Outcomes and Impact of Covid-19 on Disease Activity in Patients with Systemic Vasculitides: Data from the Reuma-Cov Brazil Register

Objectives: To assess the impact of COVID-19 on disease activity and severity outcomes in patients with systemic vasculitis. Method(s): The Reuma-CoV Brazil is a longitudinal, multi-stage cohort study, designed to monitor patients with immune-mediated rheumatologic disease (IMRD) during the SARS-CoV-2 pandemic. Systemic vasculitis patients with COVID-19 were compared with those without COVID-19. Vasculitis activity was evaluated by the patient global assessment (PGA) and Birmingham Vasculitis Activity Score 3 (BVAS 3). The prognosis was assessed by the Five-Factor Score (FFS). Result(s): Between May 2020 and January 2021, 53 patients with vasculitis were included and followed for six months, 32 (60.3%) with COVID-19 and 21 (39.6%) in the control group. In total, 79.5% were female with a mean age (SD) of 49 (16.5) years. Both groups were homogeneous regarding sex, age, and comorbidities. Thirty-eight (71.8%) patients had at least one comorbidity. Thirty-two patients were classified as small vessels vasculitis (SVV), 10 as large vessels (LVV) and 11 as vasculitis of variable caliber. There was no difference in PGA, BVAS and FFS when comparing before and after SARSCoV-2 infection (Table 1). In the group of patients with LVV, two had clinical or laboratory worsening post infection. Compared to controls, patients with vasculitis and COVID-19 were at higher risk of intensive care unit (ICU) hospitalization [OR (IC95%) = 7.98 (3.78 - 16.8), p alpha 0.001], mechanical ventilation [OR (IC95%) = 7.45 (3.16 - 17.5), p = alpha0,001] and death [OR (IC95%) = 9.69 (3.87 - 24.3), p alpha 0,001]. Of the 7 patients who died, 40%were using high-dose prednisone (>20 mg/d) and 38.8% were using rituximab. Conclusion(s): In this sample of patients with systemic vasculitis, there was no worsening of disease activity after COVID-19, but there was a higher risk of poor outcomes, possibly related to immunosuppression.

Safety and Efficacy of Covid-19 Immunization in Systemic Vasculitides - a Multicentric Cohort

Objectives: Patients with immune-mediated rheumatic diseases (IMRDs) develop more severe outcomes of Coronavirus disease 2019 (COVID-19). Recent studies have contributed to understand the safety and efficacy of COVID-19 vaccines in IMRDs, suggesting that different diseases and therapies may interfere on immunization efficacy. In this study we analyze the immunogenicity of COVID-19 vaccines in patients with Systemic Vasculitides (VASC), the rate of COVID-19 and the frequency of disease relapse following immunization. Method(s): We included patients with VASC (n = 73), a subgroup of the SAFER study (Safety and Efficacy on COVID-19 Vaccine in Rheumatic Disease), a longitudinal, multicenter, Brazilian cohort.We analyzed the geometric means of IgG antibody against receptor-biding domain of protein spike of SARS-CoV-2 (anti-RBD) after two shots of CoronaVac (Inactivated vaccine), ChadOx-1 (AstraZeneca) or BNT162b2 (Pfizer-BioNTech). IgG anti-RBD was measured by chemiluminescence test. We assessed new-onset COVID-19 episodes, adverse events (AE) and disease activity for each VASC. Result(s): The sample included Behcet's disease (BD) (n = 41), Takayasu arteritis (TAK) (n = 15), antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) (n = 14), polyarteritis nodosa (n = 7) and other small vessel VASC(n = 6). The majority of patients were female (69%) without comorbidities (49%) and a median age of 37 years. The most common medication was conventional synthetic disease-modifying anti-rheumatic drugs, followed by biologic drugs. No patient received rituximab at baseline. Most patients received CoronaVac (n = 25) or ChadOx-1 (n = 36), while four received BNT162b2. Baseline IgG-RBD means were 1.34 BAU/mL. They increased to 3.89 and 5.29 BAU/mL after the 1st and 2nd vaccine dose, respectively. ChadOx-1 had higher antibody titers than CoronaVac (p = 0.002). There were no differences between different VASC. There were 3 cases of COVID-19 after immunization with CoronaVac. BD patients had a tendency for more cutaneous-articular activity following ChadOx-1. There were no severe relapses and no serious adverse events. Conclusion(s): Our results show the safety of different SARS-CoV-2 vaccines in VASC population. A progressive increase of IgG-RBD antibodies was observed after each dose. ChadOx-1 led to higher IgG-RBDgeometricmeans compared toCoronaVac. Finally, even though ChadOx-1 presented a tendency of triggering mild disease activity, there were no significant disease activity following vaccination in VASC patients. .

