Morning SARS-CoV-2 Testing Yields Better Detection of Infection Due to Higher Viral Loads in Saliva and Nasal Swabs upon Waking

Winnett, Alexander; Porter, Michael K.; Romano, Anna E.; Savela, Emily S.; Akana, Reid; Shelby, Natasha; Reyes, Jessica A.; Schlenker, Noah W.; Cooper, Matthew M.; Carter, Alyssa M.; Ji, Jenny; Barlow, Jacob T.; Tognazzini, Colten; Feaster, Matthew; Goh, Ying-Ying; Ismagilov, Rustem F.

doi:10.1128/spectrum.03873-22

Cited by 11 publications

(11 citation statements)

References 42 publications

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“…Although not a statistically significant result, we estimated the highest mean VL among participants infected with Delta, consistent with previous literature . The strongest measured association with VL in our study was that with trial, which suggests timing of specimen collection or other factors associated with the specimen collection, storage, or VL assays across protocols may have influenced VL measurements . These results should temper expectations of future research comparing VL across trials or settings, especially given increasing diversity in preexisting immunity.…”

Section: Discussioncontrasting

confidence: 99%

SARS-CoV-2 Viral Load in the Nasopharynx at Time of First Infection Among Unvaccinated Individuals

Fisher,

Kee,

Liu

et al. 2024

JAMA Netw Open

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ImportanceSARS-CoV-2 viral load (VL) in the nasopharynx is difficult to quantify and standardize across settings, but it may inform transmission potential and disease severity.ObjectiveTo characterize VL at COVID-19 diagnosis among previously uninfected and unvaccinated individuals by evaluating the association of demographic and clinical characteristics, viral variant, and trial with VL, as well as the ability of VL to predict severe disease.Design, Setting, and ParticipantsThis secondary cross-protocol analysis used individual-level data from placebo recipients from 4 harmonized, phase 3 COVID-19 vaccine efficacy trials sponsored by Moderna, AstraZeneca, Janssen, and Novavax. Participants were SARS-CoV-2 negative at baseline and acquired COVID-19 during the blinded phase of the trials. The setting included the US, Brazil, South Africa, Colombia, Argentina, Peru, Chile, and Mexico; start dates were July 27, 2020, to December 27, 2020; data cutoff dates were March 26, 2021, to July 30, 2021. Statistical analysis was performed from November 2022 to June 2023.Main Outcomes and MeasuresLinear regression was used to assess the association of demographic and clinical characteristics, viral variant, and trial with polymerase chain reaction–measured log10 VL in nasal and/or nasopharyngeal swabs taken at the time of COVID-19 diagnosis.ResultsAmong 1667 participants studied (886 [53.1%] male; 995 [59.7%] enrolled in the US; mean [SD] age, 46.7 [14.7] years; 204 [12.2%] aged 65 years or older; 196 [11.8%] American Indian or Alaska Native, 150 [9%] Black or African American, 1112 [66.7%] White; 762 [45.7%] Hispanic or Latino), median (IQR) log10 VL at diagnosis was 6.18 (4.66-7.12) log10 copies/mL. Participant characteristics and viral variant explained only 5.9% of the variability in VL. The independent factor with the highest observed differences was trial: Janssen participants had 0.54 log10 copies/mL lower mean VL vs Moderna participants (95% CI, 0.20 to 0.87 log10 copies/mL lower). In the Janssen study, which captured the largest number of COVID-19 events and variants and used the most intensive post-COVID surveillance, neither VL at diagnosis nor averaged over days 1 to 28 post diagnosis was associated with COVID-19 severity.Conclusions and RelevanceIn this study of placebo recipients from 4 randomized phase 3 trials, high variability was observed in SARS-CoV-2 VL at the time of COVID-19 diagnosis, and only a fraction was explained by individual participant characteristics or viral variant. These results suggest challenges for future studies of interventions seeking to influence VL and elevates the importance of standardized methods for specimen collection and viral load quantitation.

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Section: Discussioncontrasting

confidence: 99%

SARS-CoV-2 Viral Load in the Nasopharynx at Time of First Infection Among Unvaccinated Individuals

Fisher,

Kee,

Liu

et al. 2024

JAMA Netw Open

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“…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.…”

Section: Resultsmentioning

confidence: 99%

“…Validation testing was performed using different bulk and single-cell RNA sequencing datasets with known infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or Zaire ebolavirus (ZEBOV) [34][35][36][37][38] . In these tests, translated search with kallisto and PalmDB was able to detect the viral RNA and correctly assign species-level taxonomy at counts correlating with viral loads measured by RT-qPCR or RNA-ISH, regardless of the technology used to generate the data (Fig.…”

