Dysregulation of the immune system and autoimmune processes play a key role in severe and long-term course of COVID-19 infections. Research has shown that autoantibodies against phospholipids, anti-cardiolipin and anti-beta-2-glycoprotein, may contribute significantly to COVID-19 related autoimmunity and disease severity. Understanding how these antibodies trigger the thrombotic manifestations of the disease is important to improve patient management and to understand the underlying pathophysiology of SARS-CoV-2 infection.
Doctors’ awareness of autoantibodies promoting COVID-19 disease and determination of these autoantibodies with reliable laboratory tests will benefit the patient and offer new business opportunities for the IVD industry.

It is now more than a year that we are all living with the Covid-19 pandemic. All over the world, medical doctors are trying to fight the virus and support infected patients, scientists are searching for vaccines, novel drugs and new ways to cope with the virus in people’s daily lives.

In these 12 months we have learned a lot about the virus, hospitals are better prepared for caring for critically ill patients and a handful of vaccines have already been developed and may now be given to the people.

On the other hand, no drug or medication has been found to be effective in preventing the serious consequences of the disease and important questions still remain:
Why are some people seriously affected, while others show only light or even no symptoms at all, who will suffer from long term COVID-19 and why, and how can we identify those at high risk for severe disease?

Age may contribute to this risk, men are more often affected, people with pre-existing conditions like diabetes should be extremely cautious, and in the last couple of months growing evidence indicates, that autoimmune mechanisms may be involved.

Autoantibodies that attack elements of the body’s immune defense or specific proteins in the blood or organ tissues are thought to induce long term damage.

Laboratory findings of autoantibodies in COVID-19 patients

Several immune-mediated disorders have been described in patients infected with the new coronavirus. These include vasculitis, myositis and the antiphospholipid syndrome (APS). Secondary APS is likely responsible for coagulopathy during COVID-19 infection. (1)

Thromboembolic complications are in the focus of severe COVID disease, and researchers have found antibodies against various phospholipids in affected patients. Bertin et al detected antiphospholipid antibodies in more than 50% of severe COVID-19 patients and especially the levels of anti-cardiolipin IgG were significantly associated with severe COVID-19 manifestations. (2)

Zuo et al analyzed samples from 172 patients hospitalized with COVID-19. They observed that half of the patients became at least transiently positive for anti-phospholipid antibodies and that these autoantibodies are potentially pathogenic. (3) Eighty-nine patients tested positive for at least one type of aPL antibody based on the manufacturer’s cutoff, representing 52% of the entire cohort.

Hasan et al report that severely ill COVID-19 patients had significantly higher anti-cardiolipin IgA and IgM, and anti-beta-2 -glycoprotein IgA than patients with moderate disease. (4)

Xiao et al. detected anti-phospholipid antibodies in 47 % of COVID-19 patients in critical condition. IgA anti-beta-2-glycoprotein 1 was the most common antibody observed in these group. The authors hypothesize, that »antiphospholipid antibodies may be transient and disappear within a few weeks, but in genetically predisposed patients, COVID-19 may trigger the development of an autoimmune condition similar to the antiphospholipid syndrome (APS), referred to as “COVID-19–induced APS-like syndrome.”»

Detection of antiphospholipid antibodies may thus be important in COVID-19 patients and ORGENTEC’s assays may contribute to COVID-19 diagnostics and management.

ORGENTEC’s phospholipid assays are well known for their high performance in detecting antibodies against Cardiolipin and beta-2 glycoprotein for several reasons:

ORGENTEC’s special know-how of ELISA plate coating

Our R&D Team have developed a proprietary method of coating for the negatively charged antigen cardiolipin. This special ORGENTEC coating technology guarantees irreversible antigen binding while preserving the capability for autoantibody binding.

Also, for anti-beta-2-glycoprotein I presenting the right conformation of the protein on the ELISA plate is essential for antibody recognition. The special ORGENTEC coating technology uses the authentic human antigen and preserves the native conformation of the protein that is needed for optimal antibody recognition.

ORGENTEC is globally known for the quality of the anti-Cardiolipin and the beta-2-Glycoprotein I assay.

Taken together, doctors should be aware of these pathogenic antibodies and their effects and have the option to initiate antibody testing with the ORGENTEC assays in COVID-19 patients with acute infection. Autoantibody analysis may be included in monitoring and follow up of long term COVID-19 patients.

1. Cavalli E, Bramanti A, Ciurleo R, Tchorbanov AI, Giordano A, Fagone P, et al. Entangling COVID-19 associated thrombosis into a secondary antiphospholipid antibody syndrome: Diagnostic and therapeutic perspectives (Review). Int J Mol Med. 2020;46(3):903-12.
2. Bertin D, Brodovitch A, Beziane A, Hug S, Bouamri A, Mege JL, et al. Anticardiolipin IgG Autoantibody Level Is an Independent Risk Factor for COVID-19 Severity. Arthritis Rheumatol. 2020;72(11):1953-5.
3. Zuo Y, Estes SK, Ali RA, Gandhi AA, Yalavarthi S, Shi H, et al. Prothrombotic autoantibodies in serum from patients hospitalized with COVID-19. Sci Transl Med. 2020;12(570).
4. Hasan Ali O, Bomze D, Risch L, Brugger SD, Paprotny M, Weber M, et al. Severe COVID-19 is associated with elevated serum IgA and antiphospholipid IgA-antibodies. Clin Infect Dis. 2020.