Extreme differences in SARS-CoV-2 viral loads among respiratory specimen types during presumed pre-infectious and infectious periods

Abstract

SARS-CoV-2 viral-load measurements from a single-specimen type are used to establish diagnostic strategies, interpret clinical-trial results for vaccines and therapeutics, model viral transmission, and understand virus–host interactions. However, measurements from a single-specimen type are implicitly assumed to be representative of other specimen types. We quantified viral-load timecourses from individuals who began daily self-sampling of saliva, anterior-nares (nasal), and oropharyngeal (throat) swabs before or at the incidence of infection with the Omicron variant. Viral loads in different specimen types from the same person at the same timepoint exhibited extreme differences, up to 109 copies/mL. These differences were not due to variation in sample self-collection, which was consistent. For most individuals, longitudinal viral-load timecourses in different specimen types did not correlate. Throat-swab and saliva viral loads began to rise as many as 7 days earlier than nasal-swab viral loads in most individuals, leading to very low clinical sensitivity of nasal swabs during the first days of infection. Individuals frequently exhibited presumably infectious viral loads in one specimen type while viral loads were low or undetectable in other specimen types. Therefore, defining an individual as infectious based on assessment of a single-specimen type underestimates the infectious period, and overestimates the ability of that specimen type to detect infectious individuals. For diagnostic COVID-19 testing, these three single-specimen types have low clinical sensitivity, whereas a combined throat–nasal swab, and assays with high analytical sensitivity, was inferred to have significantly better clinical sensitivity to detect presumed pre-infectious and infectious individuals.

The swab site of the upper airways influences the diagnostic sensitivity for the omicron variant of SARS‐CoV‐2

“…The investigation of the initial viral loads was made possible by devising strict inclusion criteria and multiple testings before and after an initial quantifiable viral load detection. Further, the author concludes that the combined nasal orifice (Na in our study) and throat (OP) offers the best possible diagnostic sensitivity 13 . The latter agrees with our finding that the combined swab offered the best diagnostic and thereby clinical sensitivity, albeit in different swabbed region OP/NP.…”

“…Since the initial swab was a combined NP/OP swab, it might be that the highly viral material has been maneuvered into the anterior nasal cavity. This claim is backed by the findings of Winnett et al 13 that that nasal swabs usually achieve low viral loads early in an infection. However, due to the study design and precise inclusion criteria, this bias could not be avoided.…”

Efficient and accurate detection of viral sequences at single-cell resolution reveals putative novel viruses perturbing host gene expression

“…2. SARS-CoV-2 viral load by RT-qPCR (copies/mL) over total raw kallisto counts for SARS-CoV species obtained by bulk RNA sequencing of 16 saliva (circle), nasal swab (triangle), and throat swab (star) specimens from patients with acute SARS-CoV-2 infection 35,36 . Each specimen underwent duplicate library preparation and paired-end sequencing; points indicate the mean among the paired reads and duplicates, and error bars show min-max values.…”

Heterogeneous SARS-CoV-2 kinetics due to variable timing and intensity of immune responses

“…Unfortunately, such detailed studies are not available in any human cohort. Studies using saliva do suggest slightly different kinetics than those from nasal swabs 57 , but it is doubtful that saliva captures total viral load in the lung.…”