A Systematic Review of New Rheumatic Immune-Mediated Inflammatory Diseases (R-Imid) Following Sars-Cov-2 Vaccinations

Background/Aims There are sporadic reports about the development of new rheumatic immune-mediated inflammatory diseases (R-IMIDs) in adults after receiving SARS-CoV-2 vaccines. This systematic review (SR) aimed to critically review and summarize the clinical profile, patient demographics, treatment, and prognosis of new-onset R-IMIDs following SARS-CoV-2 vaccination. Methods We retrieved English-language articles (Case reports and series and observational studies) on new-onset R-IMIDs following SARS-CoV-2 vaccination, published until June 2022, from standard databases (MEDLINE, Embase, Cochrane). The search strings used during the literature search incorporated 'SARS-CoV-2 vaccination' (along with related MeSH terms) and various key terms for R-IMIDs [which included (but was not limited to) inflammatory arthritis, connective tissue disease (CTD), vasculitis, systemic lupus erythematosus, Sjogren's syndrome, sarcoidosis, systemic sclerosis, idiopathic inflammatory myositis, anti-synthetase syndrome, Adult-onset Stills disease (AOSD), giant cell arteritis (GCA), and polymyalgia rheumatica (PMR)]. The protocol was registered in PROSPERO (CRD42022318561). Results Of the total 2179 articles retrieved, 1986 articles were excluded following the title- screening, and 107 articles that did not meet inclusion criteria. We included the remaining 86 articles (130 cases) upon full-text screening. Furthermore, we added four articles (six cases) based on a manual search, comprising 90 articles (136 cases) for final analysis. These 136 new R-IMID cases were reported from 27 different countries. Of these, more than one-third of the cases were reported from three countries (viz., Italy, Japan, and the USA). The patients had a mean age of 57 (range:17-90) years, and the majority were females (63.0%). Most patients developed R-IMIDs after receiving Pfizer-BioNTech vaccine (76;55%), followed by Oxford AstraZeneca vaccine (35;25%). The mean duration between SARSCoV- 2 vaccination and R-IMIDs development was 9.2 (range:1-90) days. The second dose of the vaccine resulted in more R-IMIDs (74;54%) than the first (53;39%). CTDs (34;25%) and small vessel vasculitis (33;24%) were the commonest R-IMID manifestations, followed by inflammatory arthritis and AOSD, each in 13 (9.5%) cases. Nearly half of the patients with CTDs had Idiopathic Inflammatory Myositis. PMR and GCA accounted for 16 (11.7%) and 5 (3.6%) cases, respectively. However, no cases of axial spondylarthritis were reported. Most (118;86%) R-IMID patients were treated with corticosteroids, with a small number receiving steroid-sparing drugs, such as methotrexate, rituximab and cyclophosphamide. Most (125;91%) went into either disease remission or improvement following the treatment. Only three patients were admitted to the intensive care unit (ICU) to manage their disease;One of them died due to fatal myositis and rhabdomyolysis;two surviving ICU patients had ANCA-associated vasculitis with lung involvement. Conclusion Although rare, this SR highlights the emergence of de novo R-IMIDs following SARS-CoV-2 vaccination. We cannot confirm the causality between the vaccination and the onset of R-IMID. However, further research is warranted in this area.

Cerebral small vessel disease pathology in COVID-19 patients: A systematic review.

Cerebral small vessel disease (CSVD) is the leading cause of vascular cognitive impairment and is associated with COVID-19. However, contributing factors that often accompany CSVD pathology in COVID-19 patients may influence the incidence of cerebrovascular complications. Thus, a mechanism linking COVID-19 and CSVD has yet to be uncovered and differentiated from age-related comorbidities (i.e., hypertension), and medical interventions during acute infection. We aimed to evaluate CSVD in acute and recovered COVID-19 patients and to differentiate COVID-19-related cerebrovascular pathology from the above-mentioned contributing factors by assessing the localization of microbleeds and ischemic lesions/infarctions in the cerebrum, cerebellum, and brainstem. A systematic search was performed in December 2022 on PubMed, Web of Science, and Embase using a pre-established search criterion related to history of, or active COVID-19 with CSVD pathology in adults. From a pool of 161 studies, 59 met eligibility criteria and were included. Microbleeds and ischemic lesions had a strong predilection for the corpus callosum and subcortical/deep white matter in COVID-19 patients, suggesting a distinct CSVD pathology. These findings have important implications for clinical practice and biomedical research as COVID-19 may independently, and through exacerbation of age-related mechanisms, contribute to increased incidence of CSVD.

Relationship between cognitive dysfunction and the promoter methylation of PER1 and CRY1 in patients with cerebral small vessel disease.

