{
  "abstract": "A central question in environmental epidemiology is how the weather affects infectious diseases. Time-series regression (TSR) on population level case-counts data is widely used to estimate weather effects; however, this design may be biased due to the complexities of infectious disease dynamics, including nonlinear feedback, various types of noise, and latent, dynamic variables such as population immunity. Here, we assess the reliability of incidence-based TSR through a controlled simulation study across four different climates and fifty scenarios representing different pathogens. For each scenario, we simulated 10 years of weekly case-count data using a transmission model that included real-world weather data on temperature and relative humidity. We then examined whether the ground-truth weather effects could be recovered from simulated data using negative binomial generalized additive models, a flexible class of TSR models commonly used in empirical applications. We find that these models frequently fail to yield accurate and precise estimates of weather effects, even under favorable conditions such as no process noise and low observation noise (overdispersion). Hence, our results suggest that more causally elaborated formulations of TSR models, or more mechanistic approaches like transmission models, are needed for statistical inference of weather effects from population data. Author summary: Time-series regression on case-count data at the population level is a common technique for examining how weather affects infectious diseases. However, this analytical approach overlooks the fact that these data come from complex epidemic dynamics with hidden factors, such as population immunity. In this study, we developed a parsimonious mathematical model of disease dynamics in which temperature and relative humidity directly influence transmission rates, and used real weather data from four climates to simulate 10 years of weekly case counts across a range of scenarios representing different pathogens. In a numerical experiment, we then asked whether time-series regression techniques could recover the true weather effects from these simulated case counts. We find that these methods often produce biased, imprecise estimates, even under favorable experimental conditions with minimal noise. Our results suggest that regression analyses of case-count time series can provide a misleading picture of how weather affects infectious diseases. More broadly, our findings show that mechanistic models and system-specific simulation studies are powerful strategies for testing statistical methods in infectious disease epidemiology.",
  "abstract_shown": true,
  "affiliations": [
    "Max Planck Institute for Infection Biology, Infectious Disease Epidemiology group, Berlin, Germany",
    "Institute of Public Health, Charité – Universitätsmedizin Berlin, Berlin, Germany",
    "Department of Biology, New York University, New York, New York, United States of America"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Pietro Gemo"
    },
    {
      "affs": [
        1
      ],
      "name": "Laura Andrea Barrero Guevara"
    },
    {
      "affs": [
        2
      ],
      "name": "Cana Kussmaul"
    },
    {
      "name": "Sarah C. Kramer"
    },
    {
      "name": "Matthieu Domenech de Cellès"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4z7ejbyqtxwpz.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.pcbi.1014797",
  "fulltext_url": "https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1014797",
  "id": "4z7ejbyqtxwpz",
  "issns": [
    "1553-7358"
  ],
  "landing_url": "https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1014797",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2307|Climate Change and Health Impacts"
    ],
    [
      "plos",
      "/Earth sciences/Atmospheric science/Meteorology/Humidity"
    ],
    [
      "plos",
      "/Earth sciences/Seasons"
    ],
    [
      "plos",
      "/Medicine and health sciences/Epidemiology/Disease dynamics"
    ],
    [
      "plos",
      "/Medicine and health sciences/Medical conditions/Infectious diseases"
    ],
    [
      "plos",
      "/Medicine and health sciences/Medical conditions/Infectious diseases/Respiratory infections"
    ],
    [
      "plos",
      "/Medicine and health sciences/Medical conditions/Infectious diseases/Viral diseases/Influenza"
    ],
    [
      "plos",
      "/Medicine and health sciences/Medical conditions/Respiratory disorders/Respiratory infections"
    ],
    [
      "plos",
      "/Medicine and health sciences/Pathology and laboratory medicine/Pathogens"
    ],
    [
      "plos",
      "/Medicine and health sciences/Pulmonology/Respiratory disorders/Respiratory infections"
    ],
    [
      "plos",
      "/Research and analysis methods/Simulation and modeling"
    ]
  ],
  "openalex": "W7212148835",
  "pdf_url": "https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1014797&type=printable",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-10",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/4z7ejbyqtxwpz.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:56Z",
      "native_id": "10.1371/journal.pcbi.1014797",
      "source": "plos",
      "url": "https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1014797"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "plos:infectious diseases",
      "subfield": "infectious-disease"
    }
  ],
  "title": "The pitfalls of incidence-based time series regression for inferring the effects of weather on infectious diseases",
  "title_text": "The pitfalls of incidence-based time series regression for inferring the effects of weather on infectious diseases",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:56Z",
  "url": "https://research.draconitic.com/paper/4z7ejbyqtxwpz",
  "venue": "PLOS Computational Biology",
  "versions": []
}