NEW-ONSET SYSTEMIC LUPUS ERYTHEMATOSUS AND STEVEN JOHNSONS SYNDROME WITH SEVERE ARDS HERALDED BY POST-COVID-19 INFECTION MULTISYSTEM INFLAMMATORY SYNDROME IN AN ADULT (MIS-A)

SESSION TITLE: Autoimmune Diseases Gone Wild: Rare Cases of Pulmonary Manifestations SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 01:35 pm - 02:35 pm INTRODUCTION: Post-Covid-19 Multisystem Inflammatory Syndrome (MIS) is a severe hyperinflammatory syndrome associated with either the acute or recovery phase of covid-19 infection affecting multiple organ systems requiring hospitalization. This syndrome has been described in both children (MIS-C) and adults (MIS-A). Several case reports and systematic reviews have reported an association between post-covid-19 MIS-A and several autoimmune diseases. CASE PRESENTATION: We herein report a case of a 27-year-old female with no known chronic medical condition and a non-contributory family history who was diagnosed with post-covid-19 multisystem inflammatory syndrome in adults (MIS-A). She presented with generalized partial thickness erythematous skin ulcerations with tender blistering and painful erosion of her mucus membranes (oral and vaginal mucosa). This was diagnosed as Steven Johnsons syndrome. She was pulsed with intravenous methylprednisone. During this therapy, she progressed to severe acute respiratory distress syndrome (ARDS) requiring mechanical ventilation (fig 1). Bronchoscopy revealed mild pulmonary hemorrhage fig 2a&b). Serological testing heralded a new onset systemic lupus erythematosus in light of positive antinuclear antibodies, anti Ds DNA and anti Smith antibodies. Her course was complicated by significant proteinuria and an active renal cast suggestive of lupus nephritis. This necessitated further treatment for active lupus. She was successfully extubated and discharged home. DISCUSSION: We arrived at the diagnosis of post-covid-19 multisystem inflammatory syndrome in adults (MIS-A) in light of her presenting with fever, hypotension, persistent sinus tachycardia and new onset atrial fibrillation), acute pancreatitis, acute kidney injury, elevation in transaminases, new onset skin rash, elevated inflammatory markers and a recent history of positive SARS-CoV-2 infection. Covid-19 has been reported to induce wide spread vasculitis resulting in MIS-A or MIS-C by triggering type 3 hypersensitivity (1). Also, multiple case reports and systemic reviews have reported a direct association between MIS-A and several autoimmune diseases including SLE, SJS (2). The patient recovered with high dose corticosteroid and supportive therapy indicating her severe ARDS was most likely due associated to SJS, SLE and MIS-A. Clinicians should also keep in mind that SARS-CoV-2 PCR swab may be negative at the time patient presents with symptoms of MIS-A as the infection might have occurred about 4-5weeks prior just as in our patient(3) CONCLUSIONS: We cannot underscore enough the importance of clinicians having a high index of suspicion for this syndrome in patients with acute or recent covid-19 infection, with or without a positive PCR covid-19 test. Early involvement of a multidisciplinary approach and appropriate management is essential to mitigate morbidity and mortality in these patients. Reference #1: Roncati L, Ligabue G, Fabbiani L, Malagoli C, Gallo G, Lusenti B, et al. Type 3 hypersensitivity in COVID-19 vasculitis. Clin Immunol Orlando Fla. 2020 Aug;217:108487. Reference #2: Gracia-Ramos AE, Martin-Nares E, Hernández-Molina G. New Onset of Autoimmune Diseases Following COVID-19 Diagnosis. Cells [Internet]. 2021 Dec 20 [cited 2022 Mar 22];10(12):3592. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8700122/ Reference #3: Morris SB. Case Series of Multisystem Inflammatory Syndrome in Adults Associated with SARS-CoV-2 Infection — United Kingdom and United States, March–August 2020. MMWR Morb Mortal Wkly Rep [Internet]. 2020 [cited 2022 Mar 22];69. Available from: https://www.cdc.gov/mmwr/volumes/69/wr/mm6940e1.htm DISCLOSURES: No relevant relationships by Isaac Ikwu No relevant relationships by Anthony Lyonga Ngonge No relevant relationships by Alem Mehari No relevant relationships by Noordeep Panesar no disclosure on file for Vis al Poddar;No relevant relationships by Emnet Yibeltal

"Marginal keratitis following COVID 19 vaccination".

