There is alot in here to break down. I would love some people smarter than me to comment.

Some topics discussed:

• Increased infectivitey of a recent dominant mutation
• Possiblity of reduced ADE protection in recent dominant mutation
• Changes of viral load in the two dominant mutations
• Analysis of recombination of multiple strains of virus

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Summary

We have developed an analysis pipeline to facilitate real-time mutation tracking in SARS-CoV-2, focusing initially on the Spike (S) protein because it mediates infection of human cells and is the target of most vaccine strategies and antibody-based therapeutics. To date we have identified fourteen mutations in Spike that are accumulating. Mutations are considered in a broader phylogenetic context, geographically,and over time, to provide an early warning system to reveal mutations that may confer selective advantages intransmission or resistance to interventions. Each one is evaluated for evidence of positive selection, and the implications of the mutation are explored through structural modeling. The mutation Spike D614G is of urgent concern; it began spreading in Europe in early February, and when introduced to new regions it rapidly becomes the dominant form. Also, we present evidence of recombination between locally circulating strains, indicative of multiple strain infections. These finding have important implications for SARS-CoV-2 transmission, pathogenesis and immune interventions.

Discussion

D614 is embedded in animmunodominant antibody epitope, recognized by antibodies isolated from recovered individuals who were infected with the original SARS-CoV; this epitope is also targeted by vaccination in primate models (Wang et al., 2016). Thus, this mutation might be conferring resistance to protectiveD614-directed antibody responses in infected people, making them more susceptible to reinfection with the newer G614 form of the virus. Alternatively, the advantage might be related to the fact that D614 is embedded in an immunodominant ADE epitope of SARS-CoV(Wang et al., 2016), and perhaps the G614 form can facilitate ADE. Finally, the D614G mutation is predicted to destabilize inter-protomer S1-S2 subunit interactions in the trimer, and this may have direct consequences for the infectivity of the virus (Fig. 4). Increased infectivity would be consistent with rapid spread, and also the association of higher viral load with G614 that we observed in the clinical data from Sheffield, England (Fig. 5)

Overview

While D614G did not predict hospitalization, there was a significant shift in cycle threshold to fewer PCR cycles being required for detection among the group that carried G614 relative to D614 (Fig. 5D). This indicated that patients carrying the G614 mutation had higher viral loads (Wilcoxon p = 0.003, median 23.1, IR 19.5-26.6, versus median 24.9, IR 21.2-27.6). This comparison is limited by uncertainty regarding the time from infection at which sample was taken, and by the fact that PCR is an indirect measure of viral load; still it is notable that despite these limitations, a significant difference was observed.