ANTIPHOSPHOLIPID ANTIBODIES AND VASCULAR THROMBOSIS IN PATIENTS WITH THE MOST SEVERE FORMS OF COVID-19

BackgroundThe presence of antiphospholipid antibodies (aPL) has been observed in patients with COVID-19 (1,2), suggesting that they may be associated with deep vein thrombosis, pulmonary embolism, or stroke in severe cases (3). Antiphospholipid syndrome (APS) is a systemic autoimmune disorder and the most common form of acquired thrombophilia globally. At least one clinical criterion, vascular thrombosis (arterial, venous or microthrombosis) or pregnancy morbidity and at least one laboratory criterion- positive aPL two times at least 12 weeks apart: lupus anticoagulant (LA), anticardiolipin (aCL), anti-β2-glycoprotein 1 (anti-β2GPI) antibody, have to be met for international APS classification criteria(4). Several reports also associate anti-phosphatidylserine/prothrombin antibodies (aPS/PT) with APS.ObjectivesTo combine clinical data on arterial/venous thrombosis and pregnancy complications before and during hospitalisation with aPL laboratory findings at 4 time points (hospital admission, worsening of COVID-19, hospital discharge, and follow-up) in patients with the most severe forms of COVID-19 infection.MethodsPatients with COVID-19 pneumonia were consequetively enrolled, as they were admitted to the General hospital Pancevo. Exclusion criteria were previous diagnosis of inflammatory rheumatic disease and diagnosis of APS. Clinical data were obtained from the medical records. Laboratory results, including LA, aCL, anti-β2GPI, and aPS/PT antibodies were taken at hospital admission, worsening (defined as cytokine storm, connection of the patient to the respirator, use of the anti-IL-6 drug- Tocilizumab), at hospital discharge and at 3-months follow-up and sent to University Medical Centre Ljubljana, Slovenia for analysis. Statistics was performed by using SPSS 21.Results111 patients with COVID-19 pneumonia were recruited;7 patients died during hospitalisation (none were aPL-positive on admission and at the time of worsening), 3 due to pulmonary artery embolism. All patients were treated according to a predefined protocol which included antibiotics, corticosteroids, anticoagulation therapy and specific comorbidity drugs;patients with hypoxia were supported with oxygen. During hospitalisation, pulmonary artery thrombosis occurred in 5 patients, one was aPL-positive at all time points (was diagnosed with APS), others were negative. In addition, 9/101 patients had a history of thrombosis (5 arterial thrombosis (coronary and cerebral arteries), none of whom was aPL-positive on admission and at follow-up, and 4 venous thrombosis, one of which was aPL-positive at all time points and received an APS diagnosis). Among 9/101 patients with a history of thrombosis, 55.6% were transiently positive at the time of discharge, compared to patients without prior thrombosis, in whom 26.1% were transiently positive at the hospital release (p=0.074). Two patients had a history of pregnancy complications (both had miscarriage after 10th week of gestation), but did not have aPL positivity at any time point.ConclusionAlthough aPL was expected to be associated with vascular disease in the most severe forms of COVID-19, all patients that have died in our cohort were aPL negative. At hospital discharge, 56% of patients with a history of arterial or venous thrombosis had positive aPL that became negative at the 3-months follow-up (were transienlty positive), which should be considered when prescribing therapy after hospitalisation.References[1]Trahtemberg U, Rottapel R, Dos Santos CC, et al. Anticardiolipin and other antiphospholipid antibodies in critically ill COVID-19 positive and negative patients. Annals of the Rheumatic Diseases 2021;80:1236-1240.[2]Stelzer M, Henes J, Saur S. The Role of Antiphospholipid Antibodies in COVID-19. Curr Rheumatol Rep. 2021;23(9):72-4.[3]Xie Y, Wang X, Yang P, Zhang S. COVID-19 complicated by acute pulmonary embolism. Radiology: Cardiothoracic Imaging 2020: 2: e200067.[4]Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, et al. J.Thromb.Haemost. 2006;4: 295-306.Acknowledgements:NIL.Disclosure of nterestsNone Declared.