Section: Translated Alignment Of Nucleotide Sequences To An Amino Aci...mentioning

confidence: 99%

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

Luebbert,

Sullivan,

Carilli

et al. 2023

Preprint

Self Cite

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More than 300,000 mammalian virus species are estimated to cause disease in humans. They inhabit human tissues such as the lungs, blood, and brain and often remain undetected. Efficient and accurate detection of viral infection is vital to understanding its impact on human health and to make accurate predictions to limit adverse effects, such as future epidemics. The increasing use of high-throughput sequencing methods in research, agriculture, and healthcare provides an opportunity for the cost-effective surveillance of viral diversity and investigation of virus-disease correlation. However, existing methods for identifying viruses in sequencing data rely on and are limited to reference genomes or cannot retain single-cell resolution through cell barcode tracking. We introduce a method that accurately and rapidly detects viral sequences in bulk and single-cell transcriptomics data based on highly conserved amino acid domains, which enables the detection of RNA viruses covering up to 1012virus species. The analysis of viral presence and host gene expression in parallel at single-cell resolution allows for the characterization of host viromes and the identification of viral tropism and host responses. We applied our method to identify novel viruses in rhesus macaque PBMC data that display cell type specificity and whose presence correlates with altered host gene expression.

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“…We conducted a case-ascertained COVID-19 household transmission observational cohort study in Southern California in two phases: between September 2020 and June 2021, 44,54 prior to the predominance of the Delta variant 55 , and between November 2021 and March 2022, 43 during the emergence and subsequent predominance of the Omicron variant 55 ( Table S1A ). The study was approved by the California Institute of Technology IRB (protocol #20-1026).…”

Section: Methodsmentioning

confidence: 99%

“…Specimens (saliva, anterior nares swabs, oropharyngeal swabs, Fig 1A , B ) from participants underwent laboratory testing for SARS-CoV-2 infection, as previously described (Supplementary Information). 43,44,54 Participants reported COVID-19-like symptoms at each specimen collection timepoint. At least one specimen from most households underwent viral sequencing as previously described, 43,44 to ascertain the infecting SARS-CoV-2 variant of household members.…”

Section: Methodsmentioning

confidence: 99%

Index Cases First Identified by Nasal-Swab Rapid COVID-19 Tests Had More Transmission to Household Contacts Than Cases Identified by Other Test Types

Winnett

Shelby

et al. 2023

Preprint

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Importance: At-home rapid COVID-19 tests utilize nasal-swab specimens and require high viral loads to reliably give positive results. Longitudinal studies from the onset of infection have found infectious virus can present in oral specimens days before nasal. Detection and initiation of infection-control practices may therefore be delayed when nasal-swab rapid tests are used, resulting in greater exposure and transmission to contacts. Objective: We assessed whether index cases first identified by rapid nasal-swab COVID-19 tests had more transmission to household contacts than index cases who used other test types (tests with higher analytical sensitivity but longer turnaround times, and/or that utilize non-nasal specimen types). Design: In this observational cohort study, members of households with a recent COVID-19 case were screened for infection at least daily by RT-qPCR on one or more self-collected upper-respiratory specimen types. Participants reported demographic/medical information (including COVID-19 testing), symptom and exposure information, and household infection-control practices. A two-level random intercept model was used to assess the association between the infection outcome of household contacts and each covariable (household size, race/ethnicity, age, vaccination status, viral variant, infection-control practices, and whether a rapid nasal-swab test was used to initially identify the household index case). Setting: Southern California, September 2020-June 2021 and November 2021-March 2022. Participants: Cohort of 370 individuals from 85 households. Main Outcome(s) and Measure(s): Transmission was quantified by adjusted secondary attack rates (aSAR) and adjusted odds ratios (aOR). Results: An aSAR of 53.6% (95%CI 38.8-68.3%) was observed among households where the index case first tested positive by a rapid nasal-swab COVID-19 test, which was significantly higher than the aSAR for households where the index case utilized another test type (27.2% [19.5-35.0%], P=0.003 pairwise comparisons of predictive margins). We observed an aOR of 4.90 (95%CI 1.65-14.56) for transmission to household contacts when a nasal-swab rapid test was used to identify the index case, compared to other test types. Conclusions and Relevance: Use of nasal-swab rapid COVID-19 tests for initial detection of infection and initiation of infection control may not limit transmission as well as other test types.

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Morning SARS-CoV-2 Testing Yields Better Detection of Infection Due to Higher Viral Loads in Saliva and Nasal Swabs upon Waking

Cited by 11 publications

References 42 publications

SARS-CoV-2 Viral Load in the Nasopharynx at Time of First Infection Among Unvaccinated Individuals

SARS-CoV-2 Viral Load in the Nasopharynx at Time of First Infection Among Unvaccinated Individuals

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

Index Cases First Identified by Nasal-Swab Rapid COVID-19 Tests Had More Transmission to Household Contacts Than Cases Identified by Other Test Types

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