LONG-TERM AND BOOSTER VACCINATION RESPONSES IN PATIENTS WITH GIANT CELL ARTERITIS AND POLYMYALGIA RHEUMATICA

BackgroundVaccination remains essential in preventing morbidity of SARS-CoV-2 infections. We previously showed that >10mg/day prednisolone and methotrexate use were associated with reduced antibody concentrations four weeks after primary vaccination in patients with giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) [1].ObjectivesHere, we performed a follow-up study to measure the decay of antibody concentrations over time and the immunogenicity of SARS-CoV-2 booster vaccination.MethodsGCA/PMR patients included in the primary vaccination (BNT162b2 or ChAdOx1) study were asked again to donate blood samples six months after primary vaccination (n=24) and one month after booster vaccination (n=46, BNT162b2 or mRNA1273). Data were compared to that of age-, sex-, and vaccine-matched controls (n=58 and n=42, respectively).ResultsAntibody concentrations decreased faster over time in GCA/PMR patients than in controls, but this decrease was not associated with treatment during primary vaccination. Post-booster antibody concentrations were comparable between patients and controls. Antibody concentrations post booster vaccination associated strongly with antibody concentrations post primary vaccination, but not with treatment during booster vaccination. However, the fold-change of post-booster vaccination showed a slight negative correlation with the post-primary vaccine antibodies.ConclusionThese results indicate that patients with impaired vaccine responses after primary vaccination, have slightly stronger increases in humoral immunity after booster vaccination, but this is not enough to reach a similar protection. The decrease in humoral immunity, and subsequent increase after booster vaccination, is likely not impacted by prednisolone or methotrexate treatment. Rather, these treatments put the patients at an immunogenic disadvantage during primary SARS-CoV-2 vaccination, which is not fully repaired by a single booster vaccination. This longitudinal study in GCA/PMR patients stresses the importance of repeat booster vaccination for patients that used >10mg/day prednisolone or methotrexate during primary vaccination.Reference[1]van Sleen Y, van der Geest, Kornelis SM, Reitsema RD, Esen I, Terpstra JH, Raveling-Eelsing E, et al. Humoral and cellular SARS-CoV-2 vaccine responses in patients with giant cell arteritis and polymyalgia rheumatica. RMD open 2022;8(2):e002479.Figure 1.Acknowledgements:NIL.Disclosure of InterestsYannick van Sleen: None declared, Kornelis van der Geest Speakers bureau: Speaker fees from Roche, Grant/research support from: Grant support from Abbvie, Annemarie Buisman: None declared, Maria Sandovici: None declared, Debbie van Baarle: None declared, Elisabeth Brouwer: None declared.

Coagulation Abnormalities in Patients with COVID-19

Coronavirus disease 2019 (COVID-19) is an emerging infectious disease. Bilateral pneumonia, acute respiratory failure, systemic inflammation, endothelial dysfunction, and coagulation activation have been described as key features of severe COVID-19. Fibrinogen and D-dimer are typically increased. Moreover, the risk for venous thromboembolism is markedly increased, especially in patients in the intensive care unit, often despite prophylactic-dose anticoagulation. Pulmonary microvascular thrombosis has also been described and the risk for arterial thrombotic diseases also appears to be increased. Bleeding is less common than thrombosis but can occur. Evaluation for venous thromboembolism may be challenging because symptoms of pulmonary embolism overlap with COVID-19, and imaging studies may not be feasible in all cases. All inpatients should receive thromboprophylaxis unless contraindicated. In hospitalized patients with COVID-19, prophylactic dosing rather than more intensive (intermediate or therapeutic) dosing are suggested. On the other hand, therapeutic dose of anticoagulation is always appropriate to treat deep venous thrombosis or pulmonary embolism, unless contraindicated. This article reviews evaluation and management of coagulation abnormalities in individuals with COVID-19. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.

