Vaccine-induced immune thrombotic thrombocytopenia: what do we know hitherto?

Vaccine-induced immune thrombotic thrombocytopenia (VITT), also known as thrombosis with thrombocytopenia syndrome, is a catastrophic and life-threatening reaction to coronavirus disease 2019 (COVID-19) vaccines, which occurs disproportionately in response to vaccination with non-replicating adenovirus vector (AV) vaccines. The mechanism of VITT is not well defined and it has not been resolved why cases of VITT are predominated by vaccination with AV vaccines. However, virtually all VITT patients have positive platelet-activating anti-platelet factor 4 (PF4) antibody titers. Subsequently, platelets are activated and depleted in an Fcγ-receptor IIa (FcγRIIa or CD32a)-dependent manner, but it is not clear why or how the anti-PF4 response is mounted. This review describes the pathogenesis of VITT and provides insight into possible mechanisms that prompt the formation of a PF4/polyanion complex, which drives VITT pathology, as an amalgam of current experimental data or hypotheses.

Bat ASC2 suppresses inflammasomes and ameliorates inflammatory diseases.

Bats are special in their ability to live long and host many emerging viruses. Our previous studies showed that bats have altered inflammasomes, which are central players in aging and infection. However, the role of inflammasome signaling in combating inflammatory diseases remains poorly understood. Here, we report bat ASC2 as a potent negative regulator of inflammasomes. Bat ASC2 is highly expressed at both the mRNA and protein levels and is highly potent in inhibiting human and mouse inflammasomes. Transgenic expression of bat ASC2 in mice reduced the severity of peritonitis induced by gout crystals and ASC particles. Bat ASC2 also dampened inflammation induced by multiple viruses and reduced mortality of influenza A virus infection. Importantly, it also suppressed SARS-CoV-2-immune-complex-induced inflammasome activation. Four key residues were identified for the gain of function of bat ASC2. Our results demonstrate that bat ASC2 is an important negative regulator of inflammasomes with therapeutic potential in inflammatory diseases.

Immunotherapeutic and immunomodulatory potentials of Antigen-Antibody complex vaccines

Immune system battles with deadly pathogens that mostly deteriorate health and cause morbidity and mortality. Antibodies are considered great players in the elimination of pathogens and hence, provide a shield against the future onset of various diseases. The immune complex, also known as an antigen–antibody (Ag-Ab) complex, exhibits the immunomodulatory potential leading to enhanced vaccine efficacy. A deeper understanding of Fc receptors (FcRs) and the interaction of the Fc part of an antibody with the different immune cells lead to in-depth knowledge of using this strategy for the development of immune complex vaccines. The concept of the Ag-Ab complex has been used in the prevention and therapy of various viral and bacterial diseases. Ag-Ab complex is gaining attention in COVID-19 vaccine development too, due to their greater immunoregulatory potential. The present literature highlights the importance of the Ag-Ab complex, the role of Fc receptors in immunomodulation, and their success as vaccines in viral and bacterial diseases of human and animal origin. Moreover, potential areas and lapses are explored to make better use of this prospect as a vaccine candidate. Studies revealed that the immunogenic and immunomodulatory potential of Ag-Ab complex can lead to greater protection. However, there is a dire need of establishing a link between laboratory and clinical findings to make it effective and safe tool for in vivo treatments. © 2022 Elsevier Ltd

Electrochemical Biosensor for the Determination of Specific Antibodies against SARS-CoV-2 Spike Protein.

In this article, we report the development of an electrochemical biosensor for the determination of the SARS-CoV-2 spike protein (rS). A gold disc electrode was electrochemically modified to form the nanocrystalline gold structure on the surface. Then, it was further altered by a self-assembling monolayer based on a mixture of two alkane thiols: 11-mercaptoundecanoic acid (11-MUA) and 6-mercapto-1-hexanol (6-MCOH) (SAMmix). After activating carboxyl groups using a N-(3-dimethylaminopropyl)-N'-ethyl-carbodiimide hydrochloride and N-hydroxysuccinimide mixture, the rS protein was covalently immobilized on the top of the SAMmix. This electrode was used to design an electrochemical sensor suitable for determining antibodies against the SARS-CoV-2 rS protein (anti-rS). We assessed the association between the immobilized rS protein and the anti-rS antibody present in the blood serum of a SARS-CoV-2 infected person using three electrochemical methods: cyclic voltammetry, differential pulse voltammetry, and potential pulsed amperometry. The results demonstrated that differential pulse voltammetry and potential pulsed amperometry measurements displayed similar sensitivity. In contrast, the measurements performed by cyclic voltammetry suggest that this method is the most sensitive out of the three methods applied in this research.

