Community Transmission and Viral Load Kinetics of SARS-CoV-2 Delta (B.1.617.2)Variant in Vaccinated and Unvaccinated Individuals

Singanayagam, Aran; Hakki, Seran; Dunning, Jake; Kj, Madon; Crone, Michael; Koycheva, Aleksandra; Derqui-Fernández, Nieves; Jl, Barnett; Mg, Whitfield; Varro, Robert; Charlett, André; Kundu, Rhia; Fenn, Joe; Badhan, Anjna; Dustan, Simon; Tejpal, Chitra; Vetkar, A; Cutajar, Jessica; Quinn,; Conibear, Emily; Js, Narean; Hammett, Sarah; McDermott, Eimèar; Pillay, Timesh D; Houston, Hamish; Luca, Constanta; Samuel, Jonathon; Bremang, Samuel; Anderson, Charlotte; Jackson, David; Miah, Shahjahan; Ellis, Joanna; Lackenby, Angie; Ws, Barclay; Freemont, Paul S.; Taylor, GP; Ahmad, Shazaad; Zambon, Maria; Ferguson, Neil M.; Lalvani, Ajit

doi:10.2139/ssrn.3918287

Cited by 20 publications

(27 citation statements)

References 16 publications

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“…22 Hence, observed viral loads may not be representative of viral loads at transmission, however, the strong relationship between measured Ct values and risk of onward transmission argues against this 15 (replicated here, Figure 4B). Therefore, it is possible vaccination acts by facilitating faster clearance of viable infectious virions, 17,18 but leaving damaged ineffective virions behind that still contain PCR-detectable RNA. This may mean antigen assays have advantages in predicting the risk of onward transmission in those vaccinated, but this needs further study.…”

Section: Discussionmentioning

confidence: 99%

“…22 Hence, observed Ct values are likely imperfectly representative of viral loads at transmission, despite the relationship observed between Ct values at diagnosis and risk of prior onward transmission (Figure 4B). Vaccination may act by facilitating faster clearance of viable infectious virions, 17,18 but leaving damaged ineffective virions behind that still contain PCR-detectable RNA. However this, and the performance of antigen assays post vaccination, needs further study.…”

Section: Discussionmentioning

confidence: 99%

“…14,15 However, Delta viral loads are similar in vaccinated and unvaccinated infected individuals, 8,16 although the duration of viral shedding may be reduced. 17,18 This questions whether vaccination controls Delta spread as effectively as Alpha, and whether, with increased transmissibility, 19 this explains the rapid global dissemination of Delta despite rising vaccination coverage.…”

Section: Introductionmentioning

confidence: 99%

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The impact of SARS-CoV-2 vaccination on Alpha and Delta variant transmission

Eyre

Taylor

Purver

et al. 2021

Preprint

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Background Pre-Delta, vaccination reduced transmission of SARS-CoV-2 from individuals infected despite vaccination, potentially via reducing viral loads. While vaccination still lowers the risk of infection, similar viral loads in vaccinated and unvaccinated individuals infected with Delta question how much vaccination prevents onward transmission. Methods We performed a retrospective observational cohort study of contacts of SARS-CoV-2-infected index cases using contact testing data from England. We used multivariable logistic regression to investigate the impact of index case and contact vaccination on transmission, and how this varies with Alpha and Delta variants (classified using S-gene detection/calendar trends) and time since second vaccination. Results 51,798/139,164(37.2%) contacts tested were PCR-positive. Two doses of BNT162b2 or ChAdOx1 vaccines in Alpha variant index cases independently reduced PCR-positivity in contacts (aOR, adjusted odds ratio vs. unvaccinated=0.18[95%CI 0.12-0.29] and 0.37[0.22-0.63] respectively). The Delta variant attenuated vaccine-associated reductions in transmission: two BNT162b2 doses reduced Delta transmission (aOR=0.35[0.26-0.48]), more than ChAdOx1 (aOR=0.64[0.57-0.72]; heterogeneity p<0.001). Variation in viral load (Ct values) explained only a modest proportion of vaccine-associated transmission reductions. Transmission reductions declined over time since second vaccination, for Delta reaching similar levels to unvaccinated individuals by 12 weeks for ChAdOx1 and attenuating substantially for BNT162b2. Protection from vaccination in contacts also declined in the 3 months after second vaccination. Conclusions Vaccination reduces transmission of Delta, but by less than the Alpha variant. The impact of vaccination decreased over time. Factors other than PCR-measured viral load are important in vaccine-associated transmission reductions. Booster vaccinations may help control transmission together with preventing infections.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The impact of SARS-CoV-2 vaccination on Alpha and Delta variant transmission

