Our aims were :

1 - To determine whether anti-SARS-CoV-2 antibodies can kill infected cell by ADCC or complement activation.

2- To characterise the antibody response in asymptomatic SARS-CoV-2 individuals

2/13
We Found that complement is activated at the surface of infected cells by sera from COVID-19 patient.
In this example 79% of infected cells (in blue) are covered by C3b/iC3b (top-right corner)

NHS: normal human serum
HIHS: heat-inactivated human serum (a control)
3/13
Despite this activation of the complement, we did not observed lysis of infected cells (using either A549-ACE2 or U2OS-ACE2 cells)
4/13
We next looked at Antibody-dependent cellular cytotoxicity (ADCC) by NK cells.
On this example, you can see that infected syncytia (which are GFP) almost completely disappear in the presence of NK and COVID-19 serum !
5/13
Using this system, we can track ADCC in real-time.. look what we saw !
ADCC of a SARS-CoV-2 infected cell in live!
Green : infected syncytia
Red: Dead cells
6/13
We then took advantage of two sero-epidemiological cohort studies to determine whether sera of COVID- 19 asymptomatic and symptomatic individuals differ in their ability to trigger ADCC and complement deposition.
7/13
As expected, asymptomatic individuals display reduced antibody response, but most of them neutralise and activated ADCC or CDC.
Red: symptomatic (n=76)
Blue: asymptomatic (n=19)
8/13
Using a second cohort we confirmed that asymptomatic individuals harbor a polyfunctional anti-Spike antibody response which is lower than is symptomatic individuals.

blue: asymptomatic (n=31)
red: symptomatic (n=43)
dark red: hospitalised individuals (n=21)
9/13
Finally, we look at ADCC and CDC overtime, and found a decrease which follow antibody titers.
10/13
Of course, there is some limitations, not all groups are age- or sex-matched for instance. We tried to summarise it to take it into account in the interpretation. More info in the discussion of course.
11/13
In conclusion, we found that antibody levels and functions are lower in asymptomatic individuals, but both asymptomatic and symptomatic SARS-CoV-2-infected individuals harbor polyfunctional antibodies.
12/13
Finally, HUGE thanks to all people involved 🙏👏
@Jeremy_Dufloo, @LudivineGrzelak, @alili6610, @JBuchrieser, @MOUQUETHugo1, @michaelwhite_36, @OlivierSchwartz, @Pasteur_CRT, the entire @Virus_Immunity Lab, and all those that are not on twitter!
13/13
Bonus tweet: I was fuelled by #KOMPROMAT ( @VITALICOFFICIAL & RBK Warrior) all along the time I worked on this study🙏🙏🙏. Can't wait to enjoy music in live again.
You can follow @Timothee_B.
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