Atypical Anti-Glomerular Basement Membrane Nephritis After the First Dose of the Severe Acute Respiratory Syndrome Coronavirus 2 mRNA Vaccine.

Atypical anti-glomerular basement membrane (GBM) nephritis is a slowly progressive characterized by linear deposition of immunoglobulin (Ig) G in the GBM without circulating anti-GBM antibodies or lung involvement. There is no established therapy for this disease, and efficacy of the immunosuppressive treatment is questionable. A few cases of atypical anti-GBM nephritis have been reported after administration of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine. Classic anti-GBM disease has also been reported after the administration of the second dose of the SARS-CoV-2 vaccine. Herein, we present the case of a SARS-CoV-2 vaccine-induced atypical anti-GBM nephritis that developed after the first dose and was unresponsive to immunosuppressive therapy. A 57-year-old Japanese woman developed edema 11 days after the first dose of the SARS-CoV-2 mRNA vaccine. She developed nephrotic-range proteinuria and microscopic hematuria. Renal biopsy revealed endocapillary proliferative glomerulonephritis with linear IgG deposition. However, electron-dense deposits were not detected on electron microscopy. The patient tested negative for circulating anti-GBM antibodies and was diagnosed with atypical anti-GBM nephritis. Although steroids and mizoribine were administered, the patient's renal function deteriorated. In conclusion, atypical anti-GBM nephritis may have earlier onset than the classic anti-GBM disease. Given its uncertainty of effectiveness, immunosuppressive agents should be carefully used for SARS-CoV-2 mRNA vaccine-induced atypical anti-GBM nephritis.

Sars-Cov-2 Associated Myopathy

An association between SARS-CoV-2 infection and myopathy was suspected early in the pandemic: patients with severe COVID-19 showed increased levels of creatine kinase that could not be solely explained by cardiac affection. On the other hand, myalgia and muscle weakness are frequent symptoms in patients with mild or moderate COVID-19 - as with many other viral infections -and subsets of infected patients report persistent muscular weakness and fatigue even months after the initial infection. We performed a case-control autopsy comparing patients with severe COVID-19 to patients with other critical illnesses and assessed inflammation of skeletal muscle tissue by quantification of immune cell infiltrates, expression of major histocompatibility complex (MHC) class I and class II antigens on the sarcolemma. Relevant expression of MHC class I antigens on the sarcolemma was present in 23 of 42 specimens from patients with COVID-19 (55%) and upregulation of MHC class II antigens in 7 of 42 specimens from patients with COVID-19 (17%), but neither were found in any of the controls. In a subset of patients, MHC class I and MHC class II expression showed a clear perifascicular pattern. Signs of degenerating and necrotic fibers could also be found, however there was no statistically significant difference in the frequency of occurrence when compared to non-COVID-19 critically ill patients. We interpreted this as non-specific signs of muscular damage in critically ill patients. Numbers of macrophages, lymphocytes and natural killer cells were found to be increased in muscles from patients with COVID-19. Interestingly, no relevant expression of MxA on myofibers could be found by immunohistochemistry, but in some cases, expression of MxA was found on capillaries. Ultrastructural analysis of selected muscles with perifascicular MHC-expression did not show tubuloreticular inclusions. However, capillaries of the analyzed samples showed basement membrane alterations and signs of ongoing regenerative processes. In addition, we evaluated inflammation of cardiac muscles by quantification of immune cell infiltrates in the same patients, and found that skeletal muscles showed more inflammatory features than cardiac muscles. Moreover, inflammation was most pronounced in patients with COVID-19 with chronic courses. In some muscle specimens, SARS-CoV-2 RNA was detected by reverse transcription-polymerase chain reaction, but no evidence for a direct viral infection of myofibers was found by immunohistochemistry or electron microscopy. This suggests that SARS-CoV-2 may be associated with a postinfectious, immune-mediated myopathy.

Severe epidermolysis bullosa acquisita in a patient with graft-versus-host disease: causal or coincidental?

