YHLO Solutions for Anti-Phospholipid Antibodies Detection Could Help Prevent Life-Threatening Blood Clots in COVID-19

Thrombosis is discovered to be one of the most frequent complications in critically ill coronavirus disease 2019 (COVID-19) patients. Studies from the Netherlands and France suggest that blood clots arise in 20–30% in COVID-19 patients with critically ill conditions. Blood clotting is dangerous since it can cause blood oxygen deficit and result in cell death in the obstructed parts of the body, which contributed to the high mortality of COVID-19. Accumulated evidence supports the hypothesis that APL antibodies should be responsible for the blood clots in COVID-19 patients at least to a certain extent.

APLs are autoantibodies that target phospholipid-binding proteins on membrane of cells, especially epithelial cells that consist of the inner walls of blood vessels. The activation of APLs causes thrombosis in classical approaches: the narrowness of blood vessels through plaque piling on vessel walls, and platelet aggregation. Clinical manifestations including blood clots in legs and repeated miscarriages due to the presence and activation of APLs are named anti-phospholipid syndrome (APS). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is reasonably suspected to activate aPLs as a trigger and induce APS-like thrombosis. The most recognized APS-associated aPLs are anti-cardiolipin antibodies (aCL, include IgG, IgM and IgA) and anti-β2-glycoprotein I antibodies (aβ2GPI, include IgG, IgM and IgA). According to the international expert consensus, 12 weeks of persistent presence of high-level aCL IgG, aCL IgM, aβ2GPI, or/and aβ2GPI IgM along with vascular thrombosis suggest a definite diagnosis of APS.

COVID-19 thrombosis not only shares similar clinical manifestations with APS, more importantly, APL antibodies have been found in about 50% of patients hospitalized with COIVD-196. According to a study from University of Michigan, among 172 patients hospitalized with COVID-19, 23% are positive with aCL IgM and 52% are positive with any APL antibodies. Nevertheless, an earlier study by the Peking Union Medical College Hospital (PUMCH) had found aβ2GPI IgA (28.8%) and aCL IgA (25.8%) to be the first and second highest proportions of single APL antibodies present in 66 critically ill (ICU admitted) COVID-19 patients. The variant research results could be due to the differences on severity of COVID-19 conditions and the inherent heterogeneity of APL antibodies among individuals.

Further studies have revealed the association between concentration levels of APL antibodies and predisposition to thrombotic events in COVID-19 patients. Researchers at University of Michigan injected mouse models with IgG purified from seven COVID-19 patient sera and one catastrophic APS (CAPS) patient serum. Thrombi in mice treated with high-level APL antibodies or CAPS sera were then to be found significantly greater than those in mice treated with low-level APL antibodies. Through analyzing the correlations between clinical manifestations and APL antibodies profiles and concentration levels, the research team from PUMCH also demonstrated that being positivity for multiple APL antibodies or having moderate to high titers of APL antibodies is more useful in predicting the possibility of thrombotic events in COVID-19 patients than being positivity for a single APL antibody or having low concentration levels. In the conclusions, authors from both papers suggest a broad APL antibodies screening in all COVID-19 patients to improve risk stratification.

The persistence of APL antibodies in COVID-19 patents is another great concern for relevant scientists and doctors. Although most of virus-associated APL antibodies are thought to be transient, a recent review of 163 published cases of virus-associated APL antibodies found thrombotic events in 116 cases, suggesting transient APL antibodies may still have prothrombotic potential. Moreover, in the previously mentioned research in PUMCH, researchers investigated the dynamic changes of APL antibodies in six COVID-19 patients and found APL antibodies maintained in four of the patients at least within 47 days post-disease onset, among which one patient displayed aβ2GPI IgG persistence by the 80th day post-disease onset despite interventions with plasma exchanges, and another patient maintained high levels of multiple APL antibodies for around two weeks. Only two patients had APL antibodies disappeared within 47 days. These results suggest that the levels of APL antibodies are fluctuated and exhibit different dynamic patterns among different patients with COVID-19. For some patients, APL antibodies may persist longer and require further monitoring detections. To help guide medical decision making, it is advised for the patients to get retested for APL antibodies at least once, after 12 weeks of the initial set of APL antibodies tests was positive.

Despite the dispute on which APL antibodies is most prevalent in COVID-19 patients, researchers from both University of Michigan and PUMCH agree on the high prevalence of APL antibodies in patients with severe COVID-19 conditions and the presence of APL antibodies contributes to the occurrences of blood clots. APL antibodies detection is speculated to be a possible approach to prevent blood clots in COVID-19 patients and to improve risk stratification and personalization of treatment. Considering the possibility of APS exacerbation caused by SARS-CoV-2 infection, it’s time to raise our awareness on the healthcare of APS patients and APS detections. Compared to general population, persistently APL antibody-positive patients are at a higher risk for blood clots during hospitalization. Thus, in case of COVID-19-related hospitalization, it is important for persistently APL antibody-positive patients to discuss the blood clot prevention strategies with their physicians. APS patients should follow all standard precautions including social distancing, wearing masks outdoors, frequent hand washing, and avoiding contact with sick individuals to prevent COVID-19.

YHLO’s solutions for the detection of APL antibodies that could help prevent life-threatening blood clots in COVID-19 include tests for the detetion of Cardiolipin IgG, Cardiolipin IgM, Cardiolipin IgA, Anti-Cardiolipin, β2-Glycoprotein I IgG, β2-Glycoprotein I IgA, β2-Glycoprotein I IgM, and Anti-β2-Glycoprotein I. YHLO’s SARS-CoV-2-related detection tests include iFlash-2019-nCoV Ag, iFlash-2019-nCoV Nab, iFlash-2019-nCoV IgG, iFlash-2019-nCoV IgM, and iFlash-2019-nCoV IgA. YHLO also offers tests for the detection of other infections such as Anti-TP, Anti-HCV, HBsAg, Anti-HBs, HBeAg, Anti-HBe, Anti-HBc and HIV Combo.