Medium-vessel Vasculitis Presenting with Myalgia Following COVID-19 Moderna Vaccination.

Coronavirus disease 2019 (COVID-19) vaccines have been delivered worldwide to prevent the spread of the disease, and almost all Japanese have received the mRNA vaccines "BNT162b2" (Pfizer-BioNTech) or "mRNA-1273" (Moderna). These vaccines have shown efficacy and safety with only minor adverse drug reactions. However, some patients develop severe adverse drug reactions, including autoimmune reactions. In addition, systemic vasculitis, mainly small-vessel vasculitis, following COVID-19 vaccination, has been reported. However, only a few investigators have reported medium-vessel vasculitis following vaccination. We herein report a case of medium-vessel vasculitis presenting with myalgia as the initial clinical manifestation following COVID-19 Moderna vaccination.

COVID-19 vaccination-related small vessel vasculitis with multiorgan involvement.

Since its first outbreak in 2019, coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2, has been ongoing, and the pandemic is not over yet. Vaccines developed against COVID-19 have been approved and widely used since 2020; however, vaccine safety concerns need to be addressed. Autoimmune symptoms have been reported as a side effect of many COVID-19 vaccines. In particular, several cases of COVID-19 vaccine-induced vasculitis have recently been reported. Herein, we report the case of a 77-year-old woman who developed small-vessel vasculitis with multiorgan involvement after receiving the BNT162b2 COVID-19 vaccine (Pfizer and BioNTech, New York City, NY, USA).

Monoclonal gammopathy of undetermined significance causing large vessel vasculitis.

A man in his late 50s presented with unilateral pain and discolouration of his fourth and fifth toes suggestive of digital ischaemia. He had a medical history of two unprovoked venous thromboembolisms in the preceding 18 months and a history of monoclonal gammopathy of undetermined significance (MGUS). A CT scan showed evidence of large vessels vasculitis in the absence of circulating antineutrophil cytoplasmic antibodies. Biopsy of the toes showed evidence of light chain and immunoglobulin deposition on immunofluorescence suggesting vasculitis secondary to his haematological diagnosis of MGUS. The patient was treated with high dose glucocorticoids and immunosuppressive treatment with a significant improvement in his symptoms and features of digital ischaemia.

Vasculitis flare after COVID-19: report of two cases in patients with preexistent controlled IgA vasculitis and review of the literature.

COVID-19 has been related to several autoimmune diseases, triggering the appearance of autoantibodies and endothelial dysfunction. Current evidence has drawn attention to vasculitis-like phenomena and leukocytoclastic vasculitis in some COVID-19 patients. Moreover, it has been hypothesized that COVID-19 could induce flares of preexisting autoimmune disorders. Here, we present two patients with previously controlled IgA vasculitis who developed a renal and cutaneous flare of vasculitis after mild COVID-19, one of them with new-onset ANCA vasculitis. These patients were treated with glucocorticoids and immunosuppressants achieving successful response. We also provide a focused literature review and conclude that COVID-19 may be associated with triggering of vasculitis and could induce flares of previous autoimmune diseases.

SEVERE LEUKOCYTOCLASTIC VASCULITIS AFTER COVID-19 VACCINATION - CAUSE OR COINCIDENCE? CASE REPORT AND LITERATURE REVIEW.

Vaccination has been the most powerful tool to fight the COVID-19 pandemic while the specific treatment options in clinical practice have been under review for approval and authorization by regulatory bodies. After registration of different vaccines, it is important to ensure a post-marketing surveillance to identify potential risks not observed in controlled trials. Authors report on the case of an 80-year-old male patient who developed severe leukocytoclastic vasculitis of skin and oral mucous membrane after receiving the second dose of COVID-19 mRNA vaccine. He was treated successfully with prednisolone. We also provide a literature review on other reported cases of COVID-19 vaccine induced vasculitis. This type of an adverse reaction seems to be rare. Fortunately, most cases were temporary and well controlled by corticosteroids. The majority of vaccine-associated vasculitis cases have been observed in association with BONT162b2 mRNA vaccine although other vaccines also may cause the event. The knowledge of this possible adverse event is important for early diagnosis and intervention.

COVID-19 Vasculitis and vasculopathy-Distinct immunopathology emerging from the close juxtaposition of Type II Pneumocytes and Pulmonary Endothelial Cells.

