ABSTRACT
Rationale: We have proposed to develop an at-home breath collection device to diagnose and monitor patients with COVID-19. There is currently no method to track an individual's health outside of a hospital and predict if they might require clinical intervention. The present COVID19 diagnostic tests only look for direct evidence of the virus. We hypothesize that our method looks for the human body's response to infection. This allows us to not only determine whether an individual is infected or not, but also determine the severity of their health condition through chemical analysis of their metabolism. T Methods: COVID-19 infected patients are given a device that allows them to safely, non-invasively, and painlessly collect their own breath samples, which we are screening for not only COVID- 19 infection, but for other common respiratory viral infections, such as other coronaviruses, rhinovirus and influenza. We will compare the breath biomarkers of influenza with COVID-19 with that of our identified pattern of influenza. We are assessing the sensitivity of our test to diagnose COVID-19 and the specificity to not only diagnose COVID-19 from typical influenzas and rhinoviruses, but also the specificity to diagnose COVID-19 in patients with co-infections of other pulmonary viruses. Nasopharyngeal swab will be the gold standard. Results: We have collected exhaled breath condensate samples from patients with COVI19 infection. The device is can be used safely by the patient and does not require the participation of research coordinators during the breath collection phase. Symptomatic patients are able to use the device without excessive shortness of breath or other effects. The mass spectroscopy screening of the breath samples will look at a panel of eicosanoid biomarkers related to pulmonary infection and markers of oxidative stress. Patterns are being compared to prior breath profiles found with influenza infection. Conclusion: Our breath collection device could provide an “alarm” for individuals who are potentially facing a stark decline in health and should preemptively move into a hospital or clinical setting for closer monitoring. Because this method screens for a myriad of respiratory viruses and of pulmonary health simultaneously, its impact would extend far beyond the current COVID-19 pandemic.
ABSTRACT
Rationale: Surfactant protein D (SP-D) is a major immune protective molecule produced in the respiratory epithelium. SP-D binds to specific pathogen surfaces through its carbohydrate recognition (lectin) domain, that helps in their neutralization and clearance by phagocytes. SP-D also acts as an anti-inflammatory molecule. We hypothesized that SP-D plays a protective role in COVID-19. Methods: Polar+, a novel quantum computing algorithm for molecular pruning, and classical in silico modeling were used to investigate potential binding sites between SP-D and SARS CoV2. Electronegativity and topologically oriented molecular pruning, calculation of electronic force-fields and electrostatic binding combined with protein-protein docking, geometric fitting and assessment of protein glycosylation sites were employed. SP-D-/- mouse lung was used to study expression of the SARS-CoV-2 viral entry molecules TMPRSS2 and ACE2. Plasma from COVID-19 patients was studied for SP-D leakage, cytokine levels and lipid mediators. Results: We found that SP-D potentially binds to the same SARS CoV-2 glycoprotein (S protein) that it utilizes to bind the cellular receptor, ACE2, with high affinity. However, SP-D binds to subunit 2, instead of subunit 1 (that ACE2 utilizes). Additional studies will need to determine if SP-D binding affects S protein and ACE2 interactions. We also found that SP-D-/- mice had increased expression of the TMRSS2 gene in the lung and that both TMPRSS2 and ACE2 mRNA levels were increased during lung injury, amplified by the lack of SP-D. SP-D leakage from the lung to the circulation was significantly increased in COVID- 19 patients and correlated with expression of pro-neutrophilic inflammatory markers. Conclusions: We speculate that SP-D aids in the protection from SARS CoV2 infection by both acting as a potential natural decoy to prevent coronavirus entry into airway epithelial cells and by attenuating the expression of the viral entry receptor TMPRSS2. Oxidative lung injury results in SP-D leak into the circulation denoting disease severity in COVID-19 patients. (AH) .