Thread by @sigallab

We have just posted a new paper in bioRxiv showing that once cells are infected with SARS-CoV-2, they can infect other cells in ways which are very difficult to inhibit with antibodies
biorxiv.org/content/10.110…

In cell-to-cell spread viruses manipulate cells to infect each other, helping the virus transmit. This video shows some of how this happens in SARS-CoV-2

Take a look at what happens to the cell nuclei

The key to the experiments was to measure how well neutralizing antibodies, either purified or from the blood of people previously infected with SARS-CoV-2, can inhibit infection coming from cells versus as cell-free virus.

And the key to that was to separate the infected cells you added from the new infected cells. In our system this was reasonably easy: we added single infected cells and detected infection foci, which are clusters of infected cells which happen only if there are new infection:

Image below tells the story. Each dot is an infection focus. Top row is cell-free infection with increasing amounts of antibody from right to left - the infection gets cleared at the higher antibody concentrations. Bottom row is when infection is by infected cells - no clearance.

The shutdown of neutralization was complete, regardless of the variant you use. We also confirmed our previous results showing cross-neutralization by B.1.351-elicited plasma of earlier variants but found this was not because this plasma had strong neutralization overall.

The implications may be that once some cells where the virus can do cell-to-cell spread are infected, infection becomes more damaging and may last longer - this probably happens in the lung.

You would therefore want a vaccine that results in high levels of neutralizing antibodies - to clear all the cell-free virus before it could infect the cell types which could help it to escape antibodies.

Thank you @Dr_L_Jackson, the lead on the work, and @Tuliodna, @WillemAHanekom, @farinakarim, @coolvirus, @Sandile_Cele22, @houzhou, @KhadijaBKhan24, Professor Yunus Moosa and others, and our partners @kwmakar at the Gates Foundation and @JeremyFarrar at Wellcome