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Psychological distress may be shaped by resilience, coping behaviours, and immune dysregulation. We investigated psychological distress symptoms, resilience, alcohol use, and cytokine profiles in 1440 workers from four hospitals in Fortaleza, Brazil. Participants were classified as frontline or second\u2010line workers and assessed with the SRQ\u201020, CD\u2010RISC, and AUDIT. Blood samples were analysed for SARS\u2010CoV\u20102 antibodies and cytokines. Data were collected at two time points (August\u2013October 2021; March\u2013April 2022). Frontline workers reported higher distress, with decreased vital energy and somatic symptoms most prominent. Lower resilience scores correlated with all SRQ\u201020 domains, while higher alcohol use was linked to decreased energy and depressive thoughts. Reduced anti\u2010spike antibody levels were also associated with greater distress. COVID\u201019 infection and symptom severity were associated with more persistent mental distress symptoms. Sex\u2010specific immune signatures emerged: in women, lower interleukin (IL)\u20107 and C\u2010X\u2010C motif chemokine ligand 9 (CXCL\u20109) and higher IL\u201027 correlated with depressive\u2010anxious mood and energy depletion; in men, IL\u201018, IL\u20109, and tumour necrosis factor beta (TNF\u2010\u03b2) were positively associated with distress. This study demonstrates that psychological distress among healthcare workers during COVID\u201019 was shaped by resilience, alcohol use, infection severity, and sex\u2010dependent immune alterations. Strengthening resilience and targeting inflammatory pathways may help mitigate the long\u2010term mental health burden in this workforce during future public health crises.<\/jats:p>","DOI":"10.1002\/smi.70146","type":"journal-article","created":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T04:20:21Z","timestamp":1770783621000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Psychological Distress, Resilience, and Immunoinflammatory Signatures in Healthcare Workers During COVID\u201019"],"prefix":"10.1002","volume":"42","author":[{"given":"Nat\u00e1lia Gindri","family":"Fiorenza","sequence":"first","affiliation":[{"name":"Neuropsychopharmacology Laboratory, Drug Research and Development Center, Department of Physiology and Pharmacology Federal University of Ceara  Fortaleza CE Brazil"},{"name":"Life and Health Sciences Research Institute (ICVS) and ICVS\/3B's \u2010 PT Government Associate Laboratory  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