Production of singlet oxygen from photosensitizer erythrosine for facile inactivation of coronavirus on mask.

The global health crisis caused by the COVID-19 pandemic has led to a surge in demand and use of personal protective equipment (PPE) such as masks, putting great pressure on social production and the environment.It is urgent to find an efficient and non-destructive disinfection method for the safe reuse of PPE. This study proposes a PPE disinfection method that uses erythrosine, a U.S. Food and Drug Administration-approved food dye, as photosensitizer to produce singlet oxygen for virus inactivation, and indicates the completion of disinfection by its photobleaching color change.After spraying 100 µL of 10 µM erythrosine on the surface of the mask for 3 times and light exposure for 25 min, the titer of coronavirus decreased by more than 99.999%, and the color of erythrosine on the mask surface disappeared. In addition, the structure of the mask was intact and the filtration efficiency was maintained at > 95% after 10 cycles of erythrosine treatment.Therefore, this disinfection method can provide at least 10 cycles of reuse with the advantages of high safety and convenient, and the completion of disinfection can be indicated by its photobleaching, which is suitable for hospitals and daily life to reduce the consumption of PPE.

Morphovascular changes after anti-VEGF intravitreal injection for a choroidal neovascularization secondary to COVID-19 infection in a pediatric patient.

Choroidal neovascularization (CNV) is a common pathologic lesion that occurs in various chorioretinopathy. Although the incidence of CNV is quite rare in children and adolescents, these lesions have a severe impact on visual acuity and quality of life over patients' lifetime. The management of CNV in pediatric patients is challenging, clear guidelines are limited due to a lack of randomized clinical trials. However, the more promising option is the use of vascular endothelial growth factor (VEGF) inhibitors. We reported a case of recurrent idiopathic choroidal neovascularization in a healthy pediatric patient after COVID 19 infection. Optical coherence tomography angiofraphy (OCTA) showed, in a non invasive way, a choroidal neovascularization at the posterior pole including macula and superior temporal arcade in the right eye, while the left eye was unaffected. In order to inactivate the neovascularization, intravitreal injections of anti-VEGF (Lucentis-Ranibizumab 0.3 mL) were performed in the right eye. Six months after the injections BCVA of the right eye was improved from 0.7 logMAR to 0.2 logMAR. OCT-A examination did not detect any signs of attivation of the preexistent neovascularization. It is reasonable to assert that Anti-VEGF could be the main treatment in case of choroidal neovascularization in young patients after COVID 19 infection due to the high chorioretinal level of VEGF-A described in these diseases.

Early effects of inactivated (CoronaVac) SARS-CoV-2 vaccine on retrobulbar vascular blood flow and retinal vascular density.

AIMS: We aimed to investigate the early effects of inactivated SARS-CoV-2 vaccine on retrobulbar vascular blood flow and retinal vascular density in healthy subjects. METHODS: Thirty-four eyes of 34 healthy volunteers who received the CoronaVac (Sinovac Life Sciences, China) were included in this prospective study. Resistive index (RI), pulsatility index (PI) and peak systolic velocity (PSV) of the ophthalmic artery (OA), central retinal artery (CRA), and the temporal and nasal posterior ciliary arteries (PCA) were evaluated with color Doppler ultrasonography (CDUS) before vaccination, at the 2nd and 4th weeks after vaccination. Superficial capillary plexus (SCP) and deep capillary plexus (DCP) vessel density (VD), foveal avascular zone (FAZ), and choriocapillaris blood flow (CCF) measurements were made using optical coherence tomography angiography (OCTA). RESULTS: When compared to the pre-vaccination values, there was no significant change in OA-PSV, temporal-nasal PCA-PSV, CRA-EDV, temporal-nasal PCA-EDV at 2nd and 4th weeks after vaccination. However statistically significant reductions were found in the OA-RI, OA-PI, CRA-RI, CRA-PI, temporal-nasal PCA-RI, temporal-nasal PCA-PI values, CRA-PSV at post-vaccination 2nd week (p<0.05 for all). While there was sustained reduction in OA-RI, OA-PI, CRA-PSV, and nasal PCA-RI values at 4th week after vaccination, the change in CRA-RI, CRA-PI, temporal PCA-RI, temporal-nasal PCA-PI values were not significant compared to pre-vaccination values. There was no statistically significant difference in the SCP-VD, DCP-VD, FAZ and CCF measurements. CONCLUSIONS: Our findings demonstrating that CoronaVac vaccine did not affect retinal vascular density in the early period, but it caused alterations in the retrobulbar blood flow.

