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Abstract

Almost 2 years ago, the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was discovered to be the causative agent of the disease COVID-19. Subsequently, SARS-CoV-2 has spread across the world infecting millions of people, resulting in the ongoing COVID-19 pandemic. The current ‘gold standard’ for COVID-19 diagnosis involves obtaining a nasopharyngeal swab (NPS) from the patient and testing for the presence of SARS-CoV-2 RNA in the specimen using real-time reverse transcription PCR (RT-qPCR). However, obtaining a NPS specimen is an uncomfortable and invasive procedure for the patient and is limited in its applicability to mass testing. Interest in saliva as an alternative diagnostic specimen is of increasing global research interest due to its malleability to mass testing, greater patient acceptability and overall ease of specimen collection. However, the current literature surrounding the sensitivity of saliva compared to NPS is conflicting. The aim of this review was to analyse the recent literature to assess the viability of saliva in COVID-19 diagnosis. We hypothesize that the discrepancies in the current literature are likely due to the variations in the saliva collection and processing protocols used between studies. The universal adaptation of an optimised protocol could alleviate these discrepancies and see saliva specimens be as sensitive, if not more, than NPS for COVID-19 diagnosis. Whilst saliva specimens are more complimentary to mass-testing, with the possibility of samples being collected from home, the RT-qPCR diagnostic process remains to be the rate-limiting step and therefore interest in salivary rapid antigen tests, which negate the wait-times of RT-qPCR with results available within 15–30 min, may be an answer to this.

  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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2022-05-20
2024-04-24
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References

  1. Centers for Disease Control and Prevention Emerging SARS-CoV-2 Variants; 2021 https://www.cdc.gov/coronavirus/2019-ncov/more/science-and-research/scientific-brief-emerging-variants.html
  2. Our World in Data Coronavirus (COVID-19) Vaccinations; 2021 https://ourworldindata.org/covid-vaccinations
  3. World Health Organization Laboratory testing for 2019 novel coronavirus (2019-nCoV) in suspected human cases; 2021 https://www.who.int/publications/i/item/10665-331501
  4. Li L, Chen Q-Y, Li Y-Y, Wang Y-F, Yang Z-F et al. Comparison among nasopharyngeal swab, nasal wash, and oropharyngeal swab for respiratory virus detection in adults with acute pharyngitis. BMC Infect Dis 2013; 13:281 [View Article] [PubMed]
    [Google Scholar]
  5. Lieberman D, Lieberman D, Shimoni A, Keren-Naus A, Steinberg R et al. Identification of respiratory viruses in adults: nasopharyngeal versus oropharyngeal sampling. J Clin Microbiol 2009; 47:3439–3443 [View Article]
    [Google Scholar]
  6. World Health Organization Laboratory testing strategy recommendations for COVID-19: interim guidance, 21 March 2020. Geneva: World Health Organization; 2020 2020. Contract No.: WHO/2019-nCoV/lab_testing/; 2020 https://apps.who.int/iris/handle/10665/331509 accessed 16 December 2021
  7. Centers for Disease Control and Prevention Interim Infection Prevention and Control Recommendations for Healthcare Personnel During the Coronavirus Disease 2019 (COVID-19) Pandemic; 2021 https://www.cdc.gov/coronavirus/2019-ncov/hcp/infection-control-recommendations.html
  8. Kaplan EH, Forman HP. Logistics of Aggressive Community Screening for Coronavirus 2019. JAMA Health Forum 2020; 1:e200565 [View Article]
    [Google Scholar]
  9. Frazee BW, Rodríguez-Hoces de la Guardia A, Alter H, Chen CG, Fuentes EL et al. Accuracy and discomfort of different types of intranasal specimen collection methods for molecular influenza testing in emergency department patients. Ann Emerg Med 2018; 71:509–517 [View Article] [PubMed]
