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Early Pandemic SARS-CoV-2 Clade Shift in Cleveland May Have Reduced Mortality, Study Suggests

NEW YORK – A team from the Cleveland Clinic, Case Western Reserve University, and elsewhere has used genomic epidemiology to explore relationships between outcomes in COVID-19 patients and SARS-CoV-2 variants found in Cleveland last spring.

In a paper published in JAMA Network Open on Monday, the researchers reported variant shifts that appeared to coincide with decreased mortality during the early stages of the COVID-19 pandemic in the Cleveland area.

"This cross-sectional study demonstrates a dynamic shift in SARS-CoV-2 clade diversity occurring very early in the pandemic following introduction into Cleveland, Ohio," first and corresponding author Frank Esper, a pediatric infectious disease expert at Cleveland Clinic Children's, and his colleagues wrote.

For their analysis, the researchers sequenced the genomes of SARS-CoV-2 isolates from nasopharyngeal swab samples of 302 confirmed COVID-19 cases diagnosed between early March and late April 2020, identifying more than 2,500 variants, along with several circulating SARS-CoV-2 clades. Just over 30 percent of the COVID-19 patients had to be hospitalized at some point, they noted, while 11.6 percent ended up in intensive care and 5.6 percent died.

The team noted that viral diversity dropped off relatively quickly in the area, despite the advent of viruses containing new genetic variants, including changes to the SARS-CoV-2 spike protein-coding gene. The available genomic data also revealed versions of the coronavirus that corresponded to better or worse outcomes in those infected with it.

Individuals infected with SARS-CoV-2 isolates from the so-called clade group 2 — which included the S, V, L, and Wuhan clades — tended to have higher mortality rates, the researchers reported. On the other hand, genomic and phylogenetic clues suggested that infections with viruses from clades in group 1, which were marked by a genetic change known as 23403A>G (D614G), coincided with enhanced COVID-19 patient survival after hospitalization.

"Within weeks of SARS-CoV-2 circulation, a profound shift toward 23403A>G (D614G) specific genotypes occurred," the authors reported, noting that clades implicated in relatively poor clinical outcomes appeared to be replaced with versions of the virus associated with increased survival after hospitalization, including 23403A>G (D614G).

These and other findings pointed to several distinct introductions of the virus in the area, Esper noted in an email, while the relatively speedy drop in SARS-CoV-2 diversity — despite the establishment of new viral variants in the community — appeared to reflect the introduction of health restrictions at the federal and local level at the time.

That, in turn, suggests that such restrictions likely prevented even worse outcomes in the area, he explained, by curbing spread and dialing down the advent of still other SARS-CoV-2 clades linked to severe disease.

"These findings are consistent with the observation of persistent hospitalization yet decreasing mortality as the pandemic progresses," the authors reported, noting that "SARS-CoV-2 clade assignment is an important factor in algorithms that may be used to estimate patient outcomes."