Could it be that the B.1.1.7 lineage is more deadly?

To the Editor—The world had been shocked by the emergence of a new variant (B.1.1.7) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which might have been circulated since September 2020 from the southeastern region of England.[1] As reported, this new lineage of SARS-CoV-2 has acquired 17 mutations in its genome that lead to amino acid changes within the Spike receptor-binding domain.[1] The analyses thus far have indicated that the B.1.1.7 lineage might be more transmissible than other SARS-CoV-2 lineages, with a reproduction ratio higher than those of other SARS-CoV-2 lineages by 0.4 and 0.7 (ie, up to 70% more transmissible).[2] Santos et al[3] employed in silico methods to analyze the interaction between the Spike receptor-binding domain of the B.1.1.7 variant and the ACE2 receptor. They discovered that the N501Y mutant residue on the spike protein of the B.1.1.7 variant establishes a more significant number of interactions with the ACE2 receptor, indicating an increased interaction force with the ACE2 receptor, which could explain its increased infectivity. In contrast, although the newly discovered 501Y.V2 variant, which spread rapidly in the Eastern Cape and Western Cape Provinces of South Africa, also contains the N501Y mutant residue on the spike protein, the substitutions K417N and E484K in the South African variant 501.V2 would reduce its binding affinity with ACE2 receptor, resulting in binding affinity comparable to that of the wild-type Spike receptor-binding domain.[4]

Arif[5] commented that there is uncertainty regarding the severity of disease in people infected with SARS-CoV-2 of the B.1.1.7 lineage. Nevertheless, the general assumption that the B.1.1.7 lineage would not lead to increased severity of COVID-19 may not hold true because increased binding affinity between the Spike receptor-binding domain and ACE2 receptor could lead to more ACE2 downregulation should an individual acquire this new variant compared to other variants.[6] Interestingly, the mutation in the D614G variant, which currently dominates in much of the world, does not increase Spike protein affinity for ACE2.[7] Indeed, the D614G variant is not associated with increased severity of COVID-19 compared to the ancestral strain, although with increased viral load.[8,9] Until the association between B.1.1.7 lineage and increased severity of COVID-19 is conclusively discredited, perhaps patients who acquire the new B.1.1.7 variant should be managed more aggressively with anti-inflammatory therapies, and the current antiviral armamentarium of COVID-19, especially remdesivir, should be evaluated if it preserves its efficacy against this new variant.