Photoacoustic Imaging of COVID-19 Vaccine Site Inflammation of Autoimmune Disease Patients.

Based on the observations made in rheumatology clinics, autoimmune disease (AD) patients on immunosuppressive (IS) medications have variable vaccine site inflammation responses, whose study may help predict the long-term efficacy of the vaccine in this at-risk population. However, the quantitative assessment of the inflammation of the vaccine site is technically challenging. In this study analyzing AD patients on IS medications and normal control subjects, we imaged the inflammation of the vaccine site 24 h after mRNA COVID-19 vaccinations were administered using both the emerging photoacoustic imaging (PAI) method and the established Doppler ultrasound (US) method. A total of 15 subjects were involved, including 6 AD patients on IS and 9 normal control subjects, and the results from the two groups were compared. Compared to the results obtained from the control subjects, the AD patients on IS medications showed statistically significant reductions in vaccine site inflammation, indicating that immunosuppressed AD patients also experience local inflammation after mRNA vaccination but not in as clinically apparent of a manner when compared to non-immunosuppressed non-AD individuals. Both PAI and Doppler US were able to detect mRNA COVID-19 vaccine-induced local inflammation. PAI, based on the optical absorption contrast, shows better sensitivity in assessing and quantifying the spatially distributed inflammation in soft tissues at the vaccine site.

Activatable Carbocyanine Dimers for Photoacoustic and Fluorescent Detection of Protease Activity.

Activatable contrast agents are of ongoing research interest because they offer low background and high specificity to the imaging target. Engineered sensitivity to protease activity is particularly desirable because proteases are critical biomarkers in cancer, infectious disease, inflammatory disorders, and so forth. Herein, we developed and characterized a set of peptide-linked cyanine conjugates for dual-modal detection of protease activity via photoacoustic (PA) and fluorescence imaging. The peptide-dye conjugates were designed to undergo contact quenching via intramolecular dimerization and contained n dyes (n = 2, 3, or 4) with n - 1 cleavable peptide substrates. The absorption peaks of the conjugates were blue-shifted 50 nm relative to the free dye and had quenched fluorescence. This effect was sensitive to solvent polarity and could be reversed by solvent switching from water to dimethyl sulfoxide. Employing trypsin as a model protease, we observed a 2.5-fold recovery of the peak absorbance, 330-4600-fold fluorescent enhancement, and picomolar detection limits following proteolysis. The dimer probe was further characterized for PA activation. Proteolysis released single dye-peptide fragments that produced a 5-fold PA enhancement through the increased absorption at 680 nm with nanomolar sensitivity to trypsin. The peptide substrate could also be tuned for protease selectivity; as a proof-of-concept, we detected the main protease (Mpro) associated with the viral replication in SARS-CoV-2 infection. Last, the activated probe was imaged subcutaneously in mice and signal was linearly correlated to the cleaved probe. Overall, these results demonstrate a tunable scaffold for the PA molecular imaging of protease activity with potential value in areas such as disease monitoring, tumor imaging, intraoperative imaging, in vitro diagnostics, and point-of-care sensing.

A review on human body fluids for the diagnosis of viral infections: scope for rapid detection of COVID-19.

Introduction: The unprecedented outbreaks of corona virus disease of 2019 (COVID-19) have highlighted the necessity of readily available, reliable, precise, and faster techniques for its detection. Nasopharyngeal swab has been the gold standard for the diagnosis of COVID-19. However, it is not an ideal screening procedure for massive screening as it implicates the patient's stay in the hospital or at home until diagnosis, thus causing crowding of the specimen at the diagnostic centers. Present study deal with the exploration of potential application of different body fluids using certain highly objective techniques (Optical and e-Nose) for faster detection of molecular markers thereby diagnosing viral infections.Areas covered: This report presents an evaluation of different body fluids, and their advantages for the rapid detection of COVID-19, coupled with highly sensitive optical techniques for the detection of molecular biomarkers.Expert opinion: Tears, saliva, and breath samples can provide valuable information about viral infections. Our brief review strongly recommends the application of saliva/tears and exhaled breath as clinical samples using technics such as high-performance liquid chromatography-laser-induced fluorescence, photoacoustic spectroscopy, and e-Nose, respectively, for the fast diagnosis of viral infections.