Graft-versus-host disease (GvHD) is common after haematopoietic cell transplantation (HCT). Mucocutaneous manifestations are variable and may simulate autoimmune bullous dermatoses. However, the association of GvHD with autoimmune disorders, including bullous dermatoses, is also well recognized. We describe a patient with GvHD in whom severe and relapsing epidermolysis bullosa acquisita (EBA) was diagnosed 3 years after transplant and propose a causal association with GvHD. A 66-year-old woman developed GvHD following allogeneic HCT for acute myeloid leukaemia in 2016. This affected her gastrointestinal tract and skin but improved with oral corticosteroids and ciclosporin. In 2019 she presented with a widespread rash consisting of large, tense, haemorrhagic blisters. Histological features were in keeping with EBA. Direct immunofluorescence was also consistent with EBA, demonstrating linear positivity for IgG and C3 confined to the blister base, as was detection of collagen VII antibodies on indirect immunofluorescence. She was admitted and treated with high-dose oral steroids, ciclosporin and intravenous immunoglobulin (IVIg) with eventual resolution of blistering. Although further IVIg administration was planned as an outpatient, this coincided with the start of the COVID-19 pandemic and she elected not to attend and also stopped all medication. Despite this, her EBA remained quiescent until September 2021 when she was readmitted with a severe deterioration in blistering and significant dysphagia due to an oesophageal stricture, with a weight of 31.7 kg. Once again, she responded rapidly to oral prednisolone and IVIg. Dapsone was considered but precluded by G6PD deficiency and there were clinical and adherence concerns about using mycophenolate mofetil. Upon discharge she was again nonadherent to medication and failed to attend for planned IVIg. She flared and was admitted for a third time in December 2021, requiring gastrostomy for nutritional support;her weight at this time was 26.4 kg. Her EBA is currently well controlled on prednisolone and IVIg. EBA is a rare, acquired blistering disorder secondary to autoantibodies targeting type VII collagen. Previous studies have found circulating basement membrane zone (BMZ) antibodies in 24% of chronic GvHD patients, possibly generated in response to chronic BMZ damage (Hofmann SC, Kopp G, Gall C et al. Basement membrane antibodies in sera of haematopoietic cell recipients are associated with graft-versushost disease. J Eur Acad Dermatol Venereol 2010;24: 587-94). Corresponding clinical manifestations are rare, with bullous pemphigoid the most frequently reported. EBA is much less common with four previously reported cases [Brassat S, Fleury J, Camus M, et al. (Epidermolysa bullosa acquisita and graftversus- host disease). Ann Dermatol Venereol 2014;141: 369-73 (in French)]. As a fifth case of EBA, our patient provides further evidence of a likely pathophysiological relationship between GvHD and autoimmune subepidermal bullous dermatoses, and highlights the significant challenges of managing these vulnerable patient groups during the COVID-19 pandemic.

Family History of Alport Syndrome with Spectrum of Chronic Kidney Disease, Dialysis and Transplantation

Introduction: Alport syndrome should be considered in the differential diagnosis of patients with persistent microhematuria. Electron microscopic examination of renal tissue remains the most widely available and applied means for diagnosing AS. The presence of diffuse thickening and multilamellation of the GBM predicts a progressive nephropathy, regardless of family history. Unfortunately, ultrastructural information alone does not establish the mode of transmission in a particular family. Method(s): 18 years-old male patient was followed in the clinic due to persistent microscopic haematuria and proteinuria. Family history is significant for one brother in his early 20s, who started to have the presentation early in life and his initial biopsy showed thin basement membrane disease. The brother subsequently progressed to renal failure and a repeat biopsy confirmed the presence of Alport syndrome. Another brother had end-stage renal disease and underwent renal transplantation. The patient status was revised, and genetic studies confirmed the presence of an autosomal recessive type of Alport syndrome involving collagen for A3 chain COL4A3. His kidney function remained stable initially with an estimated GFR of approximately 90 mL/min/1.73 m2. The most recent eGFR is around 70 ml/min/1.73 m2. His proteinuria disappeared once Losartan 25 mg was added to Ramipril 5 mg. His blood pressure has been on target. Creatinine increased to 147 micromol/L and he was diagnosed as having acute kidney injury on chronic renal disease which was obvious post covid infection, then back to baseline. Current proteinuria 3 g/g Cr on Angiotensin receptor blockers. BP 110/70, all other systemic examination is unremarkable. No hearing or visual abnormalities. Result(s): The initial renal manifestations in early childhood include asymptomatic-persistent microscopic hematuria and rarely gross hematuria. At the onset, the serum creatinine and blood pressure are normal. Over time, proteinuria, hypertension, and progressive renal insufficiency develop. ESRD usually occurs between the ages of 16 and 35 years and rarely can occur between 45 and 60 years. Renal biopsy findings of thinning and multilaminar splitting of the glomerular capillary basement membrane seen on electron microscopic examination are pathognomonic. In 2013, an expert panel issued guidelines recommending genetic testing as the gold standard for the diagnosis of Alport syndrome. Currently, a skin biopsy using commercially available monoclonal antibody against the type IV collagen alpha-5 chain (COL4A5). If the protein is clearly absent in a suspected male, a diagnosis of Alport syndrome can be made without further testing. Conclusion(s): Males with X-linked AS due to a deletion mutation of the alpha 5 chain of type IV collagen usually progress to ESRD by the second or third decade of life. Likewise, patients with autosomal recessive AS due to mutations affecting alpha 3 or 4 chains of type IV collagen tend to progress to ESRD by age 30. Autosomal-dominant AS with heterozygous mutations of COL4A3 or COL4A4 usually has a slower progression of CKD. Treatment is blood pressure control with RAAS inhibitors where clinically appropriate. Cyclosporine may be helpful in some patients with stage I and II CKD with significant proteinuria. Caution using calcineurin inhibitors is indicated in all patients with more advanced CKD stages due to potential nephrotoxicity. No conflict of interestCopyright © 2023

Multiple opportunistic infection in a male with systemic lupus erythematosus and concomitant human immunodeficiency virus infection