    [Google Scholar]
  10. Comber L, Walsh KA, Jordan K, O’Brien KK, Clyne B et al. Alternative clinical specimens for the detection of SARS-CoV-2: A rapid review. Rev Med Virol 2021; 31:e2185 [View Article] [PubMed]
    [Google Scholar]
  11. Sri Santosh T, Parmar R, Anand H, Srikanth K, Saritha M. A review of salivary diagnostics and its potential implication in detection of covid-19. Cureus 2020; 12:e7708 [View Article] [PubMed]
    [Google Scholar]
  12. Chan JF-W, Yuan S, Kok K-H, To KK-W, Chu H et al. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: A study of A family cluster. Lancet 2020; 395:514–523 [View Article] [PubMed]
    [Google Scholar]
  13. Gupta K, Bellino PM, Charness ME. Adverse effects of nasopharyngeal swabs: Three-dimensional printed versus commercial swabs. Infect Control Hosp Epidemiol 2021; 42:641–642 [View Article] [PubMed]
    [Google Scholar]
  14. Kim Y-G, Yun SG, Kim MY, Park K, Cho CH et al. Comparison between Saliva and Nasopharyngeal Swab Specimens for Detection of Respiratory Viruses by Multiplex Reverse Transcription-PCR. J Clin Microbiol 2017; 55:226–233 [View Article] [PubMed]
    [Google Scholar]
  15. To KK-W, Tsang OT-Y, Yip CC-Y, Chan K-H, Wu T-C et al. Consistent detection of 2019 novel coronavirus in saliva. Clin Infect Dis 2020; 71:841–843 [View Article] [PubMed]
    [Google Scholar]
  16. Ott IM, Strine MS, Watkins AE, Boot M, Kalinich CC et al. Stability of SARS-CoV-2 RNA in Nonsupplemented Saliva. Emerg Infect Dis 2021; 27:1146–1150 [View Article] [PubMed]
    [Google Scholar]
  17. World Health Organization Diagnostic testing for SARS-CoV-2; 2021 https://www.who.int/publications/i/item/diagnostic-testing-for-sars-cov-2
  18. The Goverment of the Hong Kong Special Administrative Region HA enhanced laboratory surveillance programme extends to outpatients with mild symptoms; 2021 https://www.info.gov.hk/gia/general/202002/18/P2020021800437.htm2020
  19. Wong SCY, Tse H, Siu HK, Kwong TS, Chu MY et al. Posterior Oropharyngeal Saliva for the Detection of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clin Infect Dis 2020; 71:2939–2946 [View Article] [PubMed]
    [Google Scholar]
  20. University of Illinois Shield Illinois Saliva Test; 2021 https://www.uillinois.edu/shield2020
  21. Minnesota Deparment of Health COVID-19 Test at Home; 2021 https://www.health.state.mn.us/diseases/coronavirus/testsites/athome.html
  22. U.S. Food and Drug Administration ACCELERATED EMERGENCY USE AUTHORIZATION (EUA) SUMMARY SARS-CoV-2 ASSAY (Rutgers Clinical Genomics Laboratory); 2021 https://www.fda.gov/media/136875/download
  23. Vogels CBF, Watkins AE, Harden CA, Brackney DE, Shafer J et al. SalivaDirect: A simplified and flexible platform to enhance SARS-CoV-2 testing capacity. Med (N Y) 2021; 2:263–280 [View Article] [PubMed]
    [Google Scholar]
  24. Czumbel LM, Kiss S, Farkas N, Mandel I, Hegyi A et al. Saliva as A Candidate for COVID-19 Diagnostic Testing: A Meta-Analysis. Front Med (Lausanne) 2020; 7:465 [View Article] [PubMed]
    [Google Scholar]
  25. Xu J, Li Y, Gan F, Du Y, Yao Y. Salivary Glands: Potential Reservoirs for COVID-19 Asymptomatic Infection. J Dent Res 2020; 99:989 [View Article] [PubMed]
    [Google Scholar]
  26. Xu H, Zhong L, Deng J, Peng J, Dan H et al. High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa. Int J Oral Sci 2020; 12: [View Article] [PubMed]
    [Google Scholar]
  27. Pascolo L, Zupin L, Melato M, Tricarico PM, Crovella S. TMPRSS2 and ACE2 Coexpression in SARS-CoV-2 Salivary Glands Infection. J Dent Res 2020; 99:1120–1121 [View Article] [PubMed]
    [Google Scholar]
  28. Song J, Li Y, Huang X, Chen Z, Li Y et al. Systematic analysis of ACE2 and TMPRSS2 expression in salivary glands reveals underlying transmission mechanism caused by SARS‐CoV‐2. J Med Virol 2020; 92:2556–2566 [View Article] [PubMed]
    [Google Scholar]
  29. Hamming I, Timens W, Bulthuis MLC, Lely AT, Navis GJ et al. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol 2004; 203:631–637 [View Article]
    [Google Scholar]
