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Saliva as a potential surrogate for detection of SARS-CoV-2 in the pediatric population and special care patients

The detection and monitoring of the novel coronavirus allowed profile drawing of the pathogen’s behavior, its progression around the world, and the possible emergence of Variants of Interest (VOI) (Callaway 2022CALLAWAY E. 2022. Are COVID surges becoming more predictable? New Omicron variants offer a hint. Nature 605: 204-206. doi:10.1038/d41586-022-01240-x.). Among the laboratory methods commonly used for the diagnosis of SARS-CoV-2 is the nasopharyngeal swab RT-PCR, considered the gold standard method (Pondaven-Letourmy et al. 2020PONDAVEN-LETOURMY S, ALVIN F, BOUMGHIT Y & SIMON F. 2020. How to perform a nasopharyngeal swab in adults and children in the COVID-19 era. Eur Ann Otorhinolaryngol Head Neck Dis 137(4): 325-327., Butler-Laporte et al. 2021BUTLER-LAPORTE G, LAWANDI A, SCHILLER I, YAO M, DENDUKURI N, MCDONALD EG & LEE TC. 2021. Comparison of Saliva and Nasopharyngeal Swab Nucleic Acid Amplification Testing for Detection of SARS-CoV-2: A Systematic Review and Meta-analysis. JAMA Internal Medicine 181(3): 353-360.). Despite its superiority over serological rapid tests, no test is entirely reliable and false-negative results are possible, especially concerning the Omicron variant (B.1.1.529) (Pondaven-Letourmy et al. 2020PONDAVEN-LETOURMY S, ALVIN F, BOUMGHIT Y & SIMON F. 2020. How to perform a nasopharyngeal swab in adults and children in the COVID-19 era. Eur Ann Otorhinolaryngol Head Neck Dis 137(4): 325-327., Lin et al. 2022LIN J ET AL. 2022. Where is Omicron? Comparison of SARS-CoV-2 RT-PCR and Antigen Test Sensitivity at Commonly Sampled Anatomic Sites Over the Course of Disease. MedRxiv: 2022.02.08.22270685. Preprint, submitted on February 9, 2022. doi: 10.1101/2022.02.08.22270685.). Some studies have postulated saliva collection as an alternative for virus presence analysis due to its high load on this biofluid and its expression in oral tissues (Butler-Laporte et al. 2021BUTLER-LAPORTE G, LAWANDI A, SCHILLER I, YAO M, DENDUKURI N, MCDONALD EG & LEE TC. 2021. Comparison of Saliva and Nasopharyngeal Swab Nucleic Acid Amplification Testing for Detection of SARS-CoV-2: A Systematic Review and Meta-analysis. JAMA Internal Medicine 181(3): 353-360.). Thus, this method can be useful for clinical application and with possible extension to underage children and special care patients.

Interestingly, the rate of concordance among nasopharyngeal swabs RT-PCR and saliva tests are similar, the latter showing sensitivity and specificity greater than 90% (Butler-Laporte et al. 2021BUTLER-LAPORTE G, LAWANDI A, SCHILLER I, YAO M, DENDUKURI N, MCDONALD EG & LEE TC. 2021. Comparison of Saliva and Nasopharyngeal Swab Nucleic Acid Amplification Testing for Detection of SARS-CoV-2: A Systematic Review and Meta-analysis. JAMA Internal Medicine 181(3): 353-360.). In a pioneer study, Xu et al. (2020)XU R, CUI B, DUAN X, ZHANG P, ZHOU X & YUAN Q. 2020. Saliva: potential diagnostic value and transmission of 2019-nCoV. Int J Oral Sci 12(1): 11. demonstrated that the viral load in the salivary fluid is approximately 90%, representing a potential vehicle for SARS-CoV-2 transmission. Other authors also mention the high expression of salivary IgA and IgG antibodies as a form of ensuring the validity of COVID-19 diagnosis (Costantini et al. 2021COSTANTINI VP ET AL. 2021. Development and validation of an enzyme immunoassay for detection and quantification of SARS-CoV-2 salivary IgA and IgG. medRxiv: 2021.09.03.21263078. Preprint, submitted on September 7, 2021. doi: 10.1101/2021.09.03.21263078.).