Background/Purpose: Concomitant systemic lupus erythematosus (SLE) and human immunodeficiency virus (HIV) infection cases are rare worldwide. It is established that SLE patients have an increased risk of opportunistic infection due to immune dysregulation, as well as in HIV. Method(s): A case of a 25-year- old Filipino man with systemic lupus erythematosus admitted due to a 1-week intermittent fever associated with headache, loss of appetite, and generalized body weakness was reviewed in a tertiary hospital in the Philippines. Result(s): An initial diagnosis was made from the clinical presentation of Raynaud's phenomenon, an elevated antinuclear antibody (1:320;nuclear, speckled), 2+ proteinuria, thrombocytopenia, and nail fold capillaroscopy findings consistent with mixed connective tissue disease. Patient was started on hydroxychloroquine and prednisone. He was admitted as a case of Streptococcus bacteremia with COVID-19 pneumonia after initial diagnosis, presenting as fever, and thrombocytopenia as low as 23.000/mul. Patient presented with a scaly erythematous annular lesion at his left wrist since December 2021 where a skin punch biopsy showed findings consistent with dermatophytosis. Direct immunofluorescence staining showed deposition of granular IgM (+3), C3 (+1), Fibrinogen (+3), and C1q (+1) in the basement membrane zone consistent with Lupus Erythematosus. Additional findings were oral thrush, dermatophytosis, and Pneumocystis pneumonia. Patient was started on antibiotics, remdesivir, and antifungal medications. Being severely immunocompromised, work up for HIV was initiated. Rapid HIV screening was positive, CD4 count revealed 7 (3.14%), and subsequent confirmatory western blot was positive. Additional treatment included hydroxychloroquine, methylprednisolone pulse therapy, and platelet concentrate transfusion. He was referred for CD4 monitoring, and ARV treatment enrollment, however, the patient expired a month after his discharge. Conclusion(s): This case is thereby reported to document a rare case of systemic lupus erythematosus (SLE) male patient with concomitant HIV, SARS-CoV- 2, and opportunistic infections secondary to AIDS. Diagnosis becomes challenging in patients with autoimmune diseases and multiple infectious diseases as clinical presentations tend to overlap and may show similar manifestations. In this setting, skin biopsy utilizing direct immunofluorescence can help establish an accurate diagnosis especially when clinical features and histopathology are overlapping.

Anti-Gbm Disease One and Half Years Experience in a Tertiary Care Centre

BACKGROUND: Anti-glomerular basement membrane (GBM) antibody GN is a rare glomerular disease (0.5-1 per million population) with poor outcome in terms of renal survival. It is caused by auto-antibodies against the non-collagenous domain of the a3 chain of type IV collagen and usually present as a rapidly progressive crescentic GN. Anti-GBM GN may present either as an isolated kidney disease or as a pulmonary-renal syndrome (Goodpasture's syndrome) in 40%-60% of patients. Linear staining of the GBMs for immunoglobulin ( Predominantly IgG & rarely IgA ) in renal biopsy with anti-GBM antibodies in serum is pathognomonic of Anti-GBM disease. Initiating immunosuppression with steroids and cyclophosphamide plus plasmapheresis are the cornerstone of treatment whereas no treatment is recommended if dialysis dependent at presentation 100% crescents or >50% global glomerulosclerosis in an adequate biopsy sample or not having pulmonary hemorrhage. AIM OF THE STUDY: To study demographic and clinical profile treatment administered and outcome (in terms of renal survival) in the patients with biopsy-proven anti-GBM disease. METHOD(S): Single-center prospective observational study (January 2021 to June 2022 ) and study population being the admitted patients in Nephrology Department of I.P.G.M.E.R and SSKM hospital Kolkata. RESULT(S): Total 7 patients were diagnosed as having Anti- GBM disease in this time period with median age of 42 yrs ( range from 11 yrs to 68 yrs), and Female : Male ratio was 5:2. Rapidly Progressive Renal Failure with Oliguria (71.4% ) was the most common presentation and 85.7% required Hemodialysis on presentation. 57.1% patients had 100% crescent in renal biopsy. 1 out of 7 patients had overlap with MPO and did not required RRT at presentation. 1 out of 7 patients had associated pulmonary hemorrhage. 28.5% patients received PLEX while others were treated supportively as per protocol. 28.5% patients previously had COVID 19 infection which was diagnosed retrospectively by detecting COVID 19 IgG antibody in serum. 71.4% patients end up in HD requiring renal failure while 1 patient succumbed to death. CONCLUSION(S): Most of the patients aged between 20 yrs to 60 yrs and were female (both 71.4%). Most of the patients (71.4%) received supportive treatment as per protocol. Only 1 patient (with MPO overlap) is dialysis free with discharge creatinine of 3.3 and receiving EUVAS protocol. Most of the patients who presented late with HD requiring renal failure end up in ESRD.

Association of COVID-19 and glomerulonephritis with ANCA and anti-glomerular basement membrane antibodies Report of one case

Renal involvement in COVID-19 infection is varied and worsens its outcome and prognosis. However, the association of COVID-19 infection with glomerulonephritis is exceptional. We report a 46-year-old woman with COVID-19 who had an acute kidney injury and ANCA associated glomerulonephritis two weeks after the onset of the disease. The kidney biopsy showed a crescentic glomerulonephritis and the presence of anti-glomerular basement membrane antibodies (GBM-Abs). She was treated with steroids and oral cyclophosphamide with good response without requiring plasmapheresis. Plasma anti GBM-Abs were negative. This case suggests that the presence of anti-GBM-Abs in the kidney, was temporally related to COVID-19 pulmonary damage. The absence of plasma antibodies is probably due to transient production and glomerular adsorption, but with unknown pathogenic role. © 2022 Sociedad Medica de Santiago. All rights reserved.

