
to respiratory failure or death upon SARS-CoV-2 infection and manage them before they succumb to respiratory
failure. Future studies will establish pharmacological compounds that increase CFTR function as new
therapeutics for COVID-19.
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