Translational feasibility and efficacy of nasal photodynamic disinfection of SARS-CoV-2

Pires, Layla; Wilson, Brian C.; Bremner, Rod; Lang, Amanda; Larouche, Jérémie; McDonald, Ryan; Pearson, Joel D.; Trcka, Daniel; Wrana, Jeff; Wu, James S.; Whyne, Cari

doi:10.1038/s41598-022-18513-0

Cited by 17 publications

(12 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, the effectiveness of the booster in the preset study most likely reflected the protection against symptomatic COVID-19, in line with reports from phase 3 clinical trials of the respective COVID-19 vaccines [ 21 , 22 , 23 ]. Human coronaviruses can re-infect regardless of humoral immunity due to the high tendency of mutation, allowing them to evade neutralizing antibody responses [ 24 , 25 ]. All 28 cases of re-infections in the present study occurred from 1 December 2021 onward, with the spread of the Omicron variant, whose spike protein highly diverges from previous SARS-CoV-2 strains.…”

Section: Discussionmentioning

confidence: 99%

COVID-19 Incidence and Vaccine Effectiveness in University Staff, 1 March 2020–2 April 2022

et al. 2023

View full text Add to dashboard Cite

Background: University workers undergo intense social interactions due to the frequent contact with students and colleagues and lectures in crowdy conditions. The aim of our study was to assess the incidence of COVID-19 infection and vaccine effectiveness in a cohort of workers of the University of Trieste from 1 March 2020 (start of the pandemic) through 2 April 2022. Methods: The University of Trieste implemented a number of public health policies to contain the spread of SARS-CoV-2 on the campus, including prompt contact tracing, the enhanced ventilation of all premises, fomites disinfection and the mandatory use of face masks indoors. In compliance with the surveillance protocol of the local public health department, university personnel were tested for SARS-CoV-2 by polymerase chain reaction (PCR) on a nasopharyngeal swab on demand, in the event of symptoms consistent with COVID-19 or for contact tracing, following close contact with a confirmed COVID-19 case. The incidence rates of SARS-CoV-2 infections were estimated as the number of cases by the number of person-days (p-d) at risk. The multivariable Cox proportional hazard regression model was employed to investigate the risk of primary COVID-19 infection, adjusting for a number of potential confounders and expressing the risk as the adjusted hazard ratio (aHR) with a 95% confidence interval (95% CI). Results: The incidence of SARS-CoV-2 infection among the university staff was lower than that of healthcare workers (HCWs) of the same area. Compared to unvaccinated colleagues (6.55 × 10,000 p-d), the raw incidence of SARS-CoV-2 infection was higher among university workers immunized with one (7.22 × 10,000 p-d) or two (7.48 × 10,000 p-d) doses of the COVID-19 vaccine, decreasing in those receiving the booster (1.98 × 1000 p-d). The risk of infection increased only in postgraduate medical trainees (aHR = 2.16; 95% CI: 1.04; 4.48), though this was limited to the Omicron transmission period. After the implementation of the national vaccination campaign against COVID-19, workers immunized with the booster were less likely than unvaccinated workers to be infected by SARS-CoV-2 both before (aHR = 0.10; 95% CI: 0.06; 0.16) and after (aHR = 0.37; 95% CI: 0.27; 0.52) the Omicron transmission period. The vaccine effectiveness of the booster was 90% (=(1−0.10) × 100) before versus 63% (=(1−0.37) × 100) during the Omicron wave, without a significant difference between homologous (three doses of m-RNA vaccines) and heterologous (first two doses of Vaxzevria followed by a third dose of m-RNA vaccine) immunization. Conclusions: The incidence of SARS-CoV-2 infection in the university staff was lower than that of HCWs of ASUGI, likely because the testing-on-demand schedule inevitably missed asymptomatic infections. Therefore, the observed significantly protective effect of the booster dose in university personnel referred to symptomatic SARS-CoV-2 infections. The infection prevention and control policies implemented by the University of Trieste managed to equalize the biological risk between the administrative and teaching staff.

show abstract

Section: Discussionmentioning

confidence: 99%

COVID-19 Incidence and Vaccine Effectiveness in University Staff, 1 March 2020–2 April 2022

et al. 2023

View full text Add to dashboard Cite

show abstract

“…Recent reports suggest important anti-SARS-CoV-2 activity in ex vivo models ( Lobo et al., 2022 ) and extensive in vitro PDT testing against wild strains of coronaviruses has been recently published ( Arentz and von der Heide, 2022 ). Very recently, a proof-of-concept feasibility and safety study in humans within different hospital settings has been conducted showing signals of decay in infectivity assays ( Pires et al., 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Photodynamic nasal SARS-CoV-2 decolonization shortens infectivity and influences specific T-Cell responses

