Antiphospholipid antibody profile in a group of Algerian Covid-19 patients

Background: Excessive activation of coagulation causing thrombotic complications was observed during Covid-19 infection. The objective of this study was to evaluate the frequency of antiphospholipid antibodies (aPL) in a group of patients with this infection. Method(s): 45 patients (10 Women and 35 men) diagnosed with SARS Cov2 infection were included in our study. The mean age was 63 +/- 10.7 years. Moderate, severe and critical forms were noted in 7%, 51% and 42% of patients, respectively. The IgG/IgM antibodies anti beta2 glycoprotein 1 (beta2 GP1) and IgG/ IgM anti cardiolipin (aCL) were assessed by an immuno-enzymatic assay (ELISA). Result(s): IgG, IgM anti beta2 GP1 and IgG, IgM aCL were positive in respectively 20%, 10%, 25% and 9% of patients. Stratification according to the form of infection showed a positive APL in 66%, 22% and 32% of moderate, severe and critical forms. Also, these APL were positive in 37% of deceased patients versus 23% of stable patients. Conclusion(s): The positivity of aPL appears to be high in our study. Early and effective anticoagulant treatment in Covid-19 patients is needed to avoid any complications.

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.

Case report: Covid-19 and disseminated tuberculosis coinfection unveiling catastrophic antiphospholipid antibody syndrome: An association or de novo phenomenon

Background: Disseminated infections such as tuberculosis are known to result in a systemic inflammatory response leading to thrombosis, with increasing reported cases of thrombotic event being observed in patients infected with covid-19. This is the first reported case on co-infection with COVID-19 pneumonia and disseminated tuberculosis causing catastrophic antiphospholipid syndrome (CAPS). Method(s): The report highlighted the challenges in the diagnosis and management which include the use of corticosteroid in setting of systemic infections. Another diagnostic dilemma was to explain the cause of myositis by tuberculous or autoimmune. Case Presentation: We report a 26-year- old man with HbE trait thalassemia who reported unintentional weight loss, night sweats for 1 month prior to the diagnosis of covid-19 infection on 10th March 2022. Seven days later, he was hospitalized for suspected perforated appendix. Computed tomography (CT) abdomen revealed hepatosplenomegaly, prostatitis, seminal vesiculitis. Multiple matted abdominal lymph nodes were not amenable for biopsy. Soon, he appeared toxic, dyspneic required non-invasive ventilation with bilateral parotitis. He had raised erythrocyte sedimentation (ESR) 52 mm/hour, C-reactive protein (CRP) 221 mg/dl, lactate dehydrogenase (LDH) 730U/L. Direct Coomb's antibody was positive but did not have any form of haemolysis. Complement 3 (0.45 g/L) and complement 4 (0.1 g/L) levels were low. Serum IgG4, procalcitonin, anti-nuclear antibody, cultures and virology were negative. Sputum for acid fast bacilli (AFB) was positive on Auramine O stain but the Ziehl-Nelson (ZN) stain and tuberculous PCR (GeneXpert) were negative. Diagnosis of disseminated tuberculosis was made but his abdominal pain persisted despite being on anti-tuberculous therapy (ATT), and he had new evidence of splenic infarct. CT angiogram also revealed celiac trunk and superior mesenteric artery thrombosis. Antiphospholipid (aPL) test was positive for lupus anticoagulant, beta 2 glycoprotein 1 and anti-cardiolipin antibodies. Therapeutic anticoagulation and plasma exchange were initiated for probable CAPS followed by intravenous immunoglobulin and corticosteroid. Thereafter, the patient developed severe bilateral pelvic girdle pain with evidence of myositis on the MRI (Figure 2). Serum creatine kinase was never elevated. Anti-PL- 7 and anti Ro-52 were borderline elevated. He recovered well and ambulant before discharged home. Conclusion(s): Our case highlight the complexicity of presentation of CAPS who manifested as multiple arterial thrombosis. The diagnosis of disseminated tuberculosis relied strongly on microbiological, imaging and clinical presentation as histopathological evidence was not feasible. Management challenges were deciding on corticosteroid in disseminated infection and the need for confirmation of persistent positive aPL test and to monitor myositis symptom to help guide decision making. (Figure Presented).

