Variant‐specific SARS‐CoV‐2 within‐host kinetics

Elie, Baptiste; Roquebert, Bénédicte; Sofonea, Mircea T.; Trombert‐Paolantoni, Sabine; Foulongne, Vincent; Guedj, Jérémie; Haïm-Boukobza, S.; Alizon, Samuel

doi:10.1002/jmv.27757

Cited by 18 publications

(13 citation statements)

References 41 publications

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“…The increased transmissibility of Alpha over previously circulating lineages may be explained by higher viral loads; mean N- and E-gene Ct value was approximately 1 lower for Alpha relative to wild-type lineages. This result matches other work that suggested the Alpha variant has higher viral loads than previously circulating lineages [46]. However, it is possible that both analyses have been influenced by the high growth rate of Alpha during its emergence relative to other lineages, which could lead to a difference in the observed distribution generated by differences in the average time since infection [47].…”

Section: Discussionsupporting

confidence: 87%

The use of representative community samples to assess SARS-CoV-2 lineage competition: Alpha outcompetes Beta and wild-type in England from January to March 2021

et al. 2023

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Genomic surveillance for SARS-CoV-2 lineages informs our understanding of possible future changes in transmissibility and vaccine efficacy and will be a high priority for public health for the foreseeable future. However, small changes in the frequency of one lineage over another are often difficult to interpret because surveillance samples are obtained using a variety of methods all of which are known to contain biases. As a case study, using an approach which is largely free of biases, we here describe lineage dynamics and phylogenetic relationships of the Alpha and Beta variant in England during the first 3 months of 2021 using sequences obtained from a random community sample who provided a throat and nose swab for rt-PCR as part of the REal-time Assessment of Community Transmission-1 (REACT-1) study. Overall, diversity decreased during the first quarter of 2021, with the Alpha variant (first identified in Kent) becoming predominant, driven by a reproduction number 0.3 higher than for the prior wild-type. During January, positive samples were more likely to be Alpha in those aged 18 to 54 years old. Although individuals infected with the Alpha variant were no more likely to report one or more classic COVID-19 symptoms compared to those infected with wild-type, they were more likely to be antibody-positive 6 weeks after infection. Further, viral load was higher in those infected with the Alpha variant as measured by cycle threshold (Ct) values. The presence of infections with non-imported Beta variant (first identified in South Africa) during January, but not during February or March, suggests initial establishment in the community followed by fade-out. However, this occurred during a period of stringent social distancing. These results highlight how sequence data from representative community surveys such as REACT-1 can augment routine genomic surveillance during periods of lineage diversity.

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Section: Discussionsupporting

confidence: 87%

The use of representative community samples to assess SARS-CoV-2 lineage competition: Alpha outcompetes Beta and wild-type in England from January to March 2021

et al. 2023

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“…[2][3][4] Early detection also enables earlier initiation and more effective treatments. [5][6][7][8] Testing strategies to achieve detection in the pre-infectious and infectious periods of new SARS-CoV-2 variants or new viruses requires filling two critical knowledge gaps: (1) Which respiratory specimen accumulates virus first? (2) What is the appropriate test analytical sensitivity to detect the earliest accumulation of virus (in the pre-infectious and infectious stages)?…”

Section: Introductionmentioning

confidence: 99%

“…As new SARS-CoV-2 variants-of-concern (and new respiratory viruses) emerge with different viral kinetics, 1 it is important to continually re-evaluate testing strategies (including specimen type and test analytical sensitivity) for detecting pre-infectious and infectious individuals. Early detection limits transmission within communities and the global spread of new variants.…”

