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Are antiphospholipid antibodies just a common epiphenomenon or are they causative of immune-mediated coagulopathy in COVID-19?

ABSTRACT: The coronavirus disease 2019 (COVID-19) is the largest public health emergency in recent times. A significant number of patients develop a severe form of COVID-19 characterized by coagulopathy, organ failure, and elevated mortality. In addition, an unusually high frequency of antiphospholipid antibodies (aPLs) has been found in patients with COVID-19. These clinical and serological manifestations closely resemble those seen in the antiphospholipid syndrome (APS), especially in its catastrophic form, suggesting a role of aPLs in immune-associated coagulopathy. However, government bodies such as the American Society of Hematology have spoken out against the systematic search for aPLs in patients with COVID-19. In an attempt to bridge the gap on this hot topic, we conducted a comprehensive review of currently available cohort studies and case series systematically evaluating aPLs in COVID-19 patients. In this Perspective, we seek to identify both the frequency and the type of aPLs found in patients with COVID-19, as well as the potential association of these aPLs with vascular thrombosis and other distinctive characteristics of COVID-19. Furthermore, we investigated whether there is evidence that allows us to define the occurrence of aPLs in COVID-19 as an epiphenomenon, as has been observed in other systemic viral infections, or as antibodies against self-antigens bearing hallmarks that suggest a pathogenic role in immune-mediated thrombosis. Defining whether aPLs represent an epiphenomenon or they are actually involved in hemostatic abnormalities of COVID-19 is crucial both for uncovering novel mechanisms of immune-mediated thrombosis and for identifying potential prognostic biomarkers in this devastating disease.

SUBMITTER: Castillo-Martinez D

PROVIDER: S-EPMC8024929 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Are antiphospholipid antibodies just a common epiphenomenon or are they causative of immune-mediated coagulopathy in COVID-19?

Castillo-Martínez Diana D Torres Zaira Z Amezcua-Guerra Luis M LM Pineda Carlos C

Clinical rheumatology 20210407 7

The coronavirus disease 2019 (COVID-19) is the largest public health emergency in recent times. A significant number of patients develop a severe form of COVID-19 characterized by coagulopathy, organ failure, and elevated mortality. In addition, an unusually high frequency of antiphospholipid antibodies (aPLs) has been found in patients with COVID-19. These clinical and serological manifestations closely resemble those seen in the antiphospholipid syndrome (APS), especially in its catastrophic f ...[more]

PMID: 33826045

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Project description:ObjectiveCoagulopathy is one of the characteristics observed in critically ill patients with coronavirus disease 2019 (COVID-19). Antiphospholipid antibodies (aPLs) contribute to coagulopathy, though their role in COVID-19 remains unclear. This study was undertaken to determine the prevalence and characteristics of aPLs in patients with COVID-19.MethodsSera collected from 66 COVID-19 patients who were critically ill and 13 COVID-19 patients who were not critically ill were tested by chemiluminescence immunoassay for anticardiolipin antibodies (aCLs), anti-β2 -glycoprotein I (anti-β2 GPI) (IgG, IgM, and IgA), and IgG anti-β2 GPI-domain 1 (anti-β2 GPI-D1) and IgM and IgG anti-phosphatidylserine/prothrombin (anti-PS/PT) antibodies were detected in the serum by enzyme-linked immunosorbent assay.ResultsOf the 66 COVID-19 patients in critical condition, aPLs were detected in 31 (47% ). Antiphospholipid antibodies were not present among COVID-19 patients who were not in critical condition. The IgA anti-β2 GPI antibody was the most commonly observed aPL in patients with COVID-19 and was present in 28.8% (19 of 66) of the critically ill patients, followed by IgA aCLs (17 of 66, or 25.8%) and IgG anti-β2 GPI (12 of 66, or 18.2%). For multiple aPLs, IgA anti-β2 GPI + IgA aCLs was the most common antibody profile observed (15 of 66, or 22.7%), followed by IgA anti-β2 GPI + IgA aCL + IgG anti-β2 GPI (10 of 66, or 15.2%). Antiphospholipid antibodies emerge ~35-39 days after disease onset. A dynamic analysis of aPLs revealed 4 patterns based on the persistence or transient appearance of the aPLs. Patients with multiple aPLs had a significantly higher incidence of cerebral infarction compared to patients who were negative for aPLs (P = 0.023).ConclusionAntiphospholipid antibodies were common in critically ill patients with COVID-19. Repeated testing demonstrating medium to high titers of aPLs and the number of aPL types a patient is positive for may help in identifying patients who are at risk of developing cerebral infarction. 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." Long-term follow-up of COVID-19 patients who are positive for aPLs would be of great importance in understanding the pathogenesis of this novel coronavirus.

Project description:IntroductionAs the COVID-19 pandemic transitions, understanding the intricate dynamics of the disease becomes paramount. This systematic review explores the role of antiphospholipid antibodies in COVID-19, focusing on their potential clinical implications.MethodsThis systematic review, following PRISMA guidelines, assesses studies exploring the link between antiphospholipid antibodies and COVID-19. PubMed/Medline, Embase, and Scopus were searched for relevant studies published up to December 22, 2024. Inclusion criteria comprised studies involving patients diagnosed with COVID-19 and reporting on the presence of antiphospholipid antibodies. The risk of bias in individual studies was evaluated using the Joanna Briggs Institute appraisal tool.ResultsOur Study includes 59 records involving a total of 28,489 COVID-19 patients. Antiphospholipid antibodies were tested in 14,498 COVID-19 patients. It was observed that 50.84% of patients tested positive for antiphospholipid antibodies. Various types of antiphospholipid antibodies, including Anticardiolipin, Anti beta2 glycoproteins, and Lupus anticoagulant antibody, displayed prevalence rates in the patients with thrombosis. The overall frequency of antiphospholipid antibodies in thrombosis patients was 38.55%.ConclusionThe presence of antiphospholipid antibodies in a significant proportion of COVID-19 patients underscores the need for a detailed investigation into their role in thrombotic events. Our study highlights potential avenues for targeted interventions. However, the evolving nature of COVID-19 necessitates continued research efforts to clarify clinical implications and optimize management strategies in this complex landscape of thrombosis and immunology. The review reveals some limitations, such as variability in study designs and demographics and inherent differences in methodologies among included studies. Future studies should address these limitations with standardized methodologies for more conclusive findings.

