Club Cell Secretory Protein-16 (CC16) as a Prognostic Biomarker for COVID-19 and H1N1 Viral Infections

Author:

Moore Shane1ORCID,Gopichandran Keerthana1,Sevier Elizabeth1,Gamare Siddhika1,Almuntashiri Sultan12,Ramírez Gustavo3ORCID,Regino Nora34,Jiménez-Alvarez Luis3,Cruz-Lagunas Alfredo3,Rodriguez-Reyna Tatiana S.5,Zuñiga Joaquin34,Owen Caroline A.6,Wang Xiaoyun1ORCID,Zhang Duo17ORCID

Affiliation:

1. Department of Clinical and Administrative Pharmacy, College of Pharmacy, University of Georgia, Augusta, GA 30912, USA

2. Department of Clinical Pharmacy, College of Pharmacy, University of Hail, Hail 55473, Saudi Arabia

3. Laboratory of Immunobiology and Genetics, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Tlalpan 4502, Mexico City 14080, Mexico

4. Tecnologico de Monterrey, School of Medicine and Health Sciences, Mexico City 14380, Mexico

5. Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, Mexico City 14080, Mexico

6. Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA

7. Department of Medicine, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA

Abstract

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and H1N1 viruses are inflammatory lung pathogens that can lead to acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). ALI/ARDS are still life-threatening diseases in critically ill patients with 30–40% mortality in the last decade. Currently, there are no laboratory tests for the early diagnosis or prognosis of ALI/ARDS. Club cell secretory protein (CC16) has been investigated as a potential biomarker of lung epithelial damage in various lung diseases. In this study, we evaluated whether plasma CC16 reflects the severity of COVID-19 and H1N1 infections. The plasma CC16 levels showed no significant differences between H1N1 and COVID-19 groups (p = 0.09). Among all subjects, CC16 levels were significantly higher in non-survivors than in survivors (p = 0.001). Upon the area under the receiver operating characteristic (AUROC) analysis, CC16 had an acceptable value to distinguish survivors and non-survivors (p = 0.002). In the COVID-19 group, plasma CC16 levels moderately correlated with the Acute Physiology and Chronic Health Evaluation II (APACHE II) score (r = 0.374, p = 0.003) and Sequential Organ Failure Assessment (SOFA) score (r = 0.474, p < 0.001). In the H1N1 group, a positive correlation was observed between the CC16 levels and hospital length of stay (r = 0.311, p = 0.022). Among all the patients, weak correlations between plasma CC16 levels with the SOFA score (r = 0.328, p < 0.001) and hospital length of stay (r = 0.310, p < 0.001) were observed. Thus, circulating CC16 might reflect the severity of COVID-19 and H1N1 infections.

Funder

National Institute of Allergy and Infectious Diseases

National Institutes of Health (NIH)-funded Georgia CTSA KL2 and UL1

National Heart, Lung, and Blood Institute

Publisher

MDPI AG

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