Case Report of Serum Sickness-like Reaction following the First Dose of the Chimpanzee Adenovirus-Vectored AstraZeneca COVID-19 Vaccine, ChAdOx1.

Serum sickness-like reaction from serum sickness is critical. Serum sickness-like reaction has comparable symptoms to serum sickness, but their underlying pathophysiology is distinct. This delayed hypersensitivity response was first characterized as a drug-induced reaction and is uncommon in adults; it is more common in children. COVID-19 vaccinations are now being routinely given in the COVID-19 period, and adverse reactions to immunization have been recorded. We present a case of COVID-19 vaccination-induced serum sickness-like reaction which developed after receiving the first dose of AstraZeneca COVID-19 vaccine.

Safety of ANCA-associated vasculitis patients receiving covid-19 vaccination

Background: The Covid-19 vaccines administration programs implemented in most countries, WHO showed 5.22 billion persons vaccinated at least one dose up to June 29th 2022. EULAR and ACR guidelines suggested autoimmune and inflammatory rheumatic diseases (AIIRDs) patients with stable or low disease activity should receive Covid-19 vaccination. ANCA-associated vasculitis (AAV) patients are AIIRDs subgroup during pandemic, the safety of Covid-19 vaccination has not been reported in large scale study. We analyzed publications of patients with AAV who had relapse post-vaccination and further discussed the challenges for AAV patients under B-depleting therapy with appropriate vaccination recommendations. Method(s): We used descriptive thematic analysis to find out the flare features including severity, organ involvement, therapy strategy in AAV patients after Covid-19 vaccination. This article conforms with the Scale for Assessment of Narrative Review Articles (SANRA) guidelines. After eligibility criteria and selection process, there were 6 matched articles which had 10 individual cases. Result(s): AAV could involve several organs throughout the body, most cases involved kidney and lung injury. Among the 10 cases, there were 2 cases of EGPA, 3 of MPA and 1 RLV patient with clearly written diagnosis and all patients were assessed as being in disease remission prior to vaccination. The cases were special in age characteristic with 71-85 years old. Seven patients had anti-ANCA type test in 3 cases were anti-PR3 type and another 4 cases were anti-MPO type both with higher titers than during remission. Four had new onset organ involvements rather than the recurrence of the original organ relapse after vaccination. Among them, the 74-year- old male suspended rituximab for 6 months interval before vaccination, he developed diffuse alveolar hemorrhage and infection followed under restart rituximab treatment and eventually died of respiratory failure. Another same age male was diagnosed with new crescentic pauci-immune glomerulonephritis and discharged with creatine level as 307umol/L. Conclusion(s): Patients with AAV in remission rarely experienced severe relapse after vaccination, and some involved new-onset organ while others are worsened of the original involvement. Pulmonary new onset involvement might be triggered by neutrophil extracellular traps promotion. The elderly receiving B-cell depleting therapy who are at infection risk with low humoral response should be under careful evaluation between last dose of rituximab and next dose of vaccination. Kidney injury presented mostly with good clinical treatment response. However, longer observation should be considered whether those patients received kidney replacement therapy earlier than expected. (Figure Presented).

Xuanfei Baidu Decoction suppresses complement overactivation and ameliorates IgG immune complex-induced acute lung injury by inhibiting JAK2/STAT3/SOCS3 and NF-κB signaling pathway.