Furthermore, saliva collection is a non-invasive technique with no special training required (Butler-Laporte et al. 2021BUTLER-LAPORTE G, LAWANDI A, SCHILLER I, YAO M, DENDUKURI N, MCDONALD EG & LEE TC. 2021. Comparison of Saliva and Nasopharyngeal Swab Nucleic Acid Amplification Testing for Detection of SARS-CoV-2: A Systematic Review and Meta-analysis. JAMA Internal Medicine 181(3): 353-360.). Alongside, nasopharyngeal swab RT-PCR may be an unpleasant experience in more sensitive patients, possibly discouraging them from undergoing the test (Pondaven-Letourmy et al. 2020PONDAVEN-LETOURMY S, ALVIN F, BOUMGHIT Y & SIMON F. 2020. How to perform a nasopharyngeal swab in adults and children in the COVID-19 era. Eur Ann Otorhinolaryngol Head Neck Dis 137(4): 325-327.). Furthermore, newborns, children with uncooperative behavior, as well as patients with special needs could be a target public to RT-PCR saliva, ensuring them a pleasant and trauma-free experience.

This non-invasive approach may contribute to adequate tracking of COVID-19 cases among children and, consequently, provide the basis for convincing parents to adhere to vaccination campaigns in this public (Butler-Laporte et al. 2021BUTLER-LAPORTE G, LAWANDI A, SCHILLER I, YAO M, DENDUKURI N, MCDONALD EG & LEE TC. 2021. Comparison of Saliva and Nasopharyngeal Swab Nucleic Acid Amplification Testing for Detection of SARS-CoV-2: A Systematic Review and Meta-analysis. JAMA Internal Medicine 181(3): 353-360., Pettoello-Mantovani et al. 2022PETTOELLO-MANTOVANI M, CARDEMIL C, COHEN R, LEVY C, GIARDINO I, INDRIO F & SOMEKH E. 2022. Importance of Coronavirus Disease 2019 Vaccination in Children: Viewpoint and Recommendations of the Union of European National Societies of Pediatrics. J Pediatr 243: 242-245.). Despite the relatively low risk of manifesting severe forms of the disease (Gaebler et al. 2021GAEBLER C ET AL. 2021. Evolution of antibody immunity to SARS-CoV-2. Nature 591(7851): 639-644.), the potential risk of infection and sequels should not be ignored with the loosening of pandemic control measures, and the possibility of development of new variants remains a reality (Callaway 2022CALLAWAY E. 2022. Are COVID surges becoming more predictable? New Omicron variants offer a hint. Nature 605: 204-206. doi:10.1038/d41586-022-01240-x.).

It is important to observe that some children and special care patients still exhibit comorbidities or syndromic diseases (Byrd et al. 2015BYRD G, QUINONEZ RB, OFFENBACHER S, KEELS MA & GUTHMILLER JM. 2015. Coordinated Pediatric and Periodontal Dental Care of a Child with Down syndrome. Pediatr Dent 37(4): 381-385.). For instance, in individuals with hematologic disorders, including children and other patients, nasopharyngeal swab RT-PCR often causes bleeding. To prevent this situation, the salivary test has served as an accurate and reliable diagnostic tool to detect false negative SARS-CoV-2 tests (Lopes et al. 2021LOPES J, DA COSTA SILVA CA, CUNHA RG, SOARES AM, LOPES M, DA CONCEIÇÃO NETO OC, ALVES A, DA COSTA NUNES PIMENTEL COELHO WL, AMORIM FILHO L & AMADO LEON LA. 2021. A Large Cohort Study of SARS-CoV-2 Detection in Saliva: A Non-Invasive Alternative Diagnostic Test for Patients with Bleeding Disorders. Viruses 13(12): 2361.). Therefore, these groups require priority health care and periodic monitoring, especially with the decline of antibodies against SARS-CoV-2 observed over time (Gaebler et al. 2021GAEBLER C ET AL. 2021. Evolution of antibody immunity to SARS-CoV-2. Nature 591(7851): 639-644.). A wide variety of oral manifestations has been reported in children, including cheilitis, dry mouth, and tongue swelling. In more serious cases, COVID-19-related Multisystem Inflammatory Syndrome can also be diagnosed (Halepas et al. 2021HALEPAS S, LEE KC, MYERS A, YOON RK, CHUNG W & PETERS SM. 2021. Oral manifestations of COVID-2019-related multisystem inflammatory syndrome in children: a review of 47 pediatric patients. J Am Dent Assoc 152(3): 202-208.). Collectively, these findings may play an important role in the diagnosis and management of the disease.

