Low‐frequency variants in mildly symptomatic vaccine breakthrough infections presents a doubled‐edged sword

Abstract

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) has raised questions regarding vaccine protection against SARS-CoV-2 infection, transmission, and ongoing virus evolution. Twenty-three mildly symptomatic "vaccination breakthrough" infections were identified as early as January 2021 in Alachua County, Florida, among individuals fully vaccinated with either the BNT162b2 (Pfizer) or the Ad26 (Janssen/J&J) vaccines. SARS-CoV-2 genomes were successfully generated for 11 of the vaccine breakthroughs, and 878 individuals in the surrounding area and were included for reference-based phylogenetic investigation. These 11 individuals were characterized by infection with VOCs, but also low-frequency variants present within the surrounding population. Low-frequency mutations were observed, which have been more recently identified as mutations of interest owing to their location within targeted immune epitopes (P812L) and association with increased replicative capacity (L18F).We present these results to posit the nature of the efficacy of vaccines in reducing symptoms as both a blessing and a curse-as vaccination becomes more widespread and self-motivated testing reduced owing to the absence of severe symptoms, we face the challenge of early recognition of novel mutations of potential concern. This case study highlights the critical need for continued testing and monitoring of infection and transmission among individuals regardless of vaccination status.

The complex evolutionary dynamics of SARS‐CoV‐2, a big challenge to control the pandemic of COVID‐19

“…Notably, the work published by Magalis et al 1 presents an interesting perspective that the VOC where not the only variants producing breakthrough infections in vaccinated individuals, but in addition variants of low circulation also played a part in this equation during the pandemic (Figure 2C ). The authors report a new set of mutations in the spike protein of lineage B.1.1.7 (L18F and K1191N), which have also come under positive selection during the course of the pandemic ( https://observablehq.com/ @spond/revised‐sars‐cov‐2‐analytics‐page).…”

“…I found the article published by Magalis et al 1 Magalis et al 1 particularly interesting as the information presented in this article covers two significant aspects that should be considered as a part of the control of the coronavirus disease 2019 (COVID‐19) pandemic. The first of these aspects is the potential role of the low‐frequency variants in the epidemiology of COVID‐19, an issue directly linked with the evolutionary profile of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), and the second aspect is the presentation of breakthrough infections among vaccinated individuals, a situation associated with the effectiveness of the current vaccines used during this pandemic.…”

“…(B) Circulation dynamic of different variants during the pandemic. (C) Percentage of available sequences at the GISAID database associated with the lineages described by Magalis et al, 1 representing the low circulation of these lineages during the pandemic around the world. However, it is important to consider the huge temporal and geographical biases in sequencing and the presence of locally dominant variants that might have predominated in a single region/or country for this reason the concept of low‐circulating lineage must be taken with caution.…”

Shedding of Infectious SARS-CoV-2 Despite Vaccination

“…Vaccine effectiveness, particularly against symptomatic, test-positive SARS-CoV-2 infection, wanes with time after vaccine receipt [10][11][12][13][14][15][16][17][18][19][20][21]. We therefore asked whether Ct values decreased as a function of time between last vaccination and the time at which individuals tested positive for SARS-CoV-2 infection.…”

Structural Evolution of Delta (B.1.617.2) and Omicron (BA.1) Spike Glycoproteins

“…Since its first identification, multiple vaccines that are based on different technologies and several therapeutics against SARS-CoV-2 and its associated COVID-19 disease have been successfully developed in a concerted global effort to provide effective protection against severe illness [ 17 , 18 , 19 , 20 ]. However, new emerging variants have acquired mutations that hampered drug and vaccine efficacy, with a progressive increase in breakthrough infections have been reported [ 21 , 22 , 23 ]. Therefore, obtaining a rapid and refined tri-dimensional structure analysis of the proteins that are mainly involved in the host-pathogen interaction can ensure that new variants with potential impact on public health are assessed in a timely manner.…”