# Psychological Distress, Resilience, and Immunoinflammatory Signatures in Healthcare Workers During COVID‐19

## TL;DR

This study explores how psychological distress in healthcare workers during the pandemic is linked to resilience, alcohol use, and immune responses, with differences observed between men and women.

## Contribution

The study identifies sex-specific immune signatures and factors influencing psychological distress in healthcare workers during the pandemic.

## Key findings

- Frontline healthcare workers reported higher distress and somatic symptoms compared to second-line workers.
- Sex-specific immune signatures were found, with women showing correlations between certain cytokines and depressive-anxious mood.
- Resilience and alcohol use were significant factors influencing mental health outcomes in healthcare workers.

## Abstract

The COVID‐19 pandemic has profoundly affected healthcare workers, increasing vulnerability to neuropsychiatric disorders, such as anxiety and depression. 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‐line workers and assessed with the SRQ‐20, CD‐RISC, and AUDIT. Blood samples were analysed for SARS‐CoV‐2 antibodies and cytokines. Data were collected at two time points (August–October 2021; March–April 2022). Frontline workers reported higher distress, with decreased vital energy and somatic symptoms most prominent. Lower resilience scores correlated with all SRQ‐20 domains, while higher alcohol use was linked to decreased energy and depressive thoughts. Reduced anti‐spike antibody levels were also associated with greater distress. COVID‐19 infection and symptom severity were associated with more persistent mental distress symptoms. Sex‐specific immune signatures emerged: in women, lower interleukin (IL)‐7 and C‐X‐C motif chemokine ligand 9 (CXCL‐9) and higher IL‐27 correlated with depressive‐anxious mood and energy depletion; in men, IL‐18, IL‐9, and tumour necrosis factor beta (TNF‐β) were positively associated with distress. This study demonstrates that psychological distress among healthcare workers during COVID‐19 was shaped by resilience, alcohol use, infection severity, and sex‐dependent immune alterations. Strengthening resilience and targeting inflammatory pathways may help mitigate the long‐term mental health burden in this workforce during future public health crises.