A study recently published in the journal British Medical Journal (BMJ) has assessed the mortality risk of patients infected with the newly emerged UK variant (Lineage B.1.1.7) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The findings reveal that compared to the previously circulating SARS-CoV-2 variants, the UK variant significantly increases the risk of mortality in a relatively low-risk community population.
Background
In October 2020, a new variant of SARS-CoV-2 (Lineage B.1.1.7) was identified in southeast England, which was later designated as the Variant of Concern (VOC-202012/1) by the Public Health England in December 2020. By the end of December 2020, it had become the predominant variant in the UK, accounting for almost 75% of all SARS-CoV-2 infections. To control viral transmission, the UK government implemented several control measures, including international travel restrictions.
Genetic sequencing analysis of the UK variant has confirmed the presence of 14 mutations; of which, eight are present in the spike protein required for the viral entry into host cells. According to the available literature, these mutations have caused structural alterations in the spike protein, which in turn has improved the binding affinity between the virus and host cell. This might be the reason for significantly higher transmissibility/infectivity of the UK variant than the original SARS-CoV-2 strain.
In the study, the scientists have compared the mortality risk of patients infected with the UK variant or other circulating SARS-CoV-2 variants.
Study design
The study involved almost 55,000 matched pairs of individuals who tested positive for SARS-CoV-2 during community-level testing of symptomatic cases. The study cohort mostly included younger COVID-19 patients with less severe disease. Using S gene target failure approach, the scientists categorized all SARS-CoV-2 positive results as S gene-positive results (representing infections caused by other viral variants) and S gene-negative results (representing infections caused by the UK variant). Next, they linked both S gene-positive and -negative test results with the corresponding death reports. The primary parameter they assessed was death within 28 days of the first positive diagnosis of COVID-19.
Important observations
The scientists compared a total of 54,906 S gene-positive individuals with 54,906 S gene-negative individuals who were matched on age, ethnicity, gender, geographical location, and date of test sample collection. More than 85% of all cases were followed up for 28 days. By specifically analyzing the corresponding death reports, they observed that a total of 227 and 141 individuals from the S gene-negative and -positive study cohort, respectively, died within 28 days of the first COVID-19 diagnosis. Moreover, they observed that the patients who died were mostly older and men.
By estimating the hazard ratio in the survival analysis, the scientists observed that the risk of death was on an average 64% higher among individuals infected with the UK variant than those infected with other viral variants. However, they observed that the absolute risk of death remained low in this study population, increasing from 2.5 to 4.1 deaths per 1000 cases.
For an optimal evaluation, the scientists controlled many potential biases in the study. It is known that the mortality rate can be affected by an induction in patient to healthcare staff ratio, which may potentially result from an increasing number of critically ill patients in the hospital and a simultaneous reduction in healthcare staff due to SARS-CoV-2 infection or infection-related isolation. To overcome the impact of such events on the mortality rate, they matched the patients in a way that ensured a similar level of care for both study groups. However, they could not control a possible bias associated with the timing of testing. It is possible that a large percentage of asymptomatic individuals infected with the UK variant remain undiagnosed for a longer time. These people are potentially at higher risk of death because of the diagnosis of the disease at an advanced stage. However, there is evidence suggesting that individuals infected with the UK variant are more likely to be present for testing.
Interestingly, the scientists observed that the viral load of individuals infected with the UK variant was significantly higher than those infected with other viral variants. This effect was more prominent in those who died. The scientists mention that this effect could be an intrinsic feature of mutations present in the UK variant.
Study significance
The study reveals that the newly emerged UK variant of SARS-CoV-2 could be more lethal, in addition to having increased infectivity. The study mostly involves younger individuals with less severe COVID-19. The scientists suggest that the mortality risk analysis should also be conducted on critically ill in-hospital COVID-19 patients to more accurately estimate the mortality risk associated with the UK variant.
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