In response to NOT-AI-20-031 [?Notice of Special Interest: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and Coronavirus Disease 2019 (COVID-19)?] and in line with the scope of the parent grant, the goal of this supplement is to determine the role of Club cell secretory protein (CC16) in providing resilience to COVID-19. CC16 is a homodimeric pneumoprotein that is encoded by the SCGB1A1 gene, mainly produced by Club cells in the distal airways, and readily measured in circulation. The central hypothesis of our parent grant is that CC16 exerts protective effects in the lungs by modulating susceptibility and inflammatory responses to airway infections. In addition, because CC16-secreting Club cells are among the main airway cell types expressing Angiotensin-Converting Enzyme 2 (ACE2), it is plausible that ? by infecting Club cells ? SARS-CoV-2 can affect their survival and/or secretory machinery, and in turn impact production of CC16. Here, we postulate that CC16 plays a critical role in susceptibility and host inflammatory responses to SARS-CoV-2 and propose the following specific aim:
Specific Aim - To determine the relation of circulating CC16 to the presence and clinical progression of COVID-19. In this pilot study, we will collect clinical data and biospecimens from both inpatients and outpatients with COVID-19 at Banner University Medical Center ? Tucson. Depending on the dynamics of the pandemic, we estimate that we will recruit between 75-125 inpatients and 100-200 outpatients. In addition, we will recruit a group of controls (with a target case:control ratio of 2:1). Data from these participants will be used to compare circulating levels of CC16 across the three groups of controls, COVID-19 outpatients, and COVID-19 inpatients. In addition, circulating deficits of CC16 will be tested for prediction of subsequent clinical progression of disease.
The central hypothesis of this supplement is that Club cell secretory protein (CC16) ? a protein that is produced mainly in the lungs but can be measured in blood ? has protective effects in the lungs against SARS- CoV-2, the virus responsible for COVID-19. To test this hypothesis, in this pilot study we will compare levels of CC16 in blood between patients with COVID-19 and controls and we will test whether, among patients with COVID-19, low levels of CC16 in blood predict a more aggressive clinical progression of the disease.
| Martinez, Fernando D; Guerra, Stefano (2018) Early Origins of Asthma. Role of Microbial Dysbiosis and Metabolic Dysfunction. Am J Respir Crit Care Med 197:573-579 |
| Zhai, Jing; Stern, Debra A; Sherrill, Duane L et al. (2018) Trajectories and Early Determinants of Circulating CC16 from Birth to Age 32 Years. Am J Respir Crit Care Med 198:267-270 |