AUTOANTIBODIES RELATED TO RHEUMATIC DISEASES AFTER COVID-19 INFECTION

BackgroundSARS-CoV-2(Severe acute respiratory syndrome coronavirus 2) has been circulating worldwide for three years. It mainly causes upper respiratory tract infection, which can manifest as pulmonary infection and even respiratory distress syndrome in severe cases. Different autoantibodies can be detected in patients infected with COVID-19.ObjectivesTo explore autoantibodies related to rheumatic diseases after COVID-19 infection.MethodsNinety-eight inpatients were tested for antinuclear antibodies (ANA), antibodies to extractable nuclear antigens(ENA), anti-neutrophil cytoplasmic antibodies（ANCA), anticardiolipin antibodies,a-β2GPI (IgG/IgM). They were from a tertiary hospital in Guangzhou during the COVID-19 epidemic. Data were described statistically.ResultsNinety-eight hospitalized patients were tested for relevant antibodies. The average age was 50.64±19.54;67 (68.4%) were male, 64 (65.3%) were COVID-19 positive, 90 (90.9%) had rheumatic diseases, and 56 of them were COVID-19 positive patients with rheumatic diseases.There were 76 patients tested for antinuclear antibodies;29 （38.16%）were negative, 18 （23.68%）had a 1/80 titre, and 29（28.16%） had a titre greater than 1:80. The 31 covid patients were positive for ANA. In the high-titer group, 19 patients with rheumatic diseases were positive for COVID-19, and 12 patients had an exacerbation of the rheumatic diseases (6 of whom had previously had pulmonary fibrosis). Of 31 covid patients, only two were non-rheumatic patients, and both were elderly, aged 85 and 100, respectively.Fifty-six patients had ENA results, and 29 for positive antibodies, 8 for ds-DNA antibodies, 2 for anti-Sm antibodies, 6 for anti-nucleosome antibodies, 12 for anti-U1RNP antibodies, 2 for anti-Scl-70 antibodies, 12 for anti-SS-A antibodies, 3 for anti-mitochondrial M2 antibodies, 2 for anti-centromere antibodies, 1 for anti-Po antibodies, and one for anti-Jo-1 antibody. All 56 patients had rheumatic diseases, and no new patients were found.There were 62 patients with ANCA data. P-ANCA was positive in 12 cases(19.35%), and MPO-ANCA was positive in 2 cases. An 85-year-old non-rheumatic COVID-19 patient was P-ANCA positive. She had a history of hypertension, colon cancer, CKD3, coronary heart disease, and atrial flutter.In the anticardiolipin antibodies group, there were 62 patients;only 6 were positive, and 2 were rheumatic patients infected with COVID-19. Antiphospholipid antibodies were detected in 33 patients, and a-β2GPI was tested in one patient, an 82-year-old COVID-19 patient with gout, diabetes, and cerebral infarction in the past. We did not find a statistical difference in the above results.ConclusionWe have not found a correlation between SARS-CoV-2 and serum autoantibodies of rheumatic immune diseases. It needs large samples and an extended follow-up to research.AcknowledgementsThis work was supported by Scientific and Technological Planning Project of Guangzhou City [202102020150], Guangdong Provincial Basic and Applied Basic Research Fund Project [2021A1515111172], National Natural Science Foundation of China Youth Fund [82201998] and Third Affiliated Hospital of Sun Yat-Sen University Cultivating Special Fund Project for National Natural Science Foundation of China [2022GZRPYQN01].Disclosure of Interestsone declared.