All in the Marrow - a Case of Primary Bone Marrow Oedema

Introduction/Background: Primary bone marrow oedema syndrome is an elusive and less well-defined entity. Whether Rheumatologists should consider it as a stand alone diagnosis, is debatable. It possibly would be best described as an MRI feature which could be a finding in a number of diseases which would include the initial phases of Osteonecrosis of the bone, Rheumatoid Arthritis, Spondyloarthritis, Enthesitis related, Post traumatic, OA, Infections and Cancers. The treatment options become constricted due to the paucity of evidence. Rheumatologists need to consider this as an area of unmet need with development of consensus classification criteria and treatment approaches. Description/Method: 27-year-old male, Height 174 cms Weight 90 Kgs BMI 29 Kg/m2, became symptomatic in Jan 2022 with complains of pain in the both hip joints & groin regions, pain became excruciating and he became bed-bound, with early morning stiffness lasting approximately 45 mins. Had received steroids for COVID infection in August 2020. Investigations Hb 13.5gm/dl TLC 7000/mm3 Platelet 400 x 103/mm3 Sr Bil 0.8mg/dl AST 16 IU/L. ALT 24 IU/L Sr Creatininine 1.1mg/dl Blood Sugar Levels, Fasting 89 mg/dl Post Prandial 102 mg/dl ESR 10mm in 1st hour by Wintrobes method CRP Quantitative 29.38mg/L HLA B27 by PCR Negative, RF Negative, ACCP Negative Serum, IgG, Beta2 Glycoprotein 1.44 SGU Serum, IgM, Beta2 Glycoprotein 3.44 SGU Serum, IgG, Cardiolipin antibody 8.4 GPL Serum, IgG, Cardiolipin antibody 17.45 GPL Lupus anticoagulant by DRVVT Negative Sr Cholesterol 211mg/dl HDL 29 mg/dl LDL 156mg/dl TGs 130 mg/dl MRI Hips & SI joints Transient bone marrow oedema/osteopenia of bilateral hip. PET CT Increased metabolic activity in both hip joints Bone Scan (99mTcMDP) Increased vascularity in perfusion phase, increased accumulation in soft tissue in blood pool phase and increased uptake in bilateral Hip joints in skeletal phase scan, suggestive of CRPS Type-I. Management Was initially managed with Tab Etoricoxib 90mg BD, also started on Tab Sulphaslazine and Tab Methotrexate. However, when he had no symptomatic relief he was administered Inj Infliximab on 12 May 2022 and a second dose on 9 June 2022. He had excellent pain relief after the 1st dose, however after 10 days of the administration, he again began experiencing pain especially after walking. He also had pain in the knees on this occasion. He was also administered Inj Zoledronic 4mg on 23 May 2022. He is at present not requiring any NSAIDs over the last 1 month. Discussion/Results: The patient having presented with excruciating and debilitating pain was worked up and evaluation revealed features of bone marrow oedema on MRI which was corroborated with bone scan and PET CT imaging. The acute phase reactant CRP was also significantly elevated. The patient also gave history of early morning stiffness lasting approximately 45 mins. Hence an underlying Inflammatory process such as Spondyloarthritis(Peripheral) with enthesitis was considered. The confounding factors were the pain which worsened on mobilization, HLA B27 negative status, Rheumatoid Factor and ACCP negative status and past history of having received IV Corticosteroids for COVID infection in August 2020. In view of the debilitating pain and aworking diagnosis of Spondyloarthritis, hewas started onNSAIDs alongwith rest, initially, followed by conventional synthetic disease modifying agents in Rheumatic disease followed by biologic synthetic diseasemodifying agent - Inj Infliximab. The thought process was to avoid prolonged NSAID use to prevent the associated side effects. However, since Avascular Necrosis of the Femoral head is a very likely possibility, the patient is planned to be kept under close follow up. Key learning points/Conclusion: Collaborative efforts between the Departments of Nuclear Medicine, Radiology, Orthopaedics and Rheumatology are crucial in the early detection and approach to cases of Bone Marrow oedema. Avascular necrosis of head of Femur is a far more common entity and must be kept in ind even when a diagnosis of Bone Marrow oedema syndrome is being entertained. Diagnosis of Bone Marrow oedema syndrome must be entertained only as a diagnosis of exclusion. Continued follow up and regular imaging must be pursued rigorously in patients diagnosed with Bone Marrow oedema syndromes. There is a requirement to document acute phase reactants such as CRP and ESR in patients diagnosed with Avascular necrosis of bone as this data could help us differentiate AVN from Primary Bone marrow oedema in the early stages.

