Release of infectious virus and cytokines in nasopharyngeal swabs from individuals infected with non-alpha or alpha SARS-CoV-2 variants: an observational retrospective study

Monel, Blandine; Planas, Delphine; Grzelak, Ludivine; Smith, Nikaïa; Robillard, Nicolas; Staropoli, Isabelle; Gonçalves, Pedro; Porrot, Françoise; Guivel‐Benhassine, Florence; Guinet, Nathalie Demory; Rodary, Julien; Puech, Julien; Euzen, Victor; Bélec, Laurent; Orvoën, G.; Nunes, Lea; Moulin, Véronique; Fourgeaud, Jacques; Wack, Maxime; Imbeaud, Sandrine; Campagne, Pascal; Duffy, Darragh; Santo, James P. Di; Bruel, Timothée; Péré, Hélène; Veyer, David

doi:10.1016/j.ebiom.2021.103637

“…However, increased inflammation may also induce URT secretions that help expel the virus into the environment, which may favor transmission [79, 80]. Several studies have shown that SARS-CoV-2 variants induce differential inflammatory repertoires, but limited information is available regarding inflammatory markers in the URT and the contribution of specific inflammatory signatures to transmission [53, 58, 81]. In order to link a variant’s URT inflammatory repertoire with its transmission potential, we analyzed the cytokines present in the URT shedding samples of neonatal mice infected with SARS-CoV-2 variants.…”

Section: Resultsmentioning

confidence: 99%

A neonatal mouse model characterizes transmissibility of SARS-CoV-2 variants and reveals a role for ORF8

Rodriguez-Rodriguez

¹

,

Ciabattoni

²

,

Valero-Jimenez

³

et al. 2022

Preprint

View full text Add to dashboard Cite

Small animal models have been a challenge for the study of SARS-CoV-2 transmission, with most investigators using golden hamsters or ferrets. Mice have the advantages of low cost, wide availability, less regulatory and husbandry challenges, and a versatile reagent and genetic toolbox. However, adult mice do not transmit SARS-CoV-2. Here we establish a model based on neonatal mice that allows for transmission of clinical SARS-CoV-2 isolates. We characterize tropism, respiratory tract replication and transmission of ancestral WA-1 compared to variants alpha (B.1.1.7), beta (B.1.351), gamma (P.1), delta (B.1.617.2) and omicron (B.1.1.529). We found that an index shedding threshold is a key determinant for viral transmissibility. Furthermore, we characterize two recombinant SARS-CoV-2 lacking either the ORF6 or ORF8 host antagonists. The removal of ORF8 shifts viral replication towards the lower respiratory tract, resulting in delayed and reduced transmission. Our results demonstrate the potential of our neonatal mouse model to characterize viral and host determinants of SARS-CoV-2 transmission, while revealing for the first time a role for an accessory protein this context. We now have a tractable small animal model to help us decipher and counteract some of the most decisive aspects of SARS-CoV-2 continued spread in the human population.

show abstract

“…Vero cells and their subclones or derivatives are commonly used to culture SARS-CoV-2 and Vero E6 cells expressing human transmembrane serine protease 2 (TMPRSS2) have demonstrated enhanced susceptibility and isolation of SARS-CoV-2 (11). Plaque or median tissue culture infectious dose (TCID 50 ) assays are commonly used to quantify viable virus, but new methods have been described like the S-Fuse assay that uses a cell reporter system and is based on the detection of GFP positive syncytia formation between infected and neighboring cells (12).…”

Section: Introductionmentioning

confidence: 99%

“…While some studies have described the amount of viable virus shed by individuals infected with the various SARS-CoV-2 variants (12)(13)(14), more studies are needed to better characterize infectious virus levels in vaccinated and unvaccinated individuals. This is especially important because each study uses different methods and focuses on different populations of individuals from different geographic locations.…”

Section: Introductionmentioning

confidence: 99%

Genomic and Virological Characterization of SARS-CoV-2 Variants in a Subset of Unvaccinated and Vaccinated U.S. Military Personnel

Smith

¹

,

Singh

²

,

Green

³

et al. 2022

View full text Add to dashboard Cite

The emergence of SARS-CoV-2 variants complicates efforts to control the COVID-19 pandemic. Increasing genomic surveillance of SARS-CoV-2 is imperative for early detection of emerging variants, to trace the movement of variants, and to monitor effectiveness of countermeasures. Additionally, determining the amount of viable virus present in clinical samples is helpful to better understand the impact these variants have on viral shedding. In this study, we analyzed nasal swab samples collected between March 2020 and early November 2021 from a cohort of United States (U.S.) military personnel and healthcare system beneficiaries stationed worldwide as a part of the Defense Health Agency's (DHA) Global Emerging Infections Surveillance (GEIS) program. SARS-CoV-2 quantitative real time reverse-transcription PCR (qRT-PCR) positive samples were characterized by next-generation sequencing and a subset was analyzed for isolation and quantification of viable virus. Not surprisingly, we found that the Delta variant is the predominant strain circulating among U.S. military personnel beginning in July 2021 and primarily represents cases of vaccine breakthrough infections (VBIs). Among VBIs, we found a 50-fold increase in viable virus in nasal swab samples from Delta variant cases when compared to cases involving other variants. Notably, we found a 40-fold increase in viable virus in nasal swab samples from VBIs involving Delta as compared to unvaccinated personnel infected with other variants prior to the availability of approved vaccines. This study provides important insight about the genomic and virological characterization of SARS-CoV-2 isolates from a unique study population with a global presence.

