Table A.1.
Studies that directly compared saliva use in SARS-CoV-2 detection with respiratory samples and that demonstrated good saliva results. Natal/RN, 2020.
| Authors | Study design | Study population | Sample size [Gender] | Age range [Mean] (Years) | Test | Saliva type | Saliva collection method | Respiratory sample | Results |
|---|---|---|---|---|---|---|---|---|---|
| Wyllie et al., 20206 | Cohort study | Patients who tested positive for SARS-CoV-2. Asymptomatic health professionals. |
44 [23 M, 21 F] 98 [16 M, 82 F] |
23-92 [61] 22-67 [36] |
RT-PCR | Saliva | Self-collection by spit. | OPS or NPS | 37 samples (84%) of saliva tested positive for SARS-CoV-2. SARS-CoV-2 detection in the saliva from two health professionals who tested negative by nasopharyngeal swab. |
| To et al., 20207 | Cohort study | Patients hospitalized with COVID-19 confirmed in the laboratory. | 12 [7 M, 5 F] | 37-75[62,5] | RT-PCR and viral culture | POS | Saliva with cough. | NPS | 2019-nCoV was detected in the initial saliva samples from 11 patients (91.7%). Live viruses were found in the saliva from 3 patients. |
| Azzi et al., 202012 | Cohort study | Patients with severe or very severe COVID-19. | 25 [17 M, 8 F] | 39-85 [61,5] | RT-qPCR | Saliva | Drooling technique. | NPS | All 25 initial samples showed positive results for the SARS-CoV-2 presence. |
| To et al., 202013 | Cohort study | Patients hospitalized with COVID-19 confirmed in the laboratory. | 23 [13 M, 10 F] | 37-75 [62] | RT-qPCR and EIA | POS | Saliva with cough. | NPS | 20 cases (87%) in which 2019 RNA-nCoV was detectable in saliva. |
| Iwasaki et al., 202014 | Cohort study | Patients suspicious of COVID-19 and patients with the diagnosis of COVID-19. | 76 [-] | 30-97∗[69] | RT-qPCR | Saliva | Self-collection by spit. | NPS | SARS-CoV-2 was detected in 8 (among 10 patients) with COVID-19 in nasopharyngeal and saliva samples. The overall agreement rate for virus detection was 97.4%. |
| Yokota et al., 202015 | Cohort study | Asymptomatic persons who have close contact with clinically confirmed COVID-19 patients. Asymptomatic travellers arriving at Tokyo and Kansai international airports |
161 [44 M, 26 F, 91U] 1763 [927 M, 832 F, 4U] |
29.8–66.4 [44.9] 22.6–47.4 [33.5] |
qRT-PCR and RT-LAMP | Saliva | Self-collection. | NPS | The nasopharynx and saliva samples obtained high sensitivity, with 86% and 92%, respectively, and specificity (greater than 99%) to the nucleic acid amplification test. |
| Wyllie et al., 202016 | Cohort study | COVID-19 inpatients at Yale-New Haven Hospital. | 70 [41 M, 29 F] | 13-91[61,4] | RT-PCR | Saliva | Self-collection by spit. | NPS | From 1 to 5 days after diagnosis, saliva samples (81%) were positive, while nasopharyngeal smear samples (71%) were positive, suggesting that both samples have at least similar sensitivity in the initial detection of SARS-CoV-2. |
| Han et al., 202017 | Cohort study | Mildly symptomatic and asymptomatic children with coronavirus disease. | 12 [5 M, 7 F] | 27 (days)-16 [5,6] | – | – | – | NPS | Saliva was collected from 11 children, with 8 tested positive for SARS-CoV-2. Positivity in saliva samples decreased from 80% at week 1–33% at week 2 and 11% at week 3. |
| Mao et al., 202018 | Cohort study | Patients with asymptomatic disease Patients with mild disease Patients with moderate disease |
6 [4 M, 2 F] 6 [6 M, 0 F] 22 [10 M, 12 F] |
28–48 [37] 21-57 [7,38] 21-64 [4,44] |
RT-qPCR | – | – | OPS and sputum | Saliva sample sensitivity, efficiency and specificity were only 74.10%, 83.90% and 94.40%, respectively, whereas for saliva-expectoration they were 93.40%, 94.00% and 95.20%, respectively, being a more effective diagnostic method. |
