Introduction of the South African SARS-CoV-2 variant 501Y.V2 into the UK

Tang, Julian W.; Toovey, Oliver T R; Harvey, Kirsty N.; Hui, D

doi:10.1016/j.jinf.2021.01.007

Cited by 147 publications

(115 citation statements)

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“…Our findings are only very slightly affected when taking account of test accuracy (data not shown). Finally, new variants of SARS-CoV-2 with the 484K or 501Y receptor binding area substitutions have recently appeared in Denmark, [32][33][34] with some variants known to be more transmissable then the original. 35,36 During the study period, such variants were not yet established in Denmark; although into 2021 this pattern is changing.…”

Section: Discussionmentioning

confidence: 99%

Assessment of protection against reinfection with SARS-CoV-2 among 4 million PCR-tested individuals in Denmark in 2020: a population-level observational study

et al. 2021

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Background The degree to which infection with SARS-CoV-2 confers protection towards subsequent reinfection is not well described. In 2020, as part of Denmark's extensive, free-of-charge PCR-testing strategy, approximately 4 million individuals (69% of the population) underwent 10•6 million tests. Using these national PCR-test data from 2020, we estimated protection towards repeat infection with SARS-CoV-2. Methods In this population-level observational study, we collected individual-level data on patients who had been tested in Denmark in 2020 from the Danish Microbiology Database and analysed infection rates during the second surge of the COVID-19 epidemic, from Sept 1 to Dec 31, 2020, by comparison of infection rates between individuals with positive and negative PCR tests during the first surge (March to May, 2020). For the main analysis, we excluded people who tested positive for the first time between the two surges and those who died before the second surge. We did an alternative cohort analysis, in which we compared infection rates throughout the year between those with and without a previous confirmed infection at least 3 months earlier, irrespective of date. We also investigated whether differences were found by age group, sex, and time since infection in the alternative cohort analysis. We calculated rate ratios (RRs) adjusted for potential confounders and estimated protection against repeat infection as 1-RR. Findings During the first surge (ie, before June, 2020), 533 381 people were tested, of whom 11 727 (2•20%) were PCR positive, and 525 339 were eligible for follow-up in the second surge, of whom 11 068 (2•11%) had tested positive during the first surge. Among eligible PCR-positive individuals from the first surge of the epidemic, 72 (0•65% [95% CI 0•51-0•82]) tested positive again during the second surge compared with 16 819 (3•27% [3•22-3•32]) of 514 271 who tested negative during the first surge (adjusted RR 0•195 [95% CI 0•155-0•246]). Protection against repeat infection was 80•5% (95% CI 75•4-84•5). The alternative cohort analysis gave similar estimates (adjusted RR 0•212 [0•179-0•251], estimated protection 78•8% [74•9-82•1]). In the alternative cohort analysis, among those aged 65 years and older, observed protection against repeat infection was 47•1% (95% CI 24•7-62•8). We found no difference in estimated protection against repeat infection by sex (male 78•4% [72•1-83•2] vs female 79•1% [73•9-83•3]) or evidence of waning protection over time (3-6 months of follow-up 79•3% [74•4-83•3] vs ≥7 months of follow-up 77•7% [70•9-82•9]). Interpretation Our findings could inform decisions on which groups should be vaccinated and advocate for vaccination of previously infected individuals because natural protection, especially among older people, cannot be relied on.

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Section: Discussionmentioning

confidence: 99%

Assessment of protection against reinfection with SARS-CoV-2 among 4 million PCR-tested individuals in Denmark in 2020: a population-level observational study

et al. 2021

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“…Amino acid substitutions D614G and N501Y in the S gene and L84S in ORF8a have been suggested to result in increased viral load [33,34]. S gene D614G is highly prevalent [35] and N501Y has led to COVID surges [36]. Being able to distinguish SARS-CoV-2 strains may aid in whether certain strains are associated with differential clinical outcomes and/or could provide rapid information to public health departments.…”

Section: Cas9 Analysis Of a Sars-cov-2 Variantmentioning

confidence: 99%

CRISPR/Cas9-Based Lateral Flow and Fluorescence Diagnostics

et al. 2021

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Clustered regularly interspaced short palindromic repeat (CRISPR/Cas) proteins can be designed to bind specified DNA and RNA sequences and hold great promise for the accurate detection of nucleic acids for diagnostics. We integrated commercially available reagents into a CRISPR/Cas9-based lateral flow assay that can detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequences with single-base specificity. This approach requires minimal equipment and represents a simplified platform for field-based deployment. We also developed a rapid, multiplex fluorescence CRISPR/Cas9 nuclease cleavage assay capable of detecting and differentiating SARS-CoV-2, influenza A and B, and respiratory syncytial virus in a single reaction. Our findings provide proof-of-principle for CRISPR/Cas9 point-of-care diagnosis as well as a scalable fluorescent platform for identifying respiratory viral pathogens with overlapping symptomology.