Background and purpose: The prevalence of cerebral small vessel disease (CSVD) is increasing due to the accelerating global aging process, resulting in a substantial burden on all countries, as cognitive dysfunction associated with CSVD is also on the rise. Clock genes have a significant impact on cognitive decline and dementia. Furthermore, the pattern of DNA methylation in clock genes is strongly associated with cognitive impairment. Thus, the aim of this study was to explore the connection between DNA promoter methylation of PER1 and CRY1 and cognitive dysfunction in patients with CSVD. Methods: We recruited patients with CSVD admitted to the Geriatrics Department of the Lianyungang Second People's Hospital between March 2021 and June 2022. Based on their Mini-Mental State Examination score, patients were categorized into two groups: 65 cases with cognitive dysfunction and 36 cases with normal cognitive function. Clinical data, 24-h ambulatory blood pressure monitoring parameters, and CSVD total load scores were collected. Moreover, we employed methylation-specific PCR to analyze the peripheral blood promoter methylation levels of clock genes PER1 and CRY1 in all CSVD patients who were enrolled. Finally, we used binary logistic regression models to assess the association between the promoter methylation of clock genes (PER1 and CRY1) and cognitive dysfunction in patients with CSVD. Results: (1) A total of 101 individuals with CSVD were included in this study. There were no statistical differences between the two groups in baseline clinical data except MMSE and AD8 scores. (2) After B/H correction, the promoter methylation rate of PER1 was higher in the cognitive dysfunction group than that in the normal group, and the difference was statistically significant (adjusted p < 0.001). (3) There was no significant correlation between the promoter methylation rates of PER1 and CRY1 in peripheral blood and circadian rhythm of blood pressure (p > 0.05). (4) Binary logistic regression models showed that the influence of promoter methylation of PER1 and CRY1 on cognitive dysfunction were statistically significant in Model 1 (p < 0.001; p = 0.025), and it still existed after adjusting for confounding factors in Model 2. Patients with the promoter methylation of PER1 gene (OR = 16.565, 95%CI, 4.057-67.628; p < 0.001) and the promoter methylation of CRY1 gene (OR = 6.017, 95%CI, 1.290-28.069; p = 0.022) were at greater risk of cognitive dysfunction compared with those with unmethylated promoters of corresponding genes in Model 2. Conclusion: The promoter methylation rate of PER1 gene was higher in the cognitive dysfunction group among CSVD patients. And the hypermethylation of the promoters of clock genes PER1 and CRY1 may be involved in affecting cognitive dysfunction in patients with CSVD.

When it doesn't run in the blood(vessels) - events involved in vascular disorders.

In the current issue of the Biomedical Journal the underlying pathology of hemodynamic compromise in acute small subcortical infarction are elucidated. A follow-up study in patients with childhood Kawasaki disease is presented, as well as an insight into the gradually decreasing antigen expression in cases of acute myeloid leukemia. Furthermore this issue provides an exciting update concerning COVID-19 and the use of CRISPR-Cas, a review about computational approaches in the research of kidney stone formation, factors connected to central precocious puberty, and why a rock star of paleogenetics recently received a Nobel Prize. Additionally, this issue contains an article proposing the repurposing of the lung cancer drug Capmatinib, a study of how the gut microbiome develops in neonates, an impulse about the role of the transmembrane protein TMED3 in esophageal carcinoma, and the revelation about how competing endogenous RNA influences ischemic stroke. Lastly, genetic reasons for male infertility are discussed, as well as the relation between non-alcoholic fatty liver disease and chronic kidney disease.

COVID-19 vaccine induced vasculitis-A case report

Introduction: As of June 2021, a total of 120.2 million cases of corona virus disease 2019 (COVID19), with Seven and half lakh COVID 19 related deaths occurred, as estimated by CDC Globally. Vaccination was started by the Government of India to prevent new cases. With the ongoing pandemic, several COVID-19 vaccine agents have received emergency use approval, several adverse effects are being reported with increasing administration of COVID-19 vaccines. Finding(s): Here we describe a case of Henoch Schoenlein purpura, a small vessel vasculitis which is usually seen in children with excellent prognosis in adults, on contrary HSP developed in adult male following COVID-19 vaccination had a rapid deteriorating course. Millions of people are being vaccinated around the world, and thus it is conceivable that people may develop other diseases temporally associated with vaccination but which are unrelated to the vaccine itself. Conclusion(s): Auto Immune Diseases (AID) can be triggered by vaccine but how do they behave when compared to primary AID both in terms of presentation, prognosis and treatment response are not known, thereby we concluded that Henoch Schoenlein purpura can develop post covid vaccination in adults and may have a rapid course and poor prognosis.

COVID-19 and stroke: from the cases to the causes.

During COVID-19 pandemic, a wide variety of stroke typologies have been described in patients affected by SARS-CoV-2. Investigating the case reports of acute stroke in COVID-19 patients, published since the beginning of the pandemic, we tried to trace the pathogenic mechanisms of stroke during SARS-CoV-2 infection. We conducted a systematic review analyzing demographic data, cerebrovascular risk factors, NIHSS score, vascular territory involvement and laboratory findings of 168 patients described in 89 studies, from a pool of 1243 records. Based on our results, we have identified different stroke profiles: (1) cerebral large vessel disease (CLVD) profile with a low disability, simultaneous onset of COVID-19 and stroke symptoms, good outcome and low serum levels of D-dimer and CRP; (2) intracranial bleeding (IB) profile with high disability, poor outcome and low levels of serum markers of inflammation and coagulopathy; (3) CLVD profile with a short time-lapse between COVID-19 symptoms and stroke onset, high neurological disability and very high systemic inflammatory markers; (4) multiple thrombo-embolic disease (MTED) profile with older patients, many comorbidities, disabling stroke, poor outcome, evident alteration of coagulation tests and high serum levels of both D-dimer and CRP. We therefore summarized these different profiles in a spectrum similar to that of visible light, where the violet-blue band included IB and CSVD with low inflammation and prothrombotic activity, the green-yellow band included CLVD with high inflammation and moderate prothrombotic activity and the orange-red band for MTED with moderate-high levels of inflammation and very high prothrombotic activity.