Pauci-Immune Crescentic Glomerulonephritis (PICGN) Following SARS-CoV-2 Vaccination

Introduction: We report two patients(pt) of PICGN following administration of Indian vaccines (COVISHIELD and COVAXIN) aginst COVID-19. Case Description: Pt 1: A 41-year old women with no hypertension or diabetes received COVAXIN in June 2021. Six days later she developed joint pain, fever, cough and hemoptysis along with forthy urine, pedal edema but no hematuria. Serological work up was negative for ANA, Anti GBM and pANCA. She had a positve cANCA (PR3) titer. Renal biopsy showed fibrocellular crescents with segmental sclerosis. Basement membrane showed no spikes or double contour. No endocapillary proliferation or necrotizing lesion seen. Immunoflourescence (IF) was negative. We initiated intravenous (IV) methylprednisolone 15 mg/kg/d for three days followed by PO prednisolone 0.5 mg/kg/d and IV cyclophosphamide 500 mg montly for 3 months. Five daily sessions of plasmapheresis with 1.5 times volume exchange followed by alternate day exchanges for five more sessions was completed. Serum creatinine improved to 2.0 mg/dl from a peak creatinine of 7.6 with out requiring hemodialysis (HD). Pt 2: A 45-year old women with history of hypertension treated with telmisartan and amlodipine received COVISHIELD vaccine against COVID-19 in June 2021. Next day she had vomiting and abdominal pain. No joint pains, fever, cough, hemoptysis, hematuria or frothy urine reported. Serum Creatinine was elevated at 2.85 mg/dl. ANA and Anti-GBM negative but ANCA (PR3,MPO) was positive. Renal biopsy showed a cellular crescent and a fibrocellular crescent in one glomerulus each. IF was negative. She was started on IV methylprednisolone 15 mg/kg/d for three days followed by prednisolone 0.5 mg/kg/d PO and IV cyclophosphamide 500 mg monthly for 4 months. Five daily sessions of plasmapheresis with 1.5 times volume exchange followed by alternate day exchanges for five more sessions was done. Serum creatinine improved to 2.7 mg/dl from a peak of 3 without requiring HD. Discussion(s): Both COVAXIN and COVISHIELD are developed using Whole-Virion Inactivated Vero Cell derived platform technology. Inactivated vaccines do not replicate and are therefore unlikely to revert and cause pathological effects. In our pt, causality of PICGN with these two vaccines is based on temporal association. The appearance of ANCA and PICGN shortly after vaccination raises suspicion that the two events are more than coincidence.

Can COVID-19 Vaccination Be the Culprit for New-Onset Crescentic Glomerulonephritis? The Correlation vs. Causation Conundrum

Introduction: While the development, delivery, and implementation of the mRNA vaccines have been spectacular, consideration for potential rare side effects on organ systems was not clear. Although emergency use authorization trials of these vaccines in the USA did not demonstrate major safety concerns, unique side effects after massscale vaccination are now being reported more frequently. Here, we describe a case of new-onset crescentic & sclerosing GN with linear basement membrane staining for IgG, kappa, and lambda by Immunofluorescence in a 30-yo healthy female three days after receiving her Tozinameran (Pfizer-BioNTech) booster vaccine. Case Description: 30 y/o Caucasian female with no PMH presented with a CC of gross hematuria 3 days after receiving her booster of Tozinameran. Retrospectively reported symptoms of pedal edema, generalized athralgia, tinnitus, and paresthesia of lower limbs. UA revealed dysmorphic RBCs and proteinuria. CT urethrogram, & cystoscopy revealed left hydronephrosis, no nephrolithiasis or urothelial lesions. Kidney biopsy revealed crescentic & sclerosis GN, with linear GBM staining for IgG, Kappa, & Lambda on IF. Several glomeruli showed segmental scars & fibrous crescents in addition to focal cellular crescents of varying ages raising the possibility of concurrent ANCA vasculitis. Her GBM antibody was 25. Additional workup of ANCA, PLA2R, PR3, ana, c3/c4 levels, dsDNA, and hepatitis studies returned negative. On admission, BP was 175/103, and HR 104. Labs were notable for hemoglobin 13.3, WBC 16.6k, & BUN/creatinine 16/1.5. The PE was unremarkable. She received pulse IV steroid therapy, cyclophosphamide, Lupron, and daily plasma exchange (PLEX) for 5 days until her GBM antibody cleared. She responded well to treatment. Her renal function improved, and she was discharged without requiring dialysis. Discussion(s): Our case demonstrates a possible correlation & causation scenario after receiving a Tozinameran booster shot activating anti-GBM disease with concurrent ANCA-negative vasculitis demonstrated by kidney biopsy. Although the mechanism of de novo anti-GBM disease & ANCA-negative vasculitis post-SARS-CoV-2 vaccine remains to be explained, pharmacovigilance is vital in our efforts to ascertain answers.

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

DIFFUSE ALVEOLAR HEMORRHAGE: A NOVEL ETIOLOGY?