| Kojima et al., 202019 | Cross-sectional study | Symptomatic individuals not hospitalized recently tested for SARS-CoV-2 infection. | 45 [-] | 31-52 [42] | RT-qPCR | Saliva | Self-collected oral swab with and without doctor's supervision. | NPS and nasal swab | Oral swab samples self-collected and supervised by the physician detected 26 (90%) of the 29 infected individuals. Non-monitored self-collected oral fluid swab samples detected 19 (66%). |
| Pasomsub et al., 202020 | Cross-sectional study | Patients who experience fever or acute respiratory symptoms, along with a 14-day travel history from a COVID-19 endemic area or contact with an individual who has been confirmed or COVID-19 suspected. | 200 [69 M, 131 F] | 28-48 [36] | RT-PCR | Saliva | Saliva without cough. | NPS and throat swab | The COVID-19 prevalence diagnosed by saliva RT-PCR was 9.0%, showing high sensitivity and performance 84.2% and 98.9%, respectively. |
| Chen et al., 202021 | Cross-sectional study | Positive patients for COVID-19. | 58 [28 M, 30 F] | 31-52 [38] | RT-PCR POCT | POS | Saliva with cough. | NPS | Some patients (84.5%) had a positive result in both the nasopharyngeal swab and saliva, 10.3% had a positive result only in the nasopharyngeal swab and 5.2% had a positive result only in saliva. |
| McCormick-Baw et al., 202022 | Cross-sectional study | Patients with suspected COVID-19 and hospitalized patients positive for COVID-19 without the need for mechanical ventilation. | 156 [90 M, 66 F] | [8,47] | POCT | Saliva | Saliva without cough. | NPS | 49 positive tests by nasopharyngeal swab (47 also had positive saliva samples). A single sample demonstrated detectable SARS CoV-2 nucleic acid levels in saliva, but the nasopharyngeal swab was negative. |
| Leung et al., 202023 | Cross-sectional study | Patients admitted to the Prince of Wales Hospital in Hong Kong. | 62 [26 M, 36 F] | 19-85 [42] | RT-PCR | POS | Saliva with cough. | NPS | 95 sample pairs, 75 were positive for both nasopharyngeal and saliva samples; 13 positive saliva samples had corresponding negative nasopharyngeal samples and 7 positive nasopharyngeal samples had negative saliva samples. |
| Cheuk et al., 202024 | Cross-sectional study | Tested Patients for COVID-19. | 95 [38 M, 57 F] | 4-92 [39] | RT-PCR | Saliva | Self-collection by spit. | NPS | Saliva and nasopharyngeal samples positivity was 61.6% and 53.3%, respectively. Among the 6 discordant results, 4 presented positive saliva samples and negative nasopharyngeal samples. |
| Güçlü et al., 202025 | Cross-sectional study | Hospitalized patients with and without laboratory-confirmed Covid-19, with a finding consistent with COVID-19 in the Lung Computed Tomography (CT), and patients with complaints compatible with COVID-19 but normal CT. | 64 [37 M, 27 F] | -[51,04] | RT-PCR | Saliva | Self-collection. | OP/NP swab | Among 64 patients, 23 (35.9%) obtained positive saliva and OP-NP swab samples, 4 (6.25%) had only positive saliva sample and 4 (6.25%) only the OP/N swab. NP was positive. In general, saliva sensitivity and specificity was 85.19% and 89.19%, respectively. |
| Vaz et al., 202026 | Cross-sectional study | Health professionals with signs/symptoms suggestive of COVID-19, and infirmary patients with confirmed infection. | 155 [46 M, 109 F] | 33-48,5 [40] | RT-PCR | Saliva | Saliva without cough. | NPS or OPS | RT-PCR sensitivity and specificity for saliva were 94.4% and 97.62%, respectively. In addition, there was a high general agreement (96.1%) comparing the salivary sample with the gold standard test. |
