Further to your hypothesis that an ADE like response to SARS-COV-2 could result in the virus binding to Fc receptors on Macrophages and leading to Macrophage Activation Syndrome (MAS).

ADE involves non-neutralising antibodies, often associated with a previous infection. In your hypothesis I assume that the antibodies were produced by the current SARS-COV-2 infection.

I have an alternative suggestion.

With SARS-COV-2 IgM and IgG antibodies are produced at almost the same time; this is unusual IgM is usually produced first and IgM after a considerable delay. Why?

My hypothesis is that SARS-COV-2 triggers a memory B–cell and T-cell response to a previous infection by “virus X” (possibly by cross-immunity to another common cold corona virus). The antibodies produced if they are non-neutralising could produce the ADE like response that you postulate.

Meanwhile the normal immune response proceeds and sometime latter IgG is produced to SARS-COV-2. By this time MAS has already begun.

If I am correct there will be two generations of IgG produced one for “virus X” and one for SARS-COV-2, these will be overlayed with that for “virus X” appearing earlier.

This could account for why with COVID-19 the clinical markers are not as expected in a classic cytokine storm but reflect markers for MAS.

I have wondered why convalescent plasma has not been successful, whereas monoclonal antibodies have been successful (if administered during the correct timeframe). I think that this may be because the plasma contains too many antibodies to “virus X” and not enough to SARS-COV-2.

The only way I can think of to confirm this hypothesis would be to monitor IgG production and confirm that the two generations of antibodies are apparent. Ideally the epitopes targeted by these antibodies should be identified.