Section: Introductionmentioning

confidence: 99%

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

Winnett

Akana

Shelby

et al. 2022

Preprint

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Background. Screening testing, often via self-collected specimens, remains a key strategy to detect infections early and prevent SARS-CoV-2 transmission, and to enable earlier initiation of treatment. However, which specimen type best detects the earliest days of infection remains controversial. Further, the analytical sensitivity of diagnostic tests must also be considered, as viral loads below a test's limit of detection (LOD) are likely to yield false-negative results. Comparisons of quantitative, longitudinal SARS-CoV-2 viral-load timecourses in multiple specimen types can determine the best specimen type and test analytical sensitivity for earliest detection of infection. Methods. We conducted a COVID-19 household transmission study between November 2021 and February 2022 that enrolled 228 participants and analyzed 6,825 samples using RT-qPCR to quantify viral-load timecourses in three specimen types (saliva [SA], anterior-nares swab [ANS], and oropharyngeal swab [OPS]). From this study population, 14 participants enrolled before or at the incidence of infection with the Omicron variant. We compared the viral loads in specimens collected from each person at the same timepoint, and the longitudinal viral load timecourses from each participant. Using these viral loads, we inferred the clinical sensitivity of each specimen type to detect infected, pre-infectious and infectious individuals (based on presumably infectious viral load levels) using assays with a range of analytical sensitivities. We also inferred the clinical sensitivity of computationally contrived specimen types representing combinations of single specimen types. Results. We found extreme differences (up to 109 copies/mL) in viral loads between paired specimen types in the same person at the same timepoint, and that longitudinal viral load timecourses across specimen types did not correlate. Because of this lack of correlation, infectious viral loads were often observed in different specimen types asynchronously throughout the course of the infection. In the first 4 days of infection, no single specimen type was inferred to achieve >95% detection of infected or infectious individuals, even with the highest analytical sensitivity assays. In nearly all participants (11/14), a rise in ANS viral loads was delayed (as many as 7 days) relative to SA and OPS. We also observed that ANS and OPS had the most complementary viral load timecourses, resulting in optimal inferred performance with a computationally contrived combined anterior nares-oropharyngeal (AN-OP) swab specimen type. The combination AN-OP swab had superior inferred clinical sensitivity the first 8 days of infection with both high- and low-analytical-sensitivity assays. This AN-OP swab was also inferred to significantly improve detection of pre-infectious and infectious individuals over any single specimen type. Conclusion. Our work demonstrates that the viral load in one specimen type cannot reliably predict the viral load in another specimen type. Combination specimen types may offer a more robust approach for earliest detection of new variants and respiratory viruses when viral kinetics are still unknown.

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“…138 The model with the lowest Akaike information criterion (with a ΔAIC <2) was chosen among other models in the study, where the selected model revealed a conspicuous difference in viral load between the nCoV lineage and the alpha variant with Cq values from qPCR, which were connected with the viral copies/ml values obtained from ddPCR. 138 The study also portrayed a slower decay rate of the alpha variant infections than in previous lineages. Such studies invariably show the potential use of…”

Section: Viral Concentration Monitoring In the Environmentmentioning

confidence: 99%

SARS‐CoV‐2 in digital era: Diagnostic techniques and importance of nucleic acid quantification with digital PCRs

Aravind Kumar,

Aradhana,

Harleen

et al. 2023

Reviews in Medical Virology

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Studies related to clinical diagnosis and research of SARS‐CoV‐2 are important in the current pandemic era. Although molecular biology has emphasised the importance of qualitative analysis, quantitative analysis with nucleic acids in relation to SARS‐CoV‐2 needs to be clearly emphasised, which can provide perspective for viral dynamic studies of SARS‐CoV‐2. In this regard, the requirement and utilization of digital PCR in COVID‐19 research has substantially increased during the pandemic, necessitating the aggregation of its cardinal applications and future scopes. Hence, this meta‐review comprehensively addresses and emphasises the importance of nucleic acid quantification of SARS‐CoV‐2 RNA with digital PCR (dPCR). Various quantitative techniques of clinical significance like immunological, proteomic and nucleic acid‐based diagnosis and quantification, have been comparatively discussed. Furthermore, the core part of the article focusses on the working principle and advantages of digital PCR, along with its applications in COVID‐19 research. Several important applications like viral load quantitation, environmental surveillance and assay validation have been extensively investigated and discussed. Certain key future scopes of clinical importance, like mortality prediction, viral/variant‐symbiosis, and antiviral studies were also identified, suggesting several possible digital PCR applications in COVID‐19 research.

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Variant‐specific SARS‐CoV‐2 within‐host kinetics

Cited by 18 publications

References 41 publications

The use of representative community samples to assess SARS-CoV-2 lineage competition: Alpha outcompetes Beta and wild-type in England from January to March 2021

The use of representative community samples to assess SARS-CoV-2 lineage competition: Alpha outcompetes Beta and wild-type in England from January to March 2021

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

SARS‐CoV‐2 in digital era: Diagnostic techniques and importance of nucleic acid quantification with digital PCRs

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