BACKGROUND: The significant clinical efficacy of Xuanfei Baidu Decoction (XFBD) is proven in the treatment of patients with coronavirus disease 2019 (COVID-19) in China. However, the mechanisms of XFBD against acute lung injury (ALI) are still poorly understood. METHODS: In vivo, the mouse model of ALI was induced by IgG immune complexes (IgG-IC), and then XFBD (4g/kg, 8g/kg) were administered by gavage respectively. 24 h after inducing ALI, the lungs were collected for histological and molecular analysis. In vitro, alveolar macrophages inflammation models induced by IgG-IC were performed and treated with different dosage of XFBD-containing serum to investigate the protective role and molecular mechanisms of XFBD. RESULTS: The results revealed that XFBD mitigated lung injury and significantly downregulated the production of pro-inflammatory mediators in lung tissues and macrophages upon IgG-IC stimulation. Notably, XFBD attenuated C3a and C5a generation, inhibited the expression of C3aR and C5aR and suppressed the activation of JAK2/STAT3/SOCS3 and NF-κB signaling pathway in lung tissues and macrophages induced by IgG-IC. Moreover, in vitro experiments, we verified that Colivelin TFA (CAF, STAT3 activator) and C5a treatment markedly elevated the IgG-IC-triggered inflammatory responses in macrophages and XFBD weakened the effects of CAF or C5a. CONCLUSION: XFBD suppressed complement overactivation and ameliorated IgG immune complex-induced acute lung injury by inhibiting JAK2/STAT3/SOCS3 and NF-κB signaling pathway. These data contribute to understanding the mechanisms of XFBD in COVID-19 treatment.

Vaccine-induced immune thrombotic thrombocytopenia: Updates in pathobiology and diagnosis.

Coronavirus disease 2019 (COVID-19) is a viral respiratory infection caused by the severe acute respiratory syndrome virus (SARS-CoV-2). Vaccines that protect against SARS-CoV-2 infection have been widely employed to reduce the incidence of symptomatic and severe disease. However, adenovirus-based SARS-CoV-2 vaccines can cause a rare, thrombotic disorder termed vaccine-induced immune thrombotic thrombocytopenia (VITT). VITT often develops in the first 5 to 30 days following vaccination and is characterized by thrombocytopenia and thrombosis in unusual locations (e.g., cerebral venous sinus thrombosis). The diagnosis is confirmed by testing for anti-PF4 antibodies, as these antibodies are capable of platelet activation without any cofactor. It can be clinically challenging to differentiate VITT from a similar disorder called heparin-induced thrombocytopenia (HIT), since heparin is commonly used in hospitalized patients. VITT and HIT have similar pathobiology and clinical manifestations but important differences in testing including the need for PF4-enhanced functional assays and the poor reliability of rapid immunoassays for the detection of anti-platelet factor 4 (PF4) antibodies. In this review we summarize the epidemiology of VITT; highlight similarities and differences between HIT and VITT; and provide an update on the clinical diagnosis of VITT.

Central retinal vein occlusion and occlusive vasculopathy at macula in a patient with recent COVID-19 infection.

We described a post-COVID-19 patient who presented with central retinal vein occlusion and macular ischemia. A 50-year-old male presented with decreased vision for a month in his right eye (RE). The patient had no systemic risk factors for vascular disease but recent COVID-19 infection. Fundus examination revealed dense intraretinal dot hemorrhages especially at macula and ischemia-related retinal whitening in the posterior pole in RE. Expanding of foveal avascular zone was also detected in optical coherence tomography angiography (OCTA) sections. After systemic steroid therapy, subretinal fluid resolved but visual acuity did not increase. Depending on the fundus fluorescein angiography and OCTA findings, clinical picture was compatible with previous central retinal vein occlusion with superimposed occlusive vasculopathy at macula. COVID-19 patients with visual problems must be considered with care in regard to thrombotic retinal diseases.

Immunotherapeutic and immunomodulatory potentials of Antigen-Antibody complex vaccines

Immune system battles with deadly pathogens that mostly deteriorate health and cause morbidity and mortality. Antibodies are considered great players in the elimination of pathogens and hence, provide a shield against the future onset of various diseases. The immune complex, also known as an antigen-antibody (Ag-Ab) complex, exhibits the immunomodulatory potential leading to enhanced vaccine efficacy. A deeper understanding of Fc receptors (FcRs) and the interaction of the Fc part of an antibody with the different immune cells lead to in-depth knowledge of using this strategy for the development of immune complex vaccines. The concept of the Ag-Ab complex has been used in the prevention and therapy of various viral and bacterial diseases. Ag-Ab complex is gaining attention in COVID-19 vaccine development too, due to their greater immunoregulatory potential. The present literature highlights the importance of the Ag-Ab complex, the role of Fc receptors in immunomodulation, and their success as vaccines in viral and bacterial diseases of human and animal origin. Moreover, potential areas and lapses are explored to make better use of this prospect as a vaccine candidate. Studies revealed that the immunogenic and immunomodulatory potential of Ag-Ab complex can lead to greater protection. However, there is a dire need of establishing a link between laboratory and clinical findings to make it effective and safe tool for in vivo treatments.

