SARS-CoV-2 biochemistry explains important aspect of disease pathology

A known facet of coronavirus biochemistry helps to explain the pathological features of Covid-19 and may have implications for the management of long Covid and other conditions. Failure to take this into account in the early days of the pandemic led to a sub-optimal therapeutic approach, argues David Scheim in a recent paper published in Viruses (Basel). Dr Scheim and seven distinguished co-authors describe the effects and implications in detail. Here we outline the key points.

The coronavirus spike protein (SP) attaches to host cells at glycans on the cell surface, including red blood cells (RBCs), platelets and endothelial cells.  This is a feature common to all coronaviruses. However, some e.g. the common cold viruses express a glycan-cleaving enzyme and so are able to detach. SARS, SARS-CoV-2 and MERS viruses have no glycan-cleaving enzyme and all virulent. After linking to human cells in this way the virus is able to slide over to the ACE-receptor and gain entry.  Much research effort was focused on preventing virus entry and reproduction – via the ACE2 receptor. This effectively diverted attention from other aspects of virus behaviour, in particular the SP.

It had been assumed that the SP itself was harmless because it cannot reproduce.  For this reason, it was thought to be a suitable antigen.  However, SP has other effects – RBCs coated with SP, as described, aggregate in clumps, leading to microvascular occlusion and clot formation. This is consistent with the clinical observations that microvascular clots and poor oxygenation were common in severely ill Covid patients and a prominent feature of the morbidity of Covid-19.

Of note – the authors of this study also point out that the Omicron SP was found to have 10 times the haemagglutinating activity of SP from previous variants.  They therefore advocate suspension of the use of Omicron-based COVID-19 vaccines. As these underwent no human testing and have significantly reduced efficacy compared with previous vaccines, they offer no benefits and only the reverse.

There is a further implication of SP coated RBCs; measurements of SP in plasma will be low – and misleading – because most of it is attached to cells (RBCs) which are removed by definition before plasma is tested. Whole blood measurement shows that SP persists for up to 187 days after CV19 vaccination, the authors note.

Clearly, what was needed was therapeutic strategies for early treatment that combined anti-viral agents with pro-active measures to reduce RBC aggregation.

Early in the pandemic clinicians in the field had already reported positive effects – in particular, rapid resolution of Covid-19 hypoxia –  with ivermectin, hydroxychloroquine and fluvoxamine. The latter two agents have significant activity in reducing RBC and platelet aggregation. Ivermectin, which binds with high affinity to multiple sites on the SP, is associated with rapid increases in oxygen saturation and clinical improvement. This was described to Medical Update Online by Dr Jackie Stone in 2021

In view of the persistence of SP in the bloodstream and its association with ‘long Covid’, there is a clear therapeutic basis for long term treatment with ivermectin, hydroxychloroquine or fluvoxamine. These are all cheap, generic drugs.

The figure below summarises these observations together with relevant supporting information.

This paper has been written by a team of authors with outstanding academic credentials and contains a wealth of thought-provoking detail. Given the current/recent upsurge of Covid vaccine associated thrombotic events it is important reading for clinicians and policy-makers.