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: Diffuse Alveolar Hemorrhage (DAH) is a pathological lung condition that can result in rapid respiratory failure and death, with classic cases revolving around autoimmune pathology. However, new information regarding immune dysregulation post- covid infection continues to develop. Here we describe the case of a woman diagnosed with post-covid DAH with no prior autoimmune conditions. CASE PRESENTATION: A 49 y/o female with no history of rheumatologic or connective tissue disease history was evaluated in the ED for worsening acute hypoxic respiratory failure. She reported fever, cough without hemoptysis, and shortness of breath. She was recently discharged 7 days prior on 2L of oxygen after a 10 day ICU stay requiring high flow nasal cannula support for Covid pneumonia. A new chest computed tomography (CT) showed no pulmonary embolus, but revealed increased bilateral interstitial and alveolar opacities. Prednisone 60 mg daily and empiric antimicrobial therapy were initiated, and bacterial/fungal serologies were sent. Further deterioration occurred over 2 days resulting in need for mechanical ventilation. Bronchoscopy with bronchoalveolar lavage (BAL) was performed showing increasing bloody return through each cycle raising concerns for DAH. Extensive infectious workup and connective tissue disease/vasculitis panels were negative except for a positive ANA. A steroid burst with 1 gram of solumedrol daily for 3 days was started followed by prednisone 60mg daily with a 10mg weekly taper. Remarkable clinical improvement was seen and while repeat CT showed worsening infiltrates a repeat bronchoscopy 7 days later showed no residual blood on BAL and she was extubated and rapidly titrated down to room air over 24 hours. DISCUSSION: Diffuse alveolar hemorrhage is a rare life-threatening condition brought on by disruption of the alveolar-capillary basement membrane, and carries a high mortality rate of 46% (1). There are 3 main classifications of DAH, based upon histopathologic pattern, including pulmonary capillaritis (PC), bland pulmonary hemorrhage, and diffuse alveolar damage (DAD), as seen in acute respiratory distress syndrome (2-3). In this case, DAH was likely due to a combination PC and DAD, with the former contributing heavily given her response to pulse steroids. There is much to learn about long covid auto-immune dysregulation. Since DAH mimics pneumonia on CT, in those patients returning to the hospital post-covid infection, DAH should be considered as prompt treatment is required (3). CONCLUSIONS: DAH is a rare disease that can be difficult to recognize. Only a minority of patients present with hemoptysis and CT can be mistaken for worsening multifocal pneumonia. With a wide variety of new post-covid infection syndromes being described, auto-immune dysregulation leading to DAH may represent a small but significant proportion of covid readmissions. Reference #1: Bradna P, Manak J, Soukup T, Toms J, Kodeda M. Ab0565 diffuse alveolar hemorrhage, diagnosis, treatment and 3-year prognosis in a group of 32 cases of tertiary centre. Annals of the Rheumatic Diseases. 2016;75(Suppl 2):1098-1098. Reference #2: Franks TJ, Koss MN. Pulmonary capillaritis. Curr Opin Pulm Med. 2000;6(5):430-435. Reference #3: Lara AR, Schwarz MI. Diffuse alveolar hemorrhage. Chest. 2010;137(5):1164-1171 DISCLOSURES: No relevant relationships by Nicholas Germano No relevant relationships by Bryan Krajicek

Diffuse alveolar hemorrhage as a life threatening manifestation of newly diagnosed granulomatosis with polyangiitis following COVID-19 infection - a case report.

A case report of a patient with newly diagnosed granulomatosis with polyangiitis (GPA) after undergoing COVID-19 (Coronavirus Disease 2019) is discussed. GPA is one of the ANCA-associated vasculitis, which is characterized by the presence of autoantibodies against cytoplasmic enzymes neutrophils (Anti Neutrophil Cytoplasmatic Antibodies). It is a vasculitis that mainly affects small blood vessels, leading to damage to the kidneys, lungs, and upper respiratory tract, including the paranasal sinuses and orbits. This disease can result in an acute life-threatening condition. Such complications include diffuse alveolar hemorrhage (DAH), a condition characterized by blood leakage from the pulmonary vessels into the alveoli, often leading to acute vital signs and even respiratory failure. DAH can have many causes - autoimmune diseases including vasculitides as well as non-immunological causes. Early and adequate comprehensive therapy including immunosuppressive treatment (cyclophosphamide/rituximab and glucocorticoids) can be life-saving.

Macklin Effect in the Current Pandemic: A Pathological Sequelae or Ventilator-Associated Lung Injury

