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Cell Studies on Months-Long SARS-CoV-2 Shedding, Spike Mutation, Ebola Infection Dynamics

A National Institute of Allergy and Infectious Diseases (NIAID)- and Evergreen Health-led team describes a case of infectious SARS-CoV-2 shedding that stretch out more than two months in an immunocompromised 71-year-old woman with leukemia and related complications, who experienced an asymptomatic SARS-CoV-2 infection. Using PCR testing, genome sequencing, and other approaches, the researchers detected infectious SARS-CoV-2 virus in the individual's upper respiratory tract as far out as 70 days after the infection was diagnosed, despite two rounds of convalescent plasma transfusion treatment. "Throughout the course of infection, there was a marked within-host genomic evolution of SARS-CoV-2," they report, noting that a deep sequencing analysis "revealed a continuously changing virus population structure with turnover in the relative frequency of the observed genotypes over the course of infection."

For a pre-proof paper in Cell, researchers from Imperial College London, the University of Edinburgh, Cardiff University, and elsewhere explore the potential transmissibility and pathogenicity consequences of a SARS-CoV-2 spike protein mutation known as D614G. Based on available genome sequences for more than 21,200 SARS-CoV-2 614G isolates and nearly 5,800 614D isolates, the team suggests that a strain containing the D614G spike mutation showed a substantial increase in frequency in the UK, though not all of the analyses pointed to positive selection for that version of the virus. "We do not find any indication that patients infected with the Spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients," the authors note.

Investigators at Harvard University, NIAID, Stanford University, and elsewhere present findings from a single-cell RNA sequencing and CyTOF-based protein quantification analyses of rhesus monkey peripheral blood mononuclear cells infected with Ebola virus (EBOV). The team assessed 90 individual cells collected from 21 rhesus monkeys in vivo before, during, and after EBOV infection, garnering additional single-cell transcriptomic data on still more EBOV-inoculated cells ex vivo. Among other insights into the development and dynamics of Ebola virus disease, the authors note that in the EBOV-infected monkeys, "immature, proliferative monocyte-lineage cells with reduced antigen-presentation capacity replace conventional monocyte subsets, while lymphocytes upregulate apoptosis genes and decline in abundance."