COVID-19 VACCINE SAFETY DURING PREGNANCY IN WOMEN WITH SYSTEMIC LUPUS ERYTHEMATOSUS

BackgroundVaccinations comprise a part of the antenatal care of pregnant women, including patients with systemic lupus erythematosus (SLE) who are at increased risk of adverse pregnancy outcomes (APOs). While COVID-19 vaccination has been shown to be safe in patients with SLE, data on vaccine-associated adverse events (AEs) during the antenatal and lactation period are scarce or lacking.ObjectivesTo investigate the association between COVID-19 vaccination and AEs in pregnant SLE patients.MethodsA total of 9201 complete responses were extracted on June 21st, 2022 from the COVID-19 Vaccination in Autoimmune Diseases (COVAD) 2 database, a global e-survey involving 157 collaborators from 106 countries. Among respondents, 6787 (73.8%) were women. We identified 70 (1.1%) women who were exposed to at least one COVID-19 vaccine dose during pregnancy, among those 11 with SLE. Delayed onset (>7 days) vaccine-related AEs were extracted and triangulated with disease activity, treatment changes due to flare after vaccination, and COVID-19 infections in vaccinated pregnant women with SLE. Additionally, information on health-related quality of life and physical function was recorded using PROMIS at the time of survey completion.ResultsThe age of patients ranged from 28 to 39 years;5/11 women were of Asian origin. None of these patients reported major vaccine AEs, including four patients with self-reported active SLE prior to the vaccination. None of them reported any change in the status of their autoimmune disease, and no hospitalisation or special treatment was recorded. Six women experienced minor vaccine AEs;two of them had active disease prior to vaccination. Four patients reported COVID-19 infection;two of them while they were pregnant and post-vaccination and two prior to pregnancy and vaccination. All four patients experienced symptoms of their disease, but no overt SLE flare was reported. At the time of survey completion, all patients reported their general health as being good to excellent in all aspects evaluated. Importantly, no APOs were reported.None of the patients reported thrombotic events post-vaccination, which provides some reassurance regarding COVID-19 vaccination in a patient population with a high risk for cardiovascular comorbidity and thrombosis, especially in the presence of antiphospholipid antibodies or in patients diagnosed with the antiphospholipid syndrome, a considerable portion within SLE populations. Moreover, it was reassuring to note an absence of association between experienced vaccine AEs and active disease prior to vaccination. Although minor AEs were common, they did not impair daily functioning, and the symptoms resolved in all patients after a median of 3 (IQR: 2.5–5.0) days.ConclusionOur report adds relevant evidence concerning the sensitive issue of COVID-19 vaccine AEs and flares in SLE patients during the antenatal and lactation period. Despite the small sample size, the findings provide some reassurance and can contribute to informed decisions regarding vaccination in patients with SLE and high-risk pregnancies due to their background autoimmune disease. Based on the present data, the risk/benefit ration of COVID-19 vaccination appears favourable, with vaccines both providing passive immunisation to the fetus and active immunisation to the mother with no signals of exacerbation of the mother's autoimmune disease.Figure 1.Timeline showing COVID-19 vaccination and vaccination-related minor adverse events in relation to gestational and post-partum periods in eleven pregnant/lactating women with systemic lupus erythematosus.[Figure omitted. See PDF]AcknowledgementsThe authors thank all survey respondents, as well as patient associations and all members of the COVAD study group for their invaluable role in the data collection.Disclosure of InterestsNefeli Giannopoulou: None declared, Latika Gupta: None declared, Laura Andreoli: None declared, Daniele Lini: None declared, Elena Nikiphorou: None declared, Rohit Aggarwal Grant/research support from: R.A. has a consultancy relationshi with and/or has received research funding from Bristol Myers-Squibb, Pfizer, Genentech, Octapharma, CSL Behring, Mallinckrodt, AstraZeneca, Corbus, Kezar, Abbvie, Janssen, Kyverna Alexion, Argenx, Q32, EMD-Serono, Boehringer Ingelheim, Roivant, Merck, Galapagos, Actigraph, Scipher, Horizon Therapeutics, Teva, Beigene, ANI Pharmaceuticals, Biogen, Nuvig, Capella Bioscience, and CabalettaBio., Vikas Agarwal: None declared, Ioannis Parodis Grant/research support from: I.P. has received research funding and/or honoraria from Amgen, AstraZeneca, Aurinia Pharmaceuticals, Elli Lilly and Company, Gilead Sciences, GlaxoSmithKline, Janssen Pharmaceuticals, Novartis, and F. Hoffmann-La Roche AG.

COVID-19 CHALLENGE IN THE ANTIPHOSPHOLIPID SYNDROME – AN OBSERVATIONAL STUDY OF A SERBIAN COHORT

BackgroundFacing the outburst of the COVID-19 pandemic, we gradually comprehend its pathophysiology as a coagulopathy characterized by increased risks of arterial, venous, and microvascular thrombosis. Antiphospholipid syndrome (APS) is an autoimmune, thrombo-inflammatory disease characterized by thrombosis and/or pregnancy loss in the presence of one or more antiphospholipid antibodies (aPL).ObjectivesTo evaluate the clinical scenario of COVID-19 in the APS population of patients.MethodsThis is a single-center, observational, cross-sectional study. Data regarding the severity of COVID-19 (severe COVID-19 considered if interstitial pneumonia was diagnosed), COVID-19 vaccinal status, and post-vaccinal reactions (divided into mild, consisting of fever, myalgia, nausea, and severe if thrombosis at any point occurred) were collected from 44 APS patients (21 with primary and 23 with APS associated with systemic lupus erythematosus (SLE), 90.1% female). aPL analysis included the detection of aCL (IgG/IgM), ß2GPI (IgG/IgM), and LA Results were compared to the control group consisting of 31 healthy individuals, with no APS, matched to the APS group regarding age and gender.ResultsAt the moment of COVID-19 infection, 75% of the APS group was taking Aspirin, 15.9% warfarin, 2.3% non-vitamin K oral anticoagulant, 59.1% chloroquine, 31.8% corticosteroid, 2.3% methotrexate. None of the above-mentioned medications were taken from a control group. There was no difference regarding the severity of COVID-19 between APS patients and healthy controls: 84.1% of APS had mild and 15.9% severe COVID-19 (p=0.509, p=0.292 respectively). But the difference regarding the need for hospitalization was significant (none of the healthy controls compared to 11.4% APS patients, p=0.0073). Interestingly, COVID-19 occurred in 72.7% of APS patients before the COVID-19 vaccination compared to 35.5% of healthy controls, p=0.001, conversely, a significantly lower percentage of vaccinated APS patients had COVID-19 compared to healthy controls (34.1% to 71.0%, p=0.002). 27% of APS patients had mild post-vaccinal reactions, none with severe.ConclusionDuring the COVID-19 pandemic, APS patients in Serbia were at higher risk for hospitalization. However, there was no difference in the severity of clinical presentation compared to non -the APS population. We can only speculate that APS therapy consisting of Aspirin, Chloroquine, and oral anticoagulant therapy contributed to this finding. Moreover, COVID-19 vaccination in the APS population, followed by a low incidence of mild post-vaccinal reactions, had more benefits in protection than in non-APS individuals.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