  30. Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T et al. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell 2020; 181:271–280 [View Article] [PubMed]
    [Google Scholar]
  31. Zang R, Gomez Castro MF, McCune BT, Zeng Q, Rothlauf PW et al. TMPRSS2 and TMPRSS4 promote SARS-CoV-2 infection of human small intestinal enterocytes. Sci Immunol 2020; 5:47 [View Article] [PubMed]
    [Google Scholar]
  32. Liu L, Wei Q, Alvarez X, Wang H, Du Y 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 [View Article] [PubMed]
    [Google Scholar]
  33. Huang N, Pérez P, Kato T, Mikami Y, Okuda K et al. SARS-CoV-2 infection of the oral cavity and saliva. Nat Med 2021; 27:892–903 [View Article] [PubMed]
    [Google Scholar]
  34. To KK-W, Tsang OT-Y, Leung W-S, Tam AR, Wu T-C 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 [View Article] [PubMed]
    [Google Scholar]
  35. Gupta S, Mohindra R, Chauhan PK, Singla V, Goyal K et al. SARS-CoV-2 detection in gingival crevicular fluid. J Dent Res 2021; 100:187–193 [View Article] [PubMed]
    [Google Scholar]
  36. Dawes C, Wong DTW. Role of saliva and salivary diagnostics in the advancement of oral health. J Dent Res 2019; 98:133–141 [View Article] [PubMed]
    [Google Scholar]
  37. Wyllie AL, Fournier J, Casanovas-Massana A, Campbell M, Tokuyama M et al. Saliva is more sensitive for SARS-CoV-2 detection in COVID-19 patients than nasopharyngeal swabs. N Engl J Med 2020; 383:1283–1286 [View Article]
    [Google Scholar]
  38. Rao M, Rashid FA, Sabri F, Jamil NN, Zain R et al. Comparing nasopharyngeal swab and early morning saliva for the identification of SARS-cov-2. Clin Infect Dis 2020; 72:e352–e356 [View Article]
    [Google Scholar]
  39. Leung E-M, Chow V-Y, Lee M-P, Lai R-M. Deep throat saliva as an alternative diagnostic specimen type for the detection of SARS-CoV-2. J Med Virol 2021; 93:533–536 [View Article] [PubMed]
    [Google Scholar]
  40. Yokota I, Shane PY, Okada K, Unoki Y, Yang Y et al. Mass screening of asymptomatic persons for SARS-CoV-2 using saliva. Clin Infect Dis 2020; 73:e559–e565 [View Article]
    [Google Scholar]
  41. Procop GW, Shrestha NK, Vogel S, Van Sickle K, Harrington S et al. A Direct Comparison of Enhanced Saliva to Nasopharyngeal Swab for the Detection of SARS-CoV-2 in Symptomatic Patients. J Clin Microbiol 2020; 58:e01946-20 [View Article] [PubMed]
    [Google Scholar]
  42. Teo AKJ, Choudhury Y, Tan IB, Cher CY, Chew SH et al. Saliva is more sensitive than nasopharyngeal or nasal swabs for diagnosis of asymptomatic and mild COVID-19 infection. Sci Rep 2021; 11:3134 [View Article] [PubMed]
    [Google Scholar]
  43. Tutuncu E, Ozgur D, Karamese M. Saliva Samples for Detection of SARS-CoV-2 in Mildly Symptomatic and Asymptomatic Patients. SSRN Journal 2020; 93:2932–2937 [View Article]
    [Google Scholar]
  44. Braz-Silva PH, Mamana AC, Romano CM, Felix AC, de Paula AV et al. Performance of at-home self-collected saliva and nasal-oropharyngeal swabs in the surveillance of COVID-19. J Oral Microbiol 2020; 13:1858002 [View Article] [PubMed]
    [Google Scholar]
  45. Kernéis S, Elie C, Fourgeaud J, Choupeaux L, Delarue SM et al. Accuracy of antigen and nucleic acid amplification testing on saliva and naopharyngeal samples for detection of SARS-cov-2 in ambulatory care. medRxiv 20212021
    [Google Scholar]
  46. De Santi C, Jacob B, Kroich P, Doyle S, Ward R et al. Concordance between PCR-based extraction-free saliva and nasopharyngeal swabs for SARS-CoV-2 testing. HRB Open Res 2021; 4:85 [View Article]
    [Google Scholar]
  47. LeGoff J, Kernéis S, Elie C, Mercier-Delarue S, Gastli N et al. Evaluation of a saliva molecular point of care for the detection of SARS-CoV-2 in ambulatory care. Sci Rep 2021; 11:21126 [View Article]
    [Google Scholar]
  48. Nacher M, Mergeay-Fabre M, Blanchet D, Benois O, Pozl T et al. Prospective comparison of saliva and nasopharyngeal swab sampling for mass screening for COVID-19. Epidemiology 2020; 2020:2020 [View Article]
    [Google Scholar]
