AUTHOR=Fernandez-Montero Alejandro , Zuaznabar Jon , Pina-Sanchez Manuel , Maestro Sheila , Martin-Navarro Loreto , Muñoz-Rodríguez Natalia , Olagüe Cristina , Pastrana Marta , Martínez-Fernández Maria , Camps Gracian , Rodriguez Jose Antonio , Marchese Francesco P. , Zazpe Jon , Pozuelo Marta , Del Pozo José Luis , Quiroga Jorge , Pineda-Lucena Antonio , Reina Gabriel , Kolenda Jack , Moreno-Galarraga Laura , Gonzalez-Aseguinolaza Gloria , Rua Marta , Smerdou Cristian , Carmona-Torre Francisco , Argemi Josepmaria TITLE=Photodynamic nasal SARS-CoV-2 decolonization shortens infectivity and influences specific T-Cell responses JOURNAL=Frontiers in Cellular and Infection Microbiology VOLUME=13 YEAR=2023 URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2023.1110467 DOI=10.3389/fcimb.2023.1110467 ISSN=2235-2988 ABSTRACT=Background

The 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.

Methods

We 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.

Findings

Patients 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.

Interpretation

Intranasal-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.