Early Reports Of U.K. Variant's Lethality Appear Greatly Exaggerated


 
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By Molly Walker

The COVID-19 variant B.1.1.7, also known as the U.K. variant, was not associated with more severe disease in hospitalized patients versus non-variant strains, but it does appear to be more transmissible, British researchers found.

There was no association between severe disease and death and the SARS-CoV-2 strain (adjusted prevalence ratio 1.02, 95% CI 0.76-1.38), though viral load was higher among patients with B.1.1.7 versus non-B.1.1.7 strains, reported Eleni Nastouli, MD, of University College London in England, and colleagues.

Most research supports the idea that B.1.1.7 is more transmissible, but a report released by the British government in February examining several studies concluded, "it is likely that infection with ... B.1.1.7 is associated with an increased risk of hospitalisation and death compared to infection with non-[variant] viruses."

However, the government report noted that these analyses used a proxy for B.1.1.7, the S-gene target failure on PCR assay, to determine if a case was caused by a variant or not, where research by Nastouli and colleagues used genomic sequencing to find a more definitive answer.

An accompanying editorial by David Lye, MBBS, of the National Centre for Infectious Diseases in Singapore, and colleagues noted this, as well as other reasons for differences. The populations differed, for example, with the earlier studies relying on a "community-based testing dataset," whereas the current research examined hospitalized patients who included "substantially more older adults" than the earlier studies.

"Although these large community studies found a significant difference in mortality at a population level, the absolute risk increase affecting individual patients is probably minimal," the editorialists wrote, adding that the advantages of the current research include "use of whole-genome sequencing, recruitment of hospitalised patients, and a population reflective of the spectrum of severity in whom increased virulence will have the greatest effect on outcomes."

Lye and colleagues characterized these findings as "reassuring," but emphasized that further confirmation from larger studies was needed.

Nastouli's group examined SARS-CoV-2 samples from patients at two British hospitals on or before Dec. 20, 2020. Of the 496 patients meeting inclusion criteria, 341 had samples that could be sequenced, and 58% of those were B.1.1.7.

They defined severe disease as point 6 or higher on the WHO ordinal scale within 14 days of either a positive test or symptoms, and death was defined as within 28 days. The authors used PCR cycle threshold values and sequencing read depths as a proxy for viral load, which defined transmissibility.

Compared with patients with non-B.1.1.7 strains, those with B.1.1.7 were more likely to be younger, have fewer comorbidities, and belong to an ethnic minority.

Mortality was nearly identical in the two groups: 16% of patients with B.1.1.7 died within 28 days versus 17% of those without B.1.1.7. Cycle threshold values associated with B.1.1.7 were significantly lower than with other strains, and median genomic read depths were higher.

Limitations to the data include potential confounding and the possibility of missed or misclassified data.

Reported COVID-19 Symptoms No Worse With U.K. Variant

A second study, published simultaneously by Mark Graham, PhD, of King's College London in England, and colleagues found no significant differences in reported symptoms or disease duration in patients with B.1.1.7 among users reporting their COVID-19 test results through an app.

Test results and symptom reports were collected from Sept. 28 to Dec. 20 from about 37,000 users of the COVID Symptom Study app. Graham and colleagues put that together with data on regional proportion of infections, symptoms, disease duration, reinfection rates, and transmissibility from the COVID-19 Genomics U.K. Consortium and Public Health England.

No significant association was found between the proportion of B.1.1.7 in a region and the symptoms that patients experienced. There was also no evidence of any change in total number of symptoms from people in the region with the earliest rise of B.1.1.7, and no difference in the proportion of people experiencing long COVID symptoms.

Similar to other studies, Graham and colleagues found that B.1.1.7 appeared to increase the overall reproduction number by 1.35 versus the original strain.

An accompanying editorial by Britta Jewell, MD, of Imperial College London, emphasized that while B.1.1.7 may have "similar symptomatology" as other strains, "improving genomic surveillance of variants will be essential to the goal of ending the pandemic."

She suggested that apps like the COVID Symptom Study app, which allows patients to monitor their symptoms and disease characteristics in real time, "could help to identify potentially important changes in symptomatology, transmissibility, mortality, or vaccine avoidance as early as possible."

 
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    • Editor-in Chief:
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