Two Cases of New-Onset Lichen Planus Following BNT162b2 mRNA COVID-19 Vaccine

Various cutaneous side effects have been reported to be observed following coronavirus disease-2019 (COVID-19) vaccination. Urticaria, maculopapular eruption, vasculitis, pityriasis rosea, psoriasis and papulovesicular exanthem are some dermatological diseases which are observed after COVID-19 vaccination. Hyperinflammatory environment resulting from the cytokine storm in the setting of COVID-19, immune complex deposition and direct cytopathic effects of the virus are implicated in the etiopathogenesis of the dermatological manifestations. Infectious agents, immunologic factors, vaccinations and drugs have all been blamed in the emergence of lichen planus. With the cases presented in this case report, we would like underline that new-onset cutaneous lichen planus may be seen after mRNA COVID-19 vaccination. Copyright © 2022 by Turkiye Klinikleri.

Effect of the COVID-19 Pandemic on Clinical Phenotype of Glomerular Disease: Single Centre Experience

Background: Presenting features for glomerular disease can be varied, including but not exclusively, acute kidney injury, nephrotic syndrome or haemo-proteinuria. At our regional tertiary centre we conducted a retrospective study to see whether clinical presentations of glomerular diseases had changed during the COVID-19 pandemic. Method(s): In this study, new and repeat native renal biopsies were included from January 2018 to October 2021. Glomerular pathologies of interest included minimal change disease, membranous nephropathy, IgA nephropathy, lupus nephritis and pauciimmune glomerulonephritis. We looked at three periods of time: prior to the start COVID-19 pandemic in 2018/19;during the COVID-19 pandemic in 2020;and after the introduction of COVID-19 vaccines in 2021. Result(s): 263 biopsies were identified over the 4-year period. IgA nephropathy - n = 13. Lupus nephritis - n = 43. The different classes of lupus nephritis are shown in (see figure 1) Minimal change disease - n = 57. All presented with the nephrotic syndrome. Between 6-25% over the study period presented with AKI (mean 19%) Pauci-immune glomerulonephritis - n = 85. Between 81%-91% over the study period presented with AKI, or AKI on CKD (mean 84%) Membranous glomerulopathy - n = 66. 50%, presented with the nephrotic syndrome. 20% presented with AKI in addition to proteinuria. Conclusion(s): Our analysis has not shown a significant change in clinical presentations of glomerular disease. There has not been an increased propensity in presenting with AKI in minimal change disease or membranous nephropathy. We saw the highest proportion of class IV lupus nephritis in 2021.

Effect of the COVID-19 Pandemic on Incidence of Glomerular Disease: A Single Centre Report

Background: Glomerular disease carries a significant burden of morbidity and mortality. There is emerging evidence of the impact of the COVID-19 pandemic and COVID-19 vaccination on glomerular disease. The aim of the study was to retrospectively analyse our experience of the incidence of glomerular disease between 2018 and 2021. Method(s): Native renal biopsy results were reviewed to compare the incidence of glomerular disease prior to the COVID-19 pandemic (2018/19);prior to development of COVID-19 vaccination (2020);and after the introduction of COVID-19 vaccines (2021). Biopsy data from January 2018 to October 2021 were collated from pathology records for all glomerular disease patients in our unit. We focused on the incidence of IgA nephropathy, lupus nephritis, minimal change disease, membranous nephropathy and pauci-immune glomerulonephritis. Result(s): 263 native biopsies were performed;45 biopsies in 2018, 75 in 2019, 65 in 2020 and 78 in the first ten months of 2021. The proportional incidence of each disease is shown in figure 1. The incidence of membranous nephropathy was noted to be higher in 2021, coinciding with the introduction of the COVID-19 vaccine programme in the UK, from an average of 23% of cases between 2018-2020, to 31% in the first ten months of 2021. The overall incidence of glomerular disease, excluding vasculitis, seemed to have fallen during 2020. Conclusion(s): The emergence of COVID-19 does not appear to have caused a significant increase in the overall incidence of glomerular disease in our population. We noted an increase in the incidence of membranous nephropathy following the introduction of the COVID-19 vaccination programme in 2021. The relatively lower incidence in 2020 could be related to limited access to primary health care practitioners and consequent reduction in referrals to secondary care at the time.