Macular optical coherence tomography angiography analysis in diabetes mellitus patients with a history of Covid-19.

PURPOSE: There is evidence of decreased vessel density in optical coherence tomography angiography (OCTA) after Covid-19. We aimed to investigate whether the outcome of retinal vasculopathy would be worse if patients with diabetes mellitus (DM) were infected with coronavirus using OCTA to assess retinal vessels. METHODS: One eye of each subject was included in the study. Diabetic patients without retinopathy and non-diabetic controls were divided into four groups according to their Covid-19 history: group 1=DM(-)Covid-19(-); group 2=DM(+)Covid-19(-); group 3=DM(-)Covid-19(+); and group 4=DM(+)Covid-19(+). All Covid-19 patients were not hospitalised. Macular OCTA scans were performed in a 6 × 6 mm area. RESULTS: Diabetes had no effect on the area of the foveal avascular zone (FAZ), but Covid-19 caused an increase in FAZ area. Diabetes and Covid-19 had an effect on both the superficial capillary plexus (SCP) and the deep capillary plexus (DCP) in the fovea. Eta squared (ƞ2) is a measure of effect size. The effect size of Covid-19 (ƞ2=0.180) was found to be greater than that of diabetes (ƞ2=0.158) on the SCP, whereas the effect size of diabetes (ƞ2=0.159) was found to be greater than that of Covid-19 (ƞ2=0.091) on the DCP. CONCLUSIONS: The percentage of vessel density was lower in the fovea and the FAZ area was enlarged in the diabetic patients who recovered from Covid-19. In diabetic patients Covid-19 may lead to deterioration of vascular metrics.

Retinal microvascular changes in patients recovered from COVID-19 compared to healthy controls: A meta-analysis.

PURPOSE: To investigate changes in retinal microcirculation in patients recovered from COVID-19 infection compared to healthy controls, using optical coherence tomography-angiography. METHODS: Meta-analysis of eligible studies comparing retinal microcirculation between patients recovered from COVID-19 infection and healthy controls up to 7th of September 2022 was performed, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2009 guidelines. The following search algorithm was used: (COVID-19 OR coronavirus) AND (retina OR optical coherence tomography OR optical coherence tomography angiography OR vessel density OR foveal avascular zone). Standardized Mean Difference (SMD) with 95% confidence interval (CI) was calculated to compare continuous variables. Revman 5.3 was used for the analysis. RESULTS: 12 studies were included in our analysis. Foveal avascular zone (FAZ) area was larger in patients recovered from COVID-19 infection compared to healthy controls, while there was no statistically significant difference in FAZ perimeter between the two groups. The foveal, parafoveal and whole image vessel density in the superficial capillary plexus showed no significant difference between the two groups. The foveal, parafoveal and whole image vessel density in the deep capillary plexus was statistically lower in patients recovered from COVID-19 compared to healthy controls. CONCLUSION: FAZ area was enlarged and foveal, parafoveal and whole image vessel density in deep capillary plexus were reduced in patients recovered from COVID-19 infection compared to healthy controls, suggesting that COVID-19 infection may induce long-term retinal microvascular changes in patients recovered from the virus infection.

Recent Advances in Green Metallic Nanoparticles for Enhanced Drug Delivery in Photodynamic Therapy: A Therapeutic Approach.

Globally, cancer is one of the leading causes of death among men and women, it is characterized by the unregulated proliferation of tumor cells. Some of the common risk factors associated with cancer development include the consistent exposure of body cells to carcinogenic agents such as alcohol, tobacco, toxins, gamma rays and alpha particles. Besides the above-mentioned risk factors, conventional therapies such as radiotherapy, and chemotherapy have also been linked to the development of cancer. Over the past decade, tremendous efforts have been invested in the synthesis of eco-friendly green metallic nanoparticles (NPs), and their medical application. Comparatively, metallic NPs have greater advantages over conventional therapies. Additionally, metallic NPs can be functionalized with different targeting moieties e.g., liposomes, antibodies, folic acid, transferrin, and carbohydrates. Herein, we review and discuss the synthesis, and therapeutic potential of green synthesized metallic NPs for enhanced cancer photodynamic therapy (PDT). Finally, the advantages of green hybridized activatable NPs over conventional photosensitizers (PSs) and the future perspectives of nanotechnology in cancer research are discussed in the review. Furthermore, we anticipate that the insights offered in this review will inspire the design and development of green nano-formulations for enhanced image-guided PDT in cancer treatment.