The SARS-CoV-2 virus ACE-2 receptor utilization for cellular entry and the defined ACE-2 receptor role in cardiovascular medicine hinted at dysregulated endothelial function or even direct viral endotheliitis as the key driver of severe COVID-19 vascular immunopathology including reports of vasculitis. In this article, we critically review COVID-19 immunopathology from the vasculitis perspective and highlight the non-infectious nature of vascular endothelial involvement in severe COVID-19. Whilst COVID-19 lung disease pathological changes included juxta-capillary and vascular macrophage and lymphocytic infiltration typical of vasculitis, we review the evidence reflecting that such "vasculitis" reflects an extension of pneumonic inflammatory pathology to encompass these thin-walled vessels. Definitive, extrapulmonary clinically discernible vasculitis including cutaneous and cardiac vasculitis also emerged- namely a dysregulated interferon expression or "COVID toes" and an ill-defined systemic Kawasaki-like disease. These two latter genuine vasculitis pathologies were not associated with severe COVID-19 pneumonia. This was distinct from cutaneous vasculitis in severe COVID-19 that demonstrated pauci-immune infiltrates and prominent immunothrombosis that appears to represent a novel immunothrombotic vasculitis mimic contributed to by RNAaemia or potentially diffuse pulmonary venous tree thrombosis with systemic embolization with small arteriolar territory occlusion, although the latter remains unproven. Herein, we also performed a systematic literature review of COVID-19 vasculitis and reports of post-SARS-CoV-2 vaccination related vasculitis with respect to the commonly classified pre-COVID vasculitis groupings. Across the vasculitis spectrum, we noted that Goodpasture's syndrome was rarely linked to natural SARS-CoV-2 infection but not vaccines. Both the genuine vasculitis in the COVID-19 era and the proposed vasculitis mimic should advance the understanding of both pulmonary and systemic vascular immunopathology.

Overview of infections as an etiologic factor and complication in patients with vasculitides.

Vasculitides, a form of inflammatory autoimmune disease targeting the vessels, constitute an entity with significant morbidity and mortality. Infections have long been associated with vasculitides as a result of the incident immunosuppression following treatment induction and maintenance. Several microbial pathogens have been described as etiologic factors of infections in this patient population according to the type of vessels affected. Intense research has also been recently conducted in the interplay between vasculitides and certain viral infections, namely human immunodeficiency virus and severe acute respiratory syndrome coronavirus 2. Of note, a plethora of scientific evidence is available regarding the role of infections as triggering factors for vasculitides. Among the main mechanisms implicated in this direction are the activation of B and T cells, the direct endothelial insult, the immune complex-mediated vascular injury, and the cell-mediated, type IV hypersensitivity vessel damage. Therefore, this review aims to summarize all the available evidence concerning this bidirectional interplay between infections and vasculitides.

Endothelial contribution to COVID-19: an update on mechanisms and therapeutic implications.

The global propagation of SARS-CoV-2 leads to an unprecedented public health emergency. Despite that the lungs are the primary organ targeted by COVID-19, systemic endothelial inflammation and dysfunction is observed particularly in patients with severe COVID-19, manifested by elevated endothelial injury markers, endotheliitis, and coagulopathy. Here, we review the clinical characteristics of COVID-19 associated endothelial dysfunction; and the likely pathological mechanisms underlying the disease including direct cell entry or indirect immune overreactions after SARS-CoV-2 infection. In addition, we discuss potential biomarkers that might indicate the disease severity, particularly related to the abnormal development of thrombosis that is a fatal vascular complication of severe COVID-19. Furthermore, we summarize clinical trials targeting the direct and indirect pathological pathways after SARS-CoV-2 infection to prevent or inhibit the virus induced endothelial disorders.

Intracerebral hemorrhage due to vasculitis following COVID-19 vaccination: a case report.

Several vaccines have been approved worldwide for the prevention of morbidity and mortality against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the development of these vaccines has raised concerns regarding their adverse effects. Herein, we report the first case of intracerebral hemorrhage (ICH) due to vasculitis after the first dose of mRNA vaccine (BNT162b2, Pfizer/BioN-Tech). Although this case cannot demonstrate a direct relationship between COVID-19 vaccination and vasculitis, the clinical and histological features of this patient are highly consistent with the adverse effects of COVID-19 vaccine.

First description of immune complex vasculitis after COVID-19 vaccination with BNT162b2: a case report.

BACKGROUND: Cases of immune complex vasculitis have been reported following COVID-19 infections; so far none in association with novel mRNA-based COVID-19 vaccination. This case report describes a cutaneous immune complex vasculitis after vaccination with BNT162b2. CASE PRESENTATION: A 76-year old male with liver cirrhosis developed an immune complex vasculitis 12 days after the second injection of BNT162b2. On physical examination, the patient presented with pruritic purpuric macules on hands and feet, flexor and extensor parts of both legs and thighs and lower abdomen, and bloody diarrhoea. Laboratory testing showed elevated inflammatory markers. After short treatment with oral steroids all clinical manifestations and laboratory findings resolved. CONCLUSIONS: An increasing number of clinical manifestations have been attributed to COVID-19 infection and vaccination. This is the first written report of immune complex vasculitis after vaccination with BNT162b2. We present our case report and a discussion in the light of type three hypersensitivity reaction.

Microvascular Skin Manifestations Caused by COVID-19.

Hypercoagulability and vascular injury, which characterize morbidity in COVID-19 disease, are frequently observed in the skin. Several pathomechanisms, such as inflammation caused by angiotensin-converting enzyme 2-mediated uptake into endothelial cells or SARS-CoV-2-initiated host immune responses, contribute to microthrombus formation and the appearance of vascular skin lesions. Besides pathophysiologic mechanisms observed in the skin, this review describes the clinical appearance of cutaneous vascular lesions and their association with COVID-19 disease, including acro-ischemia, reticular lesions, and cutaneous small vessel vasculitis. Clinicians need to be aware that skin manifestations may be the only symptom in SARS-CoV-2 infection, and that inflammatory and thrombotic SARS-CoV-2-driven processes observed in multiple organs and tissues appear identically in the skin as well.