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Sick factor

The SARS-CoV-2 coronavirus that causes COVID-19 disease is an enveloped virus. Meaning, it is mostly human plasma membrane, with a few viral protein units spiking through as points of attachment of the virus to human cells prior to fusing with them and causing infection. That so-called viral spike is exceptionally important from a host-pathogen point of view as it is responsible for infection. At the same time, is also the major bullseye that the immune system can target to block infection and clear the virus before it gets in the door.

Molecular surveillance of this spike from the early days of the pandemic revealed that, contrary to fears of fast mutation by the virus, essentially only one mutation occurred in the spike protein, a change of an aspartate at amino acid 614 in the viral spike protein to a glycine (D614G). The G614 form was clearly more prevalent in Europe and the East Coast of the US, including New York City, while the SARS-CoV-2 viruses in China were nearly all D614. Well, it didn’t take long for two different scientific groups to ascribe a significance to this mutation. One noted that significantly fewer PCR cycles were needed to detect the G614 form than the D614 form, among other data, and concluded based on this data that the G614 form was transmitted more easily, which the mainstream media translated as G614 being “more contagious.” Well, fewer PCR cycles means more virus for sure, but in classic scientific reasoning, more virus could equally be due to more viral replication and infection (more transmission) or due to more viral persistence (more protection from the immune system).

Indeed, quite a bit of controversy kicked up over the “more contagious” conclusion and with good reason. Either of these mechanisms could lead to the virus being more prevalent in the population, as could the classical “founder effect” of genetics, whereby the prevalence is due to one of the viruses reaching a population first. The other investigators (including one of GeneCentrix's own advisors) correlated G614 with higher case fatality rate or deaths, which has nothing to do with transmission or “contagion” per se, but is potentially more serious. This finding suggests that, independent of whether G614 is spreading faster, it might be more dangerous. The explanation provided by these investigators was immunological, namely that the viruses with this mutation were better protected from the immune system. In fact, the immunological explanation could explain both observations: viral persistence due to protection from the immune system and more severe disease due to protection from the immune system and an enhanced inflammatory response. Time will tell, but there is some smoke around the D614G mutation. If it is indeed immuno-pathologically significant, there are implications for vaccines: Most of the current vaccines are composed of the D614 form and may protect against that form, but will they protect better or worse against the G614 form? Stay tuned.

 

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