Aim and background: SARS-CoV-2 pandemic questioned many basic concepts in medicine. COVID-19 affects many organ systems despite the lung being the primary affected organ. ARDS management is challenging and a new complication during the management adds to the burden. Macklin described a pathophysiological process by which air escaped through the ruptured alveolar basement membrane causing pneumomediastinum. The occurrence of air leak syndromes (ALS) in COVID-19 made us investigate the disease and its association with the complication. Objective: To observe the clinicopathological profile of patients who developed air leak syndrome during the second wave of the pandemic. Materials and methods: A retrospective analysis was conducted on SARSCoV- 2 patients admitted to ICU due to ARDS. The study included patients admitted from March to June 2021 with rTPCR positive test for SARS-CoV-2 illness and diagnosed to have ARDS as defined by the Berlin criteria. We analyzed 195 cases admitted in the ICU who met the above criteria and received protocolised care as per national and institutional guidelines. Cases who received ventilatory support either as HFNO (high flow nasal oxygenation), NIV (noninvasive ventilation), or invasive mechanical ventilation as per ARDS NET protocol and developed ALS were included. Demographic and clinical profiles of patients and laboratory parameters like acute phase reactants, haemogram, and serum creatinine were analysed. Results: 5.6% of patients were diagnosed to have air leak syndrome, which includes subcutaneous emphysema, pneumomediastinum, pneumopericardium, and pneumothorax. 81% of the cases were men. The average age was 44.8 years. 90% of the patients had no pre-existing lung pathology or respiratory comorbidity. 81.8% did not have a documented history of smoking. 63.33% of patients had other preexisting co-morbidities. 27.2% of patients had more than one comorbidity with diabetes mellitus being the most common. The average time to develop air leak syndrome was 6 days. 81% of the patients received mechanical ventilation, 2 patients were only on HFNO. 90% of the patients were prone in view of severe ARDS. From air leak syndromes mentioned above, 72.2% developed pneumothorax, 63.3% of the patients developed subcutaneous emphysema, 54.5% of the patients developed pneumomediastinum, and 9% developed pneumopericardium. 1 patient (9%) developed the complete spectrum of ALS. 63% of the patients developed 2 or more entities of the air leak, i.e., subcutaneous emphysema, pneumomediastinum, pneumopericardium, and pneumothorax. Acute phase reactants were elevated in all patients who developed ALS. There was neutrophil predominance in the haemogram. Only one patient developed AKI. Another compelling finding was the development of secondary infection, the majority was respiratory tract infections (81%) followed by urinary tract infections. Candiduria was observed in 36.6% of patients. The average duration of stay was 21.6 days. The mortality rate was 63%. 4 patients were discharged who had an average time to resolution of 8 days. Conclusion: COVID-19 is majorly a self-limiting disease. Secondary bacterial infection and poor oxygenation was major finding in our study. Development of ALS in a previously normal lung with no preexisting lung pathology points towards the need to conclude ALS and viral pneumonias.

Leptospirosis: A Consideration When Acute Liver Failure Accompanies Acute Kidney Injury (AKI)

A 48 y.o. male maintenance worker in a rat-infested building with history of tobacco and marijuana smoking, atrial fibrillation on no medications was admitted in July 2021 for fever, headache and body aches for 5 days and new onset of hemoptysis. Initial labs notable for BUN 36 mg/dl, Cr 1.4 mg/dl urine protein 100 mg/dl RBCs 5-10/hpf, platelets 46,000. total bilirubin 3.8 mg/dl direct bilirubin 3.0 SARS-CoV-PCR negative and CXR revealed patchy bilateral infiltrates. He was intubated on day 2 and had ventricular fibrillation and cardiac arrest on day 3 with rapid return of purposeful movement. He had worsening anemia and thrombocytopenia, positive ANA and dsDNA, leading to use of steroids and plasmapheresis on Day 6 when peak bun/cr was 91/3.1 with urine protein/cr ratio 0.7, urine microscopy 2 rbc/hpf, urine Na 20 meq/l, urine osm 775 mosm/kg and cpk 400 U/l. These tests were negative or normal: Anti-GBM, ANCA, repeat ANA, repeat dsDNA, C3, C4, HIV, RF, hepatitis C RNA, cryoglobulins, ASO titer, ADAMTS13, Pneumocystis PCR, Sputum AFB, blood, AFB and fungal cultures, viral and fungal testing, hanta virus antibodies. Leptospira antibodies IgM by Dot Blot were positive and Leptospirosis diagnosis confirmed by NYC Department of Health (DOH) after obtaining confirmatory microscopic agglutination testing from the CDC. Urine and blood Leptospira DNA PCR not detected. He remained intubated with FiO2 requirement at 100% prior to his death on hospital day 16. Initially pulmonary renal syndrome considered but he was later found to have pre-renal azotemia. The elevated bilirubin led to testing for leptospirosis, his final diagnosis. In September 2021 the NYC DOH reported 14 cases of leptospirosis (increased from 5 cases in 2020), 13 of which had acute renal and hepatic failure, with 2 having severe lung involvement (1). This case is the only one in this group who died. The leptospirosis case fatality rate for severe diffuse alveolar hemorrhage exceeds 50%. Early appropriate antibiotic treatment prior to lab confirmation has been recommended by the CDC and may decrease severity of disease.

Proteinuria in Thin Basement Membrane Nephropathy: A Rare Finding

Hydrothorax occurs in approximately 2% of patients on peritoneal dialysis caused by migration of fluid from the peritoneal cavity into the pleural space via pleuroperitoneal fistulas. These diaphragmatic defects are usually congenital and right-sided, explaining the predominance of right-sided effusion.. Thoracocentesis with biochemical analysis of pleural fluid reveals a transudate with a very high glucose concentration. In uncertain cases, or when there is a clinical need to demonstrate the anatomy of the communication, an imaging approach such as peritoneal scintigraphy is required. 66-year-old Hispanic female with past medical history significant for end stage kidney disease on peritoneal dialysis for past 5 months, hypertension ,cerebrovascular accident with no residual deficit, and recent exposure to COVID19 presented with fever, shortness of breath, left eye gaze abnormality and + COVID PCR. She had been having issues with meeting ultrafiltration goals outpatient. On examination she has decreased breath sounds at right lung base, Abdomen non-tender with PD catheter in place with clean dressing, no pedal edema. Laboratory findings were consistent with a transudative effusion;no organisms were cultured and no malignant cells were visualized. CT failed to identify dispersal of contrast material into the right hemithorax. A nuclear isotope scan was subsequently done. Following administration of technetium 99m via the PD catheter, a high volume of radioactive dialysate was detected entering the right hemithorax. No tracer activity was seen in the left hemithorax. PD was stopped and switched to intermittent hemodialysis.Unfortunately she succumbed to covid 19 pneumonia and died few days later. 50% of the cases, a conservative approach allows reinstitution of CAPD Conservative approach with temporary cessation of peritoneal dialysis remains the first-line treatment. 1-4 months has been shown to be adequate cessation time and restarting with low volume PD. If conservative approach fails, Invasive approach with video-assisted thoracoscopic pleurodesis or diaphragmatic repair or both allows most of them to continue with CAPD

