Detection of SARS-CoV-2 in saliva and characterization of oral symptoms in COVID-19 patients

Lili Chen, Jiajia Zhao, Jinfeng Peng, Xiaoshuang Li, Xuliang Deng, Zhi Geng, Zhenyu Shen, Fengyuan Guo, Qianwen Zhang, Yang Jin, Lin Wang, Songlin Wang, Lili Chen, Jiajia Zhao, Jinfeng Peng, Xiaoshuang Li, Xuliang Deng, Zhi Geng, Zhenyu Shen, Fengyuan Guo, Qianwen Zhang, Yang Jin, Lin Wang, Songlin Wang

Abstract

Objectives: In order to provide a more comprehensive understanding of the effects of SARS-CoV-2 on oral health and possible saliva transmission, we performed RNA-seq profiles analysis from public databases and also a questionnaire survey on oral-related symptoms of COVID-19 patients.

Materials and methods: To analyse ACE2 expression in salivary glands, bulk RNA-seq profiles from four public datasets including 31 COVID-19 patients were recruited. Saliva and oropharyngeal swabs were collected. SARS-CoV-2 nucleic acids in saliva were detected by real-time polymerase chain reaction (RT-PCR). Additionally, a questionnaire survey on various oral symptoms such as dry mouth and amblygeustia was also carried out on COVID-19 patients.

Results: ACE2 expression was present at detectable levels in the salivary glands. In addition, of four cases with positive detection of salivary SARS-CoV-2 nucleic acids, three (75%) were critically ill on ventilator support. Furthermore, we observed the two major oral-related symptoms, dry mouth (46.3%) and amblygeustia (47.2%), were manifested by a relatively high proportion of 108 COVID-19 patients who accepted the questionnaire survey.

Conclusions: This study confirms the expression of ACE2 in the salivary glands and demonstrates the possibility of SARS-CoV-2 infection of salivary glands. Saliva may be a new source of diagnostic specimens for critically ill patients, since it can be easily collected without any invasive procedures. In addition, dry mouth and amblygeustia can be considered as initial symptoms of COVID-19 infection.

Keywords: COVID-19 patients; SARS-CoV-2; amblygeustia; dry mouth; saliva.

Conflict of interest statement

We declare no competing interests.

© 2020 The Authors. Cell Proliferation Published by John Wiley & Sons Ltd.

Figures

FIGURE 1
FIGURE 1
The expression and distribution of ACE2 in normal human tissues. A, Data from GTEx Dataset showing mRNA expression of the ACE2 gene in salivary glands (pTPM: 1.8), with the highest expression level being found in the small intestine (pTPM: 55.2). (Image available from https://www.proteinatlas.org/ENSG00000130234‐ACE2/tissue/). B, Data from HPA Dataset showing mRNA expression of the ACE2 gene being detected in normal salivary gland tissue (average pTPM: 0.5), with the highest level of expression being observed in glandular cells (Image available from https://proteinatlas.org/ENSG00000130234‐ACE2/tissue/Salivary+gland#rnaseq/). C, Data from FANTOM5 Dataset showing mRNA expression of the ACE2 gene in salivary glands (scaled tags per million: 0.4), with the highest expression level being found in the small intestine (scaled tags per million: 420.9). (Image available from https://www.proteinatlas.org/ENSG00000130234‐ACE2/tissue/). D, Data from Consensus Dataset showing mRNA expression of the ACE2 gene by salivary glands (NX: 1.1), with the highest expression level being found in the small intestine (NX: 122.0). (Image available from https://www.proteinatlas.org/ENSG00000130234‐ACE2/tissue/)
FIGURE 2
FIGURE 2
Positive percentages of two oral‐related symptoms with the highest frequency of occurrence during the initial stage of infection. A, Among the oral‐related symptoms listed, amblygeustia positive rate is 47.2% in total, 36.5% in males and 57.1% in females. B, Among the oral‐related symptoms listed, dry mouth positive rate is 46.3% in total, 46.2% in males and 46.4% in females

