key: cord-0743387-k0p931i6 authors: Soares, Luís Eduardo Silva; Guirado, Milena Miranda Goulart; Berlingieri, Giuseppina; Ramires, Marcia Christina Camargo Hernandes; Lyra, Luciana Aparecida de Oliveira P.; Teixeira, Inessa Solek; Oliveira, Patrícia Costa; Tateno, Ricardo Yudi; Palma, Luiz Felipe; Campos, Luana title: Intranasal photobiomodulation therapy for COVID-19-related olfactory dysfunction: a Brazilian multicenter case series date: 2021-10-07 journal: Photodiagnosis Photodyn Ther DOI: 10.1016/j.pdpdt.2021.102574 sha: 9a7cfbcc150ddcd31f7b2b2042e3ed37e6a23ae4 doc_id: 743387 cord_uid: k0p931i6 Olfactory dysfunction is commonly seen in COVID-19 patients; however, little is known about the pathophysiology and management. The present study aimed to report a series of cases in which three protocols of intranasal photobiomodulation therapy (PBMT) were used for COVID-19-related olfactory dysfunction. Irrespective of the PBMT protocol, olfaction recovery was noted in all cases but with varying degrees of improvement. Although intranasal PBMT seems to be a promising therapeutic modality, more research is demanded to identify the most suitable protocol. Olfactory dysfunction is commonly seen in many viral diseases in which respiratory epithelium is the primary site of both viral attachment and infection. The mechanisms of olfactory dysfunction are generally nonspecific and based on inflammatory reactions on the nasal mucosa that leads to subsequent rhinorrhea; however, the exact pathophysiology related to the novel Coronavirus Disease 19 (COVID-19) remains poorly understood [1] . Other possible explanations for olfactory alterations during COVID-19 rely on direct or indirect neurologic injuries via angiotensin-converting enzyme 2 (ACE2), the functional receptor for the virus [1, 2] . From 5.14% to 98.33% of patients with COVID-19 suffer from complete (anosmia) or partial (hyposmia) loss of olfaction [2] . Considering the sudden onset of impairment of smell and/or taste during the disease course, some advocate including these symptoms in the diagnostic criteria for COVID-19 [3] . Moreover, it has been reported that COVID-19 patients with mild or no symptoms may not fully recover their ability to detect odors within four months or more from the viral infection. Certain odors (e.g., strawberry, lemon, and soap) seem to be exaggeratedly affected, raising the hypothesis that a permanent smell reduction may occur [4] . The management of COVID-19-related olfactory dysfunction varies widely. For cases that improve spontaneously, no specific treatment is needed; however, when the impairment lasts beyond 2 weeks, some therapeutic modality should be considered. Despite very little robust scientific evidence regarding efficiency, the available treatments consist of either olfactory training or medications such as oral or intranasal corticosteroids, intranasal sodium citrate, intranasal vitamin A, and oral omega-3 [3] . Considering this background, it was hypothesized that photobiomodulation therapy (PBMT) would be beneficial for olfaction recovery, since it is capable of modulating inflammatory processes and improving tissue healing in a general manner. Moreover, this laser modality, also considered simple, low-cost, and non-invasive, has already been successfully used for different purposes in COVID-19 patients, including the treatment of orofacial lesions [5] . Thus, the present study aims to report a series of clinical cases in which intranasal PBMT was administered for the management of COVID-19-related olfactory dysfunction. Twelve female (from 20-to 59-year-old) and two male patients (from 25-to 37year-old) from five different Brazilian Health Centers and suffering from smell loss (either partially or completely) after COVID-19 infection were clinically accompanied. Data about the exact initiation of all signs and symptoms related to COVID-19, as well as its biomolecular infection confirmation, were gathered by a simple questionnaire (Table 1) . Furthermore, at the first clinical appointment and before the subsequent ones, olfaction was evaluated using a visual analog scale (VAS) ranging from 0 (normal smell) to 10 (complete absence of smell -anosmia). Three intranasal PBMT protocols were applied ( Figure 1 Up to now, there is weak evidence to support the benefits from the available therapeutic modalities for cases of COVID-19-related persistent olfactory dysfunction, either pharmacological or not [3] . It was hypothesized, therefore, that PBMT would be beneficial for olfaction recovery, since it is capable of modulating the local inflammatory processes and improving tissue vascularization [5] . Furthermore, systemically through blood cells and components, intranasal irradiation could provide neuroprotection via antiinflammatory and antioxidant pathways once the nasal cavity presents abundant blood capillaries with relatively slow blood flow [6] . Nonetheless, other possible acting mechanisms can also be proposed, including the potential to activate neural stem cells of the olfactory nerve, bulb, and endothelium, and the autonomic nervous and lymphatic systems [6] . Concerning study limitations, despite presenting three laser protocols, this study lacks a control group (e.g., sham laser) and involved a reduced number of patients. Even being ranked at the lowest level of evidence among clinical studies, case reports and case series are still highly desired, since they may bring early information and novel insights for novel and little-known conditions and diseases such as COVID-19 [5] . Given the unpredictable nature of olfactory dysfunction in COVID-19 patients and the lack of information about the available treatments, intranasal PBMT seems to be a promising therapeutic modality. The choice of the most suitable laser protocol as well as the knowledge of the exact photonic mechanisms, however, demand further clarification. Funding: nothing to declare. Conflicts of interest/Competing interests: nothing to declare. Ethics approval: not applicable. Consent to participate: written informed consent was obtained from all the patients. Consent for publication: written informed consent was obtained from all the patients. Olfactory dysfunction in the covid-19 outbreak The Prevalence of Olfactory and Gustatory Dysfunction in COVID-19 Patients: A Systematic Review and Meta-analysis, Otolaryngol. -Head Neck Surg Olfactory Dysfunction in COVID-19: Diagnosis and Management Olfactory dysfunction in SARS-CoV-2 infection: Focus on odorant specificity and chronic persistence Photobiomodulation therapy and antimicrobial photodynamic therapy for orofacial lesions in patients with COVID-19: A case series Therapeutic potential of intranasal photobiomodulation therapy for neurological and neuropsychiatric disorders: a narrative review