Psychological impact of COVID-19 containment on CADASIL patients.

INTRODUCTION: COVID-19 restrictive containment was responsible for major psychological distress and alteration of quality of life (QoL) in the general population. Their impact in a group of patients having cerebral small vessel disease (SVD) and at high risk of stroke and disability was unknown. OBJECTIVE: We aimed to determine the potential psychological impact of strict containment during the COVID-19 pandemic in a sample of CADASIL patients, a rare SVD caused by NOTCH3 gene mutations. METHODS: Interviews of 135 CADASIL patients were obtained just after the end of the strict containment in France. Depression, QoL and negative subjective experience of the containment were analysed, as well as predictors of posttraumatic and stressor-related manifestations, defined as an Impact Event Scale-Revised score ≥ 24, using multivariable logistic analysis. RESULTS: Only 9% of patients showed a depressive episode. A similar proportion had significant posttraumatic and stressor-related disorder manifestations independently associated only with socio-environment factors, rather than clinical ones: living alone outside a couple (OR 7.86 (1.87-38.32), unemployment (OR 4.73 (1.17-18.70)) and the presence of 2 or more children at home (OR 6.34 (1.35-38.34). CONCLUSION: Psychological impact of the containment was limited in CADASIL patients and did not appear related to the disease status. About 9% of patients presented with significant posttraumatic and stressor-related disorder manifestations which were predicted by living alone, unemployment, or exhaustion related to parental burden.

Small vessel childhood primary angiitis of the central nervous system with positive anti-glial fibrillary acidic protein antibodies: a case report and review of literature.

BACKGROUND: Small vessel childhood primary angiitis of the central nervous system (SV-cPACNS) is a rare disease characterized by inflammation within small vessels such as arterioles or capillaries. CASE PRESENTATION: We report a case of SV-cPACNS in an 8-year-old boy confirmed by brain biopsy. This patient was also incidentally found to have anti-glial fibrillary acidic protein (GFAP) antibodies in the cerebrospinal fluid (CSF) but had no evidence of antibody-mediated disease on brain biopsy. A literature review highlighted the rarity of SV-cPACNS and found no prior reports of CSF GFAP-associated SV-cPACNS in the pediatric age group. CONCLUSION: We present the first case of biopsy proven SV-cPACNS vasculitis associated with an incidental finding of CSF GFAP antibodies. The GFAP antibodies are likely a clinically insignificant bystander in this case and possibly in other diseases with CNS inflammation. Further research is needed to determine the clinical significance of newer CSF autoantibodies such as anti-GFAP before they are used for medical decision-making in pediatrics.

An unusual presentation of malignant Invasive Mucinous Adenocarcinoma of Lung mimicking Pulmonary Renal syndrome

Background: A 54-year- old male presented to our centre with a chronic non-productive cough and breathlessness. Recent history of COVID treated and resolved few months back. He had a history of brain surgery performed five years back but details not known. Physical examination revealed no oedema and bilateral coarse creps with bronchiolar breathing. Laboratory findings indicated neutrophilic leucocytosis, elevated inflammatory markers, with elevated troponin I and D dimers. Urine analysis suggested microscopic haematuria with sediments. While 24 hour quantification revealed sub nephrotic proteinuria. As auto immune workup and vasculitis profile was negative and patient has not improved in spite of standard of therapy hence we went ahead with CT-Chest indicating ground-glass opacities in bilateral lung parenchyma and prominent interlobular/intralobular septal thickening. Then Bronchoscopy done which revealed the blood-stained secretions in the main stem bronchi and diffuse alveolar haemorrhage in bilateral bronchial segments indicating an inflammatory study, while tuberculosis diagnostic panel and infective bio fire panel in BAL was negative. Meanwhile, his repeat BAL culture suggested Carbapenem resistant Acinetobacter baumannii complex infection. As the patient did not respond to the standard of care for vasculitis. Probability considered was a small vessel vasculitis (namely Granulomatous polyangiitis) was considered due to lung manifestation involving upper respiratory tract with epistaxis, neutrophilic leucocytosis, elevated acute reactive protein, and renal manifestation including microscopic haematuria and proteinuria. However he responded poorly to conventional standard of treatment including pulse steroids and IVIG. Hence after MDT discussion we proceeded with lung biopsy which showed linear cores of lung tissue infiltrated by a malignant neoplasm and acinar pattern suggesting Invasive mucinous adenocarcinoma. Hence we went ahead with the biopsy diagnosis for the treatment plan. As he was to be started on chemotherapy, but he suddenly collapsed and went into hypotension, bradycardia, and cardiac arrest. In spite of high supports and post 4 cycles of CPR, was unable to revive and sadly succumbed to his illness. Discussion(s): In this rare case, the original diagnosis pointed to the pulmonary-renal syndrome, an autoimmune disease characterized by diffuse pulmonary haemorrhage and glomerulonephritis. However, negative autoimmune antibodies and vasculitis profile along with lung biopsy results indicated an unusual case of malignant lung adenocarcinoma presented with pulmonary renal syndrome. Conclusion(s): In cases suggesting pulmonary-renal syndromes, if autoimmune work up is negative and response is suboptimal relook the diagnosis.