  49. Caulley L, Corsten M, Eapen L, Whelan J, Angel JB et al. Salivary Detection of COVID-19. Ann Intern Med 2021; 174:131–133 [View Article]
    [Google Scholar]
  50. Migueres M, Mengelle C, Dimeglio C, Didier A, Alvarez M et al. Saliva sampling for diagnosing SARS-CoV-2 infections in symptomatic patients and asymptomatic carriers. J Clin Virol 2020; 130:104580 [View Article]
    [Google Scholar]
  51. Williams E, Bond K, Zhang B, Putland M, Williamson DA et al. Saliva as a Noninvasive Specimen for Detection of SARS-CoV-2. J Clin Microbiol 2020; 58:e00776–20 [View Article] [PubMed]
    [Google Scholar]
  52. Van Vinh Chau N, Lam VT, Dung NT, Yen LM, Minh NNQ et al. The Natural History and Transmission Potential of Asymptomatic Severe Acute Respiratory Syndrome Coronavirus 2 Infection. Clin Infect Dis 2020; 71:2679–2687 [View Article] [PubMed]
    [Google Scholar]
  53. Griesemer SB, Van Slyke G, Ehrbar D, Strle K, Yildirim T et al. Evaluation of Specimen Types and Saliva Stabilization Solutions for SARS-CoV-2 Testing. J Clin Microbiol 2021; 59:2020 [View Article] [PubMed]
    [Google Scholar]
  54. Jamal AJ, Mozafarihashjin M, Coomes E, Powis J, Liu AX et al. Sensitivity of nasopharyngeal swabs and saliva for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2. Infectious Diseases (except HIV/AIDS) 2020 [View Article]
    [Google Scholar]
  55. Chen JH-K, Yip CC-Y, Poon RW-S, Chan K-H, Cheng VC-C et al. Evaluating the use of posterior oropharyngeal saliva in a point-of-care assay for the detection of SARS-CoV-2. Emerg Microbes Infect 2020; 9:1356–1359 [View Article]
    [Google Scholar]
  56. Chen L, Zhao J, Peng J, Li X, Deng X et al. Detection of SARS‐CoV‐2 in saliva and characterization of oral symptoms in COVID‐19 patients. Cell Prolif 2020; 53:e12923 [View Article]
    [Google Scholar]
  57. Becker D, Sandoval E, Amin A, De Hoff P, Diets A et al. Saliva is less sensitive than nasopharyngeal swabs for COVID-19 detection in the community setting. medRxiv 2020; 2020:05.11.20092338 [View Article]
    [Google Scholar]
  58. Berenger BM, Conly JM, Fonseca K, Hu J, Louie T et al. Saliva collected in universal transport media is an effective, simple and high-volume amenable method to detect SARS-CoV-2. Clin Microbiol Infect 2021; 27:656–657 [View Article]
    [Google Scholar]
  59. Trobajo-Sanmartín C, Adelantado M, Navascués A, Guembe MJ, Rodrigo-Rincón I et al. Self-Collection of Saliva Specimens as a Suitable Alternative to Nasopharyngeal Swabs for the Diagnosis of SARS-CoV-2 by RT-qPCR. JCM 2021; 10:299 [View Article]
    [Google Scholar]
  60. Rodríguez Flores SN, Rodríguez-Martínez LM, Reyes-Berrones BL, Fernández-Santos NA, Sierra-Moncada EJ et al. Comparison between a standard and SalivaDirect RNA extraction protocol for molecular diagnosis of SARS-CoV-2 using nasopharyngeal swab and saliva clinical samples. Front Bioeng Biotechnol 2021; 9:638902 [View Article] [PubMed]
    [Google Scholar]
  61. Fan J, Yu F, Wang X, Zou Q, Lou B et al. Hock-A-loogie saliva as A diagnostic specimen for SARS-CoV-2 by A PCR-based assay: A diagnostic validity study. Clin Chim Acta 2020; 511:177–180 [View Article] [PubMed]
    [Google Scholar]
  62. Babady NE, McMillen T, Jani K, Viale A, Robilotti EV et al. Performance of Severe Acute Respiratory Syndrome Coronavirus 2 Real-Time RT-PCR Tests on Oral Rinses and Saliva Samples. J Mol Diagn 2021; 23:3–9 [View Article] [PubMed]
    [Google Scholar]
  63. McCormick-Baw C, Morgan K, Gaffney D, Cazares Y, Jaworski K et al. Saliva as an alternate specimen source for detection of SARS-CoV-2 in Symptomatic Patients Using Cepheid Xpert Xpress SARS-CoV-2. J Clin Microbiol 2020; 58:e01109-20 [View Article] [PubMed]
    [Google Scholar]
  64. Yee R, Truong TT, Pannaraj PS, Eubanks N, Gai E et al. Saliva Is a Promising Alternative Specimen for the Detection of SARS-CoV-2 in Children and Adults. J Clin Microbiol 2021; 59:e02686-20 [View Article] [PubMed]
    [Google Scholar]
