Authors: Michael DePietro and Marc Salzberg, Airway Therapeutics, Marietta, GA, United States
A Commentary on
Pattern Recognition Proteins: First Line of Defense Against Coronaviruses
By Labarrere CA and Kassab GS (2021). Front. Immunol. 12:652252. doi: 10.3389/fimmu.2021.652252
Labarrere and Kassab recently wrote an informative paper that includes a very interesting overview of the role Surfactant Protein D (SP-D) plays as part of the innate immune system in the defense against several viral pathogens including SARS-CoV-2 (1). It has been described that the Carbohydrate Recognition Domain (CRD) of SP-D recognizes and binds to carbohydrates present in certain viruses such as the hemagglutinin of Influenza A Virus (2, 3) or the Spike (S)-Protein of SARS-CoV and SARS-Cov-2 (4, 5). Binding promotes agglutination and clearance of the virus (6). Additionally, SP-D modulates the inflammatory response induced by pathogens, SP-D interacts with specific receptors on the inflammatory cells such as the TLR4 complex, inhibiting the pro-inflammatory response induced by viruses (7–9).
Of particular interest given the SARS-CoV-2 pandemic, Labarrere and Kassab highlight several studies which have demonstrated a correlation of relatively high serum levels of SP-D with the development of severe COVID-19 pneumonia (10, 11). These findings suggest a role of Surfactant Protein D as a marker of disease severity as well as a potential therapeutic agent which Labarrere and Kassab discuss.
We would like to point out that in addition to high levels of serum levels being associated with COVID-19 severity, low levels of SP-D in the lung as measured in bronchoalveolar lavage fluid (BALF) have been reported in severe COVID-19 (5) and have been associated with an increased risk of the acute respiratory distress syndrome (ARDS) (12). These observations resulted in the filing of a New Investigational Drug (IND) application for a recombinant human surfactant Protein D (rhSP-D) formulation administered as a therapeutic agent for patients with severe COVID-19 with respiratory failure, as well as the initiation of a Phase 1B study this therapy, that is currently enrolling patients (NCT 04659122 http://www.ClinicalTrials.gov).