Eyre

Taylor

Purver

et al. 2021

Preprint

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“…This may then require the development of additional vaccine shots and potential new drugs. Considering these preventive/therapeutic limitations, COVID-19 may not be fully controlled [25,26]. Such reasons show the necessity of inclusive treatments against the forthcoming variants.…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal Stem Cell-Based COVID-19 Therapy: Bioengineering Perspectives

Karakaş

Ucuncuoglu

Uludağ

et al. 2022

Cells

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The novel pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). Mesenchymal stem cells (MSCs) are currently utilized in clinics for pulmonary inflammatory diseases, including acute respiratory distress syndrome and acute lung injury. Given that MSCs offer a promising treatment against COVID-19, they are being used against COVID-19 in more than 70 clinical trials with promising findings. Genetically engineered MSCs offer promising therapeutic options in pulmonary diseases. However, their potential has not been explored yet. In this review, we provide perspectives on the functionally modified MSCs that can be developed and harnessed for COVID-19 therapy. Options to manage the SARS-CoV-2 infection and its variants using various bioengineering tools to increase the therapeutic efficacy of MSCs are highlighted.

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“…COVID-19, caused by the coronavirus SARS-CoV-2, is a global health issue with more than 5.5 million fatalities to date. Vaccination has reduced both the number of hospitalisations and mortality due to COVID-19 (Singanayagam et al, 2021;Voysey et al, 2021). However, the emergence of variants, such as Omicron, that show reduced sensitivity to vaccine-induced immunity (Dejnirattisai et al, 2021a;Dejnirattisai et al, 2021b;Liu et al, 2021), provide the potential for new waves of infection.…”

Section: Introductionmentioning

confidence: 99%

Hypoxia inducible factors regulate infectious SARS-CoV-2, epithelial damage and respiratory symptoms in a hamster COVID-19 model

Wing

Prange-Barczynska

Cross

et al. 2022

Preprint

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Understanding the host pathways that define susceptibility to SARS-CoV-2 infection and disease are essential for the design of new therapies. Oxygen levels in the microenvironment define the transcriptional landscape, however the influence of hypoxia on virus replication and disease in animal models is not well understood. In this study, we identify a role for the hypoxic inducible factor (HIF) signalling axis to inhibit SARS-CoV-2 infection, epithelial damage and respiratory symptoms in Syrian hamsters. Pharmacological activation of HIF with the prolyl-hydroxylase inhibitor FG-4592 significantly reduced the levels of infectious virus in the upper and lower respiratory tract. Nasal and lung epithelia showed a reduction in SARS-CoV-2 RNA and nucleocapsid expression in treated animals. Transcriptomic and pathological analysis showed reduced epithelial damage and increased expression of ciliated cells. Our study provides new insights on the intrinsic antiviral properties of the HIF signalling pathway in SARS-CoV-2 replication that may be applicable to other respiratory pathogens and identifies new therapeutic opportunities.

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Community Transmission and Viral Load Kinetics of SARS-CoV-2 Delta (B.1.617.2)Variant in Vaccinated and Unvaccinated Individuals

Cited by 20 publications

References 16 publications

The impact of SARS-CoV-2 vaccination on Alpha and Delta variant transmission

The impact of SARS-CoV-2 vaccination on Alpha and Delta variant transmission

Mesenchymal Stem Cell-Based COVID-19 Therapy: Bioengineering Perspectives

Hypoxia inducible factors regulate infectious SARS-CoV-2, epithelial damage and respiratory symptoms in a hamster COVID-19 model

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