By Denise Baez
NEW YORK — November 5, 2020 — The second wave of coronavirus diseases 2019 (COVID-19) cases appears to be characterised by severe acute respiratory syndrome coronavirus disease 2 (SARS-CoV-2) strains with diverse genotypes, according to a study published in mBio.
After sequencing the genomes of 5,085 SARS-CoV-2 strains causing 2 COVID-19 disease waves in Houston, Texas, S. Wesley Long, MD, Houston Methodist Research Institute, and colleagues found that virtually all cases in the second and ongoing disease wave had been caused by strains with the Gly614 variant of spike protein, and that patients infected with the Gly614 variant strains had significantly higher virus loads in the nasopharynx on initial diagnosis.
“The genomes were from viruses recovered in the earliest recognised phase of the pandemic in Houston and from viruses recovered in an ongoing massive second wave of infections,” the authors wrote. “The virus was originally introduced into Houston many times independently. Virtually all strains in the second wave have a Gly614 amino acid replacement in the spike protein, a polymorphism that has been linked to increased transmission and infectivity.”
During the first wave (early March to May 11), 11,476 COVID-19 cases were reported in Houston. Early in the first wave (March 5-March 30), the researchers tested 3,080 patient specimens, of which 406 (13.2%) samples were positive for SARS-CoV-2, representing 40% of all confirmed cases in metropolitan Houston during that time period.
“As our laboratory was the first hospital-based facility to have the capacity for molecular testing for SARS-CoV-2 on site, our strain samples are likely representative of COVID-19 infections during the first wave,” the authors wrote, noting that the Houston metropolitan area is the fourth largest and most ethnically diverse city in the United States, with a population of approximately 7 million.
For the entire study period — from March 5 to July 7 — the researchers tested 68,418 specimens from 55,800 patients. Of these, 9,121 (16.4%) had a positive test result, representing 17.1% of all confirmed cases in metropolitan Houston.
“Thus, our strain samples are also representative of those responsible for COVID-19 infections in the massive second wave,” the authors noted.
To investigate the genomic architecture of the virus across the 2 waves, the researchers sequenced the genomes of 5,085 SARS-CoV-2 strains dating to the earliest time of confirmed COVID-19 cases in Houston. Analysis of SARS-CoV-2 strains causing disease in the first wave (March 5-May 1) revealed the presence of many diverse virus genomes that represent the major clades identified globally to date, the most common being clades G, GH, GR, and S. However, strains with the Gly614 amino acid variant in spike protein represented 99% of the SARS-CoV-2 strains in wave 2.
The researchers also found that patients infected with the Gly614 strains had, on average, higher virus loads on initial diagnosis than the patients infected by strains with the Asp614 variant.
“Virtually all cases in the second and ongoing disease wave had been caused by strains with the Gly614 variant of spike protein,” the authors wrote. “Amino acid residue Asp614 is located in subdomain 2 (SD-2) of the spike protein and forms a hydrogen bond and electrostatic interaction with two residues in the S2 subunit of a neighbouring protomer. Replacement of aspartate with glycine would eliminate both interactions, thereby substantively weakening the contact between the S1 and S2 subunits. We previously speculated that this weakening produces a more highly fusogenic spike protein, as S1 must first dissociate from S2 before S2 can refold and mediate fusion of virus and cell membranes.”
“Stated another way, virus strains with the Gly614 variant may be better able to enter host cells, potentially resulting in enhanced spread,” the authors stated.
They noted that analysing additional SARS-CoV-2 strains are important, especially if subsequent waves occur, as it could provide insight into molecular and epidemiologic events contributing to them.