COVID-19: Beyond the virus. The use of photodynamic therapy for the treatment of infections in the respiratory tract.

•The World today is facing a great effort for the control of infections.•Nowadays COVID-19 is the large global outbreak and is the major public health issue.•This letter to Editor highlighted the well-established photodynamic therapy protocol as a tool to decrease the viral and bacterial load in the respiratory tract.

Dear Editor-in-chef,

The World today is facing a great effort for the control of infections. Ever since the known and wrong prediction of the U.S. Surgeon General, William H. Stewart, in 1969: “We can close the books on infectious diseases,” infectious diseases have been on the rise [1]. Now, coronavirus disease (COVID-19) was declared as a Public Health Emergency and its clinical spectrum appears to be wide, encompassing asymptomatic infection, mild upper respiratory tract illness, and severe viral pneumonia with respiratory failure and even death, with many patients being hospitalized with pneumonia [2]. Thus, it is crucial to develope techniques that combat viral load and correlated infections caused by bacteria ideally avoiding intensive medical care as well as minimizing transmission to others. In this perspective, how and what can photodynamic therapy (PDT)do against SARS-CoV-2 and correlated infections?

We consider that PDT is not a “Viral Killing tool” which is able to combat the virus systemically, but rather, it can be applied as an efficient therapy to decrease the microbial load (viral and bacterial) in the respiratory tract. In this regard, PDT is a safe and well-established treatment option able to generate ROS and 1O2 which can promote the damage of viruses targets [3] such as nucleic acids (DNA or RNA), envelope and core proteins and, if present, viral lipids and membrane lipid, protein complexes, cytosolic enzymes for bacteria which can be present in a biofilm matrix [4].

The propagation of opportunistic pathogens occurs mainly through the upper respiratory tract due to its natural colonization in the oropharynx. The pharyngotonsillitis PDT can help not only to reduce the number of these microorganisms present in the oropharynx but also to prevent their penetration into the mucosal barrier and thus helping the performance of phagocytes which can decrease their access using nutrients on the mucosal surface for their proliferation. As a selected example, Blanco and co-authors reported a clinical PDT protocol against pharyngotonsillitis and a reduction more than 90 % of the symptoms related to the disease after 24 h was observed [5] (Fig. 1 ).

Fig. 1

A) Oropharyngeal illumination during PDT: B) result obtained with a group of patients. In 92 % the infection was eliminated 24 h after treatment.

Moreover, nebulization is described as an efficient method of delivering drugs directly to the respiratory tract. The Optics’s group at the CEPOF-USP performed a proof-of-concept through an efficient photodynamic protocol against bacterial pneumonia using an extracorporeal illumination in the infrared region (at 780 nm) and nebulized indocyanine green as photosensitizer [6,7] (Fig. 2 ). The authors observed no deaths occurred in PDT group, whereas 60 % of the control group died. This protocol is an important step toward clinical implementation which PDT can be applied as a single therapy or as an antibiotics adjuvant.

Fig. 2

A) Schematic figure of delivering indocyanine green photosensitizer by nebulization; B) extracorporeal illumination using an infrared light (at 780 nm); C) Kaplan-Meier curve shows survival rate (%) versus time (days) for mice infected (n = 10) with 108S. pneumoniae cells and treated with only PBS instillation (Control) and a combination of 100 μmol/L of indocyanine green instillation and 120 J/cm2 of light dose (PDT).

Thus far, many photodynamic protocols in respiratory tract have been the subject for a proof-of-principle in pre-clinical studies, showing a potential clinical treatment against infections disease like COVID-19 and its correlated infections. However, further studies are warranted to confirm the design of an "ideal" photodynamic protocol. Presently we are investigating clinical implementation for the procedure.

Funding

The authors thank FAPESP (CEPOF 2013/07276-1) and INCT “Basic Optics and Applied to Life Sciences” (FAPESP 2014/50857-8, CNPq 465360/2014-9). L. D. Dias and K. C.Blanco thank Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) for their Post-doc grants 2019/13569-8 and CePOF – CePID 2019/12694-3, respectively.

Declaration of Competing Interest

None.