key: cord-0717780-8fws8wjh
authors: Sahajpal, Nikhil Shri; Mondal, Ashis K; Njau, Allan; Ananth, Sudha; Ghamande, Salil; Hegde, Madhuri; Chaubey, Alka; M Rojiani, Amyn; Kolhe, Ravindra
title: COVID-19 screening in a healthcare or community setting: complexity of saliva as a specimen for PCR-based testing
date: 2020-11-24
journal: Future medicinal chemistry
DOI: 10.4155/fmc-2020-0255
sha: 7e240872ba4e774a19cd30344d5de60ede567267
doc_id: 717780
cord_uid: 8fws8wjh

nan

of saliva for COVID-19 testing [13] . Although these reports seem to be discrepant at the outset, a thorough analysis highlights that the results are more consistent within a particular sample collection setting. There seems to be an emerging trend that saliva, as a sample type, is a viable option in a healthcare setting where collection is aided by a healthcare professional performed in a controlled environment but not in the community setting, although further studies are needed to verify these early trends. Additionally, further analysis is also needed for analyzing the efficacy of using saliva in the asymptomatic population.

The initial studies evaluating saliva as a sample type for COVID-19 diagnosis were conducted on severely or moderately ill patients admitted in healthcare facilities. The initial report by To et al. demonstrated the sensitivity of stimulated saliva to be 91.7% compared with NPS samples [14] . Although the study was conducted on only 12 patients, the authors highlighted three critical findings: SARS-CoV-2 was detected in self-collected saliva samples, longitudinal sampling showed a declining trend and viral cultures confirmed live virus in the saliva samples. In a follow-up detailed clinical report of 23 patients performed by To et al., early-morning stimulated saliva demonstrated a sensitivity of 86.9% compared with NPS samples [15] . Similarly, Azzi et al. performed a study on 25 severely ill patients and demonstrated a 100% sensitivity of saliva (collected with drooling technique) compared with NPS samples [16] , and Yoon et al. demonstrated a 100% concordance of saliva with NPS samples with high viral titer values in saliva [17] . Although these studies highlight that saliva could be a viable sample type for COVID-19 diagnosis, they are limited by the study design in which NPS samples were considered the gold standard and only included the patients who tested positive with NPS samples. Thus, only a one-sided statistical analysis could be performed, comparing saliva with NPS samples. However, an independent study conducted by Wyllie et al. included 38 patients with matched NPS and unstimulated early morning saliva samples that were both positive and negative with NPS samples [18] . In their analysis, the SARS-CoV-2 titers in saliva were significantly higher than NPS samples. Moreover, SARS-CoV-2 was detected in saliva in 21% of samples (negative in matched NPS), whereas only 8% resulted positive with NPS (negative in matched saliva samples). Similarly, Chow et al. demonstrated comparable sensitivities among NPS (96.88% and 98.96%), sputum/deep throat saliva samples (94.03% and 97.02%) and throat swab samples (93.33% and 98.33%) by a one-step high-sensitivity (42 copies/ml) colorimetric reversetranscriptional loop-mediated isothermal amplification assay [19] . Hence, these studies demonstrate comparable or increased sensitivity of saliva compared with NPS samples in the healthcare setting. Fukumoto et al. demonstrated comparable sensitivity of self-collected unstimulated saliva and NPS but lower sensitivity of sputum in a SARS-CoV-2 detection assay without RNA extraction [20] . Conversely, Lai et al. demonstrated lowest sensitivity of deep throat saliva (68.7%) compared with sputum (89.4%) and pooled NP and throat swabs (80.9%), suggesting sputum to be more sensitive than deep throat saliva samples [21] .

To the best of our knowledge, as of this date, only one study has evaluated the clinical performance of saliva samples for COVID-19 testing in the community setting. Becker et al. demonstrated a reduced sensitivity of saliva compared with NPS samples in the community setting [13] . The percentage of samples that were positive in NPS (negative in matched saliva) varied from 13 to 20.8%, whereas only 4% were positive in the saliva sample (negative in matched NPS) employing three RT-PCR methods. Further, in a cohort of 88 patients, the one-sided test demonstrated a 30% reduced sensitivity of saliva compared with NPS samples [13] . In addition, Guest et al. demonstrated that the quality of self-collected saliva samples is comparable to that of OPS samples by evaluating the housekeeping gene in these samples collected in the community setting.

Saliva is a potentially useful sample type for COVID-19 testing, and initial reports have elicited global interest given the impact that a simple collection method could have in this pandemic. The initial trends highlight that saliva is definitely a viable sample type in the healthcare setting, but the same conclusion cannot be drawn for samples collected in a community setting. This observation may point us to approaches that could reduce the variability and errors seen when using saliva -namely, standardized precollection and collection procedures and clear instructions for oral preparation to patients, prior to collection. Use of standard NPS handling protocol is currently widespread; however, the same is not true of saliva. Review and optimization of previously published protocols on saliva collection and handling, while accommodating various clinical scenarios, lifestyles and population dynamics,

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Epub ahead of print) future science group