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To the Editor-The current outbreak of COVID-19 in India, which started in early March 2021, has created a new world record even beyond the outbreaks in the UK, the United States and Brazil. Prior to March 2021, less than 0.7% of the Indian population was infected with COVID-19. This current second wave took only 2 months to infect an additional ~0.36% of the population, and India is now recording over 0.4 million new cases per day (as of 23 April 2021). The true number is probably even higher, with some estimates putting the number of daily new cases at over 1 million, more than five times the officially recorded number 1 .The sudden surge in COVID-19 cases in India coincides with high prevalence of more-transmissible variants, associated with diagnostic test failures and antibody escape 2 . These coronavirus SARS-CoV-2 variants of concern-B.1.1.7 (501Y.V1), B.1.351 (501Y.V2) and B.1.1.28.1 (501Y.V3; also known as P.1)-were observed during the sudden surge in COVID-19 cases in the UK, South Africa and Brazil, respectively, with subsequent local transmission across the world 2,3 (Fig. 1a).In India, the frequency of 501Y.V1 is higher than that of 501Y.V2 and 501Y.V.3 (Fig. 1b). The recently designated variant of concern B.1.617 and variant of interest B.1.618 have also been gaining attention in India 3 (Fig. 1a-c). Variant B.1.617.1 shows co-occurrence of three key mutations in sequence encoding the viral spike protein: L452R, E484Q and P681R. L452R raised concerns in the United States as part of the California variants B.1.427 and B.1.429 and conferred resistance to the neutralizing monoclonal antibodies X593 and P2B-2F6 4 . E484Q shares antibody-escape features similar to those of mutation E484K, seen in variants 501Y.V2, 501Y.V3 and B.1.618 2 . P681R may enhance processing by host proteases by extending the polybasic 'RRAR' motif, which results in a greater viral load and the potential for increased transmission. Another similar variant of concern, B.1.617.2, with mutations L452R, T478K and P681R, is highly prevalent in the state of Gujrat in India 3 . There was enrichment for the mutation T478K or T478R when SARS-CoV-2 was subjected to weak neutralizing antibodies, which indicates this mutation may lead to antibody escape.

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