Eye Disorders and Neuro-ophthalmic Manifestations of COVID-19

Growing data are confirming the association between the novel coronavirus disease (COVID-19) and eye disorders, including ocular alterations and neuro-ophthalmic manifestations. The main pathophysiological mechanisms considered included a direct infection through the ocular surface, a post-viremia secretion of the virus from the lacrimal glands, and a viral dissemination through the bloodstream. According to the different ways of contagion, different structures could be involved.The most common ocular symptoms reported in COVID-19 patients were dry eye, redness, tearing, itching and pain. Among symptomatic patients, most of them presented conjunctivitis. Considering the posterior chamber, retinal artery and vein occlusions were described in few clinical reports;moreover, some studies presented cases of paracentral acute middle maculopathy occurring in COVID-19 patients. The involvement of the choroid seems to be rare, and a single case of atypical choroiditis was currently described. Between neuro-ophthalmic manifestations, optic neuritis appear to be relatively frequent and generally not associated with magnetic resonance imaging abnormalities. Some reports showed the involvement of the ocular motor nerves, often presenting with palsy. Miller Fisher syndrome has been showed in rare cases;however, this association could be corroborated by the several reports describing Guillain-Barré syndrome occurrence in COVID-19 patients.In line with well-known previous viral infection, COVID-19 seems to be associated with eye involvement. Thus, ocular and neuro-ophthalmic symptoms and signs should be carefully assessed and monitored in these patients. To reach this purpose, it is critical to implement remote diagnostic techniques. Moreover, the comprehension of the pathogenetic mechanisms is still scarce and no standardized diagnostic protocol was established for these patients, making necessary further studies to improve current understandings. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.

Public Attitudes, Awareness and Fears Related to the Spread of COVID-19 in Bulgaria

The pandemic caused by COVID-19 has led to radical lifestyle changes worldwide, particularly in the Republic of Bulgaria, and was a factor for global changes in economics, politics, healthcare and daily life. Aim(s): The aim of the study was to analyze the public attitudes, awareness and fears related to the COVID-19 disease in the Republic of Bulgaria. Material(s) and Method(s): The survey was conducted between August 1st, 2022 and September 1st, 2022 via an anonymous questionnaire consisting of 24 closed questions. A total of 1861 people, aged 18-69 years and older, took part in the survey after being selected randomly. The data were statistically processed via MS Excel. Result(s): The main source of information to the respondents on issues related to COVID-19 was the Internet (29,8%), followed by TV (26%) and the specialized website (Single information portal) - 15,9%. More than one-third (35,1%) of the respondents was afraid of getting infected and an equal share of participants reported that they have been infected with COVID-19. More than half of the respondents (52,5%) adhered to all the provisions of the governmental bodies related to limiting the COVID-19 pandemic. The most frequent symptom of post- COVID-19 syndrome was being easily fatigued (26,7%), followed by shortness of breath (13,4%) and persistent cough (11,6%). Conclusion(s): The survey could be useful in understanding what were the public attitudes, awareness and fears related to the COVID-19 disease in the Republic of Bulgaria during the pandemic.Copyright © 2023 D. Penchev et al., published by Sciendo.

COVID Cholangiopathy Can Occur Despite Mild COVID

Introduction/Objective Post-COVID-19 cholangiopathy is a novel entity first noted in patients recovering from critical COVID-19 infection. Since its initial description in May 2021, all cases reported to date have been in patients with a history of critical COVID-19, defined as requiring ICU admission, the development of respiratory or circulatory failure requiring intubation or ECMO, or vasopressor support. Here we report three cases of post-COVID-19 cholangiopathy arising in patients who recovered from non-severe COVID-19. Methods/Case Report Six cases of COVID-19-related cholangiopathy were identified by retrospective review, three of which involved patients who verifiably did not develop critical COVID-19. Histology slides for each case were reviewed and all showed features of secondary sclerosing cholangitis. Patient 1 is a 41yo female who developed COVID-19 after liver transplant (LT). Despite administration of monoclonal antibodies, she required re-transplantation 6 weeks later. Explant histology showed bile infarcts, severe hepatocytic and canalicular cholestasis, ductular reaction, organizing portal vein thrombi, and necrotic bile ducts accompanied by bile lakes. Patient 2 is a 47yo male with alcoholic cirrhosis who was diagnosed with COVID-19 at the time of LT workup, and underwent LT 90 days later. In addition to alcohol-related cirrhosis, explant histology showed dilated bile ducts with periductal fibrosis, as well as severe ductular reaction with proliferating ductules containing thick, inspissated bile. Patient 3 is a 54yo male with history of LT for PSC who developed mild COVID-19 five years after LT. Allograft function subsequently worsened and biopsy 6 months later showed bile duct damage and loss of ~35% of bile ducts;repeat biopsy 14 months after his COVID diagnosis showed periportal fibrosis with edema, ductular reaction, marked hepatocellular and canalicular cholestasis, and ductopenia with loss of 60% bile ducts. Average time between COVID-19 diagnosis and onset of COVID-related cholangiopathy was 3 months (range: 6 weeks-6 months). These patients were also all immunocompromised with two due to prior LT and one being cirrhotic. Results (if a Case Study enter NA) NA. Conclusion Although previously reported only in patients with severe COVID-19, the cases described represent the first evidence that cholangiopathy, manifested by sclerosing cholangitis, can arise even in patients who were not critically ill, although this may require an immunocompromised state to develop.