A CASE OF MICROSCOPIC POLYANGIITIS (MPA) FOLLOWING SARS-COV-2 INFECTION

SESSION TITLE: Unique Inflammatory and Autoimmune Complications of COVID-19 Infections SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/19/2022 12:45 pm - 1:45 pm INTRODUCTION: ANCA-associated vasculitis (AAV) is a systemic disease that causes inflammation of small vessels in various organs, such as the lungs, kidneys, and nervous system. We report a case of AAV following SARS-CoV-2 infection. CASE PRESENTATION: A 64-year-old female from Albania with no known medical history, presented with intermittent low-grade hemoptysis and fever for 1 week prior to admission. She had chills, myalgias, fatigue, and poor appetite 6 weeks prior. On arrival, she was febrile (101F), and hypoxic (Spo2 92% on 3L O2). Labs were significant for anemia [Hb 6.8 g/dl], acute kidney injury (AKI) [Cr 2.5 mg/dl]. She was found to be Positive for Sars-CoV-2 by PCR. Chest X-Ray showed patchy bilateral airspace opacities with peripheral and lower lobe predominance, concerning for atypical pneumonia (Fig 1). Urinalysis was significant for proteinuria (2+) and hematuria (2+). CT (Computed Tomography) thorax showed extensive bilateral airspace disease (dense consolidations and ground-glass opacities) favoring multifocal infection and mediastinal lymphadenopathy(Fig 2). Due to the chronicity of her symptoms and atypical imaging for viral pneumonia, other diagnoses were explored including bacterial superinfection, Tuberculosis, and autoimmune disease. Sputum studies were negative for infections including Acid Fast Bacilli. Workup revealed elevated Antimyeloperoxidase antibodies (MPO) and positive COVID-19 Ig G. She was started on methylprednisolone 1g for AAV. Renal biopsy revealed pauci-immune glomerulonephritis with features of cellular crescent consistent with microscopic polyangiitis (Fig 3). Follow-up CT chest showed improved airspace abnormalities and mediastinal lymphadenopathy. After induction therapy with Rituximab was initiated, she continued to recover and was discharged home. DISCUSSION: The pathogenesis of AAV is believed to be an aberrant pathogenic autoimmune response that follows an initial insult which can include infections. SARS-CoV-2 has been associated with the emergence of autoimmune diseases in susceptible patients(1). The proposed mechanism is linked to elevated levels of circulating neutrophil extracellular traps (NETs) observed in covid infection. These NETS are covered with proteins including neutrophilic enzymes which can activate complement pathways causing tissue destruction and vasculitis. The diagnosis of new-onset AAV can be challenging in COVID-19 patients as symptoms and clinical manifestations of both diseases can overlap. AAV should be considered strongly in patients who are currently infected or have been infected with SARS-CoV-2 and present with atypical or non-resolving pneumonia and other organ involvement such as AKI to avoid permanent organ damage. CONCLUSIONS: The presence of non-resolving or atypical pneumonia and AKI in a patient with SARS-CoV-2 should prompt evaluation of immunological markers to assess or rule out AAV for early diagnosis and treatment. Reference #1: Caso F, Costa L, Ruscitti P, Navarini L, Del Puente A, Giacomelli R, Scarpa R. Could Sars-coronavirus-2 trigger autoimmune and/or autoinflammatory mechanisms in genetically predisposed subjects? Autoimmun Rev. 2020;19(5):102524. doi: 10.1016/j.autrev.2020.102524 DISCLOSURES: No relevant relationships by Tarik Al-Bermani No relevant relationships by Anant Jain No relevant relationships by Ian Kaplan No relevant relationships by Alina Kifayat No relevant relationships by Lisa Paul

