Human Saliva and the COVID-19 Infection

Download Article

DOI: 10.21522/TIJPH.2013.12.03.Art011

Authors : Saranya varadarajan, Thodur Madapusi Balaji, Ambedkar Elumala, Suganya Subramanian, M. Jayakumar

Abstract:

Human saliva is a complex mixture of various organic and inorganic compounds and host-derived molecules. Performs numerous functions. This comprehensive review will discuss the roles played by saliva in defence against the SARS-CoV-2 virus and the use of saliva as a diagnostic fluid in COVID-19 screening will be discussed along with a brief note on SARS-CoV-2 transmission through saliva. Saliva and SARS Cov 2: The antimicrobial and antiviral properties of saliva are conferred by the salivary peptides such as defensins, cathelicidins, and LL 37. Antiviral activity against the herpes virus, hepatitis C virus, ebola virus and to an extent HIV has been documented. Since the COVID-19 pandemic has now occurred as a new global threat, it is being investigated if saliva has certain properties that could defend against this infection. Studies have found the regular presence of the SARS-CoV-2 virus, the aetiological agent of the COVID-19 disease in saliva, hence saliva could be used as a diagnostic tool. Some interesting findings have highlighted the presence of the virus in salivary samples but documented its absence in throat swabs which is intriguing. Despite having multifaceted roles, the drawback of saliva also lies in its contribution to the transmission of the SARS-CoV-2 virus. Studies have shown that viable viruses can be transmitted through saliva from person to person through coughing and sneezing. Hence saliva could be regarded as a double-edged sword in the COVID-19 pandemic.

References:

[1].   Anderson, P., Hector, M. P., & Rampersad, M. A., 2001, Critical pH in Resting and Stimulated Whole Saliva in Groups of Children and Adults. International Journal of Paediatric Dentistry, 11(4), 266–273, https://doi.org/10.1046/j.1365-263x.2001.00293.x

[2].   Alamoudi, N., Farsi, N., Faris, J., Masoud, I., Merdad, K., and Meisha, D., 2004, Salivary Characteristics of Children and its Relation to Oral Microorganism and Lip Mucosa Dryness. The Journal of Clinical Paediatric Dentistry, 28(3), 239–248. https://doi.org/10.17796/jcpd.28.3.h24774507006l550

[3].   Baskar, S. N., 1997, Orban’s Oral Histology and Embryology. (11th ed. St. Louis: Harcourt Asia PIE Ltd., Mosby).

[4].   Edgar, W. M.,1992, Saliva: Its Secretion, Composition and Functions. British Dental Journal, 172(8), 305–312, https://doi.org/10.1038/sj.bdj.4807861

[5].   Roth, G., Calmes, R., 1981, Salivary Glands and Saliva. Oral Biology, (CV Mosby, St Louis).

[6].   Edgar, W. M., 1990, Saliva and Dental Health. Clinical Implications of Saliva: Report of a Consensus Meeting. British Dental Journal, 169(3-4), 96–98, https://doi.org/10.1038/sj.bdj.4807284

[7].   K, H. S., R, G., Ramani, P., & Veeraraghavan, V. P., 2024, Longitudinal Study on Salivary IL-6 Trajectories in Postoperative OSCC Patients After Chemotherapy and Radiotherapy. Journal of Stomatology, Oral and Maxillofacial Surgery, 101909. Advance Online Publication. https://doi.org/10.1016/j.jormas.2024.101909

[8].   Alam, M. K., Zaman, M. U., Alqhtani, N. R., Alqahtani, A. S., Alqahtani, F., Cicciù, M., & Minervini, G., 2024, Salivary Biomarkers and Temporomandibular Disorders: A Systematic Review Conducted According to PRISMA Guidelines and the Cochrane Handbook for Systematic Reviews of Interventions. Journal of Oral Rehabilitation, 51(2), 416–426. https://doi.org/10.1111/joor.13589