A CASE OF GRANULOMATOSIS WITH POLYANGIITIS

SESSION TITLE: Critical Systemic Disease Case Report Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Granulomatosis with polyangiitis(GPA) is an autoimmune small vessel vasculitis that is included in the group of anti-neutrophilic cytoplasmic antibody(ANCA)- associated small vessel vasculitides (AAVs). GPA is a systemic disease, however acronym ELK is used to describe the most common involvement of Ear, nose, throat, Lungs, and Kidneys. We report a case of GPA, highlighting its presentation. CASE PRESENTATION: 59-year old female presented with vaginal bleeding, malaise, blurry vision, non productive cough and shortness of breath few days after receiving COVID-19 vaccine. Physical exam was remarkable for bilateral conjunctival injection with right sided ptosis and inguinal lymphadenopathy. Laboratory findings were significant for acute kidney injury and anemia. Computed tomography (CT) of chest revealed bilateral bronchovascular nodules and masses with interlobular septal thickening and enlarged mediastinal lymph nodes. Fine needle aspiration of left inguinal lymph node was negative for malignancy. Bronchoscopy with bronchial brush revealed alveolar hemorrhage with capillaritis;bronchoalveolar lavage(BAL) showed hemosiderin laden macrophages. Tissue biopsy was negative for malignancy. Testing for pulmonary renal syndrome was positive for C-ANCA and proteinase-3 (PR-3) antibodies. Anti-GBM antibody and anti-MPO antibody was negative. Plasmapheresis (PLEX) and pulse dose steroids were initiated however the patient was unable to tolerate the treatment. Her clinical condition continued to decline requiring multiple pressors, broad spectrum antibiotics and continuous renal replacement therapy. She was transitioned to comfort care per family's wishes and passed away. DISCUSSION: GPA is a rare necrotizing granulomatous vasculitis of small to medium sized vessels that can affect any organ but mainly involves the upper and lower respiratory tract. Necrotizing glomerulonephritis is common. Pulmonary involvement can include consolidation, tracheal or subglottic stenosis, diffuse alveolar hemorrhage, pleural effusion and interstitial lung disease. Lymphadenopathy, as seen in our patient is a rare presentation. Tissue biopsy is crucial for the diagnosis. Association with PR-3 ANCA is seen in more than 80% of GPA patients. Cases of AAVs after administration of COVID vaccine have been reported in the literature, although it is difficult to demonstrate causal relationship. Treatment of GPA with immunosuppression, usually corticosteroids, rituximab or cyclophosphamide, is recommended. The role of PLEX continues to evolve with emerging data, but use of this therapy is reasonable for patients with severe kidney injury and DAH secondary to active vasculitis refractory to immunosuppressive therapy. CONCLUSIONS: Early diagnosis of GPA is challenging as it can mimic metastatic lung malignancy. It should be considered in a broad range of differentials when evaluating patients presenting with pulmonary nodules. Reference #1: Greco A, Marinelli C, Fusconi M, Macri GF, Gallo A, De Virgilio A, Zambetti G, de Vincentiis M. Clinic manifestations in granulomatosis with polyangiitis. Int J Immunopathol Pharmacol. 2016 Jun;29(2):151-9. doi: 10.1177/0394632015617063. Epub 2015 Dec 18. PMID: 26684637;PMCID: PMC5806708. Reference #2: Kitching, A. R., Anders, H. J., Basu, N., Brouwer, E., Gordon, J., Jayne, D. R., Kullman, J., Lyons, P. A., Merkel, P. A., Savage, C., Specks, U., & Kain, R. (2020). ANCA-associated vasculitis. Nature reviews. Disease primers, 6(1), 71. https://doi.org/10.1038/s41572-020-0204-y Reference #3: Szymanowska-Narloch, A., Gawryluk, D., Błasińska-Przerwa, K., & Siemińska, A. (2019). Atypical manifestations of granulomatosis with polyangiitis: the diagnostic challenge for pulmonologists. Advances in respiratory medicine, 87(6), 244–253. https://doi.org/10.5603/ARM.2019.0062 DISCLOSURES: No relevant relationships by Sean Davidson No relevant relationships by Eric Flenaugh No relevant relationships by Marilyn Foreman No relevant relationships by KOMAL KAUR No relevant relationships by Gabriela Oprea-Ilies