COVID VACCINE ASSOCIATED GLOMERULAR DISEASES- A CASE SERIES

Introduction: Vaccination is a known trigger for the development of de-novo or flare of glomerular diseases. Here we present a case series of fourteen patients with COVID vaccine- associated glomerular diseases (CVAGD). Methods: Patients with new onset proteinuria, hematuria or renal failure after SARS- CoV2 vaccine were included in the study. Demographic and clinical details were collected and laboratory investigations including serum creatinine, albumin, urine microscopy and urine spot protein creatinine ratio were done. Renal biopsy specimens were subjected to light microscopy and immunofluorescence examination. Results: We cared for 14 patients with CVAGD. Of them, eight patients were males. The mean age was 25.7 years. Three patients had relapse of their previous disease while eleven patients had no previously detected renal diseases. Eleven patients had received COVISHIELD and three had received COVAXIN. All patients presented after the first vaccine dose. At presentation, seven patients had nephrotic syndrome, two patients had rapidly progressive renal failure and five patients had nephritic syndrome. The mean duration of symptom onset after vaccination was 18 days. Renal biopsy revealed IgA nephropathy in 3 patients, endocapillary proliferative glomerulonephritis in 2 patients, minimal change disease in 5 patients, pauci- immune glomerulonephritis (ANCA associated vasculitis) in one patient, lupus nephritis ISN/RPS class 3 in one and focal segmental glomerulosclerosis in two patients. There was no history of COVID infection in any of our patients. Three patients had renal failure at presentation but none required renal replacement therapy. The patients with MCD and FSGS were treated with steroids, patients with ANCA vasculitis and lupus nephritis were managed with the appropriate Cyclophosphamide and steroid regimens while the others were managed conservatively with anti-proteinuric medications. On follow up, five patients (One IgAN, three MCD, one endocapillary proliferative GN) achieved complete remission of proteinuria and resolution of renal failure, while the remaining eight patients achieved partial remission. One patient with MCD had a relapse of proteinuria 3 weeks after achieving partial remission, he responded well to steroid therapy. All 14 patients remain on close follow up. Conclusions: Although causality cannot be definitively established, there is a definite temporal association between the presentation of glomerular diseases and COVID vaccination, in the absence of other inciting factors. Hence, new-onset or relapse of glomerular diseases presenting post vaccination, although rare, should be observed as a possible adverse event. Intriguing questions such as how to proceed with the vaccination schedule in patients with CVAGD and would changing the vaccine type reduce the risk of relapse remain unanswered. No conflict of interest

Seronegative Full-House Immune Complex Glomerulonephritis Post-mRNA COVID-19 Vaccination

Immunization with COVID-19 mRNA vaccines has been associated with new-onset and relapse of glomerulonephritis (GN)1,2. We present a case of new onset, seronegative, full-house immune-complex GN after mRNA COVID-19 vaccination. A 24-year-old male with history of idiopathic portal vein thrombosis in childhood, portal hypertension post splenorenal shunt and splenectomy 5 years prior presented with 9 weeks of progressive edema, ascites, and foamy urine. His symptoms started then worsened after his 1st and 2nd doses of the mRNA- 1273 COVID-19 vaccination (Moderna). Cr peaked at 3.04mg/dl (baseline 0.7) and UPCR at 50.52 g/g. Serum albumin 0.9 g/dl. Complements were low. ANA and anti-DS DNA were negative as were other serologies. Infectious work up was also negative. Kidney biopsy showed membranoproliferative pattern of injury on light microscopy with one fibrocellular crescent and without IFTA. IF revealed “full house” staining and EM showed severe subepithelial deposits with subendothelial and mesangial deposits. No tubuloreticular inclusions were present (Figure 1). The patient received cyclophosphamide 750 mg and high dose steroids. One month after treatment, Cr improved to 0.92 and proteinuria fell to 6.05g/g. Complements returned to normal. The high potency of mRNA COVID-19 vaccine can induce a robust immune response which may incite or unmask GNs2. Our patient had a rapid and robust response to immunosuppression. Seronegative full-house immune complex GN may occur after receiving mRNA SARS-CoV-2 vaccination and nephrologists should be aware of potential association. Prompt recognition and treatment may lead to favorable outcomes. (Figure Presented)

