Surveillance and Correlation of Severe Acute Respiratory Syndrome Coronavirus 2 Viral RNA, Antigen, Virus Isolation, and Self-Reported Symptoms in a Longitudinal Study With Daily Sampling

Bonenfant, Gaston; Deyoe, Jessica E.; Wong, Terianne; Grijalva, Carlos G; Cui, Dan; Talbot, H. Keipp; Hassell, Norman; Halasa, Natasha; Chappell, James D.; Thornburg, Natalie J.; Rolfes, Melissa A; Wentworth, David E.; Zhou, Bin

doi:10.1093/cid/ciac282

Cited by 12 publications

(20 citation statements)

References 29 publications

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“…Some studies found that detection of sgRNA correlates with detection of infectious virus 4,173,174 , and that sgRNA was rarely detectable 8 dpos 67 . However, sgRNA was detected in diagnostic samples up to 17 days after initial detection of infection 175 or in culture-negative samples 176 , probably owing to the stability and nuclease resistance of double-membrane vesicles containing sgRNAs. Thus, although the absence of sgRNA would indicate absence of viral replication, the presence of sgRNA does not necessarily indicate infectiousness 19 .…”

Section: Sars-cov-2 Diagnostics In Public Healthmentioning

confidence: 99%

SARS-CoV-2 viral load and shedding kinetics

2022

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SARS-CoV-2 viral load and detection of infectious virus in the respiratory tract are the two key parameters for estimating infectiousness. As shedding of infectious virus is required for onward transmission, understanding shedding characteristics is relevant for public health interventions. Viral shedding is influenced by biological characteristics of the virus, host factors and pre-existing immunity (previous infection or vaccination) of the infected individual. Although the process of human-to-human transmission is multifactorial, viral load substantially contributed to human-to-human transmission, with higher viral load posing a greater risk for onward transmission. Emerging SARS-CoV-2 variants of concern have further complicated the picture of virus shedding. As underlying immunity in the population through previous infection, vaccination or a combination of both has rapidly increased on a global scale after almost 3 years of the pandemic, viral shedding patterns have become more distinct from those of ancestral SARS-CoV-2. Understanding the factors and mechanisms that influence infectious virus shedding and the period during which individuals infected with SARS-CoV-2 are contagious is crucial to guide public health measures and limit transmission. Furthermore, diagnostic tools to demonstrate the presence of infectious virus from routine diagnostic specimens are needed.

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Section: Sars-cov-2 Diagnostics In Public Healthmentioning

confidence: 99%

SARS-CoV-2 viral load and shedding kinetics

2022

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“…Abundance of sgRNA among SARS-CoV-2 variants is consistently predicted by levels of genomic RNA when compared to ancestral strains with D614G. Whereas previous studies of sgRNA either predated the widespread emergence of variants of concern or were not designed to compare sgRNA levels between variants [ 2 , 5 , 6 , 11 ], the current study included acute-phase samples of SARS-CoV-2 variants of concern collected across varied patient populations using different swab types. In our analysis, Delta variant samples demonstrated lower sgRNA Ct values (higher levels of sgRNA) than predicted by N2 Ct alone.…”

Section: Discussionmentioning

confidence: 99%

“…Compared to total viral RNA, sgRNA detection demonstrates improved correlation with isolation of live virus and antigen detection, providing a potential indicator of infectivity detectable in the diagnostic clinical sample [ 2 , 5–7 ]. However, the abundance of sgRNA during infections with SARS-CoV-2 variants compared to ancestral strains is relatively unknown.…”

mentioning

confidence: 99%

Subgenomic RNA Abundance Relative to Total Viral RNA Among Severe Acute Respiratory Syndrome Coronavirus 2 Variants

Ping

Nguyen

et al. 2022

Open Forum Infectious Diseases

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“…Data in longitudinal studies that captured viral load measurements from early in the course of infection 31,41,43,[47][48][49][50][51][52][53][54][55][56][57][58] present evidence that challenge the assumption that Ag-RDTs will reliably detect pre-infectious and infectious individuals. Viralload timecourses from individuals in these studies show that for some individuals, several days can pass between when viral loads reach potentially infectious levels and when viral loads rise to the limits of detection (LODs) of Ag-RDTs (approximately 10 5 to 10 7 copies/mL).…”