Fernández-Montero

Zuaznabar

Pina-Sanchez

et al. 2023

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

BackgroundThe main objective was to evaluate the efficacy of intranasal photodynamic therapy (PDT) in SARS-CoV-2 mildly symptomatic carriers on decreasing the infectivity period. SARS-CoV-2-specific immune-stimulating effects and safety were also analysed.MethodsWe performed a randomized, placebo-controlled, clinical trial in a tertiary hospital (NCT05184205). Patients with a positive SARS-CoV-2 PCR in the last 48 hours were recruited and aleatorily assigned to PDT or placebo. Patients with pneumonia were excluded. Participants and investigators were masked to group assignment. The primary outcome was the reduction in in vitro infectivity of nasopharyngeal samples at days 3 and 7. Additional outcomes included safety assessment and quantification of humoral and T-cell immune-responses.FindingsPatients were recruited between December 2021 and February 2022. Most were previously healthy adults vaccinated against COVID-19 and most carried Omicron variant. 38 patients were assigned to placebo and 37 to PDT. Intranasal PDT reduced infectivity at day 3 post-treatment when compared to placebo with a β-coefficient of -812.2 (CI95%= -478660 – -1.3, p<0.05) infectivity arbitrary units. The probability of becoming PCR negative (ct>34) at day 7 was higher on the PDT-group, with an OR of 0.15 (CI95%=0.04-0.58). There was a decay in anti-Spike titre and specific SARS-CoV-2 T cell immunity in the placebo group 10 and 20 weeks after infection, but not in the PDT-group. No serious adverse events were reported.InterpretationIntranasal-PDT is safe in pauci-symptomatic COVID-19 patients, it reduces SARS-CoV-2 infectivity and decelerates the decline SARS-CoV-2 specific immune-responses.

show abstract

“…Recently studies have explored the effectiveness and potential of PDT in the neutralization of SARS-CoV-2, with the total number of relevant publications approaching 100 since 2020 [41][42][43][44][45][46][47][48]. However, those studies used non-specific photosensitizers, and long exposure to intense excitation light was often required [47,49].…”

Section: Introductionmentioning

confidence: 99%

Targeted photodynamic neutralization of SARS-CoV-2 mediated by singlet oxygen

Yao

Hou

Zhang

et al. 2023

Photochem Photobiol Sci

View full text Add to dashboard Cite

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has been on a rampage for more than two years. Vaccines in combination with neutralizing antibodies (NAbs) against SARS-CoV-2 carry great hope in the treatment and final elimination of coronavirus disease 2019 (COVID-19). However, the relentless emergence of variants of concern (VOC), including the most recent Omicron variants, presses for novel measures to counter these variants that often show immune evasion. Hereby we developed a targeted photodynamic approach to neutralize SARS-CoV-2 by engineering a genetically encoded photosensitizer (SOPP3) to a diverse list of antibodies targeting the wild-type (WT) spike protein, including human antibodies isolated from a 2003 Severe acute respiratory syndrome (SARS) patient, potent monomeric and multimeric nanobodies targeting receptor-binding domain (RBD), and non-neutralizing antibodies (non-NAbs) targeting the more conserved N-terminal domain (NTD). As confirmed by pseudovirus neutralization assay, this targeted photodynamic approach significantly increased the efficacy of these antibodies, especially that of non-NAbs, against not only the WT but also the Delta strain and the heavily immune escape Omicron strain (BA.1). Subsequent measurement of infrared phosphorescence at 1270 nm confirmed the generation of singlet oxygen ( 1 O 2 ) in the photodynamic process. Mass spectroscopy assay uncovered amino acids in the spike protein targeted by 1 O 2 . Impressively, Y145 and H146 form an oxidization “hotspot”, which overlaps with the antigenic “supersite” in NTD. Taken together, our study established a targeted photodynamic approach against the SARS-CoV-2 virus and provided mechanistic insights into the photodynamic modification of protein molecules mediated by 1 O 2 . Graphical abstract Supplementary Information The online version contains supplementary material available at 10.1007/s43630-023-00381-w.

show abstract

Translational feasibility and efficacy of nasal photodynamic disinfection of SARS-CoV-2

Cited by 17 publications

References 51 publications

COVID-19 Incidence and Vaccine Effectiveness in University Staff, 1 March 2020–2 April 2022

COVID-19 Incidence and Vaccine Effectiveness in University Staff, 1 March 2020–2 April 2022

Photodynamic nasal SARS-CoV-2 decolonization shortens infectivity and influences specific T-Cell responses

Targeted photodynamic neutralization of SARS-CoV-2 mediated by singlet oxygen

Contact Info

Product

Resources

About