More research evidence about the immune biology of long COVID was published last week in the journal Frontiers in Immunology.
(Image above by pikisuperstar on Freepik)
The study involved a collaboration between researchers at Charité – Universitätsmedizin Berlin in Germany and a long list of scientists from around the world, many of whom are also researching ME/CFS.
The authors begin by noting that most patients with post-COVID syndrome (PCS) – the term that appears to be replacing ‘long COVID’ in the medical literature – present with a plethora of medically unexplained symptoms not linked to clear evidence of organ dysfunction. Furthermore, a subgroup of them meet diagnostic criteria for ME/CFS.
Asymmetric autoantibodies
Earlier studies in this area have shown that there are possible issues with antibody responses in PCS. Antibodies are a key part of the human immune system. They combine with substances which the body recognises as alien – such as bacteria, viruses and foreign substances in the blood (collectively known as antigens) – and mark them out for attack by triggering a cascade of responses.
This new study focused on a major class of antibodies called asymmetric autoantibodies, or AABs, and whether they might play a role in causing the symptoms of PCS by disrupting signalling between and within cells.
The researchers wanted to investigate whether AABs are affecting a family of cell receptors called G-protein coupled receptors which are important for taking messages from outside the cell and translating them into signals inside the cell. This communication will cause the cell to do different tasks, like produce more of a certain protein or do less of something.
What did they find?
Blood samples were collected from 80 patients with PCS following mild-to-moderate COVID-19, and from 78 healthy individuals. Half of the PCS patients also met diagnostic criteria for ME/CFS, and this group tended to have more severe post-exertional malaise, fatigue, disability and immune symptoms than the PCS patients without ME/CFS.
In general, patients with PCS tended to have altered levels of various AABs compared with control subjects. Importantly, some of these affected AABs are directed against receptors that regulate the autonomic nervous, cardiovascular and immune systems, suggesting their involvement in the development of PCS. In addition, changes in several of these AABs correlated with symptom severity in the PCS groups.
What does this mean?
Interestingly, while you would expect an upregulation in several AABs in response to a viral infection, some AABs were in fact downregulated in PCS patients. So this suggests that these autoantibodies can in fact both upregulate and downregulate cellular events, causing a disruption to the cell’s normal function.
Some of the AABs that were reduced in PCS patients include those that regulate how blood vessels constrict to maintain blood pressure, which is significant when considering that many individuals with PCS and/or ME/CFS are not able to control their blood pressure adequately when standing up (postural orthostatic tachycardia syndrome, or POTS).
There was very little difference in AAB levels between PCS patients with ME/CFS and those without ME/CFS, suggesting that autoimmune responses in ME/CFS may be similar to those seen in long COVID, although more work is required in this area.
The mechanisms of disease in long COVID (or post-COVID syndrome) remain poorly understood, but this study does provide evidence of both immune and vascular dysregulation that may go some way to help explain the cardinal symptoms reported by patients (which tend to be very similar to those reported by people with ME/CFS).
Ongoing inflammation, particularly in blood vessels, has long been hypothesised in ME/CFS, and may account for why long COVID and ME/CFS patients experience POTS, cold hands and problems regulating temperature. A poor oxygen supply to muscles and small blood vessels might produce other symptoms such as muscle fatigue or pain, while a poor supply to the brain may contribute to processes that result in brain fog and poor concentration.
The most intriguing finding of the study might be the emerging correlations between the levels of several AABs with the severity of fatigue, and cognitive and immune symptoms in PCS and ME/CFS patients. This finding points to a role for these AABs (or their associated pathways) in the development of both long COVID and ME/CFS.
It is expected that the authors of this study will now go on to investigate the role of these autoantibodies in ME/CFS patient cohorts.