COVID-19 PNEUMONIA: A CAUSE OF CAVITARY LUNG LESIONS

SESSION TITLE: Pathologies of the Post-COVID-19 World SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 10:15 am - 11:10 am INTRODUCTION: Cavitary lung lesions are a relatively common finding on imaging with a vast differential diagnosis. CASE PRESENTATION: A 36-year-old female with history of gestational diabetes, preeclampsia and obesity presented to an outside hospital for evaluation of acute onset shortness of breath and chest pain. The patient tested positive for COVID19 two weeks prior. She initially developed some mild symptoms including headache, nasal congestion, generalized body aches, cough with mild sputum production and shortness of breath. Despite improvement in these symptoms, she suddenly developed chest discomfort that radiated to the back and was worse with inspiration and cough. The patient had been fully vaccinated against COVID-19 and had received a booster dose as well. Upon evaluation in the emergency room, she was afebrile, respiratory rate was 20, blood pressure was 144/90 mmHg, heart rate was 88 and her oxygen saturation was 99% on room air. Her physical exam was unremarkable. Basic laboratory work up including CBC and chemistry was normal. EKG and troponins were normal as well. A chest x-ay was performed which showed bilateral nodular densities with possible cavitation. A CT chest was later performed and showed multiple bilateral subsolid pulmonary nodules, some with apparent central cavitation. The patient was admitted for further work up at our institution. The patient's subsequent evaluation was largely unrevealing. An autoimmune panel testing for SLE, rheumatoid arthritis, ANCA vasculitis, and Goodpasture's syndrome revealed only a weakly positive ANA with negative anti-DNA and anti-Smith antibody. HIV and QuantiFERON tests were negative. Blood cultures were negative as well. Unfortunately, the patient was not able to expectorate and therefore no sputum cultures were obtained. Due to the patient's clinical improvement and absence of hypoxemia, diagnostic bronchoscopy was deferred, and the patient was subsequently recommended to undergo short interval chest imaging. Repeat chest computed tomography scan one month later showed complete resolution of the previously seen cavitary pulmonary nodules. At the time of outpatient clinical follow up, the patient remained asymptomatic from a respiratory perspective. DISCUSSION: Cavitary pulmonary nodules on chest imaging is an atypical presentation of COVID19 pneumonia that has been rarely described in the literature. In our patient, the temporal correlation between her pulmonary nodules and COVID19 infection as well as her negative work up for other common infectious and inflammatory causes known to cause cavitary lung lesions, makes COVID19 the most plausible cause for her findings. The pathophysiology of these findings remains unclear but may be explained by endothelialitis and small vessel vasculitis may be implicated in the formation of these lesions. [1] CONCLUSIONS: We presented a rare case of cavitary pulmonary nodules due to COVID19 pneumonia. Reference #1: Ackermann M, Verleden SE, Kuehnel M, Haverich A, Welte T, Laenger F, Vanstapel A, Werlein C, Stark H, Tzankov A, Li WW, Li VW, Mentzer SJ, Jonigk D. Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19. N Engl J Med. 2020 Jul 9;383(2):120-128. DISCLOSURES: No relevant relationships by Karim Anis No relevant relationships by Carolyn Garcia

COVID-19 INFECTION MAY BE TRIGGER for DEVELOPMENT of IMMUNE-MEDIATED DISEASES (IMDS)

Background: As considerable evidence indicates viruses play an important role in the pathogenesis of infammatory rheumatic diseases as environmental factors. The most prominent pathogenic viruses which have been proposed in the triggering and initiation of autoimmune diseases include Parvovirus B19, Epstein-Barr-virus (EBV), Cytomegalovirus (CMV), Herpes virus-6, HTLV-1, Hepatitis A and C virus, and Rubella virus1. It is possible that COVID-19 infection is also a trigger. Because SARS-CoV-2 infection can break immune tolerance and trigger autoimmune responses, it is also likely to induce clinical autoimmunity2. Objectives: Find out a possible association between Covid-19 infection and development of IMDs. Methods: We analyzed data of 21 patients (Male 4/19 %/, female 17/81%/, mean age 45.5 ± 13,9 years), who were admitted to Rheumatology department of 'Mikayelyan' University Hospital after Covid-19 infection with newly diagnosed IMDs from June till December 2021. All of included had never had such kind of disorder before. EULAR/ACR criteria were used for diagnosis and assessment of disease activity. Results: After SARS-CoV-2 infection some patients presented with preserved fever, high levels of CRP and ESR, had rash and arthritis. Particularly, 3 (14.3%) developed systemic lupus erythematosus, 3(14.3%)-antiphospholipid syndrome, 4 (19%)-rheumatoid arthritis, 2(9.5%)-spondyloarthritis, 3 (14.3%)-sarcoidosis, 4 (19%)-erythema nodosum, 1 (4.8%)-small-vessel vasculitis, 1 (4.8%)-undifferentiated arthritis, and 1(4.8%)-Tietze syndrome. 11 (52.4%) experienced severe course of Covid-19 with pneumonia and respiratory failure, in 10 (47.6%) patients the course of disease was mild. We've found a signifcant association between severe course of Covid-19 and development of erythema nodosum. (p< 0.05). Also an association between female gender and severe course of Covid-19 was determined (p<0,05). Conclusion: In acute progression of the COVID-19 along with development of antiviral immunity, a dysregulated response of immune system may occur, represented by the marked cytokine release syndrome, macrophage activation, and systemic hyperinfammation.3 We analyzed the data of patients who didn't have any typical symptom of rheumatic diseases before coronavirus infection, therefor, on our opinion, virus played an important role to induce clinical autoimmun-ity and autoinfammation and subsequently-IMDs. Possibly, Covid-19 infection may be included in the group of trigger viruses for.