IT'S ALWAYS COCAINE: A RARE CASE OF LEVAMISOLEINDUCED COCAINE ASSOCIATED VASCULITIS WITH PULMONARY AND RENAL INVOLVEMENT

CASE: 58 year old woman presents with 1 month of dyspnea and productive cough. She also reported loss of smell and hematuria for 1 week. History was notable for hypertension, COPD, substance abuse, specifically crack cocaine, and unstable housing. On admission she was tachypneic and hypoxic, requiring supplemental O2. Exam revealed bilateral crackles, elevated JVP, and mild lower extremity edema, but no skin changes or rashes. Laboratory studies showed an elevated creatine of 7.9. CT chest imaging showed extensive bilateral ground glass opacities with increased septal lines. Infectious work-up, including SARSCoV-2 PCR, was negative. Dialysis was initiated for new renal failure. To determine the etiology of the renal failure, autoimmune studies were obtained and showed a positive ANA and p-ANCA (1:640) and a negative MPO and PR3. Kidney biopsy was consistent with levamisole-induced vasculitis (LIV) from cocaine use. Treatment with steroids was initiated. She was discharged on steroid therapy and outpatient hemodialysis. She had repeated admissions for volume overload due to missed dialysis, and she developed heart failure within the year. She was unable to make appointments to start outpatient rituximab therapy. IMPACT/DISCUSSION: Levamisole-induced vasculitis (LIV) is a complication of use of cocaine adulterated with levamisole. Levamisole is an antihelminthic medication with well known immunomodulatory effects. Increasingly used as a cocaine adulterant, it is believed to be a component of over 80% of cocaine samples in the US. Its use is thought to be driven by levamisole's synergistic effect on the dopaminergic effects of cocaine. Levamisole-induced vasculitis is a p-ANCA associated vasculitis associated with long-term use of cocaine mixed with levamisole. It has been reported with both inhaled cocaine and smoking crack cocaine. Levamisole is thought to induce production of autoantibodies including p-ANCA, ANA, and lupus anticoagulant leading to immune complex deposition and secondary hypercoagulability. The most commonly reported presentation is cutaneous purpuric lesions, most notably the ear, tip of the nose, and malar eminence. LIV can occur without skin involvement and renal and pulmonary involvement including nephritis, renal failure, and hypersensitivity pneumonitis, has been reported. LIV with significant organ involvement is often treated with steroids. Additional immunosuppressive therapies including rituximab, cyclophosphamide, and plasmapheresis have been reported in severe cases. CONCLUSION: This case illustrates a rare presentation of LIV marked by with renal failure and absence of skin lesions. While the health effects of cocaine are well known, the adverse effects of agents used to cut cocaine are less readily considered. LIV should be considered in a patient with substance use disorder presenting with new vasculitis. As this case illustrates, factors like unstable housing and ongoing substance use disorder can complicate management.

ANCA-ASSOCIATED VASCULITIS FOLLOWING PFIZER-BIONTECH COVID-19 VACCINE: TRUE ASSOCIATION OR CIRCUMSTANTIAL?

BACKGROUND AND AIMS: Antineutrophil cytoplasmatic antibody (ANCA) associated vasculitis (AAV) is a small vessel vasculitis hallmarked by the presence of antibodies against antigens in cytoplasmic granules of neutrophils. Vaccines per se stimulate the immune system, including the innate and the adaptive immune response. Therefore, it is possible that an excess of autoimmunity is observed after vaccine administration. Vaccination (notably influenza) is a recognized trigger for the relapse of ANCA-associated vasculitis. ANCA associated vasculitis and autoimmune reactions have been reported with COVID-19 infection and following vaccination. We report the case of a Caucasian, 62-year-old-man, with a previous history of type 2 diabetes mellitus, hypertension and atrial fibrillation. Blood analysis 1 year before presentation showed preserved renal function and normal urinalysis. He received the first dose of Pfizer-BioNTech COVID-19 vaccine and 2 weeks later routine blood analysis showed acute kidney injury with serum Creatinine 1.75 mg/dL with De novo hematuria, a protein-to-creatinine ratio (RPC) 1.1 mg/g and candersartan (4 mg twice daily) was started. The patient received the second dose of COVID-19 vaccine 21 days after the first injection. Two weeks later, he developed anorexia, nausea and De novo hematuria. He was admitted at the emergency department with deteriorating renal function with a sCr of 5.5 mg/dL, worsening hematuria with dysmorphic red blood cells and proteinuria (RPC 2.9 mg/g). Renal ultrasound was normal. Immunological studies revealed an elevated ANCA-MPO titer of 561. A kidney biopsy was performed and showed a crescentic necrotizing glomerulonephritis. Immunofluorescence confirmed pauci-immune glomerulonephritis. He was diagnosed with renal limited myeloperoxidase (MPO) ANCA AAV. He started three pulses of 500 mg I.V methylprednisolone followed by prednisolone 1 mg/kg/day after that. He also started rituximab (four doses of 500 mg I.V. once a week apart). Despite the immunosuppression, the patient never recovered renal function and remained dialysis dependent. CONCLUSION: Whether autoimmune diseases can be triggered after vaccination remains a matter of discussion among experts. ANCA-associated vasculitis and autoimmune reactions have been reported with COVID-19 infection and following vaccination, which prompts the question whether this response could be a direct reaction to the RNA present in the vaccine. While an association with De novo ANCA vasculitis and COVID-19 vaccine may be possible, further investigation is necessary.