May 24-30 2021
Autoantibodies could worsen the illness
The clinical signs of COVID-19 vary, but are characterised overall by an inappropriate immune response. We now know that the overactivation of the innate immune response contributes in large part to the physiopathology of the illness. We also know that neutralising antibodies protect us against infection by SARS-CoV-2. But recent studies suggest that any deregulation of the antibody response will worsen the patient’s clinical state. Certain antibodies (AAb) are a particular cause of concern. These are deviant antibodies that turn against our body’s proteins and facilitate the development of Covid-19.
In order to confirm this point, researchers at the University of Yale looked at the role of AAbs targeting the body’s circulating proteins in the progression of COVID-19. They developed a high-speed test allowing them to evaluate the reactivity of antibodies in a patient against some 2 770 human proteins plus certain proteins belonging to the coronavirus (Rapid Extracellular Autoantibody Profiling, REAP). They applied this test to a cohort of 194 COVID-19 patients (of whom 20 were medical staff) and to 30 healthy volunteers.
Overall, the results clearly indicated that COVID-19 patients, in particular severe cases, have more AAb proteins than healthy people. Certain AAbs exist prior to infection while others are acquired just after. The majority of these antibodies target proteins linked to immune mechanisms, thereby modifying their activities: cytokines, chemokines, growth factors, complement factors or proteins expressed on the surface of immune cells. The most frequent are those antibodies targeting type 1 interferons (anti-IFN-I, 5.2% of patients) and anti-IFN-λ2/λ3, which worsen the illness.
The researchers confirmed in vitro that the blood samples taken from patients blocked the action of IFN-I, GM-CSF, CXCL11 or CXCL7 antibodies and that certain anti-CD8/CD3ε stimulate the phagocytosis of healthy cells by macrophages. Patients with AAb anti-IFN-I antibodies have higher viral charges and are hospitalised for longer, typical indicators of someone’s difficulty in eliminating the virus. Patients with AAbs targeting surface proteins (CD38, FCRL3, CCR2, CD3ε…) show a corresponding decline in B or T cells, as well as a fall in anti-RBD (the domain of the spike that interacts with the receptor) antibodies. A second category of antibodies targets various tissues (vascular cells, platelets, skin…) and their presence
correlates with certain clinical characteristics such as variations in the expression of some biomarkers that indicate the severity of COVID-19 (CRP, D-dimer, ferritin).
In a model with mice expressing the ACE2 human receptor, the researchers demonstrated in vivo that the prior administration of antibodies targeting the IFN-⍺/β receptors weakens the animal and causes it to lose weight once infected with SARS-CoV-2. It was observed that the macrophages and the T cells are no longer directed towards the lungs and do not mature enough so as to be effective. Similarly, mice having received anti-IL-1β, IL-21, and GM-CSF antibodies lose weight or die more often. These results demonstrate in vivo the pertinence of REAP data.
This study suggests therefore that the presence of autoantibodies and of targets, with varying rates in patients, contributes significantly to COVID-19 pathophysiology by modulating the immune response and tissue homeostasis. Amongst the immune pathways affected, some have never previously been described. While this data requires further investigation, it highlights an underestimated aspect of COVID-19 and suggests the possibility of new therapeutic avenues to explore.