Changes in ANA Positivity Following SARS‐CoV‐2 Outbreak in Lombardy Region, Italy

The Coronavirus Disease 2019 (COVID-19) pandemic has raised concerns regarding its potential to induce autoimmune responses. Antinuclear antibodies (ANA) are hallmarks of systemic autoimmunity, and emerging evidence suggests their increased prevalence post-infection. This study aimed to assess ANA positivity rates and patterns of distribution before and after the onset of the pandemic in Lombardy, Italy. We conducted a historical analysis of 1879 matched Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) - Reverse Transcription Polymerase Chain Reaction (RT-PCR) and ANA records performed between March 2020 and December 2023. ANA positivity was assessed using indirect immunofluorescence (IIF) on Human Epithelial type 2 (HEp-2) cells and classified according to the International Consensus on ANA Patterns (ICAP). The extracted data were compared to the pre-pandemic period (2019). Cumulative risk analysis and Cox regression were used to evaluate associations among ANA and SARS-CoV-2 exposure, hospitalization, sex, and age. ANA positivity increased during the pandemic (42.4%) compared to 2019 (29.9%, p < 0.00001). Among SARS-CoV-2 positive individuals, ANA positivity was more frequent (12.9% vs 6%, OR: 2.31, p < 0.001). Cox regression confirmed that SARS-CoV-2 infection (HR:1.397), female sex (HR:1.458), hospitalization (HR 5.369) and age (HR:1.003) were independently associated with the risk of ANA positivity. Time-to-event analysis revealed that ANA positivity risk was higher in the first pandemic phases, following original and alfa variants of SARS-CoV-2 infections compared to delta and omicron variants. Nuclear anti-topo I-like anti-cell (AC)-29 pattern was more prevalent in SARS-CoV-2 positive individuals. SARS-CoV-2 infection is associated with an increased cumulative risk of ANA positivity in the Lombardy population, especially in the earlier phases of the pandemic.