INCIDENCE and RISK FACTORS of COVID-19 in PATIENTS with VASCULITIS: A DANISH NATIONWIDE COHORT STUDY

Background: Patients with small vessel vasculitis (SVV) and large vessel vas-culitis (LVV, including giant cell arteritis (GCA)) are considered at higher risk of infections compared to the general population, owing to their underlying condition and the use of immunosuppressive drugs. Thus, the risk of COVID-19 infection and related outcomes during the global pandemic is of immediate concern to rheumatologists worldwide. Objectives: To estimate the incidence of COVID-19 hospitalisation in patients with vasculitis, and to evaluate the impact of glucocorticoid treatment on the outcome between March 2020 and February 2021. Methods: With use of the Danish nationwide registers, a cohort of patients with LVV and SVV, respectively, and general population controls (GPCs) matched on age and gender was established. Hazard ratios (HR) for COVID-19 hospitalisation was estimated. National COVID-19 surveillance data was used to calculate the odds ratio (OR) of having had a positive SARS-CoV2 PCR test. Lastly, a nested case-control design and conditional logistic regression was used to estimate the impact of glucocorticoids on the risk of hospitalisation. Results: Patients with SVV (n=1090) had an increased incidence of COVID-19 hospitalisation compared with GPCs (comorbidity-adjusted HR 2·73;95% CI 1·64-4·55), whereas no increased risk was seen in patients with LVV. Patients with vasculitis had similar likelihoods of having had a positive PCR test as GPCs. Glucocorticoids did not increase the HR of hospitalisation among patients with LVV or SVV. Conclusion: Patients with SVV were more likely to be admitted with COVID-19 than the GPCs. The impact of glucocorticoid treatment on the risk of hospitalisation needs further investigation.

HEALTH-RELATED QUALITY OF LIFE AMONG PATIENTS WITH ANCA VASCULITIS

BACKGROUND AND AIMS: Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) is a debilitating disease that can have a significant impact on a patient's quality of life. The aim of this study was to assess the longitudinal quality of life amongst those diagnosed with AAV using the EQ-5D instrument, which allows for calculation of quality-adjusted life years (QALYs.) METHOD: A total of 343 patients with AAV participated in this study, of which 191 (55.7%) were male, resulting in 2746 episodes. The EQ-5D-5L standardised instrument was used to evaluate health-related quality of life in the domains of mobility, self-care, usual activities, pain/discomfort, anxiety/depression and to generate a summary index score. Overall health was also rated using a visual analogue scale (0-100). EQ-5D questionnaires were completed during routine nephrology clinic attendances and through a vasculitis patient support smartphone app. We used a random effects model to control for multiple entries relating to individual patients. RESULTS: A lower quality of life was seen amongst those with AAV (median index value 0.80, overall population average 0.856). The mean visual analogue scale score was 75.6 ± 17.3 (overall population average 82.8, Fig. 1). Patients' pain and discomfort level (mean 1.95) was most affected while self-care (mean 1.33) was least affected (Fig. 1). An increase in BVAS tightly correlated with a reduction in quality of life. Using the random effects model, the index score was seen to decrease with increasing age with a 2.7% reduction in index score per decade. A 7% reduction in index score was seen during periods of disease activity compared with periods of remission. Patients with end-stage kidney disease requiring dialysis had an 8% reduction in index score. A reduced quality of life was seen following COVID-19 lockdown with a 5% reduction in index score seen. Using a median survival rate of 6.16 years for patients with small vessel vasculitis, we calculated the QALYs for this population as 4.9 years. CONCLUSION: We have defined for the first time the EQ-5D index value over the full disease course in patients with AAV. Notably, we have identified a reduction in quality of life during periods of disease activity. Other studies have demonstrated a reduction in quality of life during active disease using the AAV-PRO questionnaire and the Medical Outcomes Study Short Form-36. A decrease in work productivity has also been noted. Previously reported mean index values of 0.72 and 0.76 were lower than our observed values, although both are significantly reduced compared with population norms. In conclusion, this research highlights the negative impact of AAV on patients' lives.

Isolated pauci-immune pulmonary capillaritis associated with an extensive bilateral hemothorax and pleuro-pericarditis

Introduction: Isolated pauci-immune pulmonary capillaritis (IPIPC) is a rare disorder characterized by small vessel vasculitis limited to alveolar capillaries in the absence of systemic manifestations. There are very few case reports of this disorder in the medical literature. Case Report: A 37-yo male with no known history of autoimmune pathology who was admitted to the hospital for evaluation and treatment of dyspnea and thoracalgia. Peripheral blood cultures, serum studies to detect Legionella and Pneumococcus antigens, and a nasopharyngeal swab test for covid-19 were all negative. Chest imaging revealed bilateral pleural effusions from the base to the apices with concomitant atelectasis of the adjacent lung parenchyma. Although the results of an 18F-PET-CT scan revealed no pathological uptake, video-assisted thoracoscopy revealed diffusely edematous pleura with crater-like patches with new onset of venous vessel varicosities, intra-alveolar hemorrhages associated with disordered vascularization, suggesting small vessel vasculitis. Histologic findings included widespread intra-alveolar hemorrhage with organizing injury, hemosiderin-laden macrophages, scattered intra-arterial thrombi, and diffuse perivascular neutrophilic infiltrates consistent with a diagnosis of capillaritis. Conclusions: Given the negative immune studies (save for a weakly-positive lupus anticoagulant and no evidence for extra-pulmonary vasculitis, the diagnosis was Isolated pauci-immune pulmonary capillaritis. The patient recovered in response to immunosuppressive/anti-inflammatory therapy.

