A new SARS-CoV-2 variant with high lethality poorly detected by RT-PCR on nasopharyngeal samples: an observational study

Fillâtre, Pierre; Dufour, Marie-José; Behillil, Sylvie; Vatan, Rémi; Reusse, Pascale; Gabellec, Alice; Velmans, N.; Montagne, Catherine; Coudret, Sophie Geffroy Du; Droumaguet, Edith; Merour, Véronique; Enouf, Vincent; Buzelé, Rodolphe; Valence, M.; Guillotel, Elena; Gagnière, Bertrand; Baidaliuk, Artem; Zhukova, Anna; Tourdjman, Mathieu; Thibault, Vincent; Grolhier, Claire; Pronier, Charlotte; Lescure, François-Xavier; Simon‐Lorière, Etienne; Costagliola, Dominique; Werf, Sylvie van der; Tattevin, Pierre; Massart, Nicolas

doi:10.1016/j.cmi.2021.09.035

Cited by 12 publications

(7 citation statements)

References 24 publications

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“…A single variant lineage, B.1.616, does contain E:T30I as a lineage-defining mutation. Interestingly, B.1.616 was associated with an extremely localised, largely nosocomial-associated outbreak, suggesting the possibility this may have been the emergence of a virus from a long-term infection ( Fillâtre et al. 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Recurrent SARS-CoV-2 mutations in immunodeficient patients

et al. 2022

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Long-term SARS-CoV-2 infections in immunodeficient patients are an important source of variation for the virus but are understudied. Many case studies have been published which describe one or a small number of long-term infected individuals but no study has combined these sequences into a cohesive dataset. This work aims to rectify this and study the genomics of this patient group through a combination of literature searches as well as identifying new case series directly from the COG-UK dataset. The spike gene receptor binding domain (RBD) and N-terminal domains (NTD) were identified as mutation hotspots. Numerous mutations associated with variants of concern were observed to emerge recurrently. Additionally a mutation in the envelope gene, T30I was determined to be the second most frequent recurrently occurring mutation arising in persistent infections. A high proportion of recurrent mutations in immunodeficient individuals are associated with ACE2 affinity, immune escape, or viral packaging optimisation. There is an apparent selective pressure for mutations which aid cell-cell transmission within the host or persistence which are often different to mutations which aid inter-host transmission, although the fact that multiple recurrent de novo mutations are considered defining for variants of concern strongly indicates that this potential source of novel variants should not be discounted.

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Section: Discussionmentioning

confidence: 99%

Recurrent SARS-CoV-2 mutations in immunodeficient patients

et al. 2022

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Section: E-gene Recurrent Mutationsmentioning

confidence: 99%

Recurrent SARS-CoV-2 Mutations in Immunodeficient Patients

Wilkinson

Richter

Casey

et al. 2022

Preprint

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Long-term SARS-CoV-2 infections in immunodeficient patients are an important source of variation for the virus but are understudied. Many case studies have been published which describe one or a small number of long-term infected individuals but no study has combined these sequences into a cohesive dataset. This work aims to rectify this and study the genomics of this patient group through a combination of literature searches as well as identifying new case series directly from the COG-UK dataset. The spike gene receptor binding domain (RBD) and N-terminal domains (NTD) were identified as mutation hotspots. Numerous mutations associated with variants of concern were observed to emerge recurrently. Additionally a mutation in the envelope gene, - T30I was determined to be the most recurrent frequently occurring mutation arising in persistent infections. A high proportion of recurrent mutations in immunodeficient individuals are associated with ACE2 affinity, immune escape, or viral packaging optimisation. There is an apparent selective pressure for mutations which aid intra-host transmission or persistence which are often different to mutations which aid inter-host transmission, although the fact that multiple recurrent de novo mutations are considered defining for variants of concern strongly indicates that this potential source of novel variants should not be discounted.

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“…In a number of the included articles a combination of exposure ascertainment approaches was adopted. One included article reported an additional exposure ascertainment approach, namely, Fillâtre et al [114] classified high-risk contacts of a COVID-19 case based on the identified variant of infection of this case. Furthermore, we presented potential selection biases (e.g., overcontrol bias, endogenous selection bias, sample truncation bias).…”

Section: Discussionmentioning

confidence: 99%

Evaluating methodological approaches to assess the severity of infection with SARS-CoV-2 variants: scoping review and applications on Belgian COVID-19 data

et al. 2022

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Background Differences in the genetic material of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants may result in altered virulence characteristics. Assessing the disease severity caused by newly emerging variants is essential to estimate their impact on public health. However, causally inferring the intrinsic severity of infection with variants using observational data is a challenging process on which guidance is still limited. We describe potential limitations and biases that researchers are confronted with and evaluate different methodological approaches to study the severity of infection with SARS-CoV-2 variants. Methods We reviewed the literature to identify limitations and potential biases in methods used to study the severity of infection with a particular variant. The impact of different methodological choices is illustrated by using real-world data of Belgian hospitalized COVID-19 patients. Results We observed different ways of defining coronavirus disease 2019 (COVID-19) disease severity (e.g., admission to the hospital or intensive care unit versus the occurrence of severe complications or death) and exposure to a variant (e.g., linkage of the sequencing or genotyping result with the patient data through a unique identifier versus categorization of patients based on time periods). Different potential selection biases (e.g., overcontrol bias, endogenous selection bias, sample truncation bias) and factors fluctuating over time (e.g., medical expertise and therapeutic strategies, vaccination coverage and natural immunity, pressure on the healthcare system, affected population groups) according to the successive waves of COVID-19, dominated by different variants, were identified. Using data of Belgian hospitalized COVID-19 patients, we were able to document (i) the robustness of the analyses when using different variant exposure ascertainment methods, (ii) indications of the presence of selection bias and (iii) how important confounding variables are fluctuating over time. Conclusions When estimating the unbiased marginal effect of SARS-CoV-2 variants on the severity of infection, different strategies can be used and different assumptions can be made, potentially leading to different conclusions. We propose four best practices to identify and reduce potential bias introduced by the study design, the data analysis approach, and the features of the underlying surveillance strategies and data infrastructure.

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A new SARS-CoV-2 variant with high lethality poorly detected by RT-PCR on nasopharyngeal samples: an observational study

Cited by 12 publications

References 24 publications

Recurrent SARS-CoV-2 mutations in immunodeficient patients

Recurrent SARS-CoV-2 mutations in immunodeficient patients

Recurrent SARS-CoV-2 Mutations in Immunodeficient Patients

Evaluating methodological approaches to assess the severity of infection with SARS-CoV-2 variants: scoping review and applications on Belgian COVID-19 data

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