RISK OF APS AND aPLs POSITIVE PATIENTS FOR THROMBOSIS WITH COVID-19

BackgroundCoagulopathy, thromboembolic events and DIC during COVID-19 infection has been reported. Antiphospholipid antibodies (aPLs), present in 1–5 % of healthy individuals. aPLs are associated with the risk of antiphospholipid syndrome (APS) which is associated with higher risk of thrombosis.ObjectivesWe wanted to see if patients with known APS or aPLs only are at higher risk of a thrombotic event compared to control when developed COVID-19. We retrospectively review EMR for over a year for thrombotic events in patients with COVID and prior history of APS or aPLs only and matched them to control.MethodsPatient characteristics and laboratory testing were summarized according to the following groups: APS, aPLs detected or control. The control were matched according to age and gender for each group. Continuous variable were summarized as median (range) and mean (standard deviation), while categorical variables were reported as frequency (percentage). The binary patient outcome of thrombotic event, hospitalization for COVID, death, and composite event (the combined occurrence of thrombotic events, hospitalization, death) were calculated and interpreted as the multiplicative increase in odds of the given outcome for aPL group compared to control group. Multivariable logistic regression models were adjusted for potential risk factors (immobilization, hypertension, coronary artery disease, diabetes mellitus, and smoking) one at a time due to the rare occurrences of events studied.ResultsIn single variable analysis (unadjusted) the odds of the patient having a thrombotic event was approximately 27 times higher in patients with aPL only compared to Controls (P<0.001). We see similar results in multivariable analyses (adjusted) adjusting for the following variables one at a time: immobilization, hypertension, coronary artery disease, diabetes mellitus, and smoking. In each of the multivariable analyses, the adjusted odds of a thrombotic event was between approximately 24 and 29 times higher in patients with aPL Antibody Only compared to Controls (all P<0.001) indicating that association of aPL Antibody Only with thrombotic event was independent of immobilization, hypertension, coronary artery disease, diabetes, and smoking. There was no statistically significant risk of thrombosis in APS group vs control. Majority of patients with APS were on chronic anticoagulation.ConclusionWe found a statistical significantly difference in patient with aPLs only versus control regarding risk of thrombosis when developed COVID-19. No statistically significant risk was noted in patients with APS. While chronic anticoagulation in APS patients is protective it seemed that patient with aPLs only do carry a high risk of thrombosis if any inciting factors like COVID-19.References[1]C. Huang, Y. Wang, X. Li et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China, Lancet 395 (2020)[2]A. Jayarangaiah, P.T. Kariyanna, X. Chen, A. Jayarangaiah, A. Kumar, COVID-19- Associated coagulopathy: an exacerbated immunothrombosis response, Clin. Appl. Thromb. 26 (2020)[3]Y. Zhang, M. Xiao, S. Zhang et al. Coagulopathy and antiphospholipid antibodies in patients with Covid-19, N. Engl. J. Med. 382 (2020)[4]K.J. Lackner, N. Müller-Calleja, Pathogenesis of antiphospholipid syndrome: recent insights and emerging concepts, Expert Rev. Clin. Immunol. 15 (2019)Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Bilateral pulmonary embolism associated with peripheral blood eosinophilia and positive antiphospholipid antibodies in a patient with cellulitis.