Ultrasound of Covid 19

We present how we used ultrasound to improve our diagnosis of lung Covid 19 and use ultrasound to diagnose the complications of Covid 19. Ultrasound was more sensitive in detecting early Covid 19 than chest radiograph. The complications of Covid 19 include renal impairment, liver impairment and vascular complications, mainly large vessel venous thrombosis, including renal vein thrombosis. We are all suffering from post-viral fatigue but lessons can be learnt from this pandemic and the use of ultrasound.

Clinical course and diagnosis of cerebral vein and sinus thrombosis associated with COVID-19 in young and middle-aged patients.

Cerebral venous thrombosis (CVT) is a form of cerebrovascular disorders that is difficult to recognize, it is potentially a life threatening condition and requires timely anticoagulant therapy. In the era of the COVID-19 pandemic, there is a steady increase in CVT (4.2% vs. 0.5-1%). At the same time, mortality in patients with CVT on the background of COVID-19 significantly exceeds the mortality in patients with CVT without COVID-19 (45.5% vs. 15%). Objective(s): to study the clinical course of CVT, to determine the diagnostic value of radiological methods and the significance of genetic risk factors for thrombosis in the development of CVT in young and middle-aged patients against the background of COVID-19. Material and methods. Seven patients were examined: six women (five of them of reproductive age) and one man, aged 26 to 57 years (mean age 37 years). The main clinical and neurological manifestations of CVT, the results of laboratory examination, neuroimaging, and the data of molecular genetic analysis of risk factors for thrombosis were analyzed. Results. The course of COVID-19 was severe in one case, and moderate in the rest of cases. The interval between the onset of COVID-19 symptoms and the development of CVT ranged from 7 to 25 days. In three cases CVT had an acute course and was accompanied by the development of a stroke (in two cases, hemorrhagic stroke was noted, in one case, multifocal ischemic stroke), in other cases, a subacute course of CVT was noted. Genetic risk factors for thrombosis were identified in all patients. Conclusion. The diagnosis of CVT in the era of the COVID-19 pandemic is particularly difficult, since the most common symptom of CVT - headache (90%) - can be regarded as a manifestation of COVID-19. At the same time, timely diagnosis of CVT and immediate initiation of anticoagulant therapy are associated with a relatively favorable prognosis.Copyright © 2023 Ima-Press Publishing House. All rights reserved.

The incidence of deep vein thrombosis following COVID-19 vaccination in an Australian population

Introduction: After the COVID-19 vaccination roll out in March 2021 patients began presenting to a Victorian Emergency Department with lower limb pain following their vaccination. As a result, requests for ultrasound examinations, to exclude post vaccination deep vein thrombosis (DVT) began appearing. Method(s): A retrospective study of ultrasound examinations and their result over a 1-year period was undertaken. Patients were identified who had a clinical indication of having been referred following COVID-19 vaccination. Bivariate analysis was conducted, using logistic regression, to determine the strength of association between independent variables. Result(s): The study found 1689 patients had a lower limb DVT ultrasound examination. Ultrasound was positive for DVT in 244/1689 patients (14.4%). 104/1689 (6.1%) patients presented for ultrasound following COVID-19 vaccination. Six of these were found to have DVT detected. The association between post vaccination and DVT was an odds ratio (OR) of 0.347 (95% CI 0.150 to 0.799, p = 0.013). All patients had recently received AstraZeneca (AZ) vaccine. Four patients were diagnosed with superficial vein thrombosis (SVT) post vaccination. Nineteen patients were identified as COVID-19 positive. Three of these had DVT detected. Conclusion(s): This study found 6 patients out of 1689 (0.35%) of lower limb ultrasound examinations over a one-year period, were positive for DVT after COVID-19 vaccination. Take home message: The results showed post vaccination patients were less likely to be diagnosed with a DVT than the population referred who had not had recent vaccination.