Highly Twisted Conformation Thiopyrylium Photosensitizers for In Vivo Near Infrared-II Imaging and Rapid Inactivation of Coronavirus.

Despite significant effort, a majority of heavy-atom-free photosensitizers have short excitation wavelengths, thereby hampering their biomedical applications. Here, we present a facile approach for developing efficient near-infrared (NIR) heavy-atom-free photosensitizers. Based on a series of thiopyrylium-based NIR-II (1000-1700 nm) dyads, we found that the star dyad HD with a sterically bulky and electron-rich moiety exhibited configuration torsion and significantly enhanced intersystem crossing (ISC) compared to the parent dyad. The electron excitation characteristics of HD changed from local excitation (LE) to charge transfer (CT)-domain, contributing to a ≈6-fold reduction in energy gap (ΔEST ), a ≈10-fold accelerated ISC process, and a ≈31.49-fold elevated reactive oxygen species (ROS) quantum yield. The optimized SP@HD-PEG2K lung-targeting dots enabled real-time NIR-II lung imaging, which precisely guided rapid pulmonary coronavirus inactivation.

The effect of various types of COVID-19 vaccines on the retinal microvasculature.

PURPOSE: To detect the effect of various types of COVID-19 vaccine on macular and optic disc microvasculature. METHOD: One hundred subjects receiving various types of COVID-19 vaccine (AstraZeneca, Sinopharm, Sinovac, Pfizer, and Moderna) were included in this study. A complete ophthalmic examination was done which included best-corrected visual acuity measurement, slit-lamp biomicroscopy, intraocular pressure measurement with Goldmann applanation tonometry, and fundus examination. Optical coherence tomography angiography (OCT-A) was done before and 1 week after receiving the vaccine. Superficial and deep macular capillary densities were measured in the form of the whole image, fovea, parafoveal, and perifoveal capillary density. Optic disc vessel density in the form of the whole disc, inside disc, and peripapillary were also measured. RESULTS: The superficial macular vessel densities, (whole image, fovea, parafoveal, and perifoveal) showed statistically non-significant changes with P-values (0.269, 0.167, 0.346, and 0.476) respectively. Also, the deep macular vessel densities showed statistically non-significant changes with P-values (0.491, 0.096, 0.724, and 0.386) for the whole image, fovea, parafoveal, and perifoveal respectively. Moreover, RPC (radial peripapillary capillary) density showed no significant changes either (the whole disc, inside disc, or peripapillary) with P-values (0.807, 0.141, 0.883) respectively. CONCLUSION: Various types of COVID-19 vaccines had no statistically significant effects on macular or optic disc microvasculature.

Evaluation of acute effects of pulmonary involvement and hypoxia on retina and choroid in coronavirus disease 2019: An optic coherence tomography study.

PURPOSE: We investigated the acute subclinical choroidal and retinal changes caused by Coronavirus Disease 2019 (COVID-19) in patients with and without pulmonary involvement, using spectral domain optic coherence tomography. METHODS: This prospective case-control study included COVID-19 patients: 50 with pulmonary involvement and 118 with non-pulmonary involvement. All patients were examined 1 month after recovering from COVID-19. The changes were followed using optic coherence tomography parameters such as choroidal and macular thickness and retinal nerve fibre layer and ganglion cell complex measurements. RESULTS: All choroidal thicknesses in the pulmonary involvement group were lower than in the non-pulmonary involvement group and the subfoveal choroidal thickness differed significantly (p=0.036). Although there were no significant differences between the central and average macular thicknesses in the two groups, they were slightly thicker in the pulmonary involvement group (p=0.152 and p=0.180, respectively). A significant decrease was detected in the pulmonary involvement group in all ganglion cell complex segments, except for the outer nasal inferior segment (p<0.05). In addition, a thinning tendency was observed in all retinal nerve fibre layer quadrants in the pulmonary involvement group compared to the non-pulmonary involvement group. CONCLUSION: In COVID-19 patients with pulmonary involvement, subclinical choroidal and retinal changes may occur due to hypoxia and ischemia in the acute period. These patients may be predisposed to ischemic retinal and optic nerve diseases in the future. Therefore, COVID-19 patients with pulmonary involvement should be followed for ophthalmological diseases.

Investigation of changes in retinal vascular parameters and choroidal vascular index values during the early recovery period of COVID-19: The COVID-OCTA study.

