Antiphospholipid antibodies and COVID-19 thrombotic vasculopathy: one swallow does not make a summer.
02 Aug 2021-Annals of the Rheumatic Diseases (BMJ Publishing Group Ltd)-Vol. 80, Iss: 9, pp 1105-1107
TL;DR: In this paper, the authors investigated whether common pathogenic mechanisms were shared by the antiphospholipid antibody syndrome (APS) and COVID-19, and found that both proinflammatory cytokine (eg, interleukin-6) and complement activation products (ie, C5a and C5b9) were thought to play a role in mediating the endothelitis together with a direct effect of SARS-CoV-2 on the endothelial surface.
Abstract: The high morbidity and mortality of COVID-19 have been associated with the thrombotic microangiopathy described in the patients in addition to the increased prevalence of thrombosis affecting medium/large arterial and venous vessels.1 2 Initial reports demonstrating prolonged activated partial thromboplastin times (aPTT) and positivity for antiphospholipid antibody (aPL) assays raised the issue of whether common pathogenic mechanisms were shared by the antiphospholipid antibody syndrome (APS) and COVID-19.3 4 In particular, the systemic thrombotic microangiopathy and the increased circulating levels of proinflammatory cytokines underlined the similarity between catastrophic APS (CAPS) and COVID-19.5 6
The similarities between APS/CAPS and COVID-19 are even more complex and intriguing as summarised in table 1. A proinflammatory environment that includes the activation of the complement system has been reported in all these conditions, although at different degrees. The involvement of several cell types playing a role in the coagulation cascade, such as platelets, monocytes and neutrophils, has been described which is closely associated with the proinflammatory and prothrombotic phenotypes.7 8 In particular, an endothelial perturbation is generally thought to be a common denominator in these diseases and several authors described it with the term ‘endothelitis’ in the COVID-19.9–11
View this table:
Table 1
Pathogenic pathways reported in APS, CAPS and COVID-19
Both proinflammatory cytokine (eg, interleukin-6) and complement activation products (ie, C5a and C5b9) were thought to play a role in mediating the endothelitis together with a direct effect of SARS-CoV-2 on the endothelium.10–12 However, the SARS-CoV-2 endothelial tropism is still a matter of debate despite the presence of the entry molecule (ie, ACE2) on the endothelial surfaces.13 So, it is not surprising that additional potential mediators of endothelial perturbation have been suggested. In particular, aPL came into the limelight because of their well-known …
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TL;DR: The 15th Dresden Symposium on Autoantibodies as discussed by the authors was focused on auto-immunity in the SARS-CoV-2 era, and a collection and distillation of the topics presented at this meeting was presented.
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TL;DR: In this paper , the authors investigated whether complement involvement is present in the early phases of the colonavirus disease and can be predictive of a negative outcome, and found that complement activation plays a role in immunothrombosis mainly in severe forms.
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TL;DR: In this article , the authors focus on biomarker discovery and other efforts to identify features that predict outcomes, and in so doing, identify possible effector and passenger mechanisms of adverse outcomes.
Abstract: Coronavirus disease 2019 (COVID-19) has had profound effects on the health of individuals and on healthcare systems worldwide. While healthcare workers on the frontlines have fought to quell multiple waves of infection, the efforts of the larger research community have changed the arch of this pandemic as well. This review will focus on biomarker discovery and other efforts to identify features that predict outcomes, and in so doing, identify possible effector and passenger mechanisms of adverse outcomes. Identifying measurable soluble factors, cell-types, and clinical parameters that predict a patient's disease course will have a legacy for the study of immunologic responses, especially stimuli, which induce an overactive, yet ineffectual immune system. As prognostic biomarkers were identified, some have served to represent pathways of therapeutic interest in clinical trials. The pandemic conditions have created urgency for accelerated target identification and validation. Collectively, these COVID-19 studies of biomarkers, disease outcomes, and therapeutic efficacy have revealed that immunologic systems and responses to stimuli are more heterogeneous than previously assumed. Understanding the genetic and acquired features that mediate divergent immunologic outcomes in response to this global exposure is ongoing and will ultimately improve our preparedness for future pandemics, as well as impact preventive approaches to other immunologic diseases.
TL;DR: In this article , the presence of antiphospholipid (APL) antibodies and ultimately patient death may be linked to the occurrence of thrombotic events in patients with COVID-19.