Key Clinical Message: This report described the pathophysiology, diagnostic workup, and management of thrombosis possibly associated with peripheral blood eosinophilia and transient positive antiphospholipid antibodies in the setting of cellulitis. Abstract: Peripheral blood eosinophilia is a risk factor for thrombosis and the presence of other prothrombotic factors such as antiphospholipid antibodies can potentiate that risk. The authors present a case of acute pulmonary embolism which developed at the peak of eosinophilia, later found to have transient positive antiphospholipid antibodies in a male patient with right lower limb cellulitis and a history of intravenous drug abuse. This report illustrates the pathophysiology, diagnosis workup, and therapeutic options of thrombosis possibly associated with peripheral blood eosinophilia and positive antiphospholipid antibodies, which include anticoagulants, corticosteroids, and immunosuppressants. Clinicians should be aware of this possible association which may guide the choice and duration of anticoagulants. Although direct oral anticoagulants are effective anticoagulants in various thromboembolic events, studies showed unfavorable outcomes for their use in antiphospholipid syndrome.

Antiphospholipid Antibodies Occurrence in Acute SARS-CoV-2 Infection without Overt Thrombosis.

We sought to determine the prevalence of antiphospholipid antibodies (aPLs) and their correlation with COVID-19 severity (in terms of clinical and laboratory parameters) in patients without thrombotic events during the early phase of infection. This was a cross-sectional study with the inclusion of hospitalized COVID-19 patients from a single department during the COVID-19 pandemic (April 2020-May 2021). Previous known immune disease or thrombophilia along with long-term anticoagulation and patients with overt arterial or venous thrombosis during SARS-CoV-2 infection were excluded. In all cases, data on four criteria for aPL were collected, namely lupus anticoagulant (LA), IgM and IgG anticardiolipin antibodies (aCL), as well as IgG anti-ß2 glycoprotein I antibodies (aß2GPI). One hundred and seventy-nine COVID-19 patients were included, with a mean age of 59.6 (14.5) years and a sex ratio of 0.8 male: female. LA was positive in 41.9%, while it was strongly positive in 4.5%; aCL IgM was found in 9.5%, aCL IgG in 4.5%, and aß2GPI IgG in 1.7% of the sera tested. Clinical correlation: LA was more frequently expressed in severe COVID-19 cases than in moderate or mild cases (p = 0.027). Laboratory correlation: In univariate analysis, LA levels were correlated with D-dimer (p = 0.016), aPTT (p = 0.001), ferritin (p = 0.012), C-reactive protein (CRP) (p = 0.027), lymphocyte (p = 0.040), and platelet (p < 0.001) counts. However, in the multivariate analysis, only the CRP levels correlated with LA positivity: OR (95% CI) 1.008 (1.001-1.016), p = 0.042. LA was the most common aPL identified in the acute phase of COVID-19 and was correlated with infection severity in patients without overt thrombosis.

Antiphospholipid antibodies in convalescent plasma of donors recovered from mild COVID-19 infection.

BACKGROUND AND OBJECTIVES: Passive immunization by the infusion of convalescent plasma (CP) obtained from patients who have recently recovered from COVID-19, thus having antibodies to severe acute respiratory syndrome coronavirus 2, is a potential strategy to reduce the severity of illness. A high prevalence of antiphospholipid antibodies (APLA) in patients with COVID-19 has been reported during the pandemic, raising a concern whether the use of CP could increase the risk of thrombosis in transfused patients. We aimed to evaluate the prevalence of APLA in COVID-19 CP (CCP) in order to assess the potential prothrombotic influence of transfused CCP to COVID-19 patients. MATERIALS AND METHODS: We studied the prevalence of APLA in 122 CCP samples collected from healthy donors who recovered from mild-COVID-19 at two time periods: September 2020-January 2021 (defined as 'early period' samples) and April-May 2021 (defined as 'late period' samples). Thirty-four healthy subjects unexposed to COVID-19 were used as controls. RESULTS: APLA were present in 7 of 122 (6%) CCP samples. One donor had anti-ß2-glycoprotein 1(anti-ß2GP1) IgG, one had anti-ß2GP1 IgM and five had lupus anticoagulant (LAC) using silica clotting time (SCT), all in 'late period' donors. In the control group, one subject had anti-ß2GP1 IgG, two had LAC using dilute Russell viper venom time (dRVVT) and four had LAC SCT (both LAC SCT and LAC dRVVT in one subject). CONCLUSION: The low prevalence of APLA in CCP donors reassures the safety of CCP administration to patients with severe COVID-19.

Antiphospholipid syndrome, antiphospholipid antibodies, and stroke.

