Use of Saliva for Diagnosis and Monitoring the SARS-CoV-2: A General Perspective

Jose J Ceron, Elsa Lamy, Silvia Martinez-Subiela, Pia Lopez-Jornet, Fernando Capela E Silva, Peter David Eckersall, Asta Tvarijonaviciute, Jose J Ceron, Elsa Lamy, Silvia Martinez-Subiela, Pia Lopez-Jornet, Fernando Capela E Silva, Peter David Eckersall, Asta Tvarijonaviciute

Abstract

In this report, updated information and future perspectives about the use of saliva as a sample for laboratory analysis of the Covid-19 are highlighted. Saliva can be used for the direct detection of the SARS-CoV-2 virus, the quantification of the specific immunoglobulins produced against it, and for the evaluation of the non-specific, innate immune response of the patient. Moreover, a deeper knowledge of potential changes in the saliva proteome in this disease may allow the identification of new diagnostic and prognostic biomarkers, or even help our understanding of the mechanisms associated with the disease. With the development of appropriate sample collection and processing methods and the use of adequate assays, saliva can provide useful clinical information about the disease and could be potentially included in guidelines for sample collection for the diagnosis, disease management, and control of Covid-19.

Keywords: Covid-19; SARS; coronavirus; saliva.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Use of saliva in Covid-19.