  65. Pasomsub E, Watcharananan SP, Boonyawat K, Janchompoo P, Wongtabtim G et al. Saliva sample as a non-invasive specimen for the diagnosis of coronavirus disease 2019: a cross-sectional study. Clin Microbiol Infect 2019; 27:285
    [Google Scholar]
  66. Skolimowska K, Rayment M, Jones R, Madona P, Moore LSP et al. Non-invasive saliva specimens for the diagnosis of COVID-19: caution in mild outpatient cohorts with low prevalence. Clin Microbiol Infect 2020; 26:1711–1713 [View Article]
    [Google Scholar]
  67. Iwasaki S, Fujisawa S, Nakakubo S, Kamada K, Yamashita Y et al. Comparison of SARS-CoV-2 detection in nasopharyngeal swab and saliva. J Infect 2020; 81:e145–e147 [View Article]
    [Google Scholar]
  68. Azzi L, Carcano G, Gianfagna F, Grossi P, Gasperina DD et al. Saliva is a reliable tool to detect SARS-cov-2. J Infect 2020; 81:e45–e50
    [Google Scholar]
  69. Landry ML, Criscuolo J, Peaper DR. Challenges in use of saliva for detection of SARS CoV-2 RNA in symptomatic outpatients. J Clin Virol 2020; 130:104567 [View Article]
    [Google Scholar]
  70. Senok A, Alsuwaidi H, Atrah Y, Al Ayedi O, Al Zahid J et al. Saliva as an Alternative Specimen for Molecular COVID-19 Testing in Community Settings and Population-Based Screening. Infect Drug Resist 2020; 13:3393–3399 [View Article] [PubMed]
    [Google Scholar]
  71. Zhang W, Du R-H, Li B, Zheng X-S, Yang X-L et al. Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes. Emerg Microbes Infect 2020; 9:386–389 [View Article] [PubMed]
    [Google Scholar]
  72. Borghi E, Massa V, Carmagnola D, Dellavia C, Parodi C et al. Saliva sampling for chasing SARS-CoV-2: A Game-changing strategy. Pharmacol Res 2021; 165:105380 [View Article] [PubMed]
    [Google Scholar]
  73. Chen Q, Zheng Z, Zhang C, Zhang X, Wu H et al. Clinical characteristics of 145 patients with corona virus disease 2019 (COVID-19) in Taizhou, Zhejiang, China. Infection 2020; 48:543–551 [View Article] [PubMed]
    [Google Scholar]
  74. Fernandes LL, Pacheco VB, Borges L, Athwal HK, Paula Eduardo F et al. Saliva in the diagnosis of COVID-19 A review and new research directions. J Dent Res 2020; 99:1435–1443 [View Article]
    [Google Scholar]
  75. Hamilton JR, Stahl EC, Tsuchida CA, Lin-Shiao E, Tsui CK et al. Robotic RNA extraction for SARS-CoV-2 surveillance using saliva samples. medRxiv 20212021.01.10.21249151 [View Article]
    [Google Scholar]
  76. Chojnowska S, Baran T, Wilińska I, Sienicka P, Cabaj-Wiater I et al. Human saliva as a diagnostic material. Adv Med Sci 2018; 63:185–191
    [Google Scholar]
  77. Tajima Y, Suda Y, Yano K. A case report of SARS-cov-2 confirmed in saliva specimens up to 37 days after onset: proposal of saliva specimens for COVID-19 diagnosis and virus monitoring. J Infect Chemother 2020; 26:1086–1089 [View Article]
    [Google Scholar]
  78. Hung K-F, Sun Y-C, Chen B-H, Lo J-F, Cheng C-M et al. New COVID-19 saliva-based test: How good is it compared with the current nasopharyngeal or throat swab test?. J Chin Med Assoc 2020; 83:891–894 [View Article]
    [Google Scholar]
  79. Eduardo F de P, Corrêa L, Heller D, Daep CA, Benitez C et al. Salivary SARS-CoV-2 load reduction with mouthwash use: A randomized pilot clinical trial. Heliyon 2021; 7:e07346 [View Article]
    [Google Scholar]
  80. Seneviratne CJ, Balan P, Ko KKK, Udawatte NS, Lai D et al. Efficacy of commercial mouth-rinses on SARS-CoV-2 viral load in saliva: randomized control trial in Singapore. Infection 2021; 49:305–311 [View Article] [PubMed]
    [Google Scholar]
  81. Nagura-Ikeda M, Imai K, Tabata S, Miyoshi K, Murahara N et al. Clinical evaluation of self-collected saliva by quantitative reverse transcription-PCR (RT-qPCR), direct RT-qPCR, reverse transcription–loop-mediated isothermal amplification, and a rapid antigen test to diagnose COVID-19. J Clin Microbiol 2020; 58:e01438–20 [View Article] [PubMed]
    [Google Scholar]
  82. Kandel C, Zheng J, McCready J, Serbanescu MA, Racher H et al. Detection of SARS-cov-2 from saliva as compared to nasopharyngeal swabs in outpatients. Viruses 2020; 12:11 [View Article]