Unique vascular complication following extended VV-ECMO support

Objectives: To present an unusual complication related to prolonged ECMO support in a patient with COVID19 induced acute respiratory syndrome (ARDS). Method(s): Clinical chart review of the care process after obtaining the informed consent from the patient. Result(s): A 48-year-old female with COVID-19 infection during second wave of pandemic in August 2021 progressed to severe ARDS. She was put on VV-ECMO support after failing conventional therapy for refractory hypoxemia. Her cannulation configuration included a 25 F venous drainage cannula in the right femoral vein and a 21 F venous return cannula in the right Internal Jugular (IJ) vein. Cannulations were performed using the ;Seldinger technique;under USG guidance, and no difficulties or complications were reported. Her hospital course was notable for delirium, and intermittent bleeding from the cannula sites. After 80 days of support, she showed adequate respiratory improvement which allowed ECMO decannulation. She continued to show improvement, and was eventually discharged after 102 days of total hospital stay. During her 6 weeks follow-up clinic visit a palpable thrill was noted at the jugular ECMO cannula site. A CT angiogram of the neck demonstrated a large venous varix connecting the right IJ and the left common carotid artery with filling from the left common carotid artery. ECMO cannulation site complications such as aneurysm, clots, infections and stenosis are well known. What was unusual in this case is the nature of the aneurysm given that there were no arterial procedures performed on the left side of the neck. She was managed by an ;Amplatzer plug;to the carotid artery at the level of the connection to the varix without any complications. Conclusion(s): Longer duration of ECMO support needs careful follow-up for timely recognition and management of vascular complications. (Figure Presented).

Association between Type 2 Diabetes Mellitus and Covid-19 Severity: A Literature Review

We conducted a review and evaluated the already documents reports for the relationship among diabetes and COVID-19. The review outcome shows that the COVID-19 severity seems to be greater among patients with diabetes as comorbidity. So, strict glycemic control is imperative in patients infected with COVID-19. Thus, world-wide diabetes burden and COVID-19 pandemic must be deliberated as diabetes increases the COVID-19 severity. Established on this, it is precise significant to follow specific treatment protocols and clinical management in COVID-19 patients affected with diabetes to prevent morbidity and mortality.Copyright © 2023 The Authors.

