Respiratory Diseases Roundup

Genetic and Functional Insights into Long COVID, School Impact

Edited by:
Kate Young

Key Highlights

  • Multi-omics framework prioritized 32 candidate causal genes and identified three symptom-based Long COVID subtypes.1
  • Among US children, ~1.4% had Long COVID at some point; those with prior Long COVID had higher odds of illness-related chronic absenteeism and functional limitations.2
  • In a population-based cohort of working adults in Spain, nearly 24% developed Long COVID, with risk significantly associated with female sex, comorbidities, acute infection severity, and modifiable workplace exposures.3
     

Multi-omics prioritizes causal genes1

Researchers developed and applied an integrative multi-omics framework that combines transcriptome-wide Mendelian randomization, control-theory network analysis, eQTL and GWAS data, RNA sequencing, and protein–protein interaction mapping to identify putative causal genes for post-acute sequelae of SARS-CoV-2 infection (Long COVID). The authors report prioritization of 32 candidate causal genes—19 previously reported and 13 novel—implicating pathways involved in viral response, immune regulation, cell-cycle control, and processes overlapping with metabolic, autoimmune, and connective tissue disorders. They provide enrichment analyses and an open-source interactive application to explore results.

Using causal gene expression signatures, the study identified three distinct symptom-based Long COVID subtypes with differing underlying molecular profiles, which the authors suggest may explain clinical heterogeneity and support precision-medicine approaches. The paper emphasizes that establishing causality via genetic instruments may help prioritize therapeutic targets but notes methodological constraints—such as the requirement for robust eQTL instruments and potential pleiotropy—and the need for further experimental validation and clinical correlation before translation to interventions. Data and code are publicly available.

Long COVID linked to absenteeism in school children2

Using nationally representative 2022–2023 National Health Interview Survey data, researchers examined functional limitations and chronic illness-related absenteeism (>18 school days) among 11,057 US children aged 5–17 years who ever or never had Long COVID (symptoms >3 months after SARS-CoV-2 infection). The authors estimated that approximately 1.4% of school-aged children had Long COVID at some point and found that, among children with prior COVID-19, those with Long COVID more frequently reported functional limitations (eg, memory difficulties) than those without Long COVID (18.3% vs 8.6%).
Adjusted analyses showed that Long COVID was associated with higher odds of illness-related chronic absenteeism; the authors discuss potential educational and social consequences and suggest consideration of school accommodations to support affected children. The cross-sectional design limits causal inference, and results rely on survey-reported history and symptom recall; the authors recommend longitudinal study to quantify duration, educational impact, and effective accommodations.

Workplace exposures linked to Long COVID risk3

Investigators from the population-based COVICAT cohort examined occupational determinants of Long COVID among working adults in Catalonia, Spain, using prospective data collected between 2020 and 2023. The analysis included 2,054 workers aged 40 to 69 years with prior SARS-CoV-2 infection who were employed during the pandemic and had detailed occupational information available. Long COVID was defined as symptoms persisting for more than 3 months after infection. Occupational exposures were assessed using 4 job-exposure matrices, and Poisson regression models were applied to estimate adjusted risk ratios (RRs) and 95% CIs for individual and workplace-related risk factors.

Overall, 23.7% of participants developed Long COVID. Individual factors associated with higher risk included female sex (RR, 1.45), multiple comorbidities (RR, 2.32 for ≥ 3 conditions), obesity, lower educational attainment, and prior symptomatic infection, with risk increasing substantially by acute COVID-19 severity. COVID-19 vaccination was associated with a reduced risk of Long COVID (RR, 0.53), as was older age. Occupational risk was elevated among workers in health and social care, education, retail, transport, and security. Specific workplace exposures linked to increased risk included close contact with colleagues or the public, inability to maintain social distancing, lack of face mask use, commuting by public transport, and night shift work. The authors conclude that several modifiable occupational factors contribute to Long COVID risk and suggest that targeted prevention strategies and recognition of Long COVID as an occupational disease may help reduce long-term public health burden.

References

  1. Pinero S, Li X, Liu L, et al. Integrative multi-omics framework for causal gene discovery in Long COVID. PLoS Comput Biol. 2025;21(12):e1013725. Published 2025 Dec 1. doi:10.1371/journal.pcbi.1013725
  2. Ford ND, Simeone RM, Pratt C, Saydah S. Functional Limitations and Illness-Related Absenteeism among School-Aged Children with and without Long COVID, United States, 2022-2023. Emerg Infect Dis. 2025;31(14):11-19. doi:10.3201/eid3114.251035
  3. De Matteis S, Consonni D, Espinosa A, et al. Occupational determinants of Long COVID in the population-based COVICAT cohort. Occup Environ Med. Published online December 5, 2025. doi:10.1136/oemed-2025-110398