Oromucosal immunomodulation as clinical spectrum mitigating factor in SARS-CoV-2 infection

Francisco Rodríguez-Argente, María Alba-Domínguez, Elena Ortiz-Muñoz, Ángel Ortega-González, Francisco Rodríguez-Argente, María Alba-Domínguez, Elena Ortiz-Muñoz, Ángel Ortega-González

Abstract

Mounting evidence supports the importance of mucosal immunity in the immune response to SARS-CoV-2. Active virus replication in the upper respiratory tract for the first days of infection opens a new perspective in immunological strategies to counteract viral pathogenicity. An effective mucosal innate immune response to SARS-CoV-2 paves the way to an also effective adaptive immune response. A strong local immune response seems to be crucial in the initial contention of the virus by the organism and for triggering the production of the necessary neutralizing antibodies in sera and mucosal secretions. However, if the innate immune response fails to overcome the immune evasion mechanisms displayed by the virus, the infection will progress and the lack of an adaptive immune response will take the patient to an overreactive but ineffective innate immune response. To revert this scenario, an immune strategy based on enhancement of immunity in the first days of infection would be theoretically well come. But serious concerns about cytokine response syndrome prevent us to do so. Fortunately, it is possible to enhance immune system response without causing inflammation through immunomodulation. Immunomodulation of local immune response at the oropharyngeal mucosa could hypothetically activate our mucosal immunity, which could send an early an effective warning to the adaptive immune system. There are studies on immunotherapeutic management of upper respiratory tract infections in children that can place us in the right path to design an immune strategy able to mitigate COVID-19 symptoms and reduce clinical progression.

Keywords: SARS-CoV-2 infection; immunomodulation; immunotherapy; mucosal immunity; nasopharyngeal-associated tissue.

Conflict of interest statement

None of the authors has ant potential conflicts of interest to disclose.

© 2020 The Authors. Scandinavian Journal of Immunology published by John Wiley & Sons Ltd on behalf of The Scandinavian Foundation for Immunology.

References

    1. Greenberg SB. Update on rhinovirus and coronavirus infections. Semin Respir Crit Care Med. 2011;32(4):433‐446.
    1. American Academy of Pediatrics . Coronaviruses, including SARS and MERS In: Kimberlin DW, Brady MT, Jackson MA, Long SS, eds. Red Book: 2018 Report of the Committee on Infectious Diseases. 31st ed. Itasca, IL: American Academy of Pediatrics; 2018:297‐301.
    1. De la Flor i Bui J. Infecciones de las vías respiratorias altas‐1: el resfríado común. Pediatr Integral. 2017;XXI(6):377‐398.
    1. de Wit E, van Doremalen N, Falzarano D, Munster VJ. SARS and MERS: recent insights into emerging coronaviruses. Nat Rev Microbiol. 2016;14(8):523‐534.
    1. Zhu N, Zhang D, Wang W, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020;382(8):727‐733.
    1. Castagnoli R, Votto M, Licari A, et al. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) infection in children and adolescents: a systematic review [published online ahead of print, 2020 Apr 22]. JAMA Pediatr. 2020;174(9):882.
    1. Instituto de Salud Global de Barcelona . Instituto de Salud Global Barcelona. COVID‐19: Lecciones y recomendaciones, 2018. Disponible en: . 2020/05/24
    1. Callow KA, Parry HF, Sergeant M, Tyrrell DA. The time course of the immune response to experimental coronavirus infection of man. Epidemiol Infect. 1990;105(2):435‐446.
    1. Shi Y, Wang Y, Shao C, et al. COVID‐19 infection: the perspectives on immune responses. Cell Death Differ. 2020;27(5):1451‐1454.
    1. Sungnak W, Huang N, Bécavin C, et al. SARS‐CoV‐2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes. Nat Med. 2020;26:681‐687.
    1. Murphy K, Weaver C. The mucosal immune system In: Murphy K, Weaver C, eds. Janeway`s Immunobiology: The Immune System in Health and Disease. New York, NY: Garland Science, Taylor & Francis Group, LLC; 2017:493‐531.
    1. Crespo HJ, Lau JT, Videira PA. Dendritic cells: a spot on sialic Acid. Front Immunol. 2013;4:491.
    1. Mubarak A, Alturaiki W, Hemida MG. Middle East Respiratory Syndrome Coronavirus (MERS‐CoV): infection, immunological response, and vaccine development. J Immunol Res. 2019;2019:6491738.
    1. Channappanavar R, Zhao J, Perlman S. T cell‐mediated immune response to respiratory coronaviruses. Immunol Res. 2014;59(1–3):118‐128.
    1. Xu Z, Shi L, Wang Y, et al. Pathological findings of COVID‐19 associated with acute respiratory distress syndrome [published correction appears in Lancet Respir Med. 2020 Feb 25]. Lancet Respir Med. 2020;8(4):420‐422.
    1. Ginaldi L, Loreto MF, Corsi MP, Modesti M, De Martinis M. Immunosenescence and infectious diseases. Microbes Infect. 2001;3(10):851‐857.
    1. Mackinnon LT. Exercise and resistance to infectious illness In: Mackinnon LT, ed. Advances in Exercise and Immunology. Champaign, IL: Human Kinetics; 1999:1‐26.
    1. Palm NW, Medzhitov R. Not so fast: adaptive suppression of innate immunity. Nat Med. 2007;13(10):1142‐1144.
    1. Wölfel R, Corman VM, Guggemos W, et al. Virological assessment of hospitalized patients with COVID‐2019 [published online ahead of print, 2020 Apr 1]. Nature. 2020;581(7809):465‐469.
    1. Livy . Ab urbe condita. Cambridge, MA: Harvard University Press; 1922.
    1. Committee on New Directions in the Study of Antimicrobial Therapeutics: Immunomodulation . Promising Approaches to the Development of Immunomodulation for the Treatment of Infectious Diseases: Report of a Workshop. Washington, DC: National Academies Press, 2006. Available from:
    1. Jesenak M, Urbancikova I, Banovcin P. Respiratory tract infections and the role of biologically active polysaccharides in their management and prevention. Nutrients. 2017;9(7):779.
    1. Somerville V, Moore R, Braakhuis A. The effect of olive leaf extract on upper respiratory illness in high school athletes: a randomised control trial. Nutrients. 2019;11(2):358.
    1. Brandtzaeg P. Secretory immunity with special reference to the oral cavity. J Oral Microbiol. 2013;5(1):20401.
    1. French MA, Moodley Y. The role of SARS‐CoV‐2 antibodies in COVID‐19: healing in most, harm at times. Respirology. 2020;25:680‐682.
    1. Beilharz MW, Cummins MJ, Bennett AL, Cummins JM. Oromucosal administration of interferon to humans. Pharmaceuticals. 2010;3(2):323‐344.

Source: PubMed

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