The gamma SARS-CoV-2 variant that emerged by the end of 2020 in the Brazilian Amazon quickly spread throughout the country causing a harsh COVID-19 2nd wave. This variant displayed high viral loads, high transmissibility and increased virulence compared to previous variants. In the state of São Paulo, the most populous state of Brazil, the toll of the COVID-19 2nd wave surpassed that of the the first eleven months of the pandemic (from March 2020 to January 2021), as 56% of the deaths occurred in the five months of the 2nd wave, between February and June 2021. The mean age of COVID-19 victims dropped even further in the pandemic's 2nd wave, declining from an average of 70 to 60 years old; the years of life lost per death per month doubled and the case-fatality rate of young adults (20-39 years old) more than trebled during this period. Herein the evolution and epidemiology of SARS-CoV-2 in the context of of the pandemic 2nd wave in the state of São Paulo is revisited. Several hypotheses that might explain the emergence and spread of the gamma variant as well as the measures that could have been taken to prevent the selection and minimise the impact of this deadly variant are raised and discussed.