BACKGROUND: COVID-19 effects microvasculature in many tissues. This study investigated whether the choroidal structure is also affected. METHODS: This cross-sectional study included 80 patients with COVID-19 and the same number of age- and gender-matched healthy individuals. All participants' right eye measurements were examined. Optical coherence tomography angiography (OCTA) was used for imaging. Otherwise, two independent researchers used the Choroidal vascular index (CVI) for choroidal parameters calculation. RESULTS: Superior and deep flow values were lower in the COVID-19 group than in the control group, and vascular density (VD) values were lower in all regions in this group. Except for the superior mean VD, there was no statistically significant difference (p = 0.003). However, the COVID-19 group had significantly lower subfoveal choroidal thickness (SFChT) measurements than the control group (p = 0.001). In addition, no significant difference was observed between the groups in evaluating mean CVI values (p>0.05). CONCLUSION: Noninvasive diagnostic tools such as OCTA and EDI-OCT can be used to monitor early changes in diseases affecting microvessels, such as from COVID-19.

Self-cleaning wearable masks for respiratory infectious pathogen inactivation by type I and type II AIE photosensitizer.

Although face masks as personal protective equipment (PPE) are recommended to control respiratory diseases with the on-going COVID-19 pandemic, improper handling and disinfection increase the risk of cross-contamination and compromise the effectiveness of PPE. Here, we prepared a self-cleaning mask based on a highly efficient aggregation-induced emission photosensitizer (TTCP-PF6) that can destroy pathogens by generating Type I and Type II reactive oxygen species (ROS). The respiratory pathogens, including influenza A virus H1N1 strain and Streptococcus pneumoniae (S. pneumoniae) can be inactivated within 10 min of ultra-low power (20 W/m2) white light or simulated sunlight irradiation. This TTCP-PF6-based self-cleaning strategy can also be used against other airborne pathogens, providing a strategy for dealing with different microbes.

Hydrophobic Rose Bengal Derivatives Exhibit Submicromolar-to-Subnanomolar Activity against Enveloped Viruses.

Rose Bengal (RB) is an anionic xanthene dye with multiple useful biological features, including photosensitization properties. RB was studied extensively as a photosensitizer, mostly for antibacterial and antitumor photodynamic therapy (PDT). The application of RB to virus inactivation is rather understudied, and no RB derivatives have been developed as antivirals. In this work, we used a synthetic approach based on a successful design of photosensitizing antivirals to produce RB derivatives for virus photoinactivation. A series of n-alkyl-substituted RB derivatives was synthesized and evaluated as antiviral photosensitizers. The compounds exhibited similar 1O2 generation rate and efficiency, but drastically different activities against SARS-CoV-2, CHIKV, and HIV; with comparable cytotoxicity for different cell lines. Submicromolar-to-subnanomolar activities and high selectivity indices were detected for compounds with C4-6 alkyl (SARS-CoV-2) and C6-8 alkyl (CHIKV) chains. Spectrophotometric assessment demonstrates low aqueous solubility for C8-10 congeners and a significant aggregation tendency for the C12 derivative, possibly influencing its antiviral efficacy. Initial evaluation of the synthesized compounds makes them promising for further study as viral inactivators for vaccine preparations.

Optimization of Anti-SARS-CoV-2 Treatments Based on Curcumin, Used Alone or Employed as a Photosensitizer.

Curcumin, the bioactive compound of the spice Curcuma longa, has already been reported as a potential COVID-19 adjuvant treatment due to its immunomodulatory and anti-inflammatory properties. In this study, SARS-CoV-2 was challenged with curcumin; moreover, curcumin was also coupled with laser light at 445 nm in a photodynamic therapy approach. Curcumin at a concentration of 10 µM, delivered to the virus prior to inoculation on cell culture, inhibited SARS-CoV-2 replication (reduction >99%) in Vero E6 cells, possibly due to disruption of the virion structure, as observed using the RNase protection assay. However, curcumin was not effective as a prophylactic treatment on already-infected Vero E6 cells. Notably, when curcumin was employed as a photosensitizer and blue laser light at 445 nm was delivered to a mix of curcumin/virus prior to the inoculation on the cells, virus inactivation was observed (>99%) using doses of curcumin that were not antiviral by themselves. Photodynamic therapy employing crude curcumin can be suggested as an antiviral option against SARS-CoV-2 infection.

Electrostatic Map of the SARS-CoV-2 Virion Specifies Binding Sites of the Antiviral Cationic Photosensitizer.

