Long Covid – can we weaken its grip?

Jan 12, 2023

#LongCovid is now affecting over 2 million people in the UK, a “mass disabling event” harming health and livelihoods. In the US, where it is reported over 20 million are afflicted with the condition, Long Covid is being described as the “next public health disaster” with an “economic impact rivalling the Great Depression”.

At Attomarker we believe we are approaching potential answers to pressing questions. We have been looking at patient antibody responses across a range of Covid variants and it is clear that individual immunity and hence vulnerability varies markedly – we are terming these individual responses ‘immunity endotypes’. It has recently been recommended, for example, that cancer patients are tested for antibodies to SARS-CoV-2.* Understanding a personal response requires a personalised diagnostic test; our CE marked Antibody Immunity Test – Attocheck, is already available for this purpose.

We have also now developed a Multi-Variant Antibody Immunity Spectrum Test, only requiring a fingerprick of blood, that we believe could be used in targeting treatments for Long Covid patients. It is a research test that is not yet licensed for commercial use and is not available on the NHS, but the test and any subsequent treatment can be arranged privately on a “named patient basis”. If you are interested in this research test and your clinician would commission the test on a named patient basis, then we could measure your antibody immunity spectrum and seek to identify your endotype. The immunity spectrum could then inform a possible treatment in discussion with your doctor.  Please email longcovid@attomarker.com if you are interested in arranging a test. If you do not have access to a clinician, please mention this is your message as we are partnering with doctors specialising in Long Covid.

BREAKTHROUGH RESEARCH

We hypothesise that a poor immunity endotype leaves one more susceptible to #Covid and #LongCovid. Encouragingly we have seen some evidence that a poor immunity endotype may be improved by, for example, switching vaccines.

One further hypothesis, which is gaining ground amongst scientists, is that recovery from an infection requires a strongly sterilising serum containing high concentrations of high-quality antibodies. Otherwise microcolonies of the Covid virus (SARS-CoV-2) can circulate anywhere in the body, potentially to the heart or the brain, triggering a T-cell response in the infected cells. This can lead to an inflammatory event and cause repeat sickness, and may increase the risk of developing #LongCovid. 

DO LONG COVID PATIENTS HAVE A WEAK IMMUNITY ENDOTYPE RENDERING THEM UNABLE TO CLEAR THE VIRUS COMPLETELY?

Our new Attomarker multi-variant antibody spectrum test looks at both concentration of antibodies and their quality (affinity or “stickiness”). We are now measuring these endotypes and producing results consistent with the weak endotype theory. If antibody levels are low and declining, then the sterilising serum will become less and less effective. Could a new vaccine type – a smart boost – or targeted immunotherapy enhance the Long Covid patient serum and make it sterilising to clear the virus microcolonies? On the other hand, is your Covid and Long Covid risk lower if your variant immunity response is strong across the board? We are working on these pressing questions with our hospital research partner.

On 11 January, 2023, our Antibody Immunity spectrum study was published on a pre-pub server – https://www.medrxiv.org/search/attomarker – and shows a full set of immunity endotypes (Figure 1). The ideal antibody response is shown in panel A which is an almost perfect response to any part of the spike protein that is conserved across all variants – the universal endotype. Looking at panel B however, there is a drop-out endotype for the Beta variant which would suggest that this patient, if exposed to Beta, would mount a poor antibody response and be vulnerable to Long Covid after the infection. More relevant to the current circulating variants are the Omicron dropouts (panels C,E,F,G,H,I) where antibody levels are very poor to the Omicron variants tested, indicating possible vulnerability to Long Covid.

Figure 1 Immunity Endotypes against variants of SARS-CoV-2 , Omicron: (A) a universal positive, U(+) [2´ Pfizer],  (B) Single Dropout  β(-) [2´ Pfizer], (C) Double Dropout [W(+)], (D) Triple Dropout [W(+)], (E) Quadruple Dropout [W(+)], (F) Quintuple Dropout [2´ AZ], (G) Sextuple Dropout [1´ Pfizer], (H) Septuple Dropout [2x AZ] and (I) Octuple Dropout [2´AZ].

POTENTIAL THERAPIES FOR LONG COVID PATIENTS WITH A WEAK IMMUNITY ENDOTYPE

The Long Covid endotype hypothesis suggests some potential therapies. Immunotherapy, sometimes given to reduce the spread of Covid-19 throughout the body, can help the body’s immune system to control the infection and reduce severe symptom risk – but we have found, with our research partner, that the efficacy of certain treatments depends on an individual patient’s levels of antibodies.

There may also be a benefit to administering current immunotherapy drugs to those with #LongCovid, once we know the precise antibody balance. Different vaccine combinations may also be effective for certain individuals; testing may inform a recommendation of a different vaccination dependent on vaccine histories.

We also show in the latest paper on MedRxiv that switching vaccines changes the endotype for some individuals; so a Long Covid patient may benefit from ‘smart-boosting’ with a different vaccine. A before and after immunity profile could be conducted to see if these interventions have worked. Knowing your immunity endotype should also inform potential levels of protection in light of new emerging variants and assist decision-making around risk for you and your family.

Further reading on recent research: https://www.medrxiv.org/search/attomarker

*https://oncology.medicinematters.com/covid-19/vaccines/antibody-testing-sars-cov-2-breakthrough-infections-cancer/23906682 Discussing the results, the team suggests that prevention of SARS-CoV-2 infection “should be prioritized” among those with the lowest level of antibody-derived protection “to minimize impact on their cancer treatments.”