The Mortality Risk and Pulmonary Fibrosis Investigated by Time-Resolved Fluorescence Spectroscopy from Plasma in COVID-19 Patients

Abstract

A method of rapidly pointing out the risk of developing persistent pulmonary fibrosis from a sample of blood is extraordinarily needed for diagnosis, prediction of death, and post-infection prognosis assessment. Collagen scar formation has been found to play an important role in the lung remodeling following SARS-CoV-2 infection. For this reason, the concentration of collagen degradation products in plasma may reflect the process of lung remodeling and determine the extent of fibrosis. According to our previously published results of an in vitro study, an increase in the concentration of type III collagen degradation products in plasma resulted in a decrease in the fluorescence lifetime of plasma at a wavelength of 450 nm. The aim of this study was to use time-resolved fluorescence spectroscopy to assess pulmonary fibrosis, and to find out if the lifetime of plasma fluorescence is shortened in patients with COVID-19. The presented study is thus far the only one to explore the fluorescence lifetime of plasma in patients with COVID-19 and pulmonary fibrosis. The time-resolved spectrometer Life Spec II with the sub-nanosecond pulsed 360 nm EPLED® diode was used in order to measure the fluorescence lifetime of plasma. The survival analysis showed that COVID-19 mortality was associated with a decreased mean fluorescence lifetime of plasma. The AUC of mean fluorescence lifetime in predicting death was 0.853 (95% CI 0.735–0.972, p < 0.001) with a cut-off value of 7 ns, and with 62% sensitivity and 100% specificity. We observed a significant decrease in the mean fluorescence lifetime in COVID-19 non-survivors (p < 0.001), in bacterial pneumonia patients without COVID-19 (p < 0.001), and in patients diagnosed with idiopathic pulmonary fibrosis (p < 0.001), relative to healthy subjects. Furthermore, these results suggest that the development of pulmonary fibrosis may be a real and serious problem in former COVID-19 patients in the future. A reduction in the mean fluorescence lifetime of plasma was observed in many patients 6 months after discharge. On the basis of these data, it can be concluded that a decrease in the mean fluorescence lifetime of plasma at 450 nm may be a risk factor for mortality, and probably also for pulmonary fibrosis in hospitalized COVID-19 patients.

Betulin and Crinum asiaticum L. bulbs extract attenuate pulmonary fibrosis by down regulating pro-fibrotic and pro-inflammatory cytokines in bleomycin-induced fibrosis mice model

“…Hydroxyproline, collagen I and collagen III are notable biomarkers in pulmonary fibrosis [ [74] , [75] , [76] ]. Their levels are increased in PF.…”

Development status of novel spectral imaging techniques and application to traditional Chinese medicine

“…[ 15 ] assessed the degree of pulmonary fibrosis in patients with COVID-19 by measuring the plasma fluorescence lifetime. The detection of the plasma fluorescence lifetime is a new method for determining the prognosis of the disease among those infected [ 16 ]. Spectroscopy combined with machine learning methods has been used to detect and analyze abnormal metabolic indicators of porphyrin derivatives and bilirubin in urine for diagnosing hepatocellular carcinoma and liver cirrhosis; the overall diagnostic accuracy is as high as 83.42% [ 17 ].…”

Time-Resolved Fluorescence Spectroscopy of Blood, Plasma and Albumin as a Potential Diagnostic Tool for Acute Inflammation in COVID-19 Pneumonia Patients

“…There is still a need for non-invasive biomarkers that are rapid and can facilitate early diagnosis as well as the assessment of severity or mortality risk in COVID-19 patients. Autofluorescence spectroscopy has demonstrated potential as a tool for detecting and assessing various disease states through the analysis of blood components [1][2][3][4][5]. Despite its initial expectations, the use of autofluorescence spectroscopy for clinical diagnosis and monitoring with blood samples, without the need for exogenous probes or labels, remains 2 of 14 in the early stages of development.…”