show abstract

“…Plaque or median tissue culture infectious dose (TCID50) assays are commonly used to quantify viable virus, but new methods have been described like the S-Fuse assay that uses a cell reporter system and is based on the detection of GFP positive syncytia formation between infected and neighboring cells (12).…”

Section: Introductionmentioning

confidence: 99%

“…While some studies have described the amount of viable virus shed by individuals infected with the various SARS-CoV-2 variants (12)(13)(14), more studies are needed to better characterize infectious virus levels in vaccinated and unvaccinated individuals. This is especially important because each study uses different methods and focuses on different populations of individuals from different geographic locations.…”

Section: Introductionmentioning

confidence: 99%

Genomic and Virological Characterization of SARS-CoV-2 Variants in a Subset of Unvaccinated and Vaccinated U.S. Military Personnel

Smith

¹

,

Singh

²

,

Green

³

et al. 2021

Preprint

0

View full text Add to dashboard Cite

The emergence of SARS-CoV-2 variants complicates efforts to control the COVID-19 pandemic. Increasing genomic surveillance of SARS-CoV-2 is imperative for early detection of emerging variants, to trace the movement of variants, and to monitor effectiveness of countermeasures. Additionally, determining the amount of viable virus present in clinical samples is helpful to better understand the impact these variants have on viral shedding. In this study, we analyzed nasal swab samples collected between March 2020 and early November 2021 from a cohort of United States (U.S.) military personnel and healthcare system beneficiaries stationed worldwide as a part of the Defense Health Agency’s (DHA) Global Emerging Infections Surveillance (GEIS) program. SARS-CoV-2 quantitative real time reverse-transcription PCR (qRT-PCR) positive samples were characterized by next-generation sequencing and a subset was analyzed for isolation and quantification of viable virus. Not surprisingly, we found that the Delta variant is the predominant strain circulating among U.S. military personnel beginning in July 2021 and primarily represents cases of vaccine breakthrough infections (VBIs). Among VBIs, we found a 50-fold increase in viable virus in nasal swab samples from Delta variant cases when compared to cases involving other variants. Notably, we found a 40-fold increase in viable virus in nasal swab samples from VBIs involving Delta as compared to unvaccinated personnel infected with other variants prior to the availability of approved vaccines. This study provides important insight about the genomic and virological characterization of SARS-CoV-2 isolates from a unique study population with a global presence.ImpactThe COVID-19 pandemic is currently a leading cause of death globally and new SARS-CoV-2 variants continue to emerge. Genomic surveillance of variants is necessary to characterize mutations that could affect transmissibility and spread, antigenicity or virulence. Furthermore, wet lab studies are necessary to evaluate how genetic differences may affect viral fitness and transmissibility. The Delta variant is currently the predominant strain globally and determining factors that drive its ability to spread rapidly is important. In this study, we characterized SARS-CoV-2 positive samples from U.S. military personnel and their beneficiaries by next-generation sequencing and isolation of viable virus. Consistent with other studies, we found higher levels of infectious virus from Delta samples when compared to non-Delta infections. Strikingly, we found the difference in titer between Delta and other strains to be so profound as to be unaffected by vaccination status, suggesting that increased transmissibility of the Delta variant is in part due to higher amounts of virus shedding. This helps explain the rapid spread of the Delta variant and provides the impetus to increase control measures such as vaccination, boosters, masking and distancing requirements. It will be necessary to continue genomic and virological characterization of new variants, such as Omicron.

show abstract

Release of infectious virus and cytokines in nasopharyngeal swabs from individuals infected with non-alpha or alpha SARS-CoV-2 variants: an observational retrospective study

Cited by 19 publications

References 49 publications

A neonatal mouse model characterizes transmissibility of SARS-CoV-2 variants and reveals a role for ORF8

A neonatal mouse model characterizes transmissibility of SARS-CoV-2 variants and reveals a role for ORF8

Genomic and Virological Characterization of SARS-CoV-2 Variants in a Subset of Unvaccinated and Vaccinated U.S. Military Personnel

Genomic and Virological Characterization of SARS-CoV-2 Variants in a Subset of Unvaccinated and Vaccinated U.S. Military Personnel

Contact Info

Product

Resources

About