Genomic Analysis of SARS-CoV-2 Variants of Concern Circulating in Hawai’i to Facilitate Public-Health Policies

Abstract

Using genomics, bioinformatics and statistics, herein we demonstrate the effect of statewide and nationwide quarantine on the introduction of SARS-CoV-2 variants of concern (VOC) in Hawai’i. To define the origins of introduced VOC, we analyzed 260 VOC sequences from Hawai’i, and 301,646 VOC sequences worldwide, deposited in the GenBank and global initiative on sharing all influenza data (GISAID), and constructed phylogenetic trees. The trees define the most recent common ancestor as the origin. Further, the multiple sequence alignment used to generate the phylogenetic trees identified the consensus single nucleotide polymorphisms in the VOC genomes. These consensus sequences allow for VOC comparison and identification of mutations of interest in relation to viral immune evasion and host immune activation. Of note is the P71L substitution within the E protein, the protein sensed by TLR2 to produce cytokines, found in the B.1.351 VOC may diminish the efficacy of some vaccines. Based on the phylogenetic trees, the B.1.1.7, B.1.351, B.1.427, and B.1.429 VOC have been introduced in Hawai'i multiple times since December 2020 from several definable geographic regions. From the first worldwide report of VOC in GenBank and GISAID, to the first arrival of VOC in Hawai’i, averages 320 days with quarantine, and 132 days without quarantine. As such, the effect of quarantine is shown to significantly affect the time to arrival of VOC in Hawai’i, both during and following quarantine. Further, the collective 2020 quarantine of 43-states in the United States demonstrates a profound impact in delaying the arrival of VOC in states that did not practice quarantine, such as Utah. Our data demonstrates that at least 76% of all definable SARS-CoV-2 VOC have entered Hawai’i from California, with the B.1.351 variant in Hawai’i originating exclusively from the United Kingdom. These data provide a foundation for policy-makers and public-health officials to apply precision public health genomics to real-world policies such as mandatory screening and quarantine.

Algorithm for the Quantitation of Variants of Concern for Rationally Designed Vaccines Based on the Isolation of SARS-CoV-2 Hawaiʻi Lineage B.1.243

“…14 Similarly, using this quantitative analysis in April 2021, we predicted the spread of the Delta variant in Hawaii and worldwide as of June 2021. 13 In this report we demonstrate the characteristic emergence and selective evolution of VOC using the B.1.1.7 VOC as an example, with a Pearson's correlation of 0.92. The B.1.1.7 VOC, the most prevalent VOC worldwide in April 2021, has spread across the globe after emerging in the United Kingdom in December 2020.…”

“…All Hawai'i sequences as of July 28, 2021, from both GenBank and GISAID were downloaded and searched for the presence of potential lineages of concern using PANGO lineage as described previously. 13,[27][28][29]…”

“…Origin tracking was accomplished as described previously. 13 The sequences from Hawai'i were obtained through both GenBank and GISAID, along with SARS-CoV-2, Isolate USA-HI498 2020 and SARS-CoV-2, Isolate USA-HI708 2020 (from this study), to accomplish the origin determination.…”

“…The final alignment for constructing the phylogenetic tree was 2,953 unique and unambiguous B.1.243 sequences. Using this method, 13 we were able to define the origin of SARS-CoV-2, Isolate USA-HI498 2020 and HI708 (Figure 5).…”

“…All four of the VOC recognized by the CDC are present in Hawai'i. 13 To answer the dilemma of redesigning next-generation SARS-CoV-2 vaccines, we present and further validate our archetype quantitative analysis 14 for determining the emergence of individual mutations and variants, alike, as an algorithm. This algorithm is a platform for monitoring the virus and determining appropriate vaccine design as we proceed into the evolution and endemicity of SARS-CoV-2.…”