A recent study posted to the medRxiv* preprint server assessed the biophysical, immunological, and biochemical characteristics of respiratory secretions in acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections.
Various studies have highlighted the importance of targeting respiratory secretions to improve coronavirus disease 2019 (COVID-19) clinical outcomes. However, extensive research is needed to understand the characteristics and composition of such secretions for the development of efficient treatment methods.
About the study
The researchers of the present study characterized the elements, rheological properties, and immunological profile of respiratory secretions from COVID-19 patients treated with mechanical ventilation.
The team obtained respiratory secretions from severe COVID-19 patients, aged between five and 70 years. Samples containing respiratory secretions were collected from patients with cystic fibrosis (CF) through spontaneous expectoration and from healthy participants via sputum induction.
Hyaluronan (HA) content of the respiratory secretions was evaluated. The team subsequently stained the samples with HA binding protein (HABP) to examine HA deposits in cadaveric lung sections of severe COVID-19 and CF patients and healthy patients. In addition, they examined the impact of alterations in HA accumulation on the hyaladherins such as versican and tumor necrosis factor-stimulated gene-6 (TSG-6). The double-stranded deoxyribonucleic acid (dsDNA) content was also analyzed in the infected and healthy respiratory secretion samples.
The team assessed lung tissue-specific immune reactions by measuring the levels of 80 cytokines, adhesion molecules, chemokines, and growth factors in the respiratory secretion samples of COVID-19-infected patients and healthy controls.
Results
The study results showed that respiratory samples obtained from healthy patients were generally clear and colorless, whereas those obtained from COVID-19 and CF patients were generally colored and opaque. This indicated that the samples comprised significant amounts of non-soluble debris and biopolymers.
Moreover, the team found that COVID-19 samples contained a substantially higher percentage of solids than healthy samples. Additionally, the protein concentrations observed in COVID-19 samples were almost 5.5 times higher than those in healthy samples. Notably, the protein concentrations were significantly higher in samples infected with COVID-19 and CF compared to samples of controls.
The team observed a 10-fold increase in HA levels in COVID-19 samples as compared to the control samples. Moreover, the average concentration of HA in samples obtained from COVID-19 patients was similar to the concentration in samples from CF patients. The insignificant amounts of HABP staining observed in hyaluronidase (HAdase)-treated samples suggested very low staining of non-specific backgrounds.
However, a noteworthy increase in HA staining was observed in the lung sections obtained from both COVID-19 and CF patients as compared to those from healthy samples, without any prior treatment with HAdase treatment. Overall, the study indicated that severe COVID-19 patients had remarkably higher levels of HA in their lungs.
In comparison with healthy control respiratory samples, lung sections obtained from both COVID-19 related acute respiratory distress syndrome (ARDS) and non-COVID-19 ARDS patients showed intense staining with HABP treatment in the alveolar-capillary barrier. Moreover, strong heterogeneous staining was observed in diffuse alveolar hemorrhage and distended alveolar-capillary membrane in the COVID-19 lung samples.
Altogether, for both COVID-19-related ARDS and non-COVID-19-related ARDS, there was a trend toward stronger staining of the blood vessels corresponding to the severity of tissue damage.
The respiratory samples obtained from COVID-19 patients showed an average of 14 times higher dsDNA content as compared to that of healthy participants; eight respiratory samples had 10 times higher dsDNA content. However, the average dsDNA concentrations were similar among COVID-19 and CF samples.
Furthermore, a significant decline in levels of antiviral type I interferon-α2 (IFN-α2) and platelet-derived growth factor AA (PDGF-AA) in COVID-19 sputum samples was found as compared to that in healthy controls. In addition, interleukin 13 (IL-13) levels in COVID-19 samples were remarkably different from those of healthy controls.
Various other chemokines and cytokines were significantly upregulated in the COVID-19 samples as compared to healthy controls, including tumor necrosis factor (TNF), IL6, IFNy, IL10, IL1β, IL18, macrophage colony-stimulating factor (M-CSF), RANTES (Regulated Upon Activation, Normal T Cell Expressed, and Secreted).
Conclusion
The study findings showed that the increase in HA and dsDNA levels in COVID-19 ARDS respiratory sputum samples was associated with a higher inflammatory burden in COVID-19. This indicated that DNA and HA may serve as efficient targets for COVID-19 therapy. The researchers believe that the development of treatments that target the respiratory secretions produced in such infections can prove instrumental in improving clinical outcomes of severe COVID-19 and ARDS.
*Important notice
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
