# Comparison Between Clinical Outcomes in Influenza A and B Infections: A Multicenter Retrospective Cohort Study

Benjamin Davido, Benoit Lemarie, Elyanne Gault, Karim Jaffal, Martin Rottman, Sebastien Beaune, Christel Mamona, Djillali Annane

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## ► To cite this version:

Benjamin Davido, Benoit Lemarie, Elyanne Gault, Karim Jaffal, Martin Rottman, et al., Comparison Between Clinical Outcomes in Influenza A and B Infections: A Multicenter Retrospective Cohort Study. Clinical microbiology and infection communications, 2025, pp.105072-105072. 10.1016/j.cmicom.2025.105072. hal-05034524

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# Comparison between clinical outcomes in influenza A and B Infections: A multicenter retrospective cohort study

Benjamin Davido<sup>a,b,*</sup>, Benoit Lemarie<sup>a</sup>, Elyanne Gault<sup>b,c</sup>, Karim Jaffal<sup>a</sup>, Martin Rottman<sup>b,d</sup>, Sebastien Beaune<sup>b,e</sup>, Christel Mamona<sup>a,b</sup>, Djillali Annane<sup>b,f</sup>

## ARTICLE INFO

Edited by Dr. Josh Nosanchuk.

### Keywords:

- Outcome

- Influenza B

- Respiratory tract infections

- Influenza

- Mortality

## ABSTRACT

**Objectives:** Influenza significantly contributes to seasonal morbidity and strains healthcare resources, yet data directly comparing types A and B remain limited. This study assesses potential differences in clinical severity and outcomes between these two influenza types.

**Methods:** We conducted a multicenter retrospective study of adult patients diagnosed with either influenza A or B. Using logistic regression, we identified predictors of adverse outcomes across demographics, comorbidities, and clinical parameters.

**Results:** The influenza A and B cohorts included 234 and 113 patients, respectively. In comparison to influenza B, influenza A patients were more likely to receive oseltamivir (43.5% vs 27.9%, *p* = 0.01) and showed similar rates of radiological abnormalities (27.8% vs 24.8%, *p* = 0.6). Age ≥65 years remained the strongest predictor of hospitalization (aOR 4.78, *p* = 0.01). Predictors of ICU admission included age<65 (aOR 3.18, *p* = 0.02), radiological bilateral involvement (aOR 19.4, *p* < 0.001), receiving oseltamivir treatment (aOR 2.43, *p* = 0.01) with a trend towards documented superinfection (aOR 2.56, *p* = 0.07). Short-term favorable outcomes were more common in influenza B (aOR 2.52, *p* = 0.02), whereas chronic respiratory disease and Charlson comorbidity index reduced likelihood of favorable outcomes (aOR 0.34, *p* = 0.04 and 0.25, *p* = 0.001, respectively). Kaplan-Meier survival curves revealed similar mortality rates at 90 days between influenza A and B types (13.4% vs 8.7%, *p* = 0.3).

**Conclusion:** Influenza type A and B exhibit distinct clinical trajectories and influenza B should not be neglected. These findings underscore the need for earlier diagnosis testing to promote earlier antiviral initiation and broader vaccination policies tailored to both influenza types.

## Introduction

Influenza A and B viruses remain significant contributors to seasonal respiratory illnesses, with substantial impacts on healthcare systems and vulnerable populations [1]. These infections are associated with high hospitalization rates and significant resource utilization, particularly among older adults and individuals with underlying comorbidities [2,3]. While both viruses share overlapping clinical presentations, influenza B circulates less widely due to its exclusive human reservoir and accounts for approximately 23% of annual cases in temperate regions [4]. Studies

evaluating the differences in their epidemiology and patient outcomes remain limited [5–8], highlighting the need for further studies and targeted interventions.

The present study, conducted during seasonal epidemics prior to the COVID-19 pandemic, compares predictors of hospitalization, ICU admission, and short-term recovery in patients with influenza A and B. Despite COVID-19 disruptions, influenza still circulates, with A/H 1N1pdm09, A/H3N2, and B/Victoria predominating, while B/Yamagata has disappeared [9]. Additionally, the CDC reports a higher burden of influenza disease in the current 2024–2025 season, with more medical

<footnote><sup>a</sup> Maladies Infectieuses, Hôpital Raymond Poincaré, AP-HP - Garches, France</footnote>

<footnote><sup>b</sup> Université Paris-Saclay, UVSQ, Montigny-Le-Bretonneux, France</footnote>

<footnote><sup>c</sup> Virologie, Hôpital Ambroise-Paré, AP-HP - Boulogne-Billancourt, France</footnote>

<footnote><sup>d</sup> Microbiologie, Hôpital Raymond Poincaré, AP-HP - Garches, France</footnote>

<footnote><sup>e</sup> Service d'Accueil des Urgences, Hôpital Ambroise Paré, AP-HP - Boulogne-Billancourt, France</footnote>

<footnote><sup>f</sup> Médecine Intensive et Réanimation, Hôpital Raymond Poincaré, AP-HP - Garches, France</footnote>

<footnote>* Corresponding author at: Maladies Infectieuses, Hôpital Raymond Poincaré, AP-HP - Garches, France.</footnote>

<footnote>E-mail address: benjamin.davido@aphp.fr (B. Davido).</footnote>
consultations and increased mortality [10].