IMPACT OF CHRONIC KIDNEY DISEASE IN PATIENTS WITH AS USING BIOLOGIC AGENTS

BackgroundAlthough renal involvement is an rare extra-articular involvement in patients with ankylosing spondylitis (AS), medications and accopamyning comorbidities may adversly affect renal functions [1].ObjectivesTo determine the frequency and impact of CKD in patients with AS using biologic disease modyfying anti-rheumatic drugs (bDMARDs).MethodsBetween 2005 and November 2021, 3207 patients diagnosed with AS according to the modified New York criteria were enrolled in the Hacettepe University biological database (HUR-BIO). The 2012 Kidney Disease: Improving Global Outcomes (KDIGO) guideline was used for the definition of CKD to evaluate the renal function of patients. Glomerular filtration rate (GFR) was calculated with the MDRD (modified Modification of Diet in Renal Disease) formula, taking into account the creatinine value, age and gender parameters of the patients [2]. CKD was detected in 39 (1,2%) patients. Age-sex matched 41 non-CKD AS patients were selected as the control group. Demographic and clinical characteristics and mortality rates of AS patients with and without CKD were compared.ResultsOf 39 AS-CKD patients, 25 (64.1%) had CKD before the initation of bDMARD and and 14 (35.8%) developed CKD during follow-up after treatment was started. Patients with AS-CKD had longer duration of symptoms and disease (Table 1). Comorbidities such as hypertension, coronary artery disease and amyloidosis were more prevalent in patients with AS-CKD. At a median follow-up of 2.48(0.1-20.1) years, mortality was observed in 11(28.2%) patients in the AS-CKD group, while no mortality was observed in the age-sex matched AS-nonCKD group (p<0.001, Figure 1). The mortality rate in patients with AS-CKD was 12.6 per 1000 patient-years, and 4 (10.2%) of deaths were during the COVID-19 pandemia.Figure 1.Table 1.AS-CKD group (n=39)AS-nonCKD group (n=41)PTotal AS patients, (n=3207)Age, mean(SD), years68.2 (12.0)58.8(12.6)-47.9±(11.2)Male, n(%)27 (69.2)27(65.9)-1716(53.5)53.1)Symptom duration, years median (min-max)20 (5-42)11(2-30)0.0110(1-44)Disease duration, years median (min-max)14,5(5-42)7(1-29)0.046(1-37)HLA-B27 positivity, n(%)13(33.3)12(29.2)0.5826/2014(41.0)Uveitis, n(%)6/354/360.2339/2946(11.5)Inflammatory bowel disease, n(%)4/353/360.4135/2946(4.58)Smoking, ever, n(%)22/34 (64.7)20/36(55.5)0.31781/2942(60.5)BMI (kg/m2), mean(SD)28 (6.08)28.2(5.01)0.828.1(5.5)Amiloidosis, n(%)14/36(38.9)1(2.4)<0.00133/2949(1.11)Comotbidities n(%)• Diabetes Mellitus,7/34(20.6)4/36(11.1)0.2199/2949(6.7)• Hypertension27/34(79.4)9/36(25)<0.001442/2949(14.9)• CAD8/21(38.1)1/25(4)0.005110/1882(5.8)• COPD5/21(23.8)0/240.004117/1774(6.59)CRP, med(min-max)1.6(0.4-12.4)1.77(0.1-23.6)0.81.07(0.1-45)• at the initiation of bDMARDs, at the last visit,0.7(0.16-14)0.55(0.1-7.5)0.30.5(0.1-14)ESR, med(min-max)• at the initiation of bDMARDs,48(12-140)30(2-96)0.119(1-140)• at the last visit, med(min-max)25(3-93)15(2-70)0.113(1-110)BASDAI, mean (SD)• At the initiation of bDMARDs4.5(±2.1) 5.46(±2.07) 0.5 5.7(±2.04) • At the last vizit3.94(±2.35)2.95(±2.33)0.093.69(±2.5)CAD: Coronary artery disease, COPD: Chronic Obstructive pulmonary disease, BMI: Body mass index, BASDAI: Bath AS Disease Activity IndexConclusionBoth comorbid disease burden and mortality seem to be increased in patients with AS-CKD. Increased mortality was more pronounced during the COVID-19 pandemia.References[1]Coşkun, B.N., et al., Anti-TNF treatment in ankylosing spondylitis patients with chronic kidney disease: Is it effective and safe? Eur J Rheumatol, 2022. 9(2): p. 68-74.[2]Stevens, P.E. and A. Levin, Evaluation and management of chronic kidney disease: synopsis of the kidney disease: improving global outcomes 2012 clinical practice guideline. Ann Intern Med, 2013. 158(11): p. 825-30.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

The use of venovenous extracorporeal membrane oxygenation in COVID-19: An updated systematic review and meta-analysis of clinical outcomes

Objectives: The objective of this study is to assess the clinical benefits and potential risks of using venovenous extracorporeal membrane oxygenation (VV ECMO) as a treatment for COVID-19 patients with severe respiratory failure. Method(s): Relevant studies were identified through searches of electronic databases, including PubMed, EMBASE, and the Cochrane Library, from January 2020 to December 2022. We included observational studies on adult patients who received venovenous (VV) ECMO support for COVID-19-induced ARDS. The primary outcome was in-hospital mortality, 3-month mortality, and complications associated with VV ECMO. Statistical analysis was performed using R version 4.0.3 and the metafor and meta packages. Result(s): The final analysis included 39 studies comprising 10,702 patients. In-hospital mortality for adults receiving ECMO was 34.2% (95% CI: 28.5% - 40.3%;I2 = 93%), while the 3-month mortality rate was 50.2% (95% CI: 44.4% - 56.0%;I2 = 51%). Bleeding requiring transfusion occurred in 33.7% of patients (95% CI, 23.9 - 45.1;I2 = 96%). The pooled estimates for other complications were as follows: overall thromboembolic events 40.9% (95% CI, 24.8 - 59.3;I2 = 97%), stroke 8.7% (95% CI, 5.7 - 13.2;I2 = 72%), deep vein thrombosis 15.4% (95% CI, 9.7 - 23.6;I2 = 80%), pulmonary embolism 15.6% (95% CI, 9.3 - 25.1;I2 = 92%), gastrointestinal haemorrhage 8.1% (95% CI, 5.5 - 11.8;I2 = 56%), and the need for any renal replacement therapy in 38.0% of patients (95% CI, 31.6 - 44.8;I2 = 84%). Bacterial pneumonia occurred in 46.4% of patients (95% CI, 32.5 - 61.0;I2 = 96%). Conclusion(s): Venovenous extracorporeal membrane oxygenation (VV ECMO) may be an effective treatment option for COVID-19 patients with severe respiratory failure. The use of VV ECMO was associated with reduced in-hospital and 3-month mortality. However, bleeding is a common complication that should be closely monitored. Further research is needed to determine the optimal use of VV ECMO in this patient population and to identify factors that may predict a favourable response to treatment.

