Antiphospholipid syndrome (APS) is a systemic autoimmune condition, in which individuals make antibodies that target their own body cells. These antibodies, known as antiphospholipid antibodies (aPL), cause blood clots, miscarriages, and other complications such as low platelet counts. A diagnosis of APS requires both clinical symptoms and positive antibodies. A person may test positive for aPL without any clinical symptoms but may not develop APS.
A severe manifestation of APS is called catastrophic antiphospholipid syndrome (CAPS), which can develop in less than 1% of APS patients. Catastrophic antiphospholipid syndrome occurs when multiple blood clots form rapidly over the course of days, usually associated with microcirculation involvement, and cause damage to multiple organs in the body, commonly the brain, lungs, and kidneys.
Coronavirus disease 2019 (COVID-19) is a systemic infectious disease caused by a strain of coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It caused a worldwide pandemic that began with its initial outbreak in Wuhan, China in December 2019. Individuals with the disease can have no symptoms, or they may develop symptoms ranging from mild cough to severe respiratory disease that requires breathing support from a ventilator. Common symptoms include fever, cough, shortness of breath and muscle/joint pain. Other potential symptoms include diarrhea and loss of taste or smell.
Emerging evidence suggests COVID-19 is associated with blood clots. Based on reviews of the medical literature, hospitalized patients with COVID-19 have higher than expected frequency of vein clots (for example, deep vein thrombosis), and lung vessel clots (pulmonary embolism). Other clots in small blood vessels (these clots are known as "microthrombi") have also been found in COVID-19 patients. (See below for details.)
COVID-19 was initially thought to be primarily a respiratory infection. However, published studies, including autopsy reports of COVID-19 patients, suggest that the disease may cause other symptoms due to inflammation and damage of the lining of small vessels. This leads to small blood clots (microthrombi) in various organs. Similarly, in APS, blood clots are formed when the aPL bind to the vessel walls, causing inflammation and subsequent blood clots. Microthrombi affecting multiple organs can develop in APS, and are part of the CAPS spectrum as discussed above.
The mechanism of blood clot formation in patients with COVID-19 remains yet to be fully elucidated. COVID-19 infection results in a systemic inflammatory response causing molecules, including cytokines, to act on certain white blood cells (monocytes/macrophages) and the lining of blood vessels (endothelial cells), leading to clot formation, loss of blood flow, and eventual organ damage.
Several studies have examined aPL as contributing factors in patients who are seriously ill from COVID-19 and requiring admission to the intensive care unit. Lupus anticoagulant (LA) – one of the main aPL tests – is occasionally positive in these critically ill patients with COVID-19. However, these results are difficult to interpret as the LA test may be affected by inflammation due to COVID-19 or be falsely positive by routine use of blood thinners in the hospital. The other two main tests that detect aPL – anticardiolipin (aCL) and anti-Beta-2-glycoprotein-I (aβ2GPI) antibodies – are less likely to be clinically significantly positive in this group of severely ill COVID-19 patients.
Thus, the positive aPL tests observed in COVID-19 patients may be falsely positive among those patients experiencing systemic inflammation or be transiently positive due to COVID-19 infection. This is the case when false positives for aPL have been observed in patients who had other infections (such as hepatitis B and C, HIV and syphilis). Studies that can demonstrate whether positive aPL tests remain persistently positive in COVID-19 patients will help us better understand what associations there may be between COVID-19 and aPL.
There is mixed evidence for whether a newly positive aPL result may be associated with increased risk of clots in COVID-19 patients. In one study from Belgium of critically ill COVID-19 patients, aPL were observed but did not appear to increase the risk of clotting complications. On the other hand, another study from the US suggests that test results showing a new, positive aPL are in fact associated with increased clots. Further studies are needed to understand the role of aPL in COVID-19, and whether their emergence during a COVID-19 infection worsens a patient’s prognosis.
Risk of severe COVID-19 appears to be related to age and comorbidities such as high blood pressure, obesity and diabetes (among others). Studies are still investigating whether COVID-19 risk or severity is related to rheumatic diseases. In patients with rheumatologic conditions, the use of systemic glucocorticoid medications (steroids, such as prednisone) has been associated with higher risk for hospitalization for COVID-19. For this reason, it is recommended that patients use the lowest possible dose of steroids to control rheumatic disease. To our knowledge, no studies have been published which focus on the risk of severe COVID-19 symptoms in patients with a history of APS or positive aPL tests.
Compared to general population, persistently aPL-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-positive patients (independent of their history of blood clots) to discuss the blood clot prevention strategies with their physicians.
Low levels of aPL, which can occur during infections, are usually transient (temporary). Very limited published data support the transient nature of these antibodies, as some COVID-19 patients with positive aPL were tested negative at one month. To help guide medical decision making, patients should get retested for aPL after 12 weeks if the initial set of aPL tests was positive.
As discussed above, there is mixed data on the association between new aPL positivity in COVID-19 patients and clotting risk. However, hospitalized COVID-19 patients have an increased frequency of blood clots and should be at least on preventive-dose blood thinners. The role of continued blood thinners after hospital discharge is still under investigation, though it is generally recommended in patients with high risk for clotting. The benefit of blood thinners in non-hospitalized COVID-19 patients is uncertain.
Patients with APS should follow all standard precautions including social distancing, wearing masks when outside of the home, frequent hand washing, and avoiding contact with sick individuals.
At this time, there are no specific treatments recommended for COVID-19 precaution in patients with APS. Recommendations may be provided on a case-by-case basis by physicians.