A key challenge in the post-COVID-19 era is managing the "triple-demic" of COVID-19, influenza, and RSV [11]. With high-dose vaccines now available for vulnerable populations, evaluating all strategies to reduce influenza's impact remains essential [12].

Our main objective was to compare the clinical outcomes between the influenza A and B types. By understanding these distinctions, we aim to inform clinical management strategies and improve healthcare resource allocation.

## Methods

### Study design

This retrospective cohort study was designed to assess clinical outcomes and predictors of severity among patients with influenza A and B. The study was conducted across three tertiary care hospitals within the Paris-Saclay University network from 2016 to 2018, as part of the SUPERFLUOUS study [13].

### Setting

Hôpital Raymond Poincaré and Hôpital Ambroise Paré (255 and 399 beds, respectively) are acute care facilities. Hôpital Ambroise Paré centralizes patient care through an emergency department (ED) that receives approximately 200 patients per day, where individuals can be either hospitalized or directly discharged following ED evaluation. Hôpital Sainte Périne is a 55-bed geriatrics acute care facility that also includes long-term care and rehabilitation beds. All three hospitals belong to the Assistance Publique des Hôpitaux de Paris (AP-HP), the largest hospital network in Europe and one of the largest in the world [14].

### Diagnostic pathways and patient selection context

Notably, at the time of the present study, influenza surveillance in France did not fully capture the impact of seasonal epidemics on hospital systems [15]. Considering that this study was hospital-based, patient inclusion occurred through EDs, which typically manage more severe cases requiring further evaluation or hospitalization. Prior to the COVID-19 pandemic, most influenza diagnoses in France occurred in outpatient settings, where general practitioners managed mild cases based on clinical presentation and current epidemic context, as rapid diagnostic tests were not routinely available. Although post-COVID-19 changes, including the broader availability of rapid antigen tests, may have modified diagnostic practices by allowing earlier identification and potential management adjustments, the present study focuses exclusively on pre-pandemic diagnostic pathways.

### Patient selection and exclusion criteria

Adult patients (≥18 years) with confirmed influenza A or B via RT-PCR were included. Originally, RT-PCR was an in-house technique, developed by the virology laboratory of Ambroise Paré Hospital [16]. It was based on the simultaneous realization of a triplex PCR (for influenza A and B and RSV), and this technique was replaced on duty or during week-end by a CEPHEID® kit test, testing exclusively influenza.

Patients were excluded if they had i) incomplete medical charts preventing clinical outcome assessment, ii) duplicate records, or iii) missing key study variables essential for analysis (e.g., lack of hospitalization status or missing virological confirmation)."

### Handling of missing data

For analyses where patient data were missing, the number of missing data are provided.

### Follow-up

All included patients had complete follow-up until hospital discharge or 90-day mortality assessment. No patients were lost to follow-up.

### Definitions

* Immunosuppression was defined as any condition or treatment impairing immune function, including: i) autoimmune diseases requiring ≥10 mg/day of prednisone equivalent for at least two weeks or immunosuppressive agents (e.g., anti-CD20 monoclonal antibodies, TNF-α inhibitors, JAK inhibitors, calcineurin inhibitors); ii) oncological conditions involving active chemotherapy, hematological malignancies, or solid organ and hematopoietic stem cell transplantation with associated immunosuppressive therapy; iii) HIV infection with CD4+ T-cell counts <200 cells/mm³ and other causes, including congenital immunodeficiencies, asplenia, and long-term immunosuppression for graft-versus-host disease.

* Short-term favorable outcome: defined as returning to pre-infection condition within five days, characterized by apyrexia, stable vital signs, and no oxygen requirement.

* Superinfection: documented bacterial infection requiring antibiotics, confirmed via cultures, antigenuria (Streptococcus pneumoniae or Legionella pneumophilia), or intracellular bacterial PCR (Mycoplasma pneumoniae and Chlamydia pneumoniae). Cases with clinical suspicion of bacterial superinfection but lacking microbiological confirmation, were classified as influenza-only infections based on the initial positive influenza A and B RT-PCR.

* Radiological Abnormalities: included alveolar consolidation or interstitial syndrome and bilateral involvement, identified through chest X-rays at the ED and/or by computed tomography upon admission.

### Outcomes

#### Primary outcome

The primary outcome was short-term favorable outcome, defined as survival without ICU admission within 30 days of diagnosis or hospital presentation. This outcome was chosen to capture early clinical recovery and the avoidance of critical care, reflecting the effectiveness of initial management strategies.

#### Secondary outcomes

The following secondary outcomes were evaluated:

* Hospital admission rate: The proportion of patients requiring hospitalization following ED evaluation.

* ICU admission: The proportion of hospitalized patients who required intensive care during their hospital stay.

* Oseltamivir initiation: The proportion of patients receiving oseltamivir treatment during hospitalization.

* 90-day all-cause mortality: Death from any cause occurring within