A RARE PRESENTATION OF COVID-19-ASSOCIATED CENTRAL VENOUS THROMBOSIS

SESSION TITLE: COVID-19 Case Report Posters 3 SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Due to a wide range of clinical presentations, central venous thrombosis (CVT) is a rare neurologic condition that can be difficult to diagnose. Since the COVID-19 pandemic, more cases of venous thromboembolic events have emerged and been found associated with COVID-19. We detail a potential case of COVID-19 associated CVT. CASE PRESENTATION: A 28-year-old female with past medical history of obesity, polycystic ovary syndrome, recurrent sinusitis, and presumed history of COVID-19 infection with anosmia, ageusia, and sinusitis symptoms three- months prior presented to the hospital with 1-month history of worsening, right-sided pain behind her ear, eye, head, posterior neck and shoulder, nausea, and photophobia, which had worsened in the last 5 days. She initially tried over-the-counter medications with no improvement. Vital signs were unremarkable. Examination was notable for frontal sinus and right postauricular tenderness to palpation. C- reactive protein was elevated at 26.2 mg/L. Non- contrasted brain computed tomography (CT) was concerning for right transverse sinus and superior sagittal sinus thrombosis. Brain magnetic resonance imaging (MRI) showed early signs of cortical edema and venous infarction and findings concerning for right mastoiditis. Intracranial venous MRI showed complete thrombosis of the right transverse and sigmoid sinus, superior sagittal sinus, and most of the superior draining cortical veins. Heparin drip was started. Initial empiric antibiotics for mastoiditis were stopped. Hyper-coagulopathy work-up with beta- 2 glycoprotein 1 antibodies and phospholipid antibodies were negative. As there were no other inciting factors for CVT found and no history of positive COVID-19 test, a COVID-19 antibody immunoassay was obtained and returned positive. The patient did not have a history of COVID vaccination. She was discharged on warfarin and enoxaparin. Anticoagulation was stopped after 6 months with repeat imaging showing resolution of clot burden. DISCUSSION: Usual risk factors associated with CVT are morbid obesity, hormone replacement therapy, oral contraceptive use, hereditary thrombophilia, and pregnancy. Literature on CVT related to COVID-19 is limited. In 41 documented cases, the average age of incidence is 50 years old and median onset of neurological symptoms from initial COVID-19 diagnosis is 7 days [0 to 21 days]. Our patient's neurological symptoms began about 3 months after her initial diagnosis, potentially making it the first known case of COVID-19 associated CVT with symptom onset past 21 days. Anticoagulation is the mainstay treatment for CVT, and duration depends on the presence of provoking factor. CONCLUSIONS: In patients with new neurologic symptoms and recent diagnosis of COVID-19, CVT should be considered in the differential diagnosis as it can initially present in a subtle manner. Early recognition could improve patient morbidity and mortality. Reference #1: Abdalkader, M., Shaikh, S. P., Siegler, J. E., Cervantes-Arslanian, A. M., Tiu, C., Radu, R. A., Tiu, V. E., Jillella, D. v., Mansour, O. Y., Vera, V., Chamorro, Á., Blasco, J., López, A., Farooqui, M., Thau, L., Smith, A., Gutierrez, S. O., Nguyen, T. N., Jovin, T. G. (2021). Cerebral Venous Sinus Thrombosis in COVID-19 Patients: A Multicenter Study and Review of Literature. Journal of Stroke and Cerebrovascular Diseases. https://doi.org/10.1016/j.jstrokecerebrovasdis.2021.105733 Reference #2: Idiculla, P. S., Gurala, D., Palanisamy, M., Vijayakumar, R., Dhandapani, S., Nagarajan, E. (2020). Cerebral Venous Thrombosis: A Comprehensive Review. European Neurology (Vol. 83, Issue 4). https://doi.org/10.1159/000509802 Reference #3: Ostovan VR, Foroughi R, Rostami M, et al. Cerebral venous sinus thrombosis associated with COVID-19: a case series and literature review. Journal of Neurology. 2021 Oct;268(10):3549-3560. DOI: 10.1007/s00415-021-10450-8. PMID: 33616740;PMCID: PMC7897893. DI CLOSURES: No relevant relationships by Shu Xian Lee No relevant relationships by Arif Sarwari No relevant relationships by Benita Wu