| Rao et al., 202027 | Cross-sectional study | Asymptomatic adult male participants in a COVID-19 quarantine center. | 160 [160 M] | 18-36 [27] | RT-PCR | POS | Saliva with cough. | NPS | A higher detection rate for SARS-CoV-2 was found in saliva compared to NPS, being 93.1% and 52.5%, respectively. E and RdRp genes Ct values from the 73 concordant samples were significantly lower in saliva than in NPS (p < 0.05). |
| Byrne et al., 202028 | Cross-sectional study | Patients with COVID-19 symptoms. | 110 [49 M, 61 F] | – | RT-qPCR | Saliva | Self-collection. | Nasal and throat swab | Among 110 paired samples, 12 saliva samples tested positive for SARS-CoV-2, while 14 nasal and throat swab samples tested positive. The general viral loads were similar among all positive samples, ranging from 36 to 3.3 × 10 6 copies/mL. |
| Hanson et al., 202029 | Cross-sectional study | Adult patients with symptoms suggestive of COVID-19. | 354 [195 M, 173 F] | 18-75 [35] | RT-PCR | Saliva | Self-collection by spit. | NPS and anterior nasal swab | NPS and saliva samples had the highest positivity rates (22.5% and 22.9%) compared to the ANS (19.7%). The average Ct values for positive samples only for NPS was 27.0, and 28.2 for positive samples only for saliva. |
| Aita et al., 202030 | Cross-sectional study | Inpatients with COVID-19. | 49 [33 M, 16 F] | 28-86 [64] (M) 25-94 [60] (F) |
rRT-PCR | Saliva | Swab with absorbed saliva. | NPS | Among 43 patients with NPS and saliva samples paired, 7 cases tested positive in both samples and 35 tested negative for both NPS and saliva. One patient tested positive for saliva (Ct = 26), but not for NPS. |
| Uwamino et al., 202031 | Cross-sectional study | Hospitalized patients with COVID-19. Symptomatic university staff. |
32 [-] 115 [-] |
– | RT-PCR | Saliva | Saliva without cough. | NPS | From 196 samples collected, 32 tested positive for SARS-CoV-2 by both NPS and saliva, 15 by NPS but negative by saliva, and 11 samples that tested positive for saliva had NPS negative. The results obtained in the first 10 days of symptom onset were 96.4%. It was possible to detect viable viruses in two saliva samples. |
| Migueres et al., 202032 | Cross-sectional study | Hospitalized and ambulatory patients. | 123 [49 M, 74 F] | - [43] | RT-PCR | Saliva | Self-collection by spit. | NPS | Thirty-four patients tested positive in both samples, three only for saliva and 7 only for NPS. Saliva samples sensitivity was high for asymptomatic and symptomatic patients tested early, with 88.2% and 94.7% respectively, and lowest (50%) for symptomatic patients tested late after symptoms onset. |
| Senok et al., 202033 | Cross-sectional study | Adult patients undergoing COVID-19 testing. | 401 [329 M, 72 F] | [5,35] | RT-PCR | Saliva | Saliva without cough. | NPS | Saliva sensitivity and specificity were 73.1% and 97.6%, respectively. The general SARS-CoV-2 detection prevalence by NPS was 6.5%, while, by saliva, it was 7%. |
| Altawalah et al., 202034 | Cross-sectional study | COVID-19 suspected patients. | 891 [-] | – | RT-PCR | POS | Saliva with cough. | NPS | The general agreement between the NPS and saliva samples was 91.25%. Saliva sensitivity and diagnostic specificity were 83.43% and 96.71%, respectively, and the detection rate was 83.43%. The median Ct values did not differ significantly between NPS and saliva. |
POS: Posterior Oropharyngeal Saliva; NPS: Nasopharyngeal swab; OPS: Oropharyngeal swab; RT-PCR: Reverse Transcription Polymerase Chain Reaction; rRT-PCR: Real-time Reverse Transcription Polymerase Chain Reaction; RT-qPCR: Quantitative Reverse Transcription Polymerase Chain Reaction; EIA: Enzyme Immunoassays; RT-LAMP: Reverse-Transcription Loop Mediated Isothermal Amplification; U: unknown; POCT: Point-of-care testing.
∗
Age group (10 patients with COVID-19).