References

    1. World Health Organization . Novel Coronavirus (2019‐nCoV): situation report, 22. Feb 27, 2020. . Accessed March 3, 2020.
    1. World Health Organization . WHO Coronavirus Disease (COVID‐19) Dashboard. 2020. . Accessed August 23, 2020.
    1. National Public Radio . Coronavirus: COVID‐19 Is Now Officially A Pandemic, WHO Says. 2020. . Accessed March 14, 2020.
    1. National Health Commission of the People's Republic of China . Diagnosis guidelines for the new coronavirus pneumonia (NCIP) of the seventh edition. 2020. . Accessed March 8, 2020.
    1. Marsh PD, Do T, Beighton D, Devine DA. Influence of saliva on the oral microbiota. Periodontol 2000. 2016;70:80‐92.
    1. Khurshid Z, Zafar MS, Khan RS, Najeeb S, Slowey PD, Rehman IU. Role of salivary biomarkers in oral cancer detection. Adv Clin Chem. 2018;86:23‐70.
    1. To K, Chan K, Ho J, et al. Respiratory virus infection among hospitalized adult patients with or without clinically apparent respiratory infection: a prospective cohort study. Clin Microbiol Infect. 2019;25(12):1539‐1545.
    1. Wang W, Chen S, Liu I, et al. Detection of SARS‐associated coronavirus in throat wash and saliva in early diagnosis. Emerg Infect Dis. 2004;10(7):1213‐1219.
    1. Lamy E, Capela‐Silva F, Tvarijonaviciute A. Research on saliva secretion and composition. Biomed Res Int. 2018;2018:7406312.
    1. Samaranayake L. Saliva as a diagnostic fluid. Int Dent J. 2007;57:295‐299.
    1. Zhou P, Yang X‐L, Wang X‐G, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579(7798):270‐273.
    1. Zhou X, Chen K, Zou J, Han P, Hao J, Han Z. The single‐cell RNA‐seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to Wuhan SARS‐CoV‐2 infection. Front Med. 2020;14(2):185‐192.
    1. Xu H, Zhong L, Deng J, et al. High expression of ACE2 receptor of SARS‐CoV‐2 on the epithelial cells of oral mucosa. Int J Oral Sci. 2020;12(1):8.
    1. World Health Organization . Global surveillance for COVID‐19 disease caused by human infection with novel coronavirus (COVID‐19): interim guidance, 27 February 2020. 2020. . Accessed March 3, 2020.
    1. National Institute for Viral Disease Control and Prevention . Specific primers and probes for detection 2019 novel coronavirus. 2020. . Accessed March 3, 2020.
    1. To K‐W, Tsang O‐Y, Yip C‐Y, et al. Consistent detection of 2019 novel coronavirus in saliva. Clin Infect Dis. 2020;71(15):841‐843.
    1. Wang D, Hu BO, Hu C, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus‐infected pneumonia in Wuhan, China. JAMA. 2020;323(11):1061‐1069.
    1. Pellegrino R, Cooper KW, Di Pizio A, Joseph PV, Bhutani S, Parma V. Coronaviruses and the chemical senses: past, present, and future. Chem Senses. 2020;45(6):415‐422.
    1. Qiu C, Cui C, Hautefort C, et al. Olfactory and gustatory dysfunction as an early identifier of COVID‐19 in adults and children: an International Multicenter Study. Preprint on medRxiv. 2020. 10.1101/2020.05.13.20100198
    1. Giacomelli A, Pezzati L, Conti F, et al. 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.
    1. Microsoft Service Network . COVID‐19 Leaves a Bad Taste, Literally, For Some Children Who Recovered from Virus. 2020. . Accessed August 13, 2020.
    1. Luo Y, Wu J, Lu J, et al. Investigation of COVID‐19‐related symptoms based on factor analysis. Ann Palliat Med. 2020;9(4):1851‐1858.
    1. Ren YF, Rasubala L, Malmstrom H, Eliav E. Dental care and oral health under the clouds of COVID‐19. JDR Clin Trans Res. 2020;5(3):202‐210.
    1. Guan W‐J, Ni Z‐Y, Hu YU, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382(18):1708‐1720.

Source: PubMed

3
Abonnere