Unearthing Clues Into a Complex Virus-Host Relationship in the Early Pandemic

Infection with B.2 lineage is associated with worse outcomes, genomic analysis finds

Epidemiologists at Cleveland Clinic have been investigating the evolution of the SARS-CoV-2 virus to help determine which patients are at risk for more severe disease. In April 2021, they published these findings in JAMA Network Open.

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Frank Esper, MD, infectious disease specialist at Cleveland Clinic Children’s and the study’s first author, says, “Over time, disease associated with infection demonstrated a decrease in length of stay and reduced case-fatality ratios, despite elevated hospitalization numbers. While the development of anti-viral medications and improved clinical care protocols have had substantial effects, the contribution of virus evolution on changes in clinical outcomes remains understudied.” 

B.2 lineage demonstrated higher renal injury, overall mortality

The research team performed a viral genome analysis of SARS-CoV-2-infected clinical specimens during the initial wave of infection and correlated SARS-CoV-2 variants to hospitalization, ICU admission, mortality and laboratory outcomes. Hospitalization and ICU admission were similar regardless of virus strain. However, infection with B.2 lineage (Clade V) demonstrated higher renal injury and overall mortality.

Within weeks of the first SARS-CoV-2 wave, a profound shift towards 23403A>G (D614G)-specific genotypes occurred. Additionally, replaced clades were associated with worse clinical outcomes, including mortality. These findings help explain persistent hospitalization, yet decreasing mortality, as the pandemic progresses.

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The importance of SARS-CoV-2 lineage assignment

SARS-CoV-2 lineage assignment is an important factor that may aid in predicting patient outcomes. Understanding those SARS-CoV-2 mutations that alter disease outcomes may provide important clues to better understanding the complex virus-host relationship.


Esper FP, Cheng YW, Adhikari TM, Tu ZJ, Li D, Li EA, Farkas DH, Procop GW, Ko JS, Chan TA, Jehi L, Rubin BP, Li J. Genomic Epidemiology of SARS-CoV-2 Infection During the Initial Pandemic Wave and Association With Disease Severity. JAMA Netw Open. 2021 Apr 1;4(4):e217746. doi: 10.1001/jamanetworkopen.2021.7746. PMID: 33900399; PMCID: PMC8076962.

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