An observational study of patients at UCLH and North Middlesex University Hospital, published in The Lancet Infectious Diseases, suggests that the B.1.1.7 variant of COVID-19 – sometimes known as the UK or Kent variant – is not associated with more severe illness and death, but appears to lead to higher virus load.
The emergence of variants has raised concerns that they could spread more easily and be more deadly, and that vaccines developed based on the original strain might be less effective against them. Preliminary data on B.1.1.7 indicated that it is more transmissible, with some evidence suggesting it could also be associated with increased hospitalisations and deaths.
The new study, led by Dr Eleni Nastouli of UCLH and UCL Great Ormond Street Institute of Child Health, in collaboration with researchers at the Advanced Pathogen Diagnostics Unit and i-sense EPSRC IRC, spanned the period between November and December 2020.
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Dr Eleni Nastouli said: “One of the real strengths of our study is that it ran at the same time that B.1.1.7 was emerging and spreading throughout London and the south of England. Analysing the variant before the peak of hospital admissions and any associated strains on the health service gave us a crucial window of time to gain vital insights into how B.1.1.7 differs in severity or death in hospitalised patients from the strain of the first wave. Our study is the first in the UK to utilise whole genome sequencing data generated in real time and embedded in an NHS clinical service and integrated granular clinical data.”
The findings of the study provide important insights into the variant’s characteristics that will help inform public health, clinical, and research responses to this and other COVID-19 variants.
Prof of Biomedical Nanotechnology at UCL and Director of i-sense, Rachel McKendry, said: “This important study highlights the power of genomics and interdisciplinary science to track the impact of emerging SARS-CoV-2 variants, and builds on our strategic collaboration between the i-sense EPSRC IRC and ADPU.”
What did the study involve?
The whole-genome sequencing and cohort study involved COVID-19 patients admitted to UCLH and North Middlesex University Hospital between 9 November and 20 December 2020. This was a critical time point when both the original and B.1.1.7 variants were circulating in London, the vaccination programme was just starting, and before a significant surge in cases in early 2021 caused a strain on the NHS.
The authors compared illness severity in people with and without B.1.1.7 and calculated viral load. Among 341 patients who had their COVID-19 test swabs sequenced, 58% (198/341) had B.1.1.7 and 42% (143/341) had a non-B.1.1.7 infection (two patients’ data were excluded from further analysis).
What conclusions were made about the severity of B.1.1.7 compared to other strains?
No evidence of an association between the variant and increased disease severity was detected, with 36% (72/198) of B.1.1.7 patients becoming severely ill or dying, compared with 38% (53/141) of those with a non-B.1.1.7 strain.
Patients with the variant tended to be younger, with 55% (109/198) of infections in people under 60 compared with 40% (57/141) for those who did not have B.1.1.7 Infections with B.1.1.7 occurred more frequently in ethnic minority groups, accounting for 50% (86/172) of cases that included ethnicity data, compared with 29% (35/120) for non-B.1.1.7 strains.
Those with B.1.1.7 were no more likely to experience severe disease after accounting for hospital, sex, age, ethnicity and underlying conditions.
Those with B.1.1.7 were no more likely to die than patients with a different strain, with 16% (31/198) of B.1.1.7. patients dying within 28 days compared with 17% (24/141) for those with a non-B.1.1.7 infection.
More patients with B.1.1.7 were given oxygen than those with a non-B.1.1.7 strain (44%, 88/198 vs 30%, 42/141, respectively). However, the authors say this is not a clear measure of disease severity, as patients may have received nasal prong oxygen for reasons unrelated to COVID-19, or as a consequence of underlying conditions.
To gain insights into the transmissibility of B.1.1.7, the authors used data generated by PCR testing of patient swabs to predict their viral load – the amount of virus in a person’s nose and throat. The data analysed – known as PCR Ct values and genomic read depth – indicated that B.1.1.7 samples tended to contain greater quantities of virus than non-B.1.1.7 swabs.
Prof of Virology at UCL Division of Infection and Immunity and i-sense co-Director, Deenan Pillay, said: “It is essential to rapidly determine the clinical implications of new viral variants as they emerge. Placed within the context of other findings, our results suggest that even though the B.1.1.7 variants may lead to higher rates of hospitalisation, our current clinical practice can manage these variants as well as earlier circulating COVID-19 viruses. Ongoing trials of new therapies aim to improve outcomes further.”
The authors acknowledge some limitations to their study. Disease severity was captured within 14 days of a positive COVID-19 test, so patients who may have deteriorated after 14 days may have been missed in the analysis, though the authors sought to mitigate this by capturing deaths at 28 days. The analyses also did not take account of any other treatments that patients were receiving – such as steroids, antiviral medications, or convalescent plasma – or the possibility that some patients may have received ventilation for reasons other than COVID-19.
A separate observational study published at the same time in The Lancet Public Health using data logged by 37,000 UK users of a self-reporting COVID-19 symptom app found no evidence that B.1.1.7 altered symptoms or likelihood of experiencing long COVID.
These important findings were made possible through the ability to capture real time clinical and laboratory data within University College London Hospital and North Middlesex Hospital through funding from UCLH NHS foundation Trust and ongoing investment by the NIHR UCLH/UCL Biomedical Research Centre and the Engineering and Physical Sciences Research Council-funded i-sense project in Early Warning Sensing Systems for Infectious Diseases.
- Dan Frampton, PhD *
- Tommy Rampling, DPhil *
- Aidan Cross, MBChB *
- Heather Bailey, PhD *
- Judith Heaney, PhD
- Matthew Byott, MSc
- Rebecca Scott, MBChB
- Rebecca Sconza, MSc
- Joseph Price, MBChB
- Marios Margaritis, DPhil
- Malin Bergstrom, BMBS
- Moira J Spyer, PhD
- Patricia B Miralhes, MBBS
- Paul Grant, PhD
- Stuart Kirk, Msc
- Chris Valerio, MBChB
- Zaheer Mangera, MA
- Thaventhran Prabhahar, FFICM
- Jeronimo Moreno-Cuesta, MD
- Nish Arulkumaran, PhD
- Prof Mervyn Singer, FRCP
- Gee Yen Shin, FRCPath
- Emilie Sanchez, MD
- Stavroula M Paraskevopoulou, MBBS
- Prof Deenan Pillay, PhD
- Prof Rachel A McKendry, PhD
- Mariyam Mirfenderesky, FRCPath
- Catherine F Houlihan, PhD †
- Eleni Nastouli, FRCPath