Pandemic stress induces systemic immune changes and placental inflammation independently of SARS-CoV-2 infection in pregnancies

Problem: Environmental stress during pregnancy has known impacts on both maternal and fetal health. In terms of theCOVID-19 pandemic, the majority of published work has focused on the impact of the infection itself, without considering the potential immune impact of pandemic related-stress.We, therefore, assessed the impact of pandemic stress, independently of SARS-CoV-2 infection, on the circulating and placental immune profiles of pregnant individuals. Method(s): Placentas from 239 patients were collected at the Sainte- Justine Hospital, Montreal, Canada. Of these, 199 patients delivered during the pandemic and were exposed to pandemic stress with (+: 79) or without (-: 120) SARS-CoV-2 infection, the latter exposed to pandemic stress only. Pre-pandemic historic controls (uncomplicated pregnancies, Ctrl: 40), were also included. Placental biopsies were collected to assess cytokine levels by ELISAs and histopathological lesions. A sub-study with 35 pre-pandemic pregnancies (unexposed) and 20 who delivered during the pandemic (exposed) was also conducted. The latter (exposed/unexposed) were all uncomplicated pregnancies. We collected maternal blood prior to delivery for immunophenotyping, and plasma/peripheral blood mononuclear cells (PBMCs) were isolated. Inflammatory mediators in the plasma were quantified by ELISAs. Co-culture assays with PBMCs and human umbilical vein endothelial cells (HUVECs) were performed to assess endothelial activation. Demographical/obstetrical data were obtained through chart review. Result(s): SARS-CoV-2+ patients were multiethnic (63.4%), had higher pre-pregnancyBMI (28.9 vs. 24.8 inCtrl, P<.05), and elevated preterm birth rate (16.5% vs. 5.8% in SARS-CoV-2-, P < .05 and 0.0% in Ctrl, P < .01). In the placentas, we observed an increase in the levels of IL- 1Ra (P < .05) and CRP (P < .05) in both SARS-CoV-2 groups, while IL-6 (P = .0790) and MCP-1 (P < .001) were elevated solely in SARS-CoV- 2-. These changes were predominant in placentas with inflammatory lesions on histopathological analysis. Moreover, we observed elevated CD45+ cells (P < .001) in the placentas from both SARS-CoV-2 groups versus Ctrl. Considering that the differences we observed were important in the SARS-CoV-2- group, we performed a study solely on uncomplicated pregnancies, either exposed or unexposed to pandemic stress. At the systemic level, we observed a decrease in the percentage of Th2 cells (P < .001), leading to a pro-inflammatory Th1/Th2 imbalance in exposed individuals. Decreased Treg (P < .05) and Th17 (P < .05) versus unexposed was also observed. Surprisingly, decreased levels of circulating IL-6 (P < .05), MCP-1 (P < .01), and CRP (P<.05) were seen in exposed versus unexposed individuals. Finally,we observed increased secretion of ICAM, a marker of endothelial activation, solely in endothelial cells co-cultured with PBMCs from exposed individuals. Conclusion(s): Overall, placental inflammatory profiles differed between pregnant individuals exposed to pandemic stress with or without SARS-CoV-2 infection. Moreover, we observed that the pandemic stress exposed group presented a systemic pro-inflammatory bias. This highlights the need to understand the differences between the effects of pandemic-related stress and the added burden of SARS-CoV-2 infection itself on maternal and fetal health. Our work also supports an association between an increased risk of hypertension/ preeclampsia and SARS-CoV-2 infection that might be driven in part by pandemic-related stress.

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.