Antiphospholipid syndrome (APS) is a prothrombotic autoimmune disease with heterogeneous clinicopathological manifestations and is a well-established cause of acute ischemic stroke (AIS) and transient ischemic attack (TIA), particularly in younger patients. There is growing recognition of a wider spectrum of APS-associated cerebrovascular lesions, including white matter hyperintensities, cortical atrophy, and infarcts, which may have clinically important neurocognitive sequalae. Diagnosis of APS-associated AIS/TIA requires expert review of clinical and laboratory information. Management poses challenges, given the potential for substantial morbidity and recurrent thrombosis, additional risk conferred by conventional cardiovascular risk factors, and limited evidence base regarding optimal antithrombotic therapy for secondary prevention. In this review, we summarize key features of APS-associated cerebrovascular disorders, with focus on clinical and laboratory aspects of diagnostic evaluation. The current status of prognostic markers is considered. We review the evidence base for antithrombotic treatment in APS-associated stroke and discuss uncertainties, including the optimal intensity of anticoagulation and efficacy of direct oral anticoagulants. Clinical practice recommendations are provided, covering antithrombotic treatment, supportive management, and options for anticoagulant-refractory cases, and we highlight the benefits of adopting a considered, multidisciplinary team approach.

Antiphospholipid Antibodies and Outcomes of Assisted Reproductive Technology Programs in Patients with a History of Covid-19

Investigation of the effect COVID-19 mediated with autoantibodies has on reproductive outcomes is important. This study aimed to evaluate the profile of antiphospholipid antibodies (aPL) and their association with the outcomes of assisted reproductive technology (ART) programs in patients with a history of COVID-19. The study included 240 patients: 105 of them did not have a history of COVID-19 (group 1) and 135 of them had a history of COVID-19 (group 2) with a mild course (subgroup 2a, n = 85) or moderate course (subgroup 2b, n = 50). With the help of ELISA, serum antibodies (M, G) to cardiolipin, beta 2-glycoprotein-I, annexin V (AnV), phosphatidylethanolamine (PE), phosphatidylserine, and phosphatidylserine/prothrombin complex were determined. The evaluated parameters were the indices of oogenesis, embryogenesis, ART intervention outcomes. In group 2, growing levels of anti-AnV and anti-PE IgG were observed more often (in 28 (20.7%) and 8 (5.9%) patients) than in group 1 (in 10 (9.5%) and 1 (0.95%);p = 0.02 and p = 0.045, respectively). In subgroup 2b we registered a higher level of anti-PE IgG and a higher incidence of early miscarriages (in 6 (12%) patients) than in group 1 (in 3 (2.9%)) (p = 0.024). Weak inverse correlations were found between the level of anti-PE IgG and the number of oocytes and zygotes. The results of this study suggest a negative impact of aPL-mediated COVID-19 on the outcomes of ART programs and the course of early pregnancy.

Rheumatic manifestations and autoimmunity associated with COVID-19

A broad spectrum of complications following COVID-19 has been documented in adults, including the new onset of autoimmune-related manifestations and rheumatic diseases. Numerous case studies, reviews, and clinical trials have been published regarding the relationship between COVID-19 and the generation of autoantibodies that may cause rheumatic and autoimmune diseases. The currently suggested pathophysiology that leads to the new onset of such disorders may include well-established mechanisms, such as molecular mimicry and hyperstimulation of the immune system. The prevailing conditions documented following COVID-19 include, yet are not limited to, rheumatoid arthritis, myositis, antiphospholipid antibodies, ITP, and thyroid dysfunction. This chapter will summarize the current documentation of the broad-spectrum rheumatic diseases and autoimmune manifestations mediated by a SARS-CoV-2 infection. © 2023 Elsevier Inc. All rights reserved.

COVID-19 in patients with Systemic Lupus Erythematosus and the antiphospholipid syndrome

In patients with Systemic Lupus Erythematosus (SLE) and Antiphospholipid Syndrome (APS), the dysregulated immune response together with the use of immunosuppressive drugs has raised some concerns about the increased susceptibility to SARS-CoV-2 infection and the efficacy of anti-SARS-CoV-2 vaccines. Moreover, COVID-19, SLE, and APS share pathogenic pathways that may be responsible of common clinical and laboratory features and may explain why some drugs approved for SLE treatment were considered as potential treatment for COVID-19 disease. Another concern relies on "post-COVID syndrome” (the persistence of debilitating symptoms such as fatigue, dyspnea, and cognitive dysfunction) that could be confused with signs of SLE or APS. This chapter describes the common pathogenic mechanisms and clinical manifestations of COVID-19, SLE, and APS. Management strategies and immunogenicity and safety of COVID-19 vaccines are addressed. A focus on pregnant patients is also provided. Finally, similarities and differences between post-COVID syndrome and SLE/APS manifestations are described. © 2023 Elsevier Inc. All rights reserved.