Abstract: Coronavirus 2 (COVID-19) has emerged as a new global pandemic, causing severe acute respiratory syndrome. Furthermore, the existence of antiphospholipid (APL) antibodies (Abs) and ultimately patient death may be linked to the occurrence of thrombotic events in patients with COVID-19. We aimed to investigate if there was a link between the presence of APL Abs and the severity of COVID-19 disease in patients at the Vali-Asr Hospital in Zanjan from June to July 2021. Real-time PCR was used to diagnose COVID-19 in 76 hospitalized patients. A total of 38 patients were hospitalized in the internal medicine ward and another 38 people were admitted to the intensive care unit of the Vali-Asr Educational Hospital in Iran's Zanjan region. Lupus anticoagulant (LAC) detection was done using the dilute Russell viper venom time method, and tests for anticardiolipin (ACL) Abs, IgG and IgM, and anti-beta2 glycoprotein 1 Abs, IgG and IgM, were done on blood and plasma samples of linked patients using the enzyme-linked immunosorbent assay technique. SPSS 24 was used to analyze data. Our findings showed that the presence of LAC was associated with disease severity in COVID-19 patients (p = 0.001). However, there was no significant relationship between APL Abs and mortality in patients affected with COVID-19. The evaluation of APL Abs, particularly LAC, in COVID-19 patients appears to be helpful in predicting the severity of the disease.
TL;DR: In this paper, despite the presence of antiphospholipid antibodies (aPLs) of various specificities and immunoglobulin isotypes, there was no link to thrombotic events.
Abstract: We thank Dr Yudong Liu1 for commenting on our manuscript and on many of the same issues we raised.2 There are, however, some comments that require clarification and a response. It is true that antiphospholipid antibodies (aPLs) of various specificities and immunoglobulin isotypes have been reported in COVID-19.3 However, despite a historical connection of aPLs with coagulopathies and antiphospholipid syndrome (APS), to date there has been no convincing evidence that aPLs has this in vivo pathogenic effect in COVID-19. In our patients, despite the presence of aPLs (eg, IgG anticardiolipin), there was no link to thrombotic events, a finding echoed by other referenced studies4 and recently reviewed.3 5 The recent publication by Chang et al 6 is mentioned, but it is important to appreciate that their results were compared with ‘normal’ controls and no clinical features (coagulopathy or APS) were reported, precluding any inferences …
References
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TL;DR: The vascular endothelium is an active paracrine, endocrine, and Endothelial cell infection and endotheliitis in COVID-19 and recruitment of immune cells can result in widespread endothelial dysfunction associated with apoptosis.
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Abstract: Background Progressive respiratory failure is the primary cause of death in the coronavirus disease 2019 (Covid-19) pandemic. Despite widespread interest in the pathophysiology of the dise...
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TL;DR: A 69-year-old man with Covid-19 diagnosed in January 2020 in Wuhan, China, along with two other critically ill patients with Covod-19 who were also seen in the same intensive care unit are described.
Abstract: Coagulopathy in Critical Illness with Covid-19 The authors describe a 69-year-old man with Covid-19 diagnosed in January 2020 in Wuhan, China, along with two other critically ill patients with Covi...
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TL;DR: The findings show that endotheliopathy is present in COVID-19 and is likely to be associated with critical illness and death, and strategies to mitigate its progression might improve outcomes in CO VID-19.
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TL;DR: Characterization of the molecular basis of the pathogenic mechanisms involved, including the putative second hits and the role of complement activation, might offer an answer to this question.
Abstract: Antiphospholipid antibodies (aPL) are both diagnostic markers for, and pathogenic drivers of, antiphospholipid syndrome (APS). Although the presence of aPL is a necessary pre-condition, APS-associated clotting is seemingly triggered by an additional 'second hit', frequently related to innate inflammatory immune responses. β(2) glycoprotein I (β(2)GPI)-dependent aPL, the most important subset of these antibodies, mediate several--not necessarily alternative--thrombogenic mechanisms, mainly on the basis of their reactivity with β(2)GPI expressed on the membrane of cells that participate in the coagulation cascade. Recurrent pregnancy complications associated with aPL cannot be explained solely by thrombosis, and alternative pathogenic mechanisms have been reported. Although one in vivo model of fetal loss suggests a mechanism of aPL-mediated acute placental inflammation, other models and the histopathological examination of APS placentae do not support a widespread inflammatory signature. β(2)GPI-dependent aPL are thought to recognize their antigen on placental tissues, inhibit the growth and differentiation of trophoblasts, and eventually cause defective placentation. Why antibodies with similar antigen specificity produce different clinical manifestations is not clear. Characterization of the molecular basis of the pathogenic mechanisms involved, including the putative second hits and the role of complement activation, might offer an answer to this question.
497 citations