OUTCOME FOR PATIENTS WITH GIANT CELL ARTERITIS (GCA) TREATED WITH TOCILIZUMAB ACCORDING TO NICE GUIDANCE IN A SINGLE TERTIARY UK CENTRE

BackgroundIn 2018 NICE and NHS England approved one year of weekly subcutaneous tocilizumab for use in relapsing or refractory GCA [1, 2]. During the COVID pandemic NHS England allowed extended use of tocilizumab in selected high risk patients [3]. This extension ended in March 2022. This has created a cohort of patients who are now no longer treated with tocilizumab and may be at risk of GCA flare. Currently, NHS England does not allow retreatment with tocilizumab.ObjectivesThis service evaluation used an intention-to-treat approach to retrospectively evaluate patients, who were ratified to receive tocilizumab for GCA according to the NICE guidance. We aimed to describe this cohort of patients for whom the use of tocilizumab had been approved, and their outcomes in terms of complications and disease control.Methods49 patients were ratified to receive tocilizumab between May 2019 and April 2022 by a specialist multidisciplinary team at a single tertiary rheumatology center. Their response was assessed in terms of relapse rates, steroid usage and complications as described below.Results80% of the 49 cohort of patients consisted of females (Table 1). 55% of patients were diagnosed with GCA on combination of clinical history, laboratory and temporal artery duplex findings. 94% (46/49) had at least a week's course of tocilizumab. Around half (51%) had relapsing disease. 6% had first dose as intravenous due to critical ischaemia. 27% (13/49) of patients developed complications whilst on treatment. Six developed cytopenia, 3 acquired infections and 4 stopped due to other reasons. As per guidelines, tocilizumab was stopped after 12 months in 25 patients (51%). 16% stopped treatment early due to complications. 18% had incomplete information. 10% had ongoing treatment. One patient died several months after finishing tocilizumab. 47% had methotrexate as DMARD therapy added prior to tocilizumab commencement (Figure 1). Out of 25 patients who completeted treatment, 24% (6/25) relapsed. 83% of these relapses were diagnosed on recurrence of symptoms and high inflammatory markers. In addition, 3 patients, who had tocilizumab suspended relapsed. 2/3 of these patients had treatment suspended due to infection. 5/9 relapse patients did not have preceding DMARD therapy. 22% (2/9) of relapse patients had PET-CT due to involvement of extra-cranial disease. 56% (5/9) relapsed following a median follow-up of 11 months. Of relapsed patients, seven were treated with increased dose of prednisolone and two patients received 6 months extension of tocilizumab with adequate tolerance and efficacy.ConclusionOur data shows good tolerability of tocilizumab and a 24% flare rate amongst patients who completed treatment. This is less than the 50% rate seen in GiACTA and other cohorts, where the majority of which occurred within 6 months of stopping treatment [4]. DMARD treatment may reduce relapse rate, but this will require further study. The data describing the efficacy of treatment beyond one year is limited [3]. However, with no established guidance for treating patients following tocilizumab, extension of treatment is a plausible option.References[1]Tocilizumab for treating giant cell arteritis, NICE Technology Appraisal Guidance, 18 April 2018. https://www.nice.org.uk/guidance/ta518/resources/tocilizumab-for-treating-giant-cell-arteritis-pdf-82606786726597[2]Stone J, Tuckwell K, Dimonaco S et al.Trial of Tocilizumab in Giant-Cell Arteritis. N Engl J Med 2017;377:317-328.[3]Regola F, Cerudelli E,Bosio G. Long-term treatment with tocilizumab in giant cell arteritis: efficacy and safety in a monocentric cohort of patients Rheumatology Adv Pract 2020;0:1–9.[4]Conway R, Putman MS, Mackie SL. Benchmarking tocilizumab use for giant cell arteritis. Rheumatol Adv Pract. 2022;6(2):rkac037.Figure 1.Table 1.GenderAge at time of diagnosisIndication for stopping treatmentMaleFemale50-5960-6970-7980-89Completed treatmentComplicationsOngoing treatmentIncomplete information18313162010251058Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Ultrasound-guided central venous access for patients in the Intensive Care Unit in prone position: report of three cases.

The prone position is extensively used to improve oxygenation in patients with severe acute respiratory distress syndrome caused by SARS-CoV-2 pneumonia. Occasionally, these patients exhibit cardiac and respiratory functions so severely compromised they cannot tolerate lying in the supine position, not even for the time required to insert a central venous catheter. The authors describe three cases of successful ultrasound-guided internal jugular vein cannulation in prone position. The alternative approach here described enables greater safety and well-being for the patient, reduces the number of episodes of decompensation, and risk of tracheal extubation and loss of in-situ vascular lines.

A review of venous thromboembolism in India.