HIGH PREVALENCE of SERUM AUTOANTIBODIES in SEVERELY ILL COVID-19 PATIENTS HOSPITALIZED in the INTENSIVE CARE UNIT

Background: Coronavirus Disease-19 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is characterized by a wide range of clinical manifestations 1. Although COVID-19 was initially considered a respiratory infection, it was shortly recognized as a multisystemic disorder associated with heightened infammatory responses, including autoimmune phenomena 1. The presence of autoantibodies (AAbs) has been described in COVID-19 patients, highlighting the state of immune dysregulation in COVID-19 1. The clinical signifcance of AAbs, however, is still elusive. Objectives: To assess the prevalence of AAbs in critically ill, mechanically ventilated COVID-19 patients admitted to the intensive care unit (ICU) and investigate whether AAbs influence the clinical outcome of these patients. Methods: The current study evaluated prospectively from March 8th, 2021 to May 10th, 2021 the presence of AAbs against nuclear antigens (ANA), extracta-ble nuclear antigens (ENA), neutrophil cytoplasmic antigens (ANCA), cyclic cit-rullinated peptides (anti-CCP), double stranded-DNA (anti-dsDNA), cardiolipin (anti-CL), β2-glycoprotein-I (anti-β2-GPI), thyroid peroxidase (anti-TPO), and thyroglobulin (anti-TG) in critically ill COVID-19 patients upon admission in the ICU (n=217). Samples from 60 COVID-19 patients that were available 15 days after ICU admission were further analyzed for the evaluation of de novo AAbs production. Serum samples of age and sex matched healthy individuals before the COVID-19 pandemic were used as a control group (n=117). Results: COVID-19 patients treated in ICU had more commonly at least one AAb compared to age and sex matched controls (174/217, 80.2% vs 73/217, 62,4%, p< 0,001). More specifcally, COVID-19 patients expressed more frequently ANAs (48.4% vs 21.4%, p<0.001), anti-dsDNA (5.1% vs 0%, p=0.01), anti-CCP (8.3% vs 1.7%, p=0.014) and anti-CL IgM AAbs (21.7% vs 9.4%, p=0.005) than controls. The majority of critical COVID-19 patients who were positive for AAbs (144, 82.8%) expressed reactivity in up to three autoantigens with the most prominent being ANA, anti-phospholipid, ANCA and anti-TPO AAbs. AAbs-positive patients demonstrated more robust anti-SARS-CoV-2 humoral responses compared to AAbs-negative patients [detectable anti-SARS-CoV-2 S1-protein IgG antibodies: 150 (86.2%) vs 28 (65.1%), p=0.001;adequate neutralizing activity: 159 (91.4%) vs. 33 (76.7%), p=0.007]. The two groups, however, did not differ in terms of clinicoepidemiologic characteristics or the incidence of death in the ICU. Convalescent COVID-19 patients (n=111) compared to those who died (n=106), did not differ in the prevalence of serum AAbs or antibody responses against SARS-CoV-2. Differences were only shown in clinicolaboratory parameters including patients' age, comorbidities, O2 saturation, infammatory markers, and in-hospi-tal prognostic scores as expected. Paired samples testing (n=60) revealed that 45 patients had at least one newly induced AAb, 28 patients lost at least one reactivity and only 6 patients didn't show any seroconversion. The most common new-onset AAb reactivity was against anti-CL (IgG isotype) (n=21) followed by ANA (n=20), anti-β2-GPI (IgG isotype) (n=11), myositis-related antigens (n=13) and ENAs (n=9);nevertheless, no associations with clinicoepidemiologic features or COVID-19 outcome were revealed. Conclusion: Patients with severe COVID-19 express AAbs more commonly than age and sex matched controls, suggesting that SARS-COV-2 infection may induce a hitherto unknown B-cell autoreactivity. The presence of autoantibodies does not play a role in the outcome of SARS-COV-2 infection. However, further studies are needed to defne their role in future development of systemic autoimmune disorders or the long-COVID syndrome.

Scleroderma Renal Crisis and COVID—Is There an Association?

