Viruses naturally evolve over time, leading to changes in their genetic makeup. These changes can result in new versions of the virus, known as variants. Some variants acquire mutations that alter their behavior, affecting how easily they spread, the severity of the illness they cause, or how they respond to treatments and vaccines. During the global pandemic, one such variant emerged, identified by the World Health Organization (WHO) as a “variant of concern” and designated as the Gamma variant.
Origin and Characteristics of the Gamma Variant
The Gamma variant, scientifically known as lineage P.1, was first detected in early January 2021. It was initially identified in four travelers arriving in Tokyo, Japan, who had recently visited Amazonas, Brazil. Soon after, the variant was confirmed to be circulating widely in Manaus, the capital of Amazonas, Brazil, where it contributed to a significant surge in cases.
The WHO later labeled this P.1 lineage as the Gamma variant. This variant carried 17 amino acid substitutions, ten in its spike protein. Among the most concerning mutations were N501Y, E484K, and K417T, all found in the receptor-binding domain of the spike protein. N501Y enhanced the virus’s binding to human ACE2 receptors, potentially increasing infectivity. E484K raised alarms for its potential to evade the immune response.
Transmissibility and Disease Severity
Gamma showed enhanced transmissibility compared to earlier strains. It was estimated to be 1.2 to 2.7 times more contagious than the original Wuhan strain. This increased transmissibility led to rapid spread, particularly in Manaus, Brazil, which experienced a widespread infection wave in early 2021.
Gamma’s impact on disease severity was complex. While some initial observations suggested no strong evidence of enhanced lethality, other studies linked its predominance to a greater increase in mortality rates. For instance, in Ribeirão Preto, Brazil, the period dominated by the Gamma variant saw a 3.4-fold increase in deaths among the 17-50 age group compared to an earlier period. The variant also caused reinfections in individuals who had recovered from earlier SARS-CoV-2 strains. However, studies on reinfected individuals suggested a low overall risk of severe Gamma reinfections, indicating that the surge in hospitalizations was mostly driven by primary infections.
Impact on Vaccines and Treatments
The mutations present in the Gamma variant, especially E484K, suggested a potential for reduced effectiveness of existing vaccines and treatments. Studies indicated Gamma was relatively resistant to neutralization by antibodies from convalescent plasma or mRNA vaccinees (Moderna/Pfizer). While a reduction in neutralizing activity was observed, the loss was modest, ranging from 3.8 to 4.8-fold.
For inactivated vaccines like CoronaVac, studies in Manaus, Brazil, showed about 50% effectiveness in preventing symptomatic illness 14 days after the first dose. Certain monoclonal antibody therapies showed reduced efficacy against Gamma. Specific monoclonal antibodies like bamlanivimab, casirivimab, and etesevimab showed significantly reduced or abolished neutralizing activity against Gamma due to its mutations. However, other monoclonal antibodies, such as imdevimab, retained activity against the variant.
Decline and Present Status
The Gamma variant’s period of widespread dominance was relatively short-lived. It was eventually outcompeted by newer, even more transmissible SARS-CoV-2 variants that emerged later. Variants like Delta and Omicron, with their distinct evolutionary advantages, rapidly displaced Gamma as the globally dominant strains.
The World Health Organization reclassified Gamma from a “variant of concern” in March 2022, reflecting its declining prevalence. Its global circulation is now very low, making it an infrequent detection in current genomic surveillance. The Gamma variant’s trajectory served as an example of viral evolution during the pandemic, highlighting the importance of global genomic surveillance to track viral changes.