The APSANTICO Study: A Prospective Observational Study to Evaluate Antiphospholipid Antibody Profiles in Patients with Thromboembolic Antiphospholipid Syndrome (APS) after COVID-19 Infection and/or Vaccination.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new virus discovered in December 2019 that causes coronavirus disease 19 (COVID-19) and various vaccinations have been developed. The extent to which COVID-19 infections and/or COVID-19 vaccinations alter antiphospholipid antibodies (aPL) in patients with thromboembolic antiphospholipid syndrome (APS) remains unclear. Eighty-two patients with confirmed thromboembolic APS were included in this prospective non-interventional trial. Blood parameters including lupus anticoagulants, anticardiolipin IgG- and IgM-antibodies, and anti-ß2-glycoprotein I IgG- and IgM-antibodies were assessed prior to and after COVID-19 vaccination and/or COVID-19 infection. No increases in aPL in the total study population were detected. In fact, low but significant decreases were observed for anticardiolipin IgG- and anti-ß2-glycoprotein I IgG-antibodies, while anticardiolipin IgM- and anti-b2-glycoprotein I IgM-antibodies slightly increased only in patients with COVID-19 infection and vaccination. Although the investigated patient group is known to have a high risk of recurrent thrombosis, only one arterial thrombotic event was diagnosed (1.2%, 1/82). This low recurrence rate was probably due to the high vaccination rates prior to infections and a high rate of effective anticoagulation. Our data show that COVID-19 infections and/or vaccinations do not deteriorate the clinical course of anticoagulated thromboembolic APS patients.

COVID-19 and antiphospholipid antibodies.

Antiphospholipid syndrome and the coagulopathy of COVID-19 share many pathophysiologic features, including endotheliopathy, hypercoagulability, and activation of platelets, complement pathways, and neutrophil extracellular traps, all acting in concert via a model of immunothrombosis. Antiphospholipid antibody production in COVID-19 is common, with 50% of COVID-19 patients being positive for lupus anticoagulant in some studies, and with non-Sapporo criteria antiphospholipid antibodies being prevalent as well. The biological significance of antiphospholipid antibodies in COVID-19 is uncertain, as such antibodies are usually transient, and studies examining clinical outcomes in COVID-19 patients with and without antiphospholipid antibodies have yielded conflicting results. In this review, we explore the biology of antiphospholipid antibodies in COVID-19 and other infections and discuss mechanisms of thrombogenesis in antiphospholipid syndrome and parallels with COVID-19 coagulopathy. In addition, we review the existing literature on safety of COVID-19 vaccination in patients with antiphospholipid antibodies and antiphospholipid syndrome.

Antiphospholipid antibodies in patients with stroke during COVID-19: A role in the signaling pathway leading to platelet activation.

Background: Several viral and bacterial infections, including COVID-19, may lead to both thrombotic and hemorrhagic complications. Previously, it has been demonstrated an "in vitro" pathogenic effect of "antiphospholipid" antibodies (aPLs), which are able to activate a proinflammatory and procoagulant phenotype in monocytes, endothelial cells and platelets. This study analyzed the occurrence of aPL IgG in patients with acute ischemic stroke (AIS) during COVID-19, evaluating the effect of Ig fractions from these patients on signaling and functional activation of platelets. Materials and methods: Sera from 10 patients with AIS during COVID-19, 10 non-COVID-19 stroke patients, 20 COVID-19 and 30 healthy donors (HD) were analyzed for anti-cardiolipin, anti-ß2-GPI, anti-phosphatidylserine/prothrombin and anti-vimentin/CL antibodies by ELISA. Platelets from healthy donors were incubated with Ig fractions from these patients or with polyclonal anti-ß2-GPI IgG and analyzed for phospho-ERK and phospho-p38 by western blot. Platelet secretion by ATP release dosage was also evaluated. Results: We demonstrated the presence of aPLs IgG in sera of patients with AIS during COVID-19. Treatment with the Ig fractions from these patients or with polyclonal anti-ß2-GPI IgG induced a significant increase of phospho-ERK and phospho-p38 expression. In the same vein, platelet activation was supported by the increase of adenyl nucleotides release induced by Ig fractions. Conclusions: This study demonstrates the presence of aPLs in a subgroup of COVID-19 patients who presented AIS, suggesting a role in the mechanisms contributing to hypercoagulable state in these patients. Detecting these antibodies as a serological marker to check and monitor COVID-19 may contribute to improve the risk stratification of thromboembolic manifestations in these patients.

Longitudinal Analysis of Antiphospholipid Antibody Dynamics after Infection with SARS-CoV-2 or Vaccination with BNT162b2.