Scleroderma renal crisis (SRC) is a rare but potentially devastating complication of systemic sclerosis as it is associated with significant morbidity and mortality. We present an interesting case of a patient who developed SRC following infection with COVID-19. A 37-year-old female presented with new-onset hypertension, AKI, anemia and thrombocytopenia. She had a history of diffuse cutaneous systemic sclerosis diagnosed 8 years ago, that had been well controlled with immunosuppression. The patient had contracted COVID-19 infection about 2 weeks ago but had remained largely asymptomatic except for a sore throat. Urinalysis revealed sub-nephrotic proteinuria but was otherwise bland. Peripheral blood smear was notable for 12-15 schistocytes per HPF. ADAMTS13 and complement levels were normal. Serologies for ANA, ANCA, anti-Scl70, anti-Jo1, anti-Sm, lupus anticoagulant, anti-beta2-glycoprotein I, anti-RNA polymerase III, RF, cryoglobulin, RPR, hepatitis and HIV, all returned negative. Renal biopsy revealed an arterial predominant thrombotic microangiopathy (TMA) (Figure) consistent with a diagnosis of SRC. The patient was treated with anti-hypertensives including an ACE-inhibitor, but her AKI continued to worsen, ultimately leading to dialysis dependence. SRC classically develops in patients with early or progressive diffuse cutaneous disease or positivity for anti-RNA polymerase III antibodies. Our patient did not have any such risk factors and rather developed SRC following infection with COVID-19. COVID-19 has been reported to cause TMA by inducing immune dysregulation via an overactive complement system. It is plausible that infection with COVID-19 triggered an exaggerated immune response, in turn leading to the development of SRC in our patient. COVID-19 may trigger SRC in patients with systemic sclerosis in the absence of other risk factors. (Figure Presented)

PROFILE OF ANTIPHOSPHOLIPID ANTIBODIES AND COMPLEMENT SYSTEM IN COVID-19 PATIENTS OF DIFFERENT SEVERITY

COVID-19, a severe acute respiratory syndrome caused by SARS-CoV-2, may predispose to thrombotic events, especially when combined with antiphospholipid antibodies (aPL). However, there are limited data on prevalence and antigenic specificity of aPL in COVID-19. Complement activation is assumed to play an important role in pathogenesis of COVID-19-associated coagulopathy. During the SARS-CoV-2 pandemic, it is necessary to identify important biomarkers for predicting severe course of COVID-19 and risk of thrombotic complications. Our objective was to evaluate the aPL profile, quantitative content and activity of complement and its components in COVID-19 patients graded by severity in the course of time. IgM and IgG antibodies to cardiolipin (CL), phosphatidylserine (PS), β2-glycoprotein-I (β2-GP-I), prothrombin (PT), annexin V (An V), as well as C1q complement component, content of its C3 and C4 components and total complement activity were determined in blood serum using ELISA approach. 141 patients with COVID-19 were included in the study. Group 1 consisted of 39 patients with mild form, group 2 (65 patients) presented with moderate form, and group 3 included 37 patients with severe form of COVID-19. Blood samples were obtained on day 3-7 of the disease (1st point) and after 14-28 days (2nd point). The results were as follows: aPL were detected in 29.1% of the total COVID-19 cohort, frequency of aPL detection by the severity grade did not differ (33.3%, 24.6% and 32.4%). In 8.5% of the patients, aPL were detected only at the 1st time point;in 14.2%, only at the 2nd point;and in 6.4% of the cases, at the both time points. Antibodies to PT (16.3%) and An V (11.3%) were revealed more frequently. The detection frequency of antibodies to PT was significantly higher than antibodies to CL and PS (7.1%), β2-GP-I (7.8%). The prevalence of aPL in groups 1 and 3 did not differ. At the 1st point in group 3, increased levels of C4 (89.2%) and C3 (24.3%) in blood, and a decrease in complement activity (35.1%) were more often observed than in group 1. At the 2nd time point in group 3, a decrease in complement activity was often detected (59.5%). The C3 levels exceeding 720 μg/ml were found to predict a 2.6-fold increased risk of severe COVID-19, and this risk became 3.3 times higher at C4 levels of > 740 μg/ml. The antibodies to PT and An V are often detected in COVID-19 patients, along with low prevalence of antibodies to CL and β2-GP-I. These antibodies can be involved in pathogenesis of COVID-19-associated coagulopathy, being detectable at the late stage of the disease, and they may trigger APS in predisposed patients and reconvalescents. Although presence of aPL antibodies is not associated with COVID-19 severity, their persistence over the period of convalescence may be an additional risk factor for thromboembolic complications. The COVID-19 patients are characterized by activation of the complement system, which increases in severe cases, and manifests with increased or decreased levels of C3 complement component, increased levels of C4 component in blood, and a decreased total complement activity. Quantitative determination of C3 and C4 complement components over the period of COVID-19 progression is of prognostic value, with respect to severity of the disease.