The Impact of the Highly Virulent SARS-CoV-2 Gamma Variant on Young Adults in the State of São Paulo: Was It Inevitable?

Abstract

Background The coronavirus disease 2019 (COVID-19) pandemic had and is still having a tremendous impact on people all over the world, but it has been particularly harsh in South America. Nine out of 13 South American countries are among the 50 countries with the highest COVID-19 death rates. The gamma severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant that emerged by the end of 2020 in the Brazilian Amazon quickly spread throughout the country causing the harsh COVID-19 second wave. This variant displayed high viral loads, high transmissibility, and increased virulence as compared to previous variants. Aims The aim of this retrospective study is to revisit and analyse the epidemiology of the COVID-19 second wave in the state of São Paulo, the most populous Brazilian state. In addition to examining the possible factors that led to the emergence and propagation of the gamma variant, measures that could have prevented its spread and that of other highly virulent variants were also investigated. Materials and methods Data from São Paulo's official sources on morbidity, mortality, age distribution, and testing prior to and during the COVID-19 second wave (February - June 2021) and data regarding the distribution of SARS-CoV-2 variants in the country were parsed, analyzed, and compared to the period that anteceded the eruption of the second COVID-19 wave. Results In the state of São Paulo, the toll of the COVID-19 second wave surpassed that of the first 11 months of the pandemic (from March 2020 to January 2021), as 56% of the deaths occurred in the five months of the second wave between February and June 2021. The mean age of COVID-19 victims, which was already below life expectancy in the state dropped even further in the pandemic's second wave, reaching an average of 60 years of age. The years of life lost per death per month doubled and the case-fatality rate (CFR) of young adults (20-39 years old) more than trebled during this period. A number of hypotheses have been raised that might explain the emergence and spread of the gamma variant and the measures that could have been taken to prevent it and minimise its impact on the population. Conclusions Over 142,000 people died as a result of the SARS-CoV-2 gamma variant sweep in São Paulo in the first semester of 2021. Due to its high viral load, the gamma variant displayed high transmissibility and a high degree of virulence resulting in increased case fatality rates across most age tiers. Notably, this second wave was marked by a very significant increase in deaths among young adults. This increase was at least partially due to a deterioration in general health provoked by non-pharmaceutical interventions. In hindsight, a safer and more effective measure might have been to allow the free spread of the virus among the young and healthy in the first wave, thus conferring immunity against more virulent variants that emerged later on.

Keywords: covid-19; mutations; pandemic; sars-cov-2; selection; voc; γ.

Figure 1. Epidemiological data of COVID-19 in the state of São Paulo

A. COVID-19 cases (red) and deaths (blue) in the state of São Paulo throughout the pandemic, from March 2020 to October 2021. B. The average age of COVID-19 deaths (red) and years of life lost per number of deaths in each month (blue) throughout the pandemic (March 2020 - October 2021) in the state of São Paulo. Asterisks represent statistically significant differences between the mean age of death in each month from February to July 2021 and the mean age of death in all other months (; ANOVA followed by post hoc Tukey analysis). C. The number of COVID-19 tests per month (red) and the evolution of the CFR (blue) in the state of São Paulo. D. CFR increase in the different age groups in the COVID-19 second wave in the state of São Paulo. The mean CFR of each age group in the Feb-Jun 2021 period was divided by the corresponding mean CFR of each age group in the Jul-Dec 2020 period. E. Frequency of SARS-CoV-2 VOCs alpha, beta, gamma and delta in Brazil (from July 2020 to October 2021). Total number of sequenced VOCs = 59,982; total number of sequenced genomes = 64,378. Red bars, gamma; green bars, delta; pink bars, alpha; blue bars, beta (almost invisible due to very low frequency). Plots shown in A, B, C, and D were calculated from data downloaded on 29.11.21 from Seade [24]. Testing data in C was downloaded from https://www.saopaulo.sp.gov.br/planosp/simi/dados-abertos/ and VOCs frequency in E was downloaded on 31.10.21 from http://www.gisaid.org. ANOVA: analysis of variance; CFR: case-fatality rate

Figure 2. Schematic representation of the transmission dynamics of different SARS-CoV-2 variants

(A) Spread of SARS-CoV-2 variants that produce low viral loads under conditions of unrestrictive physical contact; (B) spread of SARS-CoV-2 variants under physical distancing restrictions. Left: variants that produce low viral loads (and are, therefore, less virulent), cannot successfully spread throughout the host population. Right: a highly virulent/highly transmissible variant, such as gamma, produce high viral loads and has an advantage under restrictive physical distancing conditions. S represents potential susceptible hosts.