The coronavirus disease 2019 (COVID-19) survivors are frequently observed to present persistent symptoms constituting what has been called “post-acute COVID-19 syndrome” (PACS) or “long COVID-19”. Some clinical risk factors have been identified to be associated with PACS development; however, specific mechanisms responsible for PACS pathology remain unknown. This study investigates clinical, immunological, and metabolomic risk factors associated with post-acute COVID-19 syndrome (PACS) in 51 patients, assessed 7–19 months after acute infection. Among the participants, 62.7% were male and 37.2% were female, with an average age of 47.8 years. At the follow-up, 37.2% met the criteria for PACS, revealing significant differences in immunological and metabolomic profiles at the time of acute infection. Patients with PACS were characterized by elevated levels of mature low-density granulocytes (LDGs), interleukin-8 (IL-8), pyruvate, pseudouridine, and cystine. Baseline multivariate analysis showed increased pyruvate and decreased alpha tocopherol levels. At follow-up, there was a decrease in absolute B lymphocytes and an increase in non-classical monocytes and 3-hydroxyisovaleric acid levels. These findings suggest that specific immunological and metabolomic markers during acute infection can help identify patients at higher risk of developing persistent PACS.

Thrombotic microangiopathy (TMA) is an infrequent and poorly understood manifestation in dermatomyositis (DM) associated with poor outcomes and refractoriness to treatment. The aim of this study is to describe the clinical characteristics and risk factors for its development. We conducted a nested case–control study comparing patients with DM who developed TMA to those with DM without this complication. Disease activity was evaluated using the Myositis Disease Activity Assessment Tool (MDAAT), the Manual Muscle Test of eight muscle groups (MMT8), and muscle enzyme levels. A binomial logistic regression analysis was performed to identify risk factors for the development of TMA among patients with DM. All patients with TMA had DM. Patients with DM/TMA had a shorter time since disease onset (p = 0.033), lower levels of C3 (p = 0.07) and C4 (p = 0.046), as well as higher leukocyte (p = 0.044), neutrophil (p = 0.033), and creatine phosphokinase (CK) levels (p = 0.005). They also exhibited higher constitutional (p = 0.0008), pulmonary (p = 0.008), and muscle disease activity (p = 0.027). In the univariate analysis, a shorter time since disease onset (OR 0.42, p = 0.0042) indicated an increased risk for TMA, as did low complement levels (C3: OR 1.11, p = 0.01; C4: OR 1.18, p = 0.02) and higher constitutional (OR 2.27, p = 0.0014), pulmonary (OR 5.50, p = 0.0004), and muscle disease activity (OR 2.1, p = 0.003). Although elevated CK levels (OR 1.001, p = 0.0008) reached statistical significance, the effect size was minimal and should not be interpreted as a clinically relevant increase in risk. Confocal microscopy of muscle biopsy specimens demonstrated neutrophil extracellular traps (NETs) infiltrating muscle tissue. Patients with DM who develop TMA appear to exhibit a distinct clinical phenotype characterized by leukocytosis, neutrophilia, hypocomplementemia, shorter disease duration, and greater constitutional, pulmonary, and muscular disease activity. Although limited by the small sample size, these findings suggest a potential role of NETs in microvascular and tissue injury associated with DM-related TMA. Larger studies are warranted to validate these observations and further elucidate the underlying pathogenic mechanisms.

Background: Neutrophils play a role in idiopathic inflammatory myopathies (IIMs), especially in vasculopathic manifestations. While neutrophil extracellular traps (NETs) and low-density granulocytes (LDGs) have been described, the functional relevance of other subsets—such as naïve neutrophils, reverse transendothelial migration neutrophils (rTEM), myeloid-derived suppressor cells (MDSCs), and regulatory neutrophils—and their association with vasculopathy remains unknown. Objective: We aimed to characterize the phenotypic and functional profile of neutrophil subsets and their association with vasculopathic manifestations in IIM, adjusting for disease activity. Methods: We conducted a cross-sectional, single-center study including 59 IIM patients diagnosed by muscle biopsy and fulfilling 2017 ACR/EULAR criteria. Flow cytometry was used to immunophenotype myeloid subsets, and functional assays assessed phagocytosis and respiratory burst. Patients were stratified by clinical activity and presence of vasculopathy. Results: Vasculopathic patients showed expansion of LDGs (p = 0.0092), granulocytic and monocytic MDSCs expressing Arginase-1 (p = 0.0078, p = 0.0003) and PD-L1 (p = 0.0258, p = 0.0087), and rTEM neutrophils (p = 0.0775). In contrast, they exhibited a reduction in naïve neutrophils (p = 0.0004), phagocytosis (p < 0.0001) and respiratory burst (p = 0.0006). Multivariate analysis identified naïve neutrophils and activated CD177⁺ neutrophils as independent predictors of vasculopathy. A positive correlation between activated and naïve neutrophils were observed in patients with vasculopathic features (r = 0.43; p < 0.05). Conclusions: IIM patients with vasculopathic features display a distinct immune profile characterized by an imbalance between proinflammatory and regulatory neutrophil subsets, alongside persistent functional impairment.