Section: Introductionmentioning

confidence: 99%

“…Although many Ag-RDT evaluations have observed relatively high concordance between Ag-RDT results and infectiousness (as established directly by viral culture 21,34,41,46,[48][49][50][63][64][65][66][67][68][69][70] or presumed by quantitative viral loads or semiquantitative Ct values 22,[71][72][73] ), this high concordance may not hold when Ag-RDTs are used for screening testing in the community. For example, in several studies 34,46,48,64,68,[70][71][72][73] most infected participants were already symptomatic by the time sampling began, so Ag-RDT performance would not be generalizable to the early period of infection.…”

Section: Introductionmentioning

confidence: 99%

Why Daily SARS-CoV-2 Nasal Rapid Antigen Testing Poorly Detects Infected and Infectious Individuals

Winnett

Akana

Shelby

et al. 2022

Preprint

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Background. To limit viral transmission, COVID-19 testing strategies must evolve as new SARS-CoV-2 variants (and new respiratory viruses) emerge to ensure that the specimen types and test analytical sensitivities being used will reliably detect individuals during the pre-infectious and infectious periods. Our accompanying work demonstrated that there are extreme differences in viral loads among paired saliva (SA), anterior-nares swab (ANS) and oropharyngeal swab (OPS) specimens collected from the same person and timepoint. We hypothesized that these extreme differences may prevent low-analytical-sensitivity assays (such as antigen rapid diagnostic tests, Ag-RDTs) performed on a single specimen type from reliably detecting pre-infectious and infectious individuals. Methods. We conducted a longitudinal COVID-19 household-transmission study in which 228 participants collected SA, ANS, and OPS specimens for viral-load quantification by RT-qPCR, and performed an ANS Ag-RDT (Quidel QuickVue At-Home OTC COVID-19 Test) daily. We evaluated the performance of the Ag-RDT (n=2215 tests) to detect infected individuals (positive results in any specimen type by RT-qPCR) and individuals with presumed infectious viral loads (at or above thresholds of 10^4, 10^5, 10^6, or 10^7 copies/mL). Results. Overall, the daily Ag-RDT detected 44% (358/811) timepoints from infected individuals. From 17 participants who enrolled early in the course of infection, we found that daily Ag-RDT performance was higher at timepoints when symptoms were reported, but symptoms only weakly correlated with SARS-CoV-2 viral loads, so ANS Ag-RDT clinical sensitivity remained below 50%. The three specimen types exhibited asynchronous presumably-infectious periods (regardless of the infectious viral-load threshold chosen) and the rise in ANS viral loads was delayed relative to SA or OPS for nearly all individuals, which resulted in the daily ANS Ag-RDT detecting only 3% in the pre-infectious period and 63% in the infectious period. We evaluated a computationally-contrived combined AN-OP swab based on viral loads from ANS and OPS specimens collected at the same timepoint; when tested with similar analytical sensitivity as the Ag-RDT, this combined swab was predicted to have significantly better performance, detecting up to 82% of infectious individuals. Conclusion. Daily ANS rapid antigen testing missed virtually all pre-infectious individuals, and more than one third of presumed infectious individuals due to low-analytical-sensitivity of the assay, a delayed rise in ANS viral loads, and asynchronous infectious viral loads in SA or OPS. When high-analytical-sensitivity assays are not available and low-analytical-sensitivity tests such as Ag-RDTs must be used for SARS-CoV-2 detection, an AN-OP combination swab is predicted to be most effective for detection of pre-infectious and infectious individuals. More generally, low-analytical-sensitivity tests are likely to perform more robustly using oral-nasal combination specimen types to detect new SASR-CoV-2 variants and emergent upper respiratory viruses.

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Surveillance and Correlation of Severe Acute Respiratory Syndrome Coronavirus 2 Viral RNA, Antigen, Virus Isolation, and Self-Reported Symptoms in a Longitudinal Study With Daily Sampling

Cited by 12 publications

References 29 publications

SARS-CoV-2 viral load and shedding kinetics

SARS-CoV-2 viral load and shedding kinetics

Subgenomic RNA Abundance Relative to Total Viral RNA Among Severe Acute Respiratory Syndrome Coronavirus 2 Variants

Why Daily SARS-CoV-2 Nasal Rapid Antigen Testing Poorly Detects Infected and Infectious Individuals

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