Project description:BackgroundThe significance of antiphospholipid antibodies (aPL) in COVID-19 remains uncertain.ObjectivesWe determined whether aPL are associated with COVID-19 and/or thrombosis or adverse outcomes during hospitalization for COVID-19.MethodsSymptomatic adults tested for SARS-CoV-2 for clinical reasons (March-July 2020) with either ≥1 positive polymerase chain reaction (COVID-19+) or all negative (non-COVID-19) results were recruited to a biobank collecting plasma, clinical data, and outcomes. We tested baseline plasma samples (days 0-7) of all subjects (and day-30 samples in the COVID-19+ subjects, when available) for aPL (anticardiolipin immunoglobulin [Ig]M/IgG, anti-β2-glycoprotein I IgM/IgG, antiphosphatidylserine/prothrombin IgM/IgG, and lupus anticoagulant). We compared the baseline prevalence of aPL between the COVID-19+ and non-COVID-19 subjects. Among hospitalized COVID-19+ subjects, multivariable logistic regression was used to evaluate the association of aPL (and their subtypes) with arterial or venous thromboembolic events, acute kidney injury, intensive care unit admission, mechanical ventilation, and death after adjusting for potential confounders.ResultsAt baseline, 123 of 289 (43%) COVID+ subjects had ≥1 aPL versus 116 of 261 (32%) non-COVID-19 subjects (difference, 10%; 95% CI, 3%-18%). Among 89 COVID+ subjects with repeated samples, aPL persisted on day 30 in 15 of 34 (44%) subjects with baseline aPL positivity, and half of those without aPL at baseline developed one or more new aPL. In hospitalized COVID-19 subjects (n = 241), baseline aPL positivity was associated with acute kidney injury (odds ratio [OR], 1.8; 95% CI, 1.1-3.2) and mechanical ventilation (OR, 3.2; 95% CI, 1.5-6.8) but not death (OR, 1.2; 95% CI, 0.6-2.5). In secondary analyses, medium-to-high titers of anticardiolipin IgG (>40) were associated with thromboembolic events (OR, 7.3; 95% CI, 1.8-30.1).ConclusionIn patients with COVID-19, aPL may help identify an increased risk of thrombosis and other adverse outcomes.

Project description:BackgroundThrombosis is a unique complication of coronavirus disease 2019 (COVID-19). Although antiphospholipid antibodies (aPL) are detected in COVID-19 patients, their clinical significance remains elusive. We evaluated the prevalence of aPL and serum concentrations of beta-2 glycoprotein I (β2GPI), a major self-antigen for aPL, in Japanese COVID-19 patients with and without thrombosis.MethodsThis retrospective single-center nested case-control study included 594 hospitalized patients with COVID-19 between January 2020 and August 2021. Thrombotic complications were collected from medical records. Propensity score-matching method (PSM) (1:2 matching including age, sex, severity on admission, and prior history of thrombosis) was performed to compare the prevalence and titer of aPL (anti-cardiolipin (aCL) IgG/IgM, anti-β2GPI IgG/IgM/IgA, and anti-phosphatidylserine/prothrombin antibody (aPS/PT) IgG/IgM) and serum β2GPI concentration. In addition, PSM (1:1 matching including age and sex) was performed to compare the serum β2GPI concentration between COVID-19 patients and healthy donors.ResultsAmong the patients, 31 patients with thrombosis and 62 patients without were compared. The prevalence of any aPLs was indifferent regardless of the thrombosis (41.9% in those with thrombosis vs. 38.7% in those without, p =0.82). The positive rates of individual aPL were as follows: anti-CL IgG (9.7% vs. 1.6%, p =0.11)/IgM (0% vs. 3.2%, p =0.55), anti-β2GP1 IgG (22.6% vs. 9.7%, p =0.12)/IgA (9.7% vs. 9.7%, p =1.0)/IgM (0% vs. 0%, p =1.0), and anti-PS/PT IgG (0% vs. 1.6%, p =1.0)/IgM (12.9% vs. 21.0%, p =0.41), respectively. The aPL titers were also similar regardless of thrombosis. The levels of β2GPI in COVID-19 patients were lower than those in the healthy donors.ConclusionAlthough aPLs were frequently detected in Japanese COVID-19 patients, their prevalence and titer were irrelevant to thrombotic complications. While COVID-19 patients have lower levels of serum β2GPI than healthy blood donors, β2GPI levels were indifferent regardless of thrombosis. Although most of the titers were below cut-offs, positive correlations were observed among aPLs, suggesting that the immune reactions against aPL antigens were induced by COVID-19. We should focus on the long-term thromboembolic risk and the development of APS in the aPL-positive patients with high titer or multiple aPLs.

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Are antiphospholipid antibodies just a common epiphenomenon or are they causative of immune-mediated coagulopathy in COVID-19?

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Are antiphospholipid antibodies just a common epiphenomenon or are they causative of immune-mediated coagulopathy in COVID-19?

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