Cleveland Clinic researchers identified 484 unique mutations among six strains of SARS-CoV-2 isolates early in the COVID-19 pandemic, finding that the first variants were more deadly than subsequent strains and suggesting that monitoring circulating strains may help predict patient outcomes.
Their study, published yesterday in JAMA Network Open, involved sequencing the viral genomes from specimens obtained from 302 COVID-19 patients at Cleveland Clinic from Mar 11 to Apr 22, 2020, and comparing them with those of the original SARS-CoV-2 strain from Wuhan, China.
Infection with early virus subgroups, or clades, was associated with higher death rates than later strains (21.4% vs 5.6%). "These findings help explain persistent hospitalization yet decreasing mortality as the pandemic progresses," the authors wrote. "SARS-CoV-2 clade assignment is an important factor that may aid in estimating patient outcomes."
Less diversity, fewer severe outcomes
The researchers identified six coronavirus clades (G, GR, and GH, which contain the D614G variant, and V, S, and Wuhan). "Such early diversity is consistent with the interpretation that multiple SARS-CoV-2 infection events occurred in this community through repeated introduction of viruses from Asia, Europe, and elsewhere within the US," the authors noted.
But the strains quickly became less diverse and the once-dominant variants were outcompeted by the more-transmissible variants such as D614G, which were tied to improved survival in hospitalized patients (86.5% vs 58.8%). By this time, clades G, GR, and GH made up 84.4% of isolates, while the V, S, and Wuhan clades made up the remainder.
Early public health mitigation measures likely prevented more strains from entering the community, leading to a rapid reduction in virus strain diversity and lowering the overall death rate, the researchers noted.
"Our findings demonstrate that the continued evolution of SARS-CoV-2 leads to less virulence," the researchers said. "Given that our study period was during the initial weeks of the pandemic, it is unlikely that differences in survival were due to differences in patient care protocols, limitations of supplies or equipment, [intensive care unit] bed space availability, or the use of antiviral medications."
Of the 484 unique mutations identified in the samples, 53.1% were missense variants (a base-pair substitution that produces a different amino acid), and 32.4% were "silent" variants, meaning no amino acid change. On average, five variants were found in each sample.
Of the 302 patients, 30.1% required hospital admission, 11.6% required intensive care, and 5.6% died. Viral loads were similar regardless of strain. Average patient age was 52.6 years, 41.7% were men, 64.6% were White, and 42.4% were healthcare workers.
Patients in different clades were of different ages, with the Wuhan clade associated with the oldest patients (median age, 67.8 years) and the GR clade with the youngest (median, 40.8 years). No racial or sex differences were observed among the clade groups or within individual clades.
Viral sequencing, genomic surveillance
In a Cleveland Clinic news release, co-senior author Brian Rubin, MD, said that the study highlights how the different coronavirus strains evolved and competed after arrival in Cleveland. "The linkage of viral clades to outcomes is quite important and highlights the importance of viral genome sequencing to gain a deeper understanding of new diseases," he said.
Co-senior author Jing Li, PhD, of Case Western University emphasized the role of genomic surveillance. "This study further confirms the importance of studying genomic variants of the virus throughout the pandemic," he said.
The researchers also urged Americans—even if fully vaccinated against COVID-19—to continue to wear face coverings, physical distance, wash hands often, and avoid crowds until herd immunity is reached.
Herd immunity is estimated to occur when roughly 70% to 80% of the population is fully vaccinated. Currently 42.5% of the US population has received at least one vaccine dose, with 28.9% fully vaccinated, according to the Centers for Disease Control and Prevention (CDC) COVID Data Tracker.
