Discussion
infection, infectious, SARS-CoV-2 infection, otherwise-healthy
VIRUS, SARS-COV-2 INFECTION, ASYMPTOMATIC SARS-COV-2 INFECTION, RECRUITMENT, INFECTION
A 3-day treatment with intranasal PDT can reduce SARS-CoV-2 infectivity and induce specific T-cell responses in COVID-19 patients. When applied in early stages of SARS-CoV-2 infection, local decolonization of nasal passages could be clinically relevant for the inhibition of viral spread both from person to person and from upper to lower respiratory tract, in clinical and non-clinical settings. PDT has been proposed as a valid approach to inactivate SARS-CoV-2 (The primary endpoint of the trial (infectivity reduction) was achieved. We demonstrated a reduction of infectivity in mildly symptomatic, otherwise-healthy individuals with high viral load (Ct<27), when applied during the first days of the replication phase in the nasal mucosa. The treatment consisted of three consecutive day, 12 min-applications of methylene blue-based PDT. Because of the absence of prior literature in intranasal PDT treatment of SARS-CoV-2, we decided to adopt a repeated application protocol rather than the single- or double-applications tested The effects of PDT were observed as soon as 3 days after treatment using an We observed a sharp decrease in viral load in our entire population (placebo and PDT) between day 3 and 7, which presumably masked the true magnitude of the PDT. This was probably related to the fact that vaccination is associated with faster viral RNA decline (The titer of anti-S and anti-N antibodies at 10 and 20 weeks after treatment was not different between the control and the intervention group. In both groups the amount of anti-S and anti-N antibody decreased at 20 weeks, revealing the decline of humoral response already described in other studies of SARS-CoV-2 infection (Similar to what we found in the humoral response, no significant differences were seen in the specific T-cell immunity against SARS-CoV-2 between control and intervention groups. Paralleling the humoral response, subjects in both groups experienced a reduction of the specific T cell responses between the week 10 and 20. Interestingly, the decline was significant only in placebo-treated patients for both CD4 and CD4+CD8 anti-S T-Cell responses, but not in PDT-treated subjects (Other studies with different local treatments have been performed. A double-blind, randomized, placebo-controlled trial in patients with mildly symptomatic SARS-CoV-2 infections (n=306) of treatment with nitric oxide nasal spray (NONS) was evaluated. NONS was self-administered six times daily for 7 days (The present study had several limitations, the power of the study was planned for the infectivity assay, but full recruitment was unable to be completed due to the decrease in SARS-CoV-2 cases in February 2022 in Spain. The study was not powered to detect differences in the IFN assays, but based on the differences observed between groups, a higher sample size would probably reveal consistently significant results. Finally, the present study only incorporated individuals infected with the Omicron strain. In future studies, to better characterize the immunological effect of PDT in clinical setting, flow cytometry studies could be used to describe the activation of innate immune cells (including NK and Dendritic Cells) and the specific phenotype of CD4 T lymphocytes (naïve, regulatory or memory T cells), before and after PDT treatment. In addition, circulating cytokines and chemokines, especially at short times, could help in defining the immune landscape of these patients, and whether the treatment with PDT can alter it.Strengths of the study included the high retention rate, the follow-up period and the infectivity assays along with humoral and cellular immunity evaluations up to 20 weeks after infection, all of which help to better elucidate the effect of nasal PDT on SARS-CoV-2 colonization and immunization. The impact of PDT in different settings such as ENT or dentistry clinics, Intensive Care Units, first responder settings, or GI laboratories where contact with potentially infectious patients could jeopardize efficiency of diagnostic and therapeutic procedures warrants further investigation. Development of new affordable and wearable nasal illuminators might provide an alternative, low-cost, widely accessible, respiratory virus treatment during future pandemics.