Electrostatics is an important part of virus life. Understanding the detailed distribution of charges over the surface of a virus is important to predict its interactions with host cells, antibodies, drugs, and different materials. Using a coarse-grained model of the entire viral envelope developed by D. Korkin and S.-J. Marrink's scientific groups, we created an electrostatic map of the external surface of SARS-CoV-2 and found a highly heterogeneous distribution of the electrostatic potential field of the viral envelope. Numerous negative patches originate mainly from negatively charged lipid domains in the viral membrane and negatively charged areas on the "stalks" of the spike (S) proteins. Membrane (M) and envelope (E) proteins with the total positive charge tend to colocalize with the negatively charged lipids. In the E protein pentamer exposed to the outer surface, negatively charged glutamate residues and surrounding lipids form a negative electrostatic potential ring around the channel entrance. We simulated the interaction of the antiviral octacationic photosensitizer octakis(cholinyl)zinc phthalocyanine with the surface structures of the entire model virion using the Brownian dynamics computational method implemented in ProKSim software (version r661). All mentioned negatively charged envelope components attracted the photosensitizer molecules and are thus potential targets for reactive oxygen generated in photosensitized reactions.

Infectivity and Morphology of Bovine Coronavirus Inactivated In Vitro by Cationic Photosensitizers.

Bovine coronaviruses (BCoVs), which cause gastrointestinal and respiratory diseases in cattle, and are genetically related to the human coronavirus HCoV-OC43, which is responsible for up to 10% of common colds, attract increased attention. We applied the method of photodynamic inactivation with cationic photosensitizers (PSs) to reduce the titers of BCoV and studied the morphological structure of viral particles under various modes of photodynamic exposure. The samples of virus containing liquid with an initial virus titer of 5 Log10 TCID50/mL were incubated with methylene blue (MB) or octakis(cholinyl)zinc phthalocyanine (Zn-PcChol8+) at concentrations of 1-5 µM for 10 min in the dark at room temperature. After incubation, samples were irradiated with LED (emission with maximum at 663 nm for MB or at 686 nm for Zn-PcChol8+) with light doses of 1.5 or 4 J/cm2. Next, the irradiation titrated virus containing liquid was studied using negative staining transmission electron microscopy. MB and Zn-PcChol8+ at concentrations of 1-5 µM, in combination with red light from LED sources in the low doses of 1.5-4.0 J/cm2, led to a decrease in BCoV titers by at least four orders of magnitude from the initial titer 5 Log10 TCID50/mL. Morphological changes in photodamaged BCoVs with increasing PS concentrations were loss of spikes, change in shape, decreased size of virus particles, destruction of the envelope, and complete disintegration of viruses. BCoV has been found to be sensitive to MB, which is the well-known approved drug, even in the absence of light.

Tuning riboflavin derivatives for photodynamic inactivation of pathogens.

The development of effective pathogen reduction strategies is required due to the rise in antibiotic-resistant bacteria and zoonotic viral pandemics. Photodynamic inactivation (PDI) of bacteria and viruses is a potent reduction strategy that bypasses typical resistance mechanisms. Naturally occurring riboflavin has been widely used in PDI applications due to efficient light-induced reactive oxygen species (ROS) release. By rational design of its core structure to alter (photo)physical properties, we obtained derivatives capable of outperforming riboflavin's visible light-induced PDI against E. coli and a SARS-CoV-2 surrogate, revealing functional group dependency for each pathogen. Bacterial PDI was influenced mainly by guanidino substitution, whereas viral PDI increased through bromination of the flavin. These observations were related to enhanced uptake and ROS-specific nucleic acid cleavage mechanisms. Trends in the derivatives' toxicity towards human fibroblast cells were also investigated to assess viable therapeutic derivatives and help guide further design of PDI agents to combat pathogenic organisms.

Management of orofacial lesions with antimicrobial photodynamic therapy and photobiomodulation protocols in patients with COVID-19: A multicenter case series.

Several oral lesions related to COVID-19 have been described in the scientific literature. The COVID-19 pandemic highlighs importance of supportive protocols, which can reduce the inflammation and aid in tissue repair in severe cases. Photobiomodulation therapy (PBMT) alone or in combination with antimicrobial photodynamic therapy (aPDT) can be used to manage orofacial lesions in confirmed cases of COVID-19. Here, we sought to describe the clinical presentation and specificities of three cases in which aPDT and PBMT were used to manage orofacial lesions in patients with COVID-19. The laser protocols were effective with improvement of the orofacial lesions within a few days.