References

    1. Gabutti G., d’Anchera E., Sandri F., Savio M., Stefanati A. Coronavirus: Update Related to the Current Outbreak of COVID-19. Infect. Dis. Ther. 2020 doi: 10.1007/s40121-020-00295-5.
    1. Yan C.H., Faraji F., Prajapati D.P., Boone C.E., DeConde A.S. Association of chemosensory dysfunction and Covid-19 in patients presenting with influenza-like symptoms. Int. Forum Allergy Rhinol. 2020 doi: 10.1002/alr.22579.
    1. Tvarijonaviciute A., Martinez-Subiela S., Lopez-Jornet P., Lamy E., editors. Saliva in Health and Disease. The Present and Future of A Unique Sample for Diagnosis. Springer Nature; Cham, Switzerland: 2020.
    1. Contreras-Aguilar M.D., Escribano D., Martínez-Subiela S., Martínez-Miró S., Rubio M., Tvarijonaviciute A., Tecles F., Cerón J.J. Influence of the way of reporting alpha-amylase values in saliva in different naturalistic situations: A pilot study. PLoS ONE. 2017;12:e0180100. doi: 10.1371/journal.pone.0180100.
    1. Sabino-Silva R., Jardim A.C.G., Siqueira W.L. Coronavirus COVID-19 impacts to dentistry and potential salivary diagnosis. Clin. Oral Investig. 2020;24:1–3. doi: 10.1007/s00784-020-03248-x.
    1. Khurshid Z., Asiri F.Y.I., Al Wadaani H. Human Saliva: Non-Invasive Fluid for Detecting Novel Coronavirus (2019-nCoV) Int. J. Environ. Res. Public Health. 2020;17:2225. doi: 10.3390/ijerph17072225.
    1. First Saliva Test for COVID-19 Approved for Emergency Use by FDA|The Scientist Magazine®. [(accessed on 13 May 2020)]; Available online: .
    1. To K.K.W., Yip C.C.Y., Lai C.Y.W., Wong C.K.H., Ho D.T.Y., Pang P.K.P., Ng A.C.K., Leung K.H., Poon R.W.S., Chan K.H., et al. Saliva as a diagnostic specimen for testing respiratory virus by a point-of-care molecular assay: A diagnostic validity study. Clin. Microbiol. Infect. 2019;25:372–378. doi: 10.1016/j.cmi.2018.06.009.
    1. Huang C., Wang Y., Li X., Ren L., Zhao J., Hu Y., Zhang L., Fan G., Xu J., Gu X., et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497–506. doi: 10.1016/S0140-6736(20)30183-5.
    1. Wang W.K., Chen S.Y., Liu I.J., Chen Y.C., Chen H.L., Yang C.F., Chen P.J., Yeh S.H., Kao C.L., Huang L.M., et al. Detection of SARS-associated coronavirus in throat wash and saliva in early diagnosis. Emerg. Infect. Dis. 2004;10:1213–1219. doi: 10.3201/eid1007.031113.
    1. Tvarijonaviciute A., Martinez-Lozano N., Rios R., Marcilla de Teruel M.C., Garaulet M., Cerón J.J. Saliva as a non-invasive tool for assessment of metabolic and inflammatory biomarkers in children. Clin. Nutr. 2019 doi: 10.1016/j.clnu.2019.10.034.
    1. To K., Tsang O., Chik-Yan Yip C., Chan K., Wu C., Chan J., Leung W., Chik T., Choi C., Kandamby D., et al. Consistent Detection of 2019 Novel Coronavirus in Saliva | Clinical Infectious Diseases|Oxford Academic. Clin. Infect. Dis. 2020 doi: 10.1093/cid/ciaa149.
    1. To K.K.-W., Tsang O.T.-Y., Leung W.-S., Tam A.R., Wu T.-C., Lung D.C., Yip C.C.-Y., Cai J.-P., Chan J.M.-C., Chik T.S.-H., et al. Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: An observational cohort study. Lancet Infect. Dis. 2020;20:565–574. doi: 10.1016/S1473-3099(20)30196-1.
    1. Azzi L., Carcano G., Gianfagna F., Grossi P., Gasperina D.D., Genoni A., Fasano M., Sessa F., Tettamanti L., Carinci F., et al. Saliva is a reliable tool to detect SARS-CoV-2. J. Infect. 2020 doi: 10.1016/j.jinf.2020.04.005.
    1. Xu J., Li Y., Gan F., Du Y., Yao Y. Salivary Glands: Potential Reservoirs for COVID-19 Asymptomatic Infection. J. Dent. Res. 2020 doi: 10.1177/0022034520918518.
    1. Han M., Seong M., Heo E., Park J., Kim N., Shin S., Cho S., Park S., Choi E. Sequential Analysis of Viral Load in a Neonate and Her Mother Infected With SARS-CoV-2-PubMed. Clin. Infect. Dis. 2020 doi: 10.1093/cid/ciaa447.
    1. Drosten C., Chiu L.L., Panning M., Leong H.N., Preiser W., Tam J.S., Günther S., Kramme S., Emmerich P., Ng W.L., et al. Evaluation of Advanced Reverse Transcription-PCR Assays and an Alternative PCR Target Region for Detection of Severe Acute Respiratory Syndrome-Associated Coronavirus. J. Clin. Microbiol. 2004;42:2043–2047. doi: 10.1128/JCM.42.5.2043-2047.2004.
    1. Liu L., Wei Q., Alvarez X., Wang H., Du Y., Zhu H., Jiang H., Zhou J., Lam P., Zhang L., et al. Epithelial Cells Lining Salivary Gland Ducts Are Early Target Cells of Severe Acute Respiratory Syndrome Coronavirus Infection in the Upper Respiratory Tracts of Rhesus Macaques. J. Virol. 2011;85:4025–4030. doi: 10.1128/JVI.02292-10.
    1. To K.K., Lu L., Yip C.C., Poon R.W., Fung A.M., Cheng A., Lui D.H., Ho D.T., Hung I.F., Chan K.H., et al. Additional molecular testing of saliva specimens improves the detection of respiratory viruses. Emerg. Microbes Infect. 2017;6:1–7. doi: 10.1038/emi.2017.35.
    1. Bjustrom-Kraft J., Woodard K., Giménez-Lirola L., Rotolo M., Wang C., Sun Y., Lasley P., Zhang J., Baum D., Gauger P., et al. Porcine epidemic diarrhea virus (PEDV) detection and antibody response in commercial growing pigs. BMC Vet. Res. 2016;12:99. doi: 10.1186/s12917-016-0725-5.