    [Google Scholar]
  83. Vaz SN, Santana D de, Netto EM, Pedroso C, Wang W-K et al. Saliva is a reliable, non-invasive specimen for SARS-CoV-2 detection. Braz J Infect Dis 2020; 24:422–427 [View Article] [PubMed]
    [Google Scholar]
  84. Byrne RL, Kay GA, Kontogianni K, Brown L, Collins AM et al. Saliva offers a sensitive, specific and non-invasive alternative to upper respiratory swabs for SARS-CoV-2 diagnosis. medRxiv 20202020.07.09.20149534 [View Article]
    [Google Scholar]
  85. Matic N, Stefanovic A, Leung V, Lawson T, Ritchie G et al. Practical challenges to the clinical implementation of saliva for SARS-CoV-2 detection. Eur J Clin Microbiol Infect Dis 2021; 40:447–450 [View Article]
    [Google Scholar]
  86. Barat B, Das S, De Giorgi V, Henderson DK, Kopka S et al. Pooled Saliva Specimens for SARS-CoV-2 Testing. J Clin Microbiol 2021; 59:e02486-20 [View Article]
    [Google Scholar]
  87. Ji X, Wang M, Li L, Chen F, Zhang Y et al. The Impact of Repeated Freeze-Thaw Cycles on the Quality of Biomolecules in Four Different Tissues. Biopreserv Biobank 2017; 15:475–483 [View Article]
    [Google Scholar]
  88. Centers for Disease Control and Prevention Interim Guidelines for Collecting and Handling of Clinical Specimens for COVID-19 Testing; 2021 https://www.cdc.gov/coronavirus/2019-ncov/lab/guidelines-clinical-specimens.html#shipping-specimens
  89. Higgins TS, Wu AW, Ting JY. SARS-CoV-2 Nasopharyngeal Swab Testing-False-Negative Results From a Pervasive Anatomical Misconception. JAMA Otolaryngol Head Neck Surg 2020; 146:993–994 [View Article]
    [Google Scholar]
  90. Wyllie AL, Fournier J, Casanovas-Massana A, Campbell M, Tokuyama M et al. Saliva or Nasopharyngeal Swab Specimens for Detection of SARS-CoV-2. N Engl J Med 2020; 383:1283–1286 [View Article]
    [Google Scholar]
  91. Savela ES, Winnett A, Romano AE, Porter MK, Shelby N et al. SARS-cov-2 is detectable using sensitive RNA saliva testing days before viral load reaches detection range of low-sensitivity nasal swab tests. medRxiv 20212021.04.02.21254771 [Preprint]
    [Google Scholar]
  92. Lippi G, Simundic A-M, Plebani M. Potential preanalytical and analytical vulnerabilities in the laboratory diagnosis of coronavirus disease 2019 (COVID-19). Clin Chem Lab Med 2020; 58:1070–1076 [View Article] [PubMed]
    [Google Scholar]
  93. Vandenberg O, Martiny D, Rochas O, van Belkum A, Kozlakidis Z. Considerations for diagnostic COVID-19 tests. Nat Rev Microbiol 2021; 19:171–183 [View Article] [PubMed]
    [Google Scholar]
  94. Wang W, Xu Y, Gao R, Lu R, Han K et al. Detection of SARS-CoV-2 in Different Types of Clinical Specimens. JAMA 2020; 323:1843–1844 [View Article]
    [Google Scholar]
  95. Kucirka LM, Lauer SA, Laeyendecker O, Boon D, Lessler J. Variation in False-Negative Rate of Reverse Transcriptase Polymerase Chain Reaction-Based SARS-CoV-2 Tests by Time Since Exposure. Ann Intern Med 2020; 173:262–267 [View Article]
    [Google Scholar]
  96. Mason RJ. Pathogenesis of COVID-19 from a cell biology perspective. Eur Respir J 2020; 55:2000607 [View Article]
    [Google Scholar]
  97. Zhu J, Guo J, Xu Y, Chen X. Viral dynamics of SARS-CoV-2 in saliva from infected patients. J Infect 2020; 81:e48–e50 [View Article]
    [Google Scholar]
  98. Bhattacharya D, Parai D, Rout UK, Nanda RR, Kanungo S et al. Saliva as a Potential Clinical Specimen for Diagnosis of SARS-CoV-2. SSRN Journal 2020 [View Article]
    [Google Scholar]
  99. Fernández-González M, Agulló V, de la Rica A, Infante A, Carvajal M et al. Performance of Saliva Specimens for the Molecular Detection of SARS-CoV-2 in the Community Setting: Does Sample Collection Method Matter?. J Clin Microbiol 2021; 59:e03033-20 [View Article] [PubMed]
    [Google Scholar]
  100. Pasomsub E, Watcharananan SP, Watthanachockchai T, Rakmanee K, Tassaneetrithep B et al. Saliva sample pooling for the detection of SARS-CoV-2. J Med Virol 2021; 93:1506–1511 [View Article] [PubMed]
    [Google Scholar]