Venous thromboembolism (VTE), which entails the formation of a thrombus (blood clot) in a vein, has a significant disease burden worldwide. While VTE has traditionally been considered to predominantly affect Caucasian populations, recent studies have indicated a gradual shift in the disease burden towards Asian populations, with added significance of it being a key driver of post-operative mortality. It is imperative to develop a sound understanding of the various factors that affect VTE in stratified local populations. However, there is a glaring paucity of quality data on VTE and its ramifications among Indians - both in terms of quality of life and cost of healthcare. This review aims to throw light on the disease burden, epidemiology, risk factors, environmental factors, food and nutrition that plays a key role in VTE. We also explored the association of VTE with coronavirus disease 2019 to grasp the interplay between the two most significant public health crises of our time. It is vital to place a special emphasis on future research on VTE in India to plug the gaps, which exist in our current knowledge of the disease, particularly with respect to Indian population.

Prognostic modelling of number of patients with retinal vein occlusion in anti-VEGF therapy.

PURPOSE: The purpose of the study was to evaluate temporal changes in age- and sex-stratified incidence rates of retinal vein occlusion (RVO) commenced in anti-vascular endothelial growth factor (anti-VEGF) treatment, proportion of patients remaining in active anti-VEGF therapy over time, and to develop a forecasting model for future number of patients with RVO in active anti-VEGF therapy. METHODS: This was a registry-based study of patients with RVO in the Capital Region of Denmark from commenced in anti-VEGF therapy from 1 January 2007 to 30 June 2022. Census data were extracted from Statistics Denmark for incidence rate analyses and forecasting data of future demographics. RESULTS: A total of 2641 patients with RVO were commenced in anti-VEGF therapy, of which 2192 were later discontinued. Number of patients rose dramatically during the first years of introduction of anti-VEGF therapy, after which growth was slower and followed the demographic changes. Trend analyses revealed that the COVID-19 epidemics impacted with fewer referrals and more aggressive discontinuation practices. Annual incidence of RVO in 2012-2021 was 13.1 per 100 000 (95% CI: 12.6-13.6 per 100 000). Proportion of patients with RVO remaining in active anti-VEGF treatment was 55.0%, 40.1%, 30.8% and 12.1% after Years 1, 2, 3 and 8, respectively. According to our forecast, number of patients with RVO in active anti-VEGF therapy will grow slowly but continually at least until year 2035. CONCLUSION: Our study reports incidence rates and provides prognostic modelling of number of patients with RVO in anti-VEGF therapy.

Ocular Adverse Events after Coronavirus Disease 2019 mRNA Vaccination: Matched Cohort and Self-Controlled Case Series Studies Using a Large Database.

PURPOSE: To investigate the risk of ocular adverse events after Coronavirus Disease 2019 (COVID-19) mRNA vaccination. DESIGN: Matched cohort and self-controlled case series (SCCS) studies. PARTICIPANTS: We used a population-based database of medical claims and vaccination records in a large Japanese city. In the matched cohort study, we identified individuals who received COVID-19 vaccination (BNT162b2) from February 2021 to September 2021. One control was selected from nonvaccinated individuals by matching time, date of birth, sex, Charlson comorbidity index, and the enrollment period for health insurance. In the SCCS study, we analyzed individuals who developed ocular adverse events. METHODS: In the matched cohort study, we applied the Kaplan-Meier estimator to estimate the cumulative incidence of ocular adverse events over 21 days after the first dose and 84 days after the second dose. In the SCCS method, we used conditional Poisson regression to estimate the incidence rate ratio (IRR) of ocular adverse events during the risk periods (0-21 days after the first dose and 0-84 days after the second dose) compared with the remaining periods. MAIN OUTCOME MEASURES: Composite outcome of uveitis, scleritis, retinal vein occlusion (RVO), and optic neuritis. RESULTS: There were 99 718 pairs eligible for the matched cohort study after the first dose (mean age, 69.3 years; male, 44%). The vaccinated and control groups developed 29 and 21 events, respectively, over 21 days after the first dose, and 79 and 28 events, respectively, over 84 days after the second dose. The differences in cumulative incidence (reference, the control group) were 2.9 (95% confidence interval, -14.5 to 19.1) events/100 000 persons and 51.3 (16.2-84.3) events/100 000 persons, respectively, for the first and second doses. The SCCS study showed the IRRs of 0.89 (0.62-1.28) and 0.89 (0.71-1.11) for the first and second doses, respectively. CONCLUSIONS: The matched cohort analysis found an increased risk for the composite outcome after the second dose; however, the SCCS analysis showed no increased risk. Considering that the SCCS can cancel out time-invariant confounders, the current results suggest that COVID-19 vaccination is unlikely to causally increase the risk of ocular adverse events. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.