[9].   Thomas, J. T., Joseph, B., Varghese, S., Thomas, N. G., Kamalasanan Vijayakumary, B., Sorsa, T., Anil, S., & Waltimo, T., 2024, Association Between Metabolic Syndrome and Salivary MMP-8, Myeloperoxidase in Periodontitis. Oral Diseases, Advance Online Publication. https://doi.org/10.1111/odi.15014

[10].  Fathima, R., Ramamoorthi, R., Gopalakrishnan, S., Jayaseelan, V. P., & Muniapillai, S., 2024, Expression of Salivary Levels of S100A7 in Oral Submucous Fibrosis and Oral Leukoplakia. Journal of Oral and Maxillofacial Pathology: JOMFP, 28(1), 84–89. https://doi.org/10.4103/jomfp.jomfp_113_23

[11].  Dawes, C., 1998, Recent Research on Calculus. The New Zealand Dental Journal, 94(416), 60–62.

[12].  Malamud, D., Abrams, W. R., Barber, C. A., Weissman, D., Rehtanz, M., & Golub, E., 2011, Antiviral Activities in Human Saliva. Advances in Dental Research, 23(1), 34–37. https://doi.org/10.1177/0022034511399282

[13].  Wu, Z., Van, Ryk, D., Davis, C., Abrams, W. R., Chaiken, I., Magnani, J., & Malamud, D., 2003, Salivary Agglutinin Inhibits HIV Type 1 Infectivity Through Interaction with Viral Glycoprotein 120. AIDS Research and Human Retroviruses, 19(3), 201–209, https://doi.org/10.1089/088922203763315704

[14].  White, M. R., Crouch, E., Vesona, J., Tacken, P. J., Batenburg, J. J., Leth-Larsen, R., Holmskov, U., and Hartshorn, K. L., 2005, Respiratory Innate Immune Proteins Differentially Modulate the Neutrophil Respiratory Burst Response to Influenza a Virus. Lung Cellular and Molecular Physiology. American Journal of Physiology, 289(4), L606–L616, https://doi.org/10.1152/ajplung.00130.2005

[15].  Nagashunmugam, T., Malamud, D., Davis, C., Abrams, W. R., & Friedman, H. M.,1998, Human Submandibular Saliva Inhibits Human Immunodeficiency Virus Type 1 Infection by Displacing Envelope Glycoprotein gp120 from the Virus. The Journal of Infectious Diseases, 178(6), 1635–1641, https://doi.org/10.1086/314511

[16].  Banerjee, A., Kulcsar, K., Misra, V., Frieman, M., & Mossman, K., 2019, Bats and Coronaviruses. Viruses, 11(1), 41, https://doi.org/10.3390/v11010041

[17].  Yang, D., & Leibowitz, J. L., 2015, The Structure and Functions of Coronavirus Genomic 3' and 5' Ends. Virus Research, 206, 120–133, https://doi.org/10.1016/j.virusres.2015.02.025

[18].  Ramaiah. A., Arumugaswami, V., 2020, Insights into Cross-Species Evolution of Novel Human Coronavirus 2019-nCoV and Defining Immune Determinants for Vaccine Development. bioRxiv https://doi:10.1101/2020.01.29.925867

[19].  Chan, J. F., Kok, K. H., Zhu, Z., Chu, H., To, K. K., Yuan, S., and Yuen, K. Y., 2020, Genomic Characterization of the 2019 Novel Human-Pathogenic Coronavirus Isolated from a Patient with Atypical Pneumonia After Visiting Wuhan. Emerging Microbes & Infections, 9(1), 221–236, https://doi.org/10.1080/22221751.2020.1719902

[20].  Wu, A., Peng, Y., Huang, B., Ding, X., Wang, X., Niu, P., Meng, J., Zhu, Z., Zhang, Z., Wang, J., Sheng, J., Quan, L., Xia, Z., Tan, W., Cheng, G., & Jiang, T., 2020, Genome Composition and Divergence of the Novel Coronavirus (2019-nCoV) Originating in China. Cell Host & Microbe, 27(3), 325–328, https://doi.org/10.1016/j.chom.2020.02.001