Antiphospholipid antibodies (aPL) comprise a group of autoantibodies that reflect prothrombotic risk in antiphospholipid syndrome (APS) but may also be present in a small proportion of healthy individuals. They are often transiently elevated in infections, including SARS-CoV-2, and may also be associated with vaccine-induced autoimmunity. Therefore, we aimed to investigate the dynamics of aPL in COVID-19 patients and in individuals (healthcare professionals-HCPs) after receiving BNT162b2 vaccine and to compare aPL levels and positivity with those found in APS patients. We measured solid-phase identifiable aPL, including anticardiolipin (aCL), anti-ß2 glycoprotein I (anti-ß2GPI), and anti-prothrombin/phosphatidylserine (aPS/PT) antibodies in 58 HCPs before and after vaccination (at 3 weeks, 3, 6, and 9 months after the second dose, and 3 weeks after the third booster dose), in 45 COVID-19 patients hospitalized in the ICU, in 89 COVID-19 patients hospitalized in the non-ICU (at admission, at hospital discharge, and at follow-up), and in 52 patients with APS. The most frequently induced aPL in COVID-19 patients (hospitalized in non-ICU) were aCL (50.6% of patients had positive levels at at least one time point), followed by anti-ß2GPI (21.3% of patients had positive levels at at least one time point). In 9/89 COVID-19 patients, positive aPL levels persisted for three months. One HCP developed aCL IgG after vaccination but the persistence could not be confirmed, and two HCPs developed persistent anti-ß2GPI IgG after vaccination with no increase during a 1-year follow-up period. Solid-phase aPL were detected in 84.6% of APS patients, in 49.4% of COVID-19 patients hospitalized in the non-ICU, in 33.3% of COVID-19 patients hospitalized in the ICU, and in only 17.2% of vaccinated HCPs. aPL levels and multiple positivity were significantly lower in both infected groups and in vaccinated individuals compared with APS patients. In conclusion, BNT162b2 mRNA vaccine may have induced aPL in a few individuals, whereas SARS-CoV-2 infection itself results in a higher percentage of aPL induction, but the levels, persistence, and multiple positivity of aPL do not follow the pattern observed in APS.

Anti-phospholipid antibodies were associated with clinical symptoms, disease severity and mortality among hospitalized COVID-19 patient

Background: This study was aimed to find the correlation of anti-phospholipid antibodies in the risk of coagulopathy and disease severity in coronavirus disease-19 (COVID-19). Method(s): Clinical and laboratory findings were obtained from 50 confirmed COVID-19 patients hospitalized in Saiful Anwar General Hospital, Malang, Indonesia from September to November 2020. Anti-phospholipid antibodies were measured by finding of IgM anti-beta2 glycoprotein, lupus anticoagulant and IgM anti-cardiolipin. Clinical Symptoms, thrombotic events, and mortality during hospitalization were recorded. Disease severity was defined by COVID-19 Treatment by multi-departement guidelines, Ministry of Health, Year 2020, Indonesia. Result(s): Among 50 patients, 5 patient (10%) were positive of IgM anti-beta2 glycoprotein (2%), IgG anti-cardiolipin (2%) and IgM anti-cardiolipin (8%). Anti-phospholipid antibodies were associated with anosmia OR 8.1 (1.1-57.9) (P = 0.018), nausea and vomiting OR 12.4 (1.2-122.6) (P = 0.010), diarrhea OR 9.8 (1.3-70.9) (P = 0.010), cardiovascular disease OR 1.4 (1.0-1.9), (P = 0.001), chronic kidney disease OR 12.0 (1.6-90.1) (P = 0.05), acute coronary syndrome (P = 0.001), moderate OR 0.11 (0.01-1.1) (P = 0.031) and severe OR 18.5 (1.8-188.4) (P = 0.002) disease severity, and in-hospital mortality OR 8.1 (1.1-57.9) (P = 0.018). Conclusion(s): In conclusion, anti-phospholipid antibodies show a low prevalence in COVID-19 patients and are associated with increased risk of acute coronary syndrome, clinical manifestations, disease severity, and mortality. Anti-phospholipid antibodies in COVID-19 patients are mainly directed against anti-cardiolipin.

Clinical And Laboratory Characteristics Of Covid-19

The significance of D-dimer coagulation (DD), prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT) and fibrinogen (Fg) and PCT in predicting the severity and prognosis of COVID-19 was studied. Violation of the function of blood coagulation occurred in almost all, more often in severe patients. Indicators of hemostatic homeostasis, such as D-dimer, prothrombin time, fibrinogen and procalcitonin, can be used as predictors of disease severity in patients. Copyright © 2022 Wolters Kluwer Medknow Publications. All rights reserved.