While the pandemic of COVID-19 has ended according to the WHO, new emerging cases are still documented worldwide. In addition, due to the huge number of recovered individuals, the sequelae of COVID-19 constitute a real challenge for the medical community. Of importance, is the autoimmune-nature of SARS-CoV-2. Hereby, in our editorial we aimed to shed light over the autoimmune aspects of COVID-19. Understanding the aspects presented aid in the early detection and management of affected patients.

The Ro/SSA antigen complex contains Ro60 (TROVE2), Ro52 (TRIM21), and Y-RNA molecules that have recently emerged as the cornerstone of intracellular immunity and are thought to be the main target of autoantibodies in systemic autoimmune diseases. For decades, the precise nature of the Ro60-Ro52 interaction has been a matter of controversy. We have recently shown that the Ro60-Ro52 complex is transient and dynamic under physiological conditions. These results not only improve our understanding of Ro antigen biology but also highlight the possibility of targeted modulation approaches for autoimmune diseases. This communication explores a fascinating and largely unexplored aspect of intracellular humoral immunity through the Ro60-Ro52 complex, aiming to deepen our understanding of this pivotal interaction and its implications for cellular processes and disease.

Varicella arthritis (VA) is a very rare complication of Varicella zoster virus infection, typically presenting as mainly monoarthritis in pediatric populations. This report describes the case of a previously healthy 12-year-old boy who developed arthritis following varicella infection. Clinical evaluation and laboratory findings confirmed the diagnosis of VA, characterized by arthritis of the right knee, mild anemia, leukocytosis, thrombocytosis, and elevated inflammatory markers. Autoimmune and infectious serologies excluded other etiologies. The patient was treated with meloxicam, leading to the complete resolution of symptoms and normalization of inflammatory markers within six weeks. This case underscores the importance of considering VA in children presenting with varicella infection, confirmed by serology, and develops arthritis and highlights the favorable prognosis with appropriate management. Molecular mimicry, immune complex deposition, and pro-inflammatory cytokine release are possible contributing factors to the development of VA.

Viruses may be involved in the pathogenesis of autoimmune diseases. In particular, the viral etiology of systemic lupus erythematosus (SLE) has been discussed and extensively investigated. Epstein Barr virus may be implicated in the pathogenesis of SLE. The SARS-CoV-2 virus has been implicated in the pathogenesis of autoimmunity. The COVID-19 infection has been associated with the development of subacute thyroiditis, diabetes mellitus type 1, rheumatoid arthritis, ankylosing spondylitis and SLE. The case of a female patient is described who developed fatigue, arthralgias, edema, joint pain and a generalized skin rash following a mild COVID-19 infection. Laboratory investigations were compatible with SLE. In conclusion, the case of a patient is described who developed SLE after a mild COVID-19 infection. This case shows that the SARS-CoV-2 virus may cause autoimmunity and that viruses may be implicated in the pathogenesis of systemic autoimmune diseases.

Systemic sclerosis (SSc) is a complex autoimmune disorder characterized by progressive fibrosis and obliterative vasculopathy affecting the skin and various internal organs, including the kidneys, lungs, cardiovascular system, and gastrointestinal tract. The disease manifests in two major clinical subtypes: limited cutaneous systemic sclerosis (lcSSc) and diffuse cutaneous systemic sclerosis (dcSSc), distinguished primarily by the extent of skin involvement and the pattern of internal organ involvement. Biomarkers, serving as quantifiable indicators of biological processes in SSc, hold significant potential for refining disease classification, predicting progression, assessing therapeutic responses, and evaluating clinical outcomes. Unlike other autoimmune diseases, SSc lacks highly specific biomarkers. Given its heterogeneity and multifactorial pathogenesis, the development of a composite biomarker panel may represent the most effective approach for future diagnostic and longitudinal monitoring strategies in SSc.

The COVID-19 pandemic has not only reshaped human health through its acute effects but has also induced long-term consequences, particularly in emerging autoimmune diseases. This introduces the concept of Immune-Repertoire Alteration Syndrome (IRAS), a post-infectious autoimmune phenotype, which describes how pathogen-induced changes in the immune system lead to lasting predispositions for autoimmune disorders. The immune system’s adaptive response to infection, including modifying T-cell repertoires, may inadvertently result in autoimmunity due to cross-reactivity with self-antigens. This phenomenon, referred to as pathogen-induced autoimmune imprinting, leaves a persistent “scar” on the immune system, predisposing individuals to autoimmune diseases long after the initial infection has resolved. This highlights how SARS-CoV-2 and similar pathogens can initiate this process, altering immune responses in a way that may trigger conditions such as autoimmune thyroid disease, lupus, and vasculitis. Additionally, the concept of antigenic imprinting explains how infections and vaccinations influence the immune system’s future responses, often leading to mistaken recognition of self. Finally, the Human Disease Continuum Project (HDCP) is introduced as a research initiative that aims to decode the links between pathogen exposure and autoimmune disease susceptibility. Through comprehensive immune profiling and longitudinal studies, the HDCP seeks to unravel the molecular and immunological mechanisms that underlie these diseases, paving the way for early detection, prevention, and personalized treatment strategies in the post-COVID-19 era. Understanding autoimmune imprinting will unravel new avenues for precision medicine and provides critical insights into the long-term impact of global pandemics on human health.

Autoimmune syndromes are associated with changes in neuropsychological functioning. Neuropsychological functioning can be altered on cognitive, emotional, and behavioral levels. Understanding and recognizing neuropsychological functions and symptoms are essential for diagnostic procedures in autoimmune patients. These procedures require a solid theoretical foundation and suitable tools for both clinical and scientific settings. The availability of standardized neuropsychological diagnostic tests and batteries with good psychometric properties is the most effective tool for this purpose.