The SARS-CoV-2 main protease induces capillary cell death by cleaving NEMO in brain endothelial cells

Background: Several lines of evidence suggest that neurological symptoms in patients suffering from Coronavirus disease 2019 (COVID-19) occur partially due to damage to small vessels in the brain. However, the potential mechanisms underlying this pathology are unclear. Aim: Here, we describe a novel pathway by which SARSCoV- 2 affects the brain vasculature and thereby potentially induces neurocognitive impairment in patients. Method: We examined brain tissue of deceased COVID- 19 patients and different animal models of this disease for microvascular pathology. Using several techniques like mass spectrometry, high resolution microscopy, transgenic animals, and AAV-mediated gene transfer, we investigated the effect of the SARS-CoV-2 main protease (Mpro) on brain endothelial cells. Results/Conclusions: In brains of SARS-CoV-2-infected individuals and animal models, we found an increased number of empty basement membrane tubes, so-called string vessels representing remnants of lost capillaries. We obtained evidence that brain endothelial cells are infected, and that Mpro cleaves NEMO, the essential modulator of nuclear factor-jB. By ablating NEMO, Mpro induces the death of human brain endothelial cells and the occurrence of string vessels in mice. Deletion of RIPK3, a mediator of regulated cell death, blocks the vessel rarefaction and disruption of the blood-brain barrier due to NEMO ablation. Importantly, a pharmacological inhibitor of RIPK signaling prevented the Mpro-induced microvascular pathology. These data suggest a novel mechanism by which SARS-CoV-2 affects the brain vasculature and a potential therapeutic option to interfere with the neurological consequences of COVID-19.

Bullous pemphigoid with subsequent milia en plaque following administration of the Pfizer-BioNTech COVID-19 vaccine

We present the case of a 68-year-old woman who presented with a blistering skin eruption 5 days after the administration of the first dose of Pfizer-BioNTech mRNA COVID-19 vaccine. Examination revealed tense bullae in a localized distribution confined to the dorsal aspect of her hands, forearms and ears only. This was preceded by severe pruritus. She had no mucosal involvement and was otherwise systemically well. She had a background of chronic obstructive pulmonary disease and hypercholesterolaemia with no previous history of COVID-19. Skin biopsy revealed a subepidermal bulla containing numerous eosinophils in keeping with bullous pemphigoid (BP). The diagnosis was confirmed with a positive direct immunofluorescence (IF) which showed linear IgG and C3 deposition at the basement membrane zone. Indirect IF was positive for anti-BP180 and anti-BP230. The patient was treated with oral prednisolone and doxycycline to good effect She proceeded to have the second dose of the Pfizer-BioNTech vaccine while on treatment and did not experience a flare of BP. However, a week later, she developed erythematous annular plaques with milia over the dorsi of her hands. Skin biopsy revealed multiple milia within the papillary dermis in keeping with milia en plaque. To to our knowledge, this is the first case of a patient developing BP with subsequent milia en plaque following the Pfizer-BioNTech mRNA COVID-19 vaccine (Damiani G, Pacifico A, Pelloni F, Iorizzo M. The first dose of COVID-19 vaccine may trigger pemphigus and bullous pemphigoid flares: is the second dose therefore contraindicated? J Eur Acad Dermatol Venereol 2021;35: e645-7). She has since been weaned off systemic treatment for BP;however, she continues to require ongoing input for the management of milia en plaque.

Bullous pemphigoid onset following Pfizer-BioNTech COVID-19 vaccine (COMIRNATY®): coincidence or a new emerging adverse effect?

We report the case of a 61-year-old man referred to the dermatology clinic with a new onset of itchy rash with blisters within 2 weeks following the first dose of the Pfizer-BioNTech COVID-19 vaccine (COMIRNATY®). After the second dose of the same vaccine within 72 h, he developed a widespread rash with tense blisters with oral mucosal involvement. His medical history included obesity (body mass index 47.8 kg m-2), type 2 diabetes mellitus, hypertension and hypothyroidism. His regular medications included alogliptin (established for 3 years) and levothyroxine. There were no recent changes or additions to his drugs reported. On examination, he had extensive erythematous plaques with tense bullae and oral ulcers. Skin anti-epi basement membrane antibodies were positive, and anti-epidermal intercellular antibodies were negative. We considered the diagnosis of bullous pemphigoid (BP) on the clinical picture and indirect immunofluorescence studies. Topical treatment started with 50: 50 white soft paraffin, clobetasol propionate ointment and systemic oral prednisolone with doxycycline with reasonable disease control within 4 weeks. We were faced with a diagnostic conundrum. We postulated two possibilities: new-onset BP coincidental and unrelated to vaccination or BP secondary to the vaccine as suggested by the time-dose relationship. As the patient was established on alogliptin for 3 years, we considered it unlikely this drug had contributed to the disease onset. Case reports are now emerging of BP following vaccination with other COVID- 19 vaccines. This phenomenon has implications for future inoculation with the booster vaccine, requiring careful consideration and discussion with our patients. This case is registered on the Yellow Card scheme (Pérez-López I, Moyano- Bueno D, Ruiz-Villaverde R. Bullous pemphigoid and COVID-19 vaccine. Med Clin (Engl Ed) 2021;157: e333-4;Agharbi F, Eljazouly M, Basri G et al. Bullous pemphigoid induced by the AstraZeneca COVID-19 vaccine. Ann Dermatol Venereol 2022;149: 56-7).

