Atopy-Linked Immune Pattern Tied to Longer Hospital Stays in Infants With Pertussis

Young infants hospitalized with pertussis who carried a set of allergy-related features showed measurably different immune profiles and, in an exploratory analysis, stayed in the hospital longer than infants without those features. The finding comes from a single-center retrospective study of 120 infants aged one to three months, published in Frontiers in Pediatrics, that examined how a locally defined allergy signature relates to lymphocyte subsets, cytokine levels, and length of stay during pertussis infection.

The researchers, based at the Children’s Hospital Affiliated of Zhengzhou University in Henan, China, defined what they call an operational atopy-related phenotype, or OAP. To qualify, an infant needed a total IgE level above 15 IU/mL plus at least one additional feature: eosinophilia, eczema, or a parental history of allergic disease. Of the 120 infants with pertussis, 75 were confirmed by PCR testing and 45 were diagnosed clinically with a documented epidemiological contact. A comparison group of 50 infants who tested PCR-negative for pertussis and had pneumonia served as disease controls.

In the primary analysis, restricted to the pertussis patients, the team compared 45 OAP-positive infants with 75 OAP-negative infants. The models adjusted for chronological age, sex, PCR status, cough duration before sampling, and admission year. Because many immune measures were tested at once, the investigators applied false-discovery-rate correction separately within the lymphocyte and cytokine outcome families, a statistical safeguard against spurious significant results.

The adjusted results pointed to a shift in T-cell composition among OAP-positive infants. Their CD4-positive cell percentage was higher by an adjusted mean difference of 5.25 percentage points, with a 95 percent confidence interval of 2.92 to 7.57. Their CD8-positive percentage was lower by 2.36 percentage points, with an interval of minus 4.38 to minus 0.34. Consequently, the CD4-to-CD8 ratio was higher by 0.44, with an interval of 0.21 to 0.68.

Cytokine measurements told a complementary story. OAP-positive infants had lower interferon-gamma, with an adjusted geometric mean ratio of 0.72 and a confidence interval of 0.58 to 0.90, and lower interleukin-2, at a ratio of 0.70 with an interval of 0.52 to 0.94. Interleukin-6, by contrast, was higher, at a ratio of 2.07 with an interval of 1.65 to 2.59. The ratio of interferon-gamma to interleukin-6 was lower at 0.35, with an interval of 0.25 to 0.48. All of these comparisons carried q values below 0.05 after the false-discovery-rate adjustment.

The authors report that the core findings held up under a stricter version of the phenotype definition and when the analysis was limited to PCR-confirmed pertussis cases, suggesting the pattern was not an artifact of the clinically diagnosed subgroup or of a loose phenotype threshold.

Hospitalization duration was examined in a separate exploratory model using negative-binomial regression, a method suited to count-like outcomes such as days of stay. In that model, OAP-positive status was associated with longer hospitalization, with an adjusted incidence rate ratio of 1.33 and a confidence interval of 1.14 to 1.55. Notably, the continuous cytokine ratio itself, interferon-gamma relative to interleukin-6, was not associated with length of stay, showing a rate ratio of 0.98 per doubling with an interval of 0.92 to 1.03. The allergy-linked phenotype, rather than the cytokine balance measure, tracked with the longer stays.

The study’s authors are careful about interpretation. The associations are described as hypothesis-generating. They do not establish that these infants have atopy as a diagnosis, since the phenotype was an operational definition built from IgE levels and recorded features rather than a clinical workup. Nor do the data identify a pertussis-specific mechanism, and the researchers state that the findings do not demonstrate prognostic utility, meaning the phenotype cannot yet be used to predict outcomes for individual infants.

Several design features shape how far the conclusions reach. The study was retrospective and single-center, so the infants reflect one hospital’s catchment and record-keeping practices. The phenotype definition was prespecified but locally chosen, and its components, including total IgE thresholds and parental allergy history, may not generalize directly to other populations. The length-of-stay result was explicitly exploratory and was not part of the corrected primary outcome families, so it should be treated as a signal for further study rather than a confirmed effect.

What the study does offer is a detailed, concurrently recorded picture of how allergy-related features coexist with the immune response to pertussis in the youngest patients, a group in which host responses may vary considerably. The combination of higher CD4 fractions, lower interferon-gamma and interleukin-2, higher interleukin-6, and a shifted CD4-to-CD8 balance gives researchers a concrete pattern to test in future prospective cohorts, ideally across multiple centers and with longer follow-up, to determine whether this operational phenotype has any role in guiding care for infants with pertussis.

Subject of Research: Immune profiles associated with an atopy-related phenotype in young infants with pertussis

Article Title: Peripheral immune profiles associated with an operational atopy-related phenotype in young infants with pertussis: a single-center retrospective study

Article References: Zhang, L., Ren, Y., & Wang, J. (2026). Peripheral immune profiles associated with an operational atopy-related phenotype in young infants with pertussis: a single-center retrospective study. Frontiers in Pediatrics, 14, Article 1987917. https://doi.org/10.3389/fped.2026.1987917

Image Credits: AI Generated

DOI: 10.3389/fped.2026.1987917

Keywords: pertussis, infants, atopy, IgE, T lymphocytes, cytokines, interferon-gamma, interleukin-6, hospitalization length, retrospective study, Peripheral, immune