The "Delta plus" COVID-19 Variant Has Evolved to Become the Next Potential Variant of Concern

Abstract

Since the first case of coronavirus disease 2019 (COVID-19) in Wuhan of Hubei province, China back in December 2019, waves of outbreak caused by the severe acute respiratory coronavirus 2 (SARS-CoV-2) have continued to claim lives in different regions of the world [1]. As of August 30, 2021, the World Health Organization (WHO) reports more than 216 million confirmed COVID-19 cases with almost 4.5 million casualties [2]. Although multiple vaccines have been discovered which are being administered worldwide, the virus continues to rage on, mainly due to its rapid mutations that keep enhancing its potency by imparting unique characteristics [3]. Viruses keep evolving as it replicates, and it is only natural for newer variants of a virus to develop over time. Since the pandemic began, numerous mutant strains of SARS-CoV-2 have been identified. They have been classified into three categories-variant of interest, variant of concern, and a variant of high consequence by the SARS-CoV-2 Interagency Group of the US Department of Health and Human Services [4]. In December 2020, the first reports of these variants of concern were emerging. The B.1.1.7 variant (WHO label: Alpha) had a mutation (N501Y) in the receptor-binding domain of its spike protein which increased its rate of transmission and caused an unexpected rise of COVID-19 cases in the United Kingdom [5]. Another variant, B.1.351 (WHO label: Beta) has three concerning mutations (N501Y, E484K, and K417N) in its spike protein and it spread like wildfire in South Africa [6] due to its increased transmission rate and potential to escape antibodies [7]. Later on, the P.1 variant (WHO label: Gamma) discovered in Manaus, Brazil was found to have a set of mutations (N501Y, E484K, and K417T) in its spike protein which probably contributed to the country’s massive death toll from COVID-19 infection over the first half of 2021 [8]. However, the most concerning variant right now is B.1.617.2 (WHO label: Delta) that has become the predominant SARS-CoV-2 strain in the world with unique sets of mutations (T478K, P681R, and L452R) that makes it highly contagious and evade neutralizing antibodies in previously infected or vaccinated people [9]. Since the first detection of the Delta variant in India in late 2020, the strain has caused an upsurge of COVID-19 infection in different countries. It has continued to evolve as well, extending its lineage into various subtypes. On June 11, 2021, Public Health England began to report on the AY.1 sub-lineage of delta variant in its technical briefings, which has an additional K417N mutation in its spike protein [10]. This AY.1 variant, also known as the “Delta Plus” variant, is feared to have even more antibody escaping properties because of the K417N mutation which was previously seen in the Beta variant. As of August 31, 2021, 895 genome sequences of the Delta Plus variant have been identified in at least 32 countries around the world, the majority of them being in the United States [11]. The Delta Plus variant was found to have reduced neutralization in COVID-19 naïve or recovered patients who were vaccinated by the BBV152 (Covaxin) vaccine in India [12]. It has also been reported to resist monoclonal antibodies such as Casirivimab and Imdevimab which are used against COVID-19 and it has been suggested of having increased transmissibility and greater affinity to the mucosal lining of lungs compared to other variants [13]. India has already announced Delta Plus to be a variant of concern in June, after around 40 cases were reported in Maharashtra, Kerala, and Madhya Pradesh [14]. However, U.S. Centers for Disease Control and Prevention and the WHO have not done so yet as some experts believe that it is still unclear how dangerous the variant is [15]. We have presented epidemiological evidence of the current variants of concern and the Delta Plus variant in Table 1.