[21].  Yuan, Y., Cao, D., Zhang, Y., Ma, J., Qi, J., Wang. Q., et al., 2017, Cryo-EM Structures of MERS-CoV and SARS-CoV Spike Glycoproteins Reveal the Dynamic Receptor Binding Domains. Nat Commun, 8:15092, https://doi:10.1038/ncomms15092

[22].  Walls, A. C., Xiong, X., Park, Y. J., Tortorici, M. A., Snijder, J., Quispe, J., Cameroni, E., Gopal, R., Dai, M., Lanzavecchia, A., Zambon, M., Rey, F. A., Corti, D., & Veesler, D., 2019, Unexpected Receptor Functional Mimicry Elucidates Activation of Coronavirus Fusion. Cell, 176(5), 1026–1039.e15. https://doi.org/10.1016/j.cell.2018.12.028

[23].  Paules, C. I., Marston, H, D., & Fauci, A. S., 2020, Coronavirus Infections-More than Just the Common Cold. JAMA, 323(8), 707–708, https://doi.org/10.1001/jama.2020.0757

[24].  Xu, H., Zhong, L., Deng, J., Peng, J., Dan, H., Zeng, X., Li, T., & Chen, Q., 2020, High Expression of ACE2 Receptor of 2019-nCoV on the Epithelial Cells of Oral Mucosa. International Journal of Oral Science, 12(1), 8, https://doi.org/10.1038/s41368-020-0074-x

[25].  Iwabuchi, H., Fujibayashi, T., Yamane, G. Y., Imai, H., & Nakao, H., 2012, Relationship Between Hyposalivation and Acute Respiratory Infection in Dental Outpatients. Gerontology, 58(3), 205–211. https://doi.org/10.1159/000333147

[26].  Magister, S., & Kos, J., 2013, Cystatins in Immune System. Journal of Cancer, 4(1), 45–56. https://doi.org/10.7150/jca.5044

[27].  Collins, A. R., & Grubb, A., Cystatin, D., 1998, A Natural Salivary Cysteine Protease Inhibitor, Inhibits Coronavirus Replication at its Physiologic Concentration. Oral Microbiology and Immunology, 13(1), 59–61, https://doi.org/10.1111/j.1399-302x.1998.tb00753.x

[28].  Dawes, C., Pedersen, A. M., Villa, A., Ekström, J., Proctor, G. B., Vissink, A., Aframian, D., McGowan, R., Aliko, A., Narayana, N., Sia, Y. W., Joshi, R. K., Jensen, S. B., Kerr, A. R., & Wolff, A., 2015, The Functions of Human Saliva: A Review Sponsored by the World Workshop on Oral Medicine VI. Archives of Oral Biology, 60(6), 863–874, https://doi.org/10.1016/j.archoralbio.2015.03.004

[29].  Irmak, M. K., Erdem, U., & Kubar, A., 2012, Antiviral Activity of Salivary microRNAs for Ophthalmic Herpes Zoster. Theoretical Biology and Medical Modelling, 9(1), 21, https://doi.org/10.1186/1742‐4682‐9‐21

[30].  Baghizadeh Fini, M., 2020, Oral Saliva and COVID-19. Oral Oncology, 108, 104821. https://doi.org/10.1016/j.oraloncology.2020.104821

[31].  Centers for Disease Control and Prevention Transmission of Coronavirus Disease 2019 (COVID-19). Accessed 18th Mar 2020, Available at: https://www.cdc.gov/coronavirus/2019-ncov/about/transmission.html

[32].  To, K. K., Tsang, O. T., Yip, C. C., Chan, K. H., Wu, T. C., Chan, J. M., Leung, W. S., Chik, T. S., Choi, C. Y., Kandamby, D. H., Lung, D. C., Tam, A. R., Poon, R. W., Fung, A. Y., Hung, I. F., Cheng, V. C., Chan, J. F., & Yuen, K. Y., 2020, Consistent Detection of 2019 Novel Coronavirus in Saliva. Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America, 71(15), 841–843. https://doi.org/10.1093/cid/ciaa149