Purpose: To describe a novel case of marginal keratitis following COVID 19 vaccination. Methods: Case report. Results: A 68-year-old female received the Moderna COVID 19 vaccine. She then developed ocular irritation and peripheral corneal opacities that are characteristic of marginal keratitis. Her symptoms responded well to steroid and antibiotic ophthalmic medications. She received her second dose of the Moderna vaccine while still taking her eye drops and was then able to taper off her drops without a recurrence of symptoms. Conclusions: Marginal keratitis represents a localized type III hypersensitivity reaction of the cornea. The SARS-CoV-2 virus that causes COVID 19 gains entry into the cell via binding of the spike protein with the ACE2 receptor. It is this spike protein that is the target for mRNA COVID-19 vaccines, such as the Moderna vaccine, allowing spike protein antigen recognition by the human immune system. The cornea has been found to have significant levels of ACE2 receptors, potentially allowing for the cornea to become a site for the antigen-antibody complex deposition necessary for a type III hypersensitivity response. This reaction should be recognized so that treatment may be provided during the initial episode and the cornea may be monitored following subsequent vaccinations.

First documented case of urticarial vasculitis following the AstraZeneca COVID-19 vaccine

The COVID-19 pandemic resulted in a rapid requirement for a safe and effective vaccination programme. Currently, three types of vaccines exist: mRNA (Pfizer), adenoviral vector (AstraZeneca) and inactivated whole-virus vaccines (Sinofarm). These all have reported cutaneous side-effects, including papulovesicular, pityriasis rosea-like and papulosquamous eruptions (McMahon DE, Kovarik CL, Damsky W et al. Clinical and pathologic correlation of cutaneous COVID-19 vaccine reactions including V-REPP: a registry-based study. J Am Acad Dermatol 2021;86: 113-21). We present a case of delayed type III hypersensitivity reaction clinically resembling urticarial vasculitis (UV) in a 66-year-old woman following AstraZeneca vaccine. She initially reported urticarial lesions on the hands after the first vaccination;these settled spontaneously. On subsequent vaccination she developed a florid rash 4 days later, presenting to Accident & Emergency with angio-oedema, malaise and urticaria. The eruption was presumed viral given the mildly elevated C-reactive protein, and negative lateral flow test for COVID-19. She was given fexofenadine 180 mg QDS for 6 weeks;however, the rash persisted and became more widespread over the following 4 weeks. The initial urticated wheals persisted >24 h, becoming bruise-like and painful. Skin biopsy confirmed UV. ANA, complement, ANCA and COVID-19 polymerase chain reaction were nonsignificant. We believe this is the first documented case of UV triggered by the AstraZeneca vaccine and the third case of UV following a Sars-CoV-2 vaccine reported in English literature. The two other cases were secondary to Pfizer and whole-virus vaccine, respectively. From the literature it is believed UV is potentially caused by the coronavirus particles rather than vaccine additives, as the Sars-CoV-2 nucleocapsid has been demonstrated in skin lesions of asymptomatic COVID-19 patients with UV (Criado PR, Criado RFJ, Gianotti R et al. Urticarial vasculitis revealing immunolabelled nucleocapsid protein of SARS-CoV-2 in two Brazilian asymptomatic patients: the tip of the COVID-19 hidden iceberg? J Eur Acad Dermatol Venereol 2021;35: e563-6). Thus, although rare, clinicians should be aware of this entity.

An unusually "complex" glomerulonephritis.

A 53-year-old man with granulomatosis with polyangiitis presented with fever and acute kidney injury with nephrotic-range proteinuria following the second dose of the mRNA COVID-19 vaccine. Renal biopsy revealed an unexpected immune complex-glomerulonephritis (IC-GN) without vasculitis. Further workup found the patient to have HIV that was unmasked following the treatment of IC-GN. This case report explores the possible relationship between COVID-19 vaccines and the immune response in the setting of chronic HIV.

The perplexing question of trained immunity vs adaptive memory in COVID-19.

The wide spectrum of symptoms observed in coronavirus disease 2019 appears to defy explanation. Apart from geographic limitation to people with prior exposure to other coronaviruses and air pollutants, inflammatory comorbidities and older ages are also among the main factors of susceptibility to severe illness. The unusual epidemiological data pointed out in children and African territories have revealed new insights in host-pathogen interplay with more focus on epigenetic regulation of cognitive compartments belonging to innate immunity. Should trained immunity be proven to be involved in timely immune responsiveness against severe acute respiratory syndrome coronavirus 2 and that adaptive memory could be detrimental, both treatment regimens and vaccine design will tremendously change accordingly with more focus on upper respiratory tissue innate immunity to subdue this threat underway.

Type 3 hypersensitivity in COVID-19 vasculitis.

Coronavirus Disease 2019 (COVID-19) is an ongoing public health emergency and new knowledge about its immunopathogenic mechanisms is deemed necessary in the attempt to reduce the death burden, globally. For the first time in worldwide literature, we provide scientific evidence that in COVID-19 vasculitis a life-threatening escalation from type 2 T-helper immune response (humoral immunity) to type 3 hypersensitivity (immune complex disease) takes place. The subsequent deposition of immune complexes inside the vascular walls is supposed to induce a severe inflammatory state and a cytokine release syndrome, whose interleukin-6 is the key myokine, from the smooth muscle cells of blood vessels.