Olfactory Immune Response to SARS-CoV-2

Overview

Journal Cell Mol Immunol

Date 2023 Dec 24

PMID 38143247

Authors

Sebastian A Wellford

E Ashley Moseman

Affiliations

Soon will be listed here.

Abstract

Numerous pathogens can infect the olfactory tract, yet the pandemic caused by SARS-CoV-2 has strongly emphasized the importance of the olfactory mucosa as an immune barrier. Situated in the nasal passages, the olfactory mucosa is directly exposed to the environment to sense airborne odorants; however, this also means it can serve as a direct route of entry from the outside world into the brain. As a result, olfactotropic infections can have serious consequences, including dysfunction of the olfactory system, CNS invasion, dissemination to the lower respiratory tract, and transmission between individuals. Recent research has shown that a distinctive immune response is needed to protect this neuronal and mucosal tissue. A better understanding of innate, adaptive, and structural immune barriers in the olfactory mucosa is needed to develop effective therapeutics and vaccines against olfactotropic microbes such as SARS-CoV-2. Here, we summarize the ramifications of SARS-CoV-2 infection of the olfactory mucosa, review the subsequent immune response, and discuss important areas of future research for olfactory immunity to infectious disease.

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References

Milligan E, Olstad K, Williams C, Mallory M, Cano P, Cross K . Infant rhesus macaques immunized against SARS-CoV-2 are protected against heterologous virus challenge 1 year later. Sci Transl Med. 2022; 15(685):eadd6383. PMC: 9765459. DOI: 10.1126/scitranslmed.add6383. View

Zheng M, Wakim L . Tissue resident memory T cells in the respiratory tract. Mucosal Immunol. 2021; 15(3):379-388. PMC: 8526531. DOI: 10.1038/s41385-021-00461-z. View

Jiao L, Yang Y, Yu W, Zhao Y, Long H, Gao J . The olfactory route is a potential way for SARS-CoV-2 to invade the central nervous system of rhesus monkeys. Signal Transduct Target Ther. 2021; 6(1):169. PMC: 8065334. DOI: 10.1038/s41392-021-00591-7. View

Giacomelli A, Pezzati L, Conti F, Bernacchia D, Siano M, Oreni L . Self-reported Olfactory and Taste Disorders in Patients With Severe Acute Respiratory Coronavirus 2 Infection: A Cross-sectional Study. Clin Infect Dis. 2020; 71(15):889-890. PMC: 7184514. DOI: 10.1093/cid/ciaa330. View

Beretta S, Cristillo V, Camera G, Colleoni C, Pellitteri G, Viti B . Incidence and Long-term Functional Outcome of Neurologic Disorders in Hospitalized Patients With COVID-19 Infected With Pre-Omicron Variants. Neurology. 2023; 101(9):e892-e903. PMC: 10501088. DOI: 10.1212/WNL.0000000000207534. View

Premraj L, Kannapadi N, Briggs J, Seal S, Battaglini D, Fanning J . Mid and long-term neurological and neuropsychiatric manifestations of post-COVID-19 syndrome: A meta-analysis. J Neurol Sci. 2022; 434:120162. PMC: 8798975. DOI: 10.1016/j.jns.2022.120162. View

Lechien J, Vaira L, Saussez S . Prevalence and 24-month recovery of olfactory dysfunction in COVID-19 patients: A multicentre prospective study. J Intern Med. 2022; 293(1):82-90. PMC: 9538281. DOI: 10.1111/joim.13564. View

Kumari P, Rothan H, Natekar J, Stone S, Pathak H, Strate P . Neuroinvasion and Encephalitis Following Intranasal Inoculation of SARS-CoV-2 in K18-hACE2 Mice. Viruses. 2021; 13(1). PMC: 7832889. DOI: 10.3390/v13010132. View

Croy I, Nordin S, Hummel T . Olfactory disorders and quality of life--an updated review. Chem Senses. 2014; 39(3):185-94. DOI: 10.1093/chemse/bjt072. View

10.

Nelson C, Namasivayam S, Foreman T, Kauffman K, Sakai S, Dorosky D . Mild SARS-CoV-2 infection in rhesus macaques is associated with viral control prior to antigen-specific T cell responses in tissues. Sci Immunol. 2022; :eabo0535. PMC: 8995035. DOI: 10.1126/sciimmunol.abo0535. View

11.

Dieterle M, Haslwanter D, Bortz 3rd R, Wirchnianski A, Lasso G, Vergnolle O . A Replication-Competent Vesicular Stomatitis Virus for Studies of SARS-CoV-2 Spike-Mediated Cell Entry and Its Inhibition. Cell Host Microbe. 2020; 28(3):486-496.e6. PMC: 7332447. DOI: 10.1016/j.chom.2020.06.020. View

12.

van Doremalen N, Lambe T, Spencer A, Belij-Rammerstorfer S, Purushotham J, Port J . ChAdOx1 nCoV-19 vaccine prevents SARS-CoV-2 pneumonia in rhesus macaques. Nature. 2020; 586(7830):578-582. PMC: 8436420. DOI: 10.1038/s41586-020-2608-y. View

13.

Cantuti-Castelvetri L, Ojha R, Pedro L, Djannatian M, Franz J, Kuivanen S . Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity. Science. 2020; 370(6518):856-860. PMC: 7857391. DOI: 10.1126/science.abd2985. View

14.

Flanagan C, Wise S, DelGaudio J, Patel Z . Association of decreased rate of influenza vaccination with increased subjective olfactory dysfunction. JAMA Otolaryngol Head Neck Surg. 2015; 141(3):225-8. DOI: 10.1001/jamaoto.2014.3399. View

15.

Shi J, Li Z, Zhang J, Xu R, Lan Y, Guan J . PHEV infection: A promising model of betacoronavirus-associated neurological and olfactory dysfunction. PLoS Pathog. 2022; 18(6):e1010667. PMC: 9282652. DOI: 10.1371/journal.ppat.1010667. View

16.

Toomre D, Kandula S, Shaman J . Longitudinal Association of COVID-19 Hospitalization and Death with Online Search for Loss of Smell or Taste. Emerg Infect Dis. 2023; 29(8):1711-1713. PMC: 10370832. DOI: 10.3201/eid2908.230071. View

17.

Ssemaganda A, Nguyen H, Nuhu F, Jahan N, Card C, Kiazyk S . Expansion of cytotoxic tissue-resident CD8 T cells and CCR6CD161 CD4 T cells in the nasal mucosa following mRNA COVID-19 vaccination. Nat Commun. 2022; 13(1):3357. PMC: 9186487. DOI: 10.1038/s41467-022-30913-4. View

18.

Arunachalam J, U R A, Verma K, Rajendran R, Chidambaram S . SARS-CoV-2: The Road Less Traveled-From the Respiratory Mucosa to the Brain. ACS Omega. 2021; 6(10):7068-7072. PMC: 7970566. DOI: 10.1021/acsomega.1c00030. View

19.

Xydakis M, Albers M, Holbrook E, Lyon D, Shih R, Frasnelli J . Post-viral effects of COVID-19 in the olfactory system and their implications. Lancet Neurol. 2021; 20(9):753-761. PMC: 8324113. DOI: 10.1016/S1474-4422(21)00182-4. View

20.

Fodoulian L, Tuberosa J, Rossier D, Boillat M, Kan C, Pauli V . SARS-CoV-2 Receptors and Entry Genes Are Expressed in the Human Olfactory Neuroepithelium and Brain. iScience. 2020; 23(12):101839. PMC: 7685946. DOI: 10.1016/j.isci.2020.101839. View