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“…Organization has reported over 108 million confirmed clinical cases of COVID-19 and over 2.3 million deaths worldwide (https://www.who.int/emergencies/diseases/novel -coronavirus-2019/situation-reports). Notably, the emergence and rapid spread of new pathogenic variants of SARS-COV-2 (1)(2)(3)(4)(5) and the recent resurgence of COVID-19 in Brazil (6) are making this global health crisis more intractable. There is therefore urgent global demand for tools and resources to investigate numerous aspects of SARS-COV-2 biology.…”

mentioning

confidence: 99%

Infectious Clones Produce SARS-CoV-2 That Causes Severe Pulmonary Disease in Infected K18-Human ACE2 Mice

Liu

Zaid

Freitas

et al. 2021

mBio

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Newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic, which has caused extensive mortality and morbidity and wreaked havoc on socioeconomic structures. The urgent need to better understand SARS-CoV-2 biology and enable continued development of effective countermeasures is aided by the production of laboratory tools that facilitate SARS-CoV-2 research. We previously created a directly accessible SARS-CoV-2 toolkit containing user-friendly reverse genetic (RG) infectious clones of SARS-CoV-2. Here, using K18-human ACE2 (hACE2) mice, we confirmed the validity of RG-rescued SARS-CoV-2 viruses to reproduce the infection profile, clinical disease, and pathogenesis already established in mice infected with natural SARS-CoV-2 isolates, often patient derived. RG-rescued SARS-CoV-2-infected K18-hACE2 mice developed substantial clinical disease and weight loss by day 6 postinfection. RG-rescued SARS-CoV-2 was recovered from the lungs and brains of infected K18-hACE2 mice, and infection resulted in viral pneumonia with considerable changes in lung pathology, as seen previously with natural SARS-CoV-2 infection. In mice infected with RG-rescued SARS-CoV-2-mCherry, mCherry was detected in areas of lung consolidation and colocalized with clinically relevant SARS-CoV-2-assocated immunopathology. RG-rescued SARS-CoV-2 viruses successfully recapitulated many of the features of severe COVID-19 associated with the K18-hACE2 model of SARS-CoV-2 infection. With utility in vivo, the RG-rescued SARS-CoV-2 viruses will be valuable resources to advance numerous areas of SARS-CoV-2 basic research and COVID-19 vaccine development. IMPORTANCE To develop COVID-19 countermeasures, powerful research tools are essential. We produced a SARS-COV-2 reverse genetic (RG) infectious clone toolkit that will benefit a variety of investigations. In this study, we further prove the toolkit’s value by demonstrating the in vivo utility of RG-rescued SARS-CoV-2 isolates. RG-rescued SARS-CoV-2 isolates reproduce disease signs and pathology characteristic of the K18-hACE2 mouse model of severe COVID-19 in infected mice. Having been validated as a model of severe COVID-19 previously using only natural SARS-CoV-2 isolated from patients, this is the first investigation of RG-rescued SARS-CoV-2 viruses in K18-hACE2 mice. The RG-rescued SARS-CoV-2 viruses will facilitate basic understanding of SARS-CoV-2 and the preclinical development of COVID-19 therapeutics.

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Introduction of the South African SARS-CoV-2 variant 501Y.V2 into the UK

Cited by 147 publications

References 4 publications

Assessment of protection against reinfection with SARS-CoV-2 among 4 million PCR-tested individuals in Denmark in 2020: a population-level observational study

Assessment of protection against reinfection with SARS-CoV-2 among 4 million PCR-tested individuals in Denmark in 2020: a population-level observational study

CRISPR/Cas9-Based Lateral Flow and Fluorescence Diagnostics

Infectious Clones Produce SARS-CoV-2 That Causes Severe Pulmonary Disease in Infected K18-Human ACE2 Mice

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