CLINICAL AND MORPHOLOGICAL FEATURES OF KIDNEY DAMAGE IN PATIENTS WITH ARTERIAL HYPERTENSION DIED OF SARSCOV- 2 INFECTION

Objective: To assess clinical and pathomorphological features of kidney damage in patients with arterial hypertension (AH) who died of the new coronavirus infection COVID-19. Design and method: A complex analysis of 268 kidney autopsies was carried out, including the study of macro- and microscopic changes reflected in the protocols of pathological and anatomical autopsies and identified during the histological examination. In 224 patients (83.6%) with AH, the diagnosis was confirmed by isolating the SARS-CoV-2 RNA using the polymerase chain reaction;in 44 (16.4%) - through computed tomography of the lungs. The causes of deaths were the following: in 31 patients (11.6%) acute myocardial infarction;in 40 (14.9%) cerebrovascular accident;in 11 (4.1%) pulmonary embolism;222 patients (83%) had acute respiratory distress syndrome. The analysis included 130 men aged 36 to 92 (72.6 years old on average) and 138 women aged 40 to 106 (77.1 years old on average). Results: In the kidneys we detected ischemic changes caused by disturbances in the microvasculature. These are stases, sludges, erythrocyte and fibrin thrombi predominantly in the medulla. In the glomeruli diapedesis hemorrhages, mesangial cells proliferation, basement membrane thickening and fibrinoid necrosis of the capillary wall were observed. In the epithelium of the convoluted tubules, a granular, hyaline-drop dystrophy and a necrosis as the extreme degree of the damage were noted. In the kidneys, a pronounced lymphoid and leukocyte infiltration was detected. These changes were accompanied by inflammation and renal failure symptoms. In particular, the level of C-reactive protein was 140.6 ± 7.42 mg/l;blood ferritin 1258.0 ± 110.1 mcg/l;blood leukocytes 15.0 ± 0.67 10

A CASE OF FSGS IN A PREVIOUSLY HEALTHY MALE AFTER THE SECOND DOSE OF COVID-19 MRNA VACCINE

Case Report Background COVID-19 infection and COVID-19 mRNA vaccines have been associated with the occurrence of de-novo and relapsing glomerulopathies. Although, Focal Segmental Glomerulosclerosis (FSGS) similar HIV associated Nephropathy (HIVAN) has been reported with COVID-19 infection in African American population with Apolipoprotein L1 gene mutation, amongst the few reported cases post-vaccine, Minimal change disease (MCD), IgA nephropathy (IgAN), Anti-Glomerular basement membrane glomerulonephritis (Anti GBM GN), and membranous glomerulonephritis (MGN) have been reported. Case A 26-year-old Caucasian male with a history of tobacco use complained of Frothy urine and edema for 3 weeks post second dose of Moderna COVID-19 vaccine on 06/01/21. He received the first dose on 5/04/21. On his annual wellness visit on 5/18/21, he had no complaints, normal physical examination with serum albumin 5g/dl, and urinalysis significant for trace proteinuria. A repeat urinalysis post-onset of symptoms on 7/18/21 revealed 3+ proteinuria, no RBCs, 24- hour urine revealed 3.2g proteinuria. Further investigations revealed Hypoalbuminemia (2g/dl), persistent proteinuria, and an unremarkable renal ultrasound, ANA, ANCA, Anti-dsDNA, Anti-PLA2R, anti-streptolysin, RF, HIV, hepatitis panel, and serum complement levels. Renal biopsy revealed Tip lesion variant of FSGS with 100% effacement of podocyte foot process. Therapy with Prednisone 60 mg daily was initiated, following which an improvement in edema and serum albumin levels (2.7 g/dl) were noted. Discussion A few de-novo cases of anti-GBM GN, ANCA positive vasculitis, MCD and IgAN, and relapsing cases of IgAN, MCD, MGN, and Thrombotic microangiopathy have been reported post-COVID 19 mRNA vaccination. Most reported cases of MCD occurred after the first dose whereas IgAN flare-up occurred after the second dose. Our case is unique as our Caucasian patient developed FSGS post-second dose of Moderna vaccine. Although the pathogenesis is unclear, it is thought to be related to an acute T-cell immune response involving cytokine production to COVID 19 spike protein which is responsible for inducing or worsening existing podocytopathies. Interestingly fewer cases have been reported following adenovirus vector or inactivated virus vaccination. Most of the reported cases of IgAN flare-up have been mild and a small number of MCN cases required ICU admission for management of fluid overload. As observed in a few prior case reports our patient had a slow response to steroid therapy. Although guidelines on COVID 19 vaccination in patients with existing glomerulopathies remain unclear and are based on case-by-case scenarios, the benefit of COVID 19 vaccination, may in general, outweighs the risk of glomerular diseases. We encourage further studies on this topic, especially in the era of booster doses with ongoing discussion about mixing two types of vaccines.