A late diagnosis of eosinophilic granulomatosis with polyangiitis

Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is a medium and small vessel vasculitis. Discussion: A 58-years man was admitted to the Emergency Department in January 2022 for myalgia and weakness of lower limbs in recent COVID-19 infection. He had a clinical history of allergic asthma and eosinophilic pneumonia (ANCA negative) diagnosed as secondary to sensitization work-related in 2001. Blood test showed a severe hypereosinophilia (absolute eosinophil count: 9875/microL) and elevated creatine kinase (CK: 7555 U/L). He was hospitalized in HUB COVID. During hospitalization reported paraesthesia of upper and lower limbs and fever;blood test showed elevation of inflammation markers. Autoimmune screening showed a antineutrophil cytoplasmic antibodies positivity (ANCA anti-MPO 178UI/mL). A sinus CT showed nasal polyposis. A neurological evaluation and electromyography were performed with the evidence of polyneuropathy. Muscle biopsy showed eosinophil-associated vascular occlusion and eosinophilassociated tissue damage. The investigation excluded renal, cardiac, pulmonary and gastro-intestinal involvement. A steroid therapy (Prednisone 1 mg/kg/die) was started with clinical improvement. Conclusions: EGPA is a multisystemic disorder, typically suspected based on a combination of clinical findings, such as asthma, nasal and sinus symptoms, peripheral neuropathy, and eosinophilia ≥1500/microL. ANCA antibodies are positive in around 40% of patients and diagnosis can often be challenging and delayed.

A case report of granulomatosis with polyangiitis in a middle aged women

Background: Wegener's granulomatosis (Granulomatosis with polyangiitis) is a rare systemic autoimmune disease of unknown etiology characterised by triad of necrotising granulomatous inflammation of upper and lower respiratory tract, glomerulonephritis, and disseminated vasculitis. Case Study: A 50 year old female presented with complaints of running nose since last 8 months. Patient also had low grade fever, generalised body pain, productive cough, shortness of breath on exertion, pedal oedema for last 2 months. She had an 2-3 episodes of blood in sputum 15 days back. On examination saddle nose found. HRCT chest shows multiple cavitating nodules with consolidation. Lab findings shows raised ESR, CRP, COVID RT PCR negative and positive C-ANCA (Anti neutrophilic cytoplasmic antibody), red blood cell casts, and albumin present in urine. Sputum for AFB negative. Patient discharged on corticosteroids and cyclophosphamide and advised for regular follow up. Discussion: Wegener's granulomatosis is an antineutrophilic cytoplasmic antibody associated small vessel vasculitis. Prevalence of this disease varies from 3/1,00,000 to 16/1,00,000. Typically this involve the lungs and kidneys. It can be of generalised severe form or localised limited form. Our patient clinical course, CT findings and his strongly positive C-ANCA were considered diagnostic of wegener's granulomatosis. Treatment include corticosteroids and immunosuppressants. Conclusion: The early diagnosis and prompt treatment of multisystem disorder is necessary to prevent complication such as diffuse alveolar haemorrhage CT is the imaging modality of choice for diagnosis, surveillance and follow up in patients with wegener's granulomatosis.

Obstructive sleep apnea and white matter hyperintensities: correlation or causation?

Obstructive sleep apnea (apnea) is thought to cause small vessel ischemic episodes in the brain from hypoxic events, postulated as white matter hyperintensities (hyperintensities) identified on MRI which are implicated in cognitive decline. This study sought to evaluate these correlations. A retrospective evaluation of adults who underwent polysomnography (4/1/2016 to 4/30/2017) and a brain MRI prior to apnea diagnosis or within a year post-diagnosis was completed. MRI visual evaluation of hyperintensities using Fazekas scores were collected blind to clinical data. Collated clinical/MRI data were stratified and analyzed using chi-square, fishers t-tests, ANOVA/ANCOVA and linear regression. Stratification by apnea category revealed no significant differences in any variables including hyperintensity measures (Fazekas p=0.1584; periventricular p=0.3238; deep p=0.4618; deep total p=0.1770). Stratification by Fazekas category, periventricular and deep hyperintensities revealed increasing prevalence with age (p=0.0001); however, apnea categories were not significantly associated (Fazekas p=0.1479; periventricular p=0.3188; deep p=0.4503), nor were any individual apnea indicators. Continuous apnea measurements werre not associated with any hyperintensity factor; total deep hyperintensities were not associated with any apnea factors. Continuous BMI was not found to be associated with any apnea or hyperintensity factors. Only hypertension was noted to be associated with Fazekas (p=0.0045), deep (p=0.0010) and total deep (p=0.0021) hyperintensities; however, hypertension was not associated with apnea category (p=0.3038) or any associated factors. These data suggest apneas alone from OSA are insufficient to cause WMH, but other factors appear to contribute to the complex development of small vessel ischemic injury associated with age and cognitive decline.