  101. Watkins AE, Fenichel EP, Weinberger DM, Vogels CBF, Brackney DE et al. Pooling saliva to increase SARS-CoV-2 testing capacity. medRxiv 2020; 2020:2020 [View Article] [PubMed]
    [Google Scholar]
  102. Yamazaki W, Matsumura Y, Thongchankaew-Seo U, Yamazaki Y, Nagao M. Development of a point-of-care test to detect SARS-CoV-2 from saliva which combines a simple RNA extraction method with colorimetric reverse transcription loop-mediated isothermal amplification detection. J Clin Virol 2021; 136:104760 [View Article] [PubMed]
    [Google Scholar]
  103. Azzi L, Maurino V, Baj A, Dani M, d’Aiuto A et al. Diagnostic Salivary Tests for SARS-CoV-2. J Dent Res 2020; 100:115–123 [View Article] [PubMed]
    [Google Scholar]
  104. Lalli MA, Langmade SJ, Chen X, Fronick CC, Sawyer CS et al. Rapid and extraction-free detection of SARS-cov-2 from saliva by colorimetric reverse-transcription loop-mediated isothermal amplification. Clin Chem 2020; 67:415–424 [View Article]
    [Google Scholar]
  105. Janíková M, Hodosy J, Boor P, Klempa B, Celec P. Loop-mediated isothermal amplification for the detection of SARS-CoV-2 in saliva. Microb Biotechnol 2021; 14:307–316 [View Article]
    [Google Scholar]
  106. Taki K, Yokota I, Fukumoto T, Iwasaki S, Fujisawa S et al. SARS-CoV-2 detection by fluorescence loop-mediated isothermal amplification with and without RNA extraction. J Infect Chemother 2021; 27:410–412 [View Article]
    [Google Scholar]
  107. Food US, Administration D. Xpert® Xpress SARS-CoV-2; 2021 https://www.fda.gov/media/136314/download2020
  108. Vaz SN, Santana DS de, Netto EM, Wang W-K, Brites C. Validation of the GeneXpert Xpress SARS-CoV-2 PCR assay using saliva as biological specimen. Braz J Infect Dis 2021; 25:101543 [View Article]
    [Google Scholar]
  109. Azzi L, Baj A, Alberio T, Lualdi M, Veronesi G et al. Rapid Salivary Test suitable for A mass screening program to detect SARS-CoV-2: A diagnostic accuracy study. J Infect 2020; 81:e75–e78 [View Article] [PubMed]
    [Google Scholar]
  110. Kashiwagi K, Ishii Y, Aoki K, Yagi S, Maeda T et al. Immunochromatographic test for the detection of SARS-CoV-2 in saliva. J Infect Chemother 2021; 27:384–386 [View Article] [PubMed]
    [Google Scholar]
  111. Mak GC, Cheng PK, Lau SS, Wong KK, Lau CS et al. Evaluation of rapid antigen test for detection of SARS-CoV-2 virus. J Clin Virol 2020; 129:104500 [View Article] [PubMed]
    [Google Scholar]
  112. Agulló V, Fernández-González M, Tabla V, Gonzalo-Jiménez N, García JA et al. Evaluation of the rapid antigen test panbio COVID-19 in saliva and nasal swabs in a population-based point-of-care study. J Infect 202030768–4
    [Google Scholar]
  113. Uwamino Y, Nagata M, Aoki W, Nakagawa T, Inose R et al. Accuracy of rapid antigen detection test for nasopharyngeal swab specimens and saliva samples in comparison with RT-PCR and viral culture for SARS-CoV-2 detection. J Infect Chemother 2021; 27:1058–1062 [View Article] [PubMed]
    [Google Scholar]
  114. Corman VM, Haage VC, Bleicker T, Schmidt ML, Mühlemann B et al. Comparison of seven commercial SARS-CoV-2 rapid point-of-care antigen tests: a single-centre laboratory evaluation study. Lancet Microbe 2021; 2:e311–e319 [View Article] [PubMed]
    [Google Scholar]
  115. Pray IW, Ford L, Cole D, Lee C, Bigouette JP et al. Performance of an Antigen-Based Test for Asymptomatic and Symptomatic SARS-CoV-2 Testing at Two University Campuses - Wisconsin, September-October 2020. MMWR Morb Mortal Wkly Rep 2021; 69:1642–1647 [View Article] [PubMed]
    [Google Scholar]
  116. Larremore DB, Wilder B, Lester E, Shehata S, Burke JM et al. Test sensitivity is secondary to frequency and turnaround time for COVID-19 surveillance. medRxiv 20202020.06.22.20136309 [View Article] [PubMed]
    [Google Scholar]
  117. Peto T. UK COVID-19 Lateral Flow Oversight Team COVID-19: Rapid Antigen detection for SARS-CoV-2 by lateral flow assay: a national systematic evaluation for mass-testing. medRxiv 20212021.01.13.21249563 [View Article]
    [Google Scholar]