[33].  Hong, K. H., Lee, S. W., Kim, T. S., Huh, H. J., Lee, J., Kim, S. Y., Park, J. S., Kim, G. J., Sung, H., Roh, K. H., Kim, J. S., Kim, H. S., Lee, S. T., Seong, M. W., Ryoo, N., Lee, H., Kwon, K. C., & Yoo, C. K., 2020, Guidelines for Laboratory Diagnosis of Coronavirus Disease 2019 (COVID-19) in Korea. Annals of Laboratory Medicine, 40(5), 351–360. https://doi.org/10.3343/alm.2020.40.5.351

[34].  Ng, K., Poon, B. H., Kiat Puar, T. H., Shan Quah, J. L., Loh, W. J., Wong, Y. J., Tan, T. Y., & Raghuram, J., 2020, COVID-19 and the Risk to Health Care Workers: A Case Report. Annals of Internal Medicine, 172(11), 766–767. https://doi.org/10.7326/L20-0175

[35].  Chojnowska, S., Baran, T., Wilińska, I., Sienicka, P., Cabaj-Wiater, I., & Knaś, M., 2018, Human Saliva as a Diagnostic Material. Advances in Medical Sciences, 63(1), 185–191, https://doi.org/10.1016/j.advms.2017.11.002

[36].  To, K. K., Tsang, O. T., Yip, C. C., Chan, K. H., Wu, T. C., Chan, J. M., Leung, W. S., Chik, T. S., Choi, C. Y., Kandamby, D. H., Lung, D. C., Tam, A. R., Poon, R. W., Fung, A. Y., Hung, I. F., Cheng, V. C., Chan, J. F., & Yuen, K. Y., 2020, Consistent Detection of 2019 Novel Coronavirus in Saliva. Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America, 71(15), 841–843. https://doi.org/10.1093/cid/ciaa149

[37].  To, K. K., Tsang, O. T., Leung, W. S., Tam, A. R., Wu, T. C., Lung, D. C., Yip, C. C., Cai, J. P., Chan, J. M., Chik, T. S., Lau, D. P., Choi, C. Y., Chen, L. L., Chan, W. M., Chan, K. H., Ip, J. D., Ng, A. C., Poon, R. W., Luo, C. T., Cheng, V. C., Yuen, K. Y., 2020, Temporal Profiles of Viral Load in Posterior Oropharyngeal Saliva Samples and Serum Antibody Responses During Infection by SARS-CoV-2: An Observational Cohort Study. The Lancet. Infectious diseases, 20(5), 565–574, https://doi.org/10.1016/S1473-3099(20)30196-1

[38].  Azzi, L., Carcano, G., Gianfagna, F., Grossi, P., Gasperina, D. D., Genoni, A., Fasano, M., Sessa, F., Tettamanti, L., Carinci, F., Maurino, V., Rossi, A., Tagliabue, A., & Baj, A., 2020, Saliva is a Reliable Tool to Detect SARS-CoV-2. The Journal of Infection, 81(1), e45–e50, https://doi.org/10.1016/j.jinf.2020.04.005

[39].  Han, M. S., Seong, M. W., Heo, E. Y., Park, J. H., Kim, N., Shin, S., Cho, S. I., Park, S. S., & Choi, E. H., 2020, Sequential Analysis of Viral Load in a Neonate and Her Mother Infected With Severe Acute Respiratory Syndrome Coronavirus 2. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 71(16), 2236–2239, https://doi.org/10.1093/cid/ciaa447

[40].  Wan, S., Xiang, Y., Fang, W., Zheng, Y., Li, B., Hu, Y., Lang, C., Huang, D., Sun, Q., Xiong, Y., Huang, X., Lv, J., Luo, Y., Shen, L., Yang, H., Huang, G., & Yang, R., 2020, Clinical Features and Treatment of COVID-19 Patients in Northeast Chongqing. Journal of Medical Virology, 92(7), 797–806, https://doi.org/10.1002/jmv.25783

