Generation of potentially inhibitory autoantibodies to ADAMTS13 in coronavirus disease 2019, 2023, Doevelaar et al.

Generation of potentially inhibitory autoantibodies to ADAMTS13 in coronavirus disease 2019
Doevelaar, Adrian A. N.; Bachmann, Martin; Hölzer, Bodo; Seibert, Felix S.; Rohn, Benjamin J.; Zgoura, Panagiota; Witzke, Oliver; Dittmer, Ulf; Brenner, Thorsten; Paniskaki, Krystallenia; Yilmaz, Serap; Dittmer, Rita; Schneppenheim, Sonja; Wilhelm, Jochen; Stervbo, Ulrik; Babel, Nina; Budde, Ulrich; Westhoff, Timm H.

It has recently been shown that von Willebrand factor (VWF) multimers contribute to immunothrombosis in Coronavirus disease 2019 (COVID-19). Since COVID-19 is associated with an increased risk of autoreactivity, the present study investigates, whether the generation of autoantibodies to ADAMTS13 contributes to this finding.

In this observational prospective controlled multicenter study blood samples and clinical data of patients hospitalized for COVID-19 were collected from April to November 2020. The study included 156 individuals with 90 patients having confirmed COVID-19 of mild to critical severity. 30 healthy individuals and 36 critically ill ICU patients without COVID-19 served as controls. ADAMTS13 antibodies occurred in 31 (34.4%) COVID-19 patients.

Antibodies occurred more often in critically ill COVID-19 patients (55.9%) than non-COVID-19 ICU patients and healthy controls (5.6% and 6.7%; p < 0.001), respectively. Generation of ADAMTS13 antibodies in COVID-19 was associated with lower ADAMTS13 activity (56.5%, interquartile range (IQR) 21.25 vs. 71.5%, IQR 24.25, p = 0.0041), increased disease severity (severe or critical in 90% vs. 62.3%, p = 0.019), and a trend to higher mortality (35.5% vs. 18.6%, p = 0.077). Median time to antibody development was 11 days after first positive SARS-CoV-2-PCR specimen. Gel analysis of VWF multimers resembled the constellation in patients with TTP.

The present study demonstrates for the first time, that generation of ADAMTS13 antibodies is frequent in COVID-19, associated with lower ADAMTS13 activity and increased risk of an adverse disease course. These findings provide a rationale to include ADAMTS13 antibodies in the diagnostic workup of SARS-CoV-2 infections.

Link | PDF (Nature Scientific Reports)

 

Expanding on The ADAMTS13‐von Willebrand factor axis in COVID‐19 patients (2021, Journal of Thrombosis and Haemostasis) in acute patients —

Does this persist and contribute to LC findings (+/- symptoms)? Is this specific to LC and not present in ME from non-SARS2 causes?

Long-term persistence is suggested in Analysis of thrombogenicity under flow reveals new insights into the prothrombotic state of patients with post-COVID syndrome (2022, Journal of Thrombosis and Haemostasis) —

 

On post-Covid long-term symptoms relating to vWF:ADAMTS13 we had —

Impaired exercise capacity in post-COVID syndrome: the role of VWF-ADAMTS13 axis (2022)

 

I'm not sure how this could work. Perhaps the degree of effect on ADAMTS13 and the ratio with vWF is relatively mild and/or the specific antibody has a different effect. The extreme end of this condition is thrombotic thrombocytopaenic purpura, which is a very bad condition that is quite well known, but previously was pretty fatal.

Now it's treatable, eg summary from Wikipedia —

A state of the art paper: TTP: long-term outcomes following recovery (2018, Hematology) has the following abstract —

and had the following passage on fatigue —

 

I'm assuming ADAMTS13 and vWF will have been looked at long ago in ME/CFS itself. I can't find anything in PubMed, but maybe my search terms are inadequate?

A permissive search of "((chronic fatigue syndrome[MeSH Terms]) OR (myalgic encephalomyelitis[MeSH Terms]) OR (fibromyalgia[MeSH Terms])) AND (adamts13)" gives zero hits.

Similarly "((chronic fatigue syndrome[MeSH Terms]) OR (myalgic encephalomyelitis[MeSH Terms]) OR (fibromyalgia[MeSH Terms])) AND (von willebrand factor)" gives zero hits.

A "control" search of "((chronic fatigue syndrome[MeSH Terms]) OR (myalgic encephalomyelitis[MeSH Terms]) OR (fibromyalgia[MeSH Terms])) AND (virus)" has 794 hits.

Similarly "((thrombotic thrombocytopenic purpura[MeSH Terms]) AND (adamts13))" gives 1557 hits.

 

Possibly related:

SERPINA5 is an anticoagulant.

https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04179-3