    1. Niederwerder M.C., Nietfeld J.C., Bai J., Peddireddi L., Breazeale B., Anderson J., Kerrigan M.A., An B., Oberst R.D., Crawford K., et al. Tissue localization, shedding, virus carriage, antibody response, and aerosol transmission of Porcine epidemic diarrhea virus following inoculation of 4-week-old feeder pigs. J. Vet. Diagn. Investig. 2016;28:671–678. doi: 10.1177/1040638716663251.
    1. Khurshid Z., Zafar M., Khan E., Mali M., Latif M. Human saliva can be a diagnostic tool for Zika virus detection. J. Infect. Public Health. 2019;12:601–604. doi: 10.1016/j.jiph.2019.05.004.
    1. Boppana S.B., Ross S.A., Shimamura M., Palmer A.L., Ahmed A., Michaels M.G., Sánchez P.J., Bernstein D.I., Tolan R.W., Novak Z., et al. Saliva polymerase-chain-reaction assay for cytomegalovirus screening in newborns. N. Engl. J. Med. 2011;364:2111–2118. doi: 10.1056/NEJMoa1006561.
    1. Parry J.V., Perry K.R., Mortimer P.P. Sensitive assays for viral antibodies in saliva: An alternative to tests on serum. Lancet. 1987;330:72–75. doi: 10.1016/S0140-6736(87)92737-1.
    1. McKie A., Vyse A., Maple C. Novel methods for the detection of microbial antibodies in oral fluid. Lancet Infect. Dis. 2002;2:18–24. doi: 10.1016/S1473-3099(01)00169-4.
    1. Hettegger P., Huber J., Paßecker K., Soldo R., Kegler U., Nöhammer C., Weinhäusel A. High similarity of IgG antibody profiles in blood and saliva opens opportunities for saliva based serology. PLoS ONE. 2019;14:e0218456. doi: 10.1371/journal.pone.0218456.
    1. Mortimer P.P., Parry J.V. Detection of antibody to HIV in saliva: A brief review. Clin. Diagn. Virol. 1994;2:231–243. doi: 10.1016/0928-0197(94)90048-5.
    1. González V., Martró E., Folch C., Esteve A., Matas L., Montoliu A., Grífols J.R., Bolao F., Tural C., Muga R., et al. Detection of hepatitis C virus antibodies in oral fluid specimens for prevalence studies. Eur. J. Clin. Microbiol. Infect. Dis. 2008;27:121–126. doi: 10.1007/s10096-007-0408-z.
    1. Flodgren G. Immunity after SARS-CoV-2 Infection. Rapid Review 2020. Norwegian Institute of Public Health; Oslo, Norway: 2020.
    1. Wan S., Xiang Y., Fang W., Zheng Y., Li B., Hu Y., Lang C., Huang D., Sun Q., Xiong Y., et al. Clinical features and treatment of COVID-19 patients in northeast Chongqing. J. Med. Virol. 2020 doi: 10.1002/jmv.25783.
    1. 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. Clinical characteristics and outcomes of 112 cardiovascular disease patients infected by 2019-nCoV. Zhonghua Xin Xue Guan Bing Za Zhi. 2020;48:E004.
    1. Cerón J.J., Martinez-Subiela S., Ohno K., Caldin M. A seven-point plan for acute phase protein interpretation in companion animals. Vet. J. 2008;177:6. doi: 10.1016/j.tvjl.2007.12.001.
    1. Wan S., Yi Q., Fan S., Lv J., Zhang X., Guo L., Lang C., Xiao Q., Xiao K., Yi Z., et al. Relationships among Lymphocyte Subsets, Cytokines, and the Pulmonary Inflammation Index in Coronavirus (COVID-19) Infected Patients. Br. J. Haematol. 2020;189:428–437. doi: 10.1111/bjh.16659.
    1. Parra M.D., Tecles F., Subiela S.M., Cerón J.J. C-Reactive Protein Measurement in Canine Saliva. J. Vet. Diagn. Investig. 2005;17:139–144. doi: 10.1177/104063870501700207.
    1. Tvarijonaviciute A., Zamora C., Martinez-Subiela S., Tecles F., Pina F., Lopez-Jornet P. Salivary adiponectin, but not adenosine deaminase, correlates with clinical signs in women with Sjögren’s syndrome: A pilot study. Clin. Oral Investig. 2019;23:1407–1414. doi: 10.1007/s00784-018-2570-3.
    1. Cerón J.J. Acute phase proteins, saliva and education in laboratory science: An update and some reflections. BMC Vet. Res. 2019;15:197. doi: 10.1186/s12917-019-1931-8.
    1. Franco-Martínez L., Rubio C.P., Contreras-Aguilar M.D. Methodology Assays for the Salivary Biomarkers’ Identification and Measurement. In: Tvarijonaviciute A., Martinez-Subiela S., Lopez-Jornet P., Lamy E., editors. Saliva in Health and Disease. Springer Nature; Cham, Switzerland: 2020. pp. 67–95.
    1. Katsani K.R., Sakellari D. Saliva proteomics updates in biomedicine. J. Biol. Res. 2019;26:17. doi: 10.1186/s40709-019-0109-7.
    1. Gautier J.-F., Ravussin Y. A New Symptom of COVID-19: Loss of Taste and Smell. Obesity. 2020;28:848. doi: 10.1002/oby.22809.
    1. Lamy E., Torregrossa A.-M., Castelo P.M., Capela e Silva F. Saliva in Ingestive Behavior Research: Association with Oral Sensory Perception and Food Intake. In: Tvarijonaviciute A., Martinez-Subiela S., Lopez-Jornet P., Lamy E., editors. Saliva in Health and Disease. Springer Nature; Cham, Switzerland: 2020. pp. 23–48.
    1. Barranco T., Rubio C.P., Tvarijonaviciute A., Rubio M., Damia E., Lamy E., Cugat R., Cerón J.J., Tecles F., Escribano D. Changes of salivary biomarkers under different storage conditions: Effects of temperature and length of storage. Biochem. Med. 2019;29:94–111. doi: 10.11613/BM.2019.010706.
    1. Cantos-Barreda A., Escribano D., Egui A., Thomas M.C., López M.C., Tecles F., Bernal L.J., Cerón J.J., Martínez-Subiela S. One-year follow-up of anti-Leishmania antibody concentrations in serum and saliva from experimentally infected dogs. Int. J. Parasitol. 2019;49:893–900. doi: 10.1016/j.ijpara.2019.06.002.

Source: PubMed

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