[41].  Peng, Y. D., Meng, K., Guan, H. Q., Leng, L., Zhu, R. R., Wang, B. Y., He, M. A., Cheng, L. X., Huang, K., & Zeng, Q. T., 2020, Zhonghua Xin Xue Guan Bing Za Zhi, 48(6), 450–455, https://doi.org/10.3760/cma.j.cn112148-20200220-00105

[42].  Cerón, J. J., Martinez-Subiela, S., Ohno, K., & Caldin, M., 2008, A Seven-Point Plan for Acute Phase Protein Interpretation in Companion Animals. Veterinary Journal (London, England: 1997), 177(1), 6–7, https://doi.org/10.1016/j.tvjl.2007.12.001

[43].  Wan, S., Yi, Q., Fan, S., Lv, J., Zhang, X., Guo, L., Lang, C., Xiao, Q., Xiao, K., Yi, Z., Qiang, M., Xiang, J., Zhang, B., Chen, Y., & Gao, C., 2020, Relationships Among Lymphocyte Subsets, Cytokines, and the Pulmonary Inflammation Index in Coronavirus (COVID-19) Infected Patients. British Journal of Haematology, 189(3), 428–437, https://doi.org/10.1111/bjh.16659

[44].  Tvarijonaviciute, A., Martinez-Lozano, N., Rios, R., Marcilla de Teruel, M. C., Garaulet, M., and Cerón, J. J., 2020, Saliva as a Non-Invasive Tool for Assessment of Metabolic and Inflammatory Biomarkers in Children. Clinical Nutrition (Edinburgh, Scotland), 39(8), 2471–2478, https://doi.org/10.1016/j.clnu.2019.10.034

[45].  Parra, M. D., Tecles, F., Martínez-Subiela, S., & Cerón, J. J., 2005, C-Reactive Protein Measurement in Canine Saliva. Official Publication of the American Association of Veterinary Laboratory Diagnosticians. Journal of Veterinary Diagnostic Investigation Inc, 17(2), 139–144. https://doi.org/10.1177/104063870501700207

[46].  Chen, L., Zhao, J., Peng, J., Li, X., Deng, X., Geng, Z., Shen, Z., Guo, F., Zhang, Q., Jin, Y., Wang, L., & Wang, S., 2020, Detection of SARS-CoV-2 in Saliva and Characterization of Oral Symptoms in COVID-19 patients. Cell proliferation, 53(12), e12923. https://doi.org/10.1111/cpr.12923

[47].  Williams, E., Bond, K., Zhang, B., Putland, M., & Williamson, D. A., 2020, Saliva as a Noninvasive Specimen for Detection of SARS-CoV-2. Journal of Clinical Microbiology, 58(8), e00776-20. https://doi.org/10.1128/JCM.00776-20

[48].  Sagar, S., Ramani, P., Moses, S., Gheena, S., & Selvaraj, J., 2024, Correlation of Salivary Cytokine IL-17A and 1,25 Dihydroxycholecalciferol in Patients Undergoing Orthodontic Treatment. Odontology, 112(3), 966–975. https://doi.org/10.1007/s10266-023-00890-1

[49].   Alam, M. K., Zaman, M. U., Alqhtani, N. R., Alqahtani, A. S., Alqahtani, F., Cicciù, M., & Minervini, G., 2024, Salivary Biomarkers and Temporomandibular Disorders: A Systematic Review conducted according to PRISMA guidelines and the Cochrane Handbook for Systematic Reviews of Interventions. Journal of oral rehabilitation, 51(2), 416–426. https://doi.org/10.1111/joor.13589

[50].   Kritika, S., Mahalaxmi, S., Srinivasan, N., & Krithikadatta, J., 2023, Deciphering the Role of Saliva in COVID 19: A Global Cross-Sectional Study on the Knowledge, Awareness and Perception Among Dentists. BMC Oral Health,23(1), 424. https://doi.org/10.1186/s12903-023-03152-2