Thread by @andreaprinzi

Ok, sort of weird to say...but today I'm dedicating some time to SPIT (formally known as #Saliva). It's the super hot topic this week in the ever-changing #COVID19 diagnostic landscape we are living in, so let's take a quick peek at some of the evidence out there (thread)

I completely understand the importance of testing saliva, particularly as it relates to lack of supplies and resources. It can be a feasible option that basically eliminates HCW risk of infxn during collection. It can also save supplies: no swabs, media, possibly fewer reagents.

First paper is here: DOI: 10.1128/JCM.01659-20
-53 paired samples from OP and/or NP swabs, and saliva were collected
-Standard RNA extraction methods were used for the swab samples, a quick extraction method was used for saliva. Handling high-viscosity samples is discussed.

-All patients in this study were symptomatic.
-There was a difference in viral load (geometric mean): Saliva samples had significantly higher titers than swabs.
-Authors conclude that performance is acceptable, testing of saliva may have big impact in limited-resource areas.

Second paper is here: doi.org/10.1093/infdis…
This was a prospective study performed at two regional hospitals in Hong Kong.
-Examined 563 serial samples collected during the clinical course of 50 patients: 150 deep-throat saliva (DTS), 309 pooled NP+throat swabs, 104 sputum.

When the whole viral shedding period was considered, saliva showed the lowest mean RT-PCR positive rate per individual patient (72.3%) compared to sputum (91.7%) and pooled swabs (82.6%).

Further subgroup analyses of different collection periods showed that for early (1-5 days), mid (6-10 days) and late (11-15 days) saliva had the lowest mean positive rate compared to the other sample types.

-The mean viral RNA concentration for saliva was lower than the other sources, but was not statistically significant.
-In patients with severe disease, this difference was not seen.
-Important: patients in study ranged from asymptomatic, mild, moderate, to severe and critical.

-Authors do not recommend testing of saliva when other specimen types are feasible, and in locations where PPE can be provided and infection risk can be controlled.
**This study suggests caution before promoting widespread use of testing saliva samples.

Third paper is here: doi.org/10.1101/2020.0…
*Proceed with caution. Pre-print that is not peer-reviewed*
-Samples were collected from patients with confirmed COVID-19 every three days for their entire clinical course. (NP swabs and saliva).

IMPORTANT: These pts were all very sick (inpatient status, ICU, on vent, deceased).
- Analysis on patient-matched NP and saliva samples ( n =38 for each) =SARS-CoV-2 titers from saliva were significantly higher than NP swabs.

Longitudinal analysis performed to determine result consistency between specimen types = 5 instances where a patient's swab was negative, followed by a positive
result during the next collection (5/33 repeats, 33%).

In longitudinal saliva collections from 12 patients, there were no instances where a sample tested neg and was followed by a pos result.
-The researchers also enrolled a cohort of 98 asymptomatic healthcare workers who submitted swabs + saliva.

-The purpose of the HCW cohort is to study the use of saliva testing in an asymptomatic population.
-The authors report that at the time of writing, 2 healthcare workers tested pos (twice) from saliva samples but neg from NP swabs.

Authors conclude:
"That saliva is a viable and more sensitive alternative to nasopharyngeal swabs and could enable at-home
self-administered sample collection for accurate large-scale SARS-CoV-2 testing." (YIKES! Really big +broad conclusion).

There are some really important things to consider here:
1. The study was performed in sick hospital inpatients. We know that more severe disease = higher viral load, which likely = better sensitivity.
2. As the authors state in the paper, the HCW data are VERY limited...

We have to be careful about making big claims from so few results. While I find the results to be interesting, more work needs to be done in the pre-symptomatic + asymptomatic realm. Other studies that include asymptomatic members of the population don't have similar findings.

I do wish the title included something like, "Saliva is more sensitive for SARS-CoV-2 detection in HOSPITALIZED
COVID-19 patients with MODERATE TO SEVERE DISEASE than nasopharyngeal swabs."

As is true with most #COVID19 diagnostics, patient population and test setting will be really important in determining the best role for saliva testing moving forward.
#Microbiology #ASMClinMicro @ASCLS #IDTwitter

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