  118. Isho B, Abe KT, Zuo M, Jamal AJ, Rathod B et al. Persistence of serum and saliva antibody responses to SARS-CoV-2 spike antigens in COVID-19 patients. Sci Immunol 2020; 5:52 [View Article] [PubMed]
    [Google Scholar]
  119. Randad PR, Pisanic N, Kruczynski K, Manabe YC, Thomas D et al. Infectious Diseases (except HIV/AIDS) 2020 [View Article]
    [Google Scholar]
  120. Tan SH, Allicock O, Armstrong-Hough M, Wyllie AL. Saliva as a gold-standard sample for SARS-CoV-2 detection. Lancet Respir Med 2021; 9:562–564 [View Article]
    [Google Scholar]
  121. Hanson KE, Barker AP, Hillyard DR, Gilmore N, Barrett JW et al. Self-Collected Anterior Nasal and Saliva Specimens versus Health Care Worker-Collected Nasopharyngeal Swabs for the Molecular Detection of SARS-CoV-2. J Clin Microbiol 2020; 58:e01824-20 [View Article]
    [Google Scholar]
  122. Guest JL, Sullivan PS, Valentine-Graves M, Valencia R, Adam E et al. Suitability and Sufficiency of Telehealth Clinician-Observed, Participant-Collected Samples for SARS-CoV-2 Testing: The iCollect Cohort Pilot Study. JMIR Public Health Surveill 2020; 6:e19731 [View Article] [PubMed]
    [Google Scholar]
  123. Valentine-Graves M, Hall E, Guest JL, Adam E, Valencia R et al. At-home self-collection of saliva, oropharyngeal swabs and dried blood spots for SARS-CoV-2 diagnosis and serology: Post-collection acceptability of specimen collection process and patient confidence in specimens. PLoS ONE 2020; 15:e0236775 [View Article]
    [Google Scholar]
  124. Sullivan PS, Sailey C, Guest JL, Guarner J, Kelley C et al. Detection of SARS-CoV-2 RNA and Antibodies in Diverse Samples: Protocol to Validate the Sufficiency of Provider-Observed, Home-Collected Blood, Saliva, and Oropharyngeal Samples. JMIR Public Health Surveill 2020; 6:e19054 [View Article] [PubMed]
    [Google Scholar]
  125. Sagredo-Olivares K, Morales-Gómez C, Aitken-Saavedra J. Evaluation of saliva as a complementary technique to the diagnosis of COVID-19: a systematic review. Med Oral Patol Oral Cir Bucal 2021; 26:e526–e532 [View Article] [PubMed]
    [Google Scholar]
  126. Michailidou E, Poulopoulos A, Tzimagiorgis G. Salivary diagnostics of the novel corona virus SARS-cov-2 (COVID-19). Oral Dis 2022; 28:867–877
    [Google Scholar]
  127. World Health Organization Coronavirus disease 2019 (COVID-19) Situation Report - 46. WHO; 2021 https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200306-sitrep-46-covid-19.pdf?sfvrsn=96b04adf_2020
  128. Liu Y, Yan L-M, Wan L, Xiang T-X, Le A et al. Viral dynamics in mild and severe cases of COVID-19. Lancet Infect Dis 2020; 20:656–657 [View Article] [PubMed]
    [Google Scholar]
  129. Meng M, Zhou X, Zhang Q, Zou J. The positive rate of saliva for the detection of 2019-nCoV and possible factors related to the sensitivity results. J Med Virol 2021; 93:4136–4140 [View Article] [PubMed]
    [Google Scholar]
  130. Kojima N, Turner F, Slepnev V, Bacelar A, Deming L et al. Self-Collected Oral Fluid and Nasal Swabs Demonstrate Comparable Sensitivity to Clinician Collected Nasopharyngeal Swabs for Covid-19 Detection. medRxiv 2020 [View Article]
    [Google Scholar]
  131. Moreno-Contreras J, Espinoza MA, Sandoval-Jaime C, Cantú-Cuevas MA, Barón-Olivares H et al. Saliva Sampling and Its Direct Lysis, an Excellent Option To Increase the Number of SARS-CoV-2 Diagnostic Tests in Settings with Supply Shortages. J Clin Microbiol 2020; 58:e01659-20 [View Article] [PubMed]
    [Google Scholar]
  132. Goldfarb DM, Tilley P, Al-Rawahi GN, Srigley JA, Ford G et al. Self-Collected Saline Gargle Samples as an Alternative to Health Care Worker-Collected Nasopharyngeal Swabs for COVID-19 Diagnosis in Outpatients. J Clin Microbiol 2021; 59:e02427-20 [View Article] [PubMed]
    [Google Scholar]
  133. Echavarria M, Reyes NS, Rodriguez PE, Ypas M, Ricarte C et al. Self-collected saliva for SARS-CoV-2 detection: A prospective study in the emergency room. J Med Virol 2021; 93:3268–3272 [View Article] [PubMed]
    [Google Scholar]
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