Finally, salivary RT-PCR has the potential to consolidate itself as a key test for the diagnosis of COVID-19, and assist in monitoring the circulation of the virus in vulnerable groups, particularly at the current stage of the pandemic, with the lifting of control measures and “social living” in the “new normal”.

REFERENCES

  • BUTLER-LAPORTE G, LAWANDI A, SCHILLER I, YAO M, DENDUKURI N, MCDONALD EG & LEE TC. 2021. Comparison of Saliva and Nasopharyngeal Swab Nucleic Acid Amplification Testing for Detection of SARS-CoV-2: A Systematic Review and Meta-analysis. JAMA Internal Medicine 181(3): 353-360.
  • BYRD G, QUINONEZ RB, OFFENBACHER S, KEELS MA & GUTHMILLER JM. 2015. Coordinated Pediatric and Periodontal Dental Care of a Child with Down syndrome. Pediatr Dent 37(4): 381-385.
  • CALLAWAY E. 2022. Are COVID surges becoming more predictable? New Omicron variants offer a hint. Nature 605: 204-206. doi:10.1038/d41586-022-01240-x.
  • COSTANTINI VP ET AL. 2021. Development and validation of an enzyme immunoassay for detection and quantification of SARS-CoV-2 salivary IgA and IgG. medRxiv: 2021.09.03.21263078. Preprint, submitted on September 7, 2021. doi: 10.1101/2021.09.03.21263078.
  • GAEBLER C ET AL. 2021. Evolution of antibody immunity to SARS-CoV-2. Nature 591(7851): 639-644.
  • HALEPAS S, LEE KC, MYERS A, YOON RK, CHUNG W & PETERS SM. 2021. Oral manifestations of COVID-2019-related multisystem inflammatory syndrome in children: a review of 47 pediatric patients. J Am Dent Assoc 152(3): 202-208.
  • LIN J ET AL. 2022. Where is Omicron? Comparison of SARS-CoV-2 RT-PCR and Antigen Test Sensitivity at Commonly Sampled Anatomic Sites Over the Course of Disease. MedRxiv: 2022.02.08.22270685. Preprint, submitted on February 9, 2022. doi: 10.1101/2022.02.08.22270685.
  • LOPES J, DA COSTA SILVA CA, CUNHA RG, SOARES AM, LOPES M, DA CONCEIÇÃO NETO OC, ALVES A, DA COSTA NUNES PIMENTEL COELHO WL, AMORIM FILHO L & AMADO LEON LA. 2021. A Large Cohort Study of SARS-CoV-2 Detection in Saliva: A Non-Invasive Alternative Diagnostic Test for Patients with Bleeding Disorders. Viruses 13(12): 2361.
  • PETTOELLO-MANTOVANI M, CARDEMIL C, COHEN R, LEVY C, GIARDINO I, INDRIO F & SOMEKH E. 2022. Importance of Coronavirus Disease 2019 Vaccination in Children: Viewpoint and Recommendations of the Union of European National Societies of Pediatrics. J Pediatr 243: 242-245.
  • PONDAVEN-LETOURMY S, ALVIN F, BOUMGHIT Y & SIMON F. 2020. How to perform a nasopharyngeal swab in adults and children in the COVID-19 era. Eur Ann Otorhinolaryngol Head Neck Dis 137(4): 325-327.
  • XU R, CUI B, DUAN X, ZHANG P, ZHOU X & YUAN Q. 2020. Saliva: potential diagnostic value and transmission of 2019-nCoV. Int J Oral Sci 12(1): 11.

Publication Dates

  • Publication in this collection
    02 Dec 2022
  • Date of issue
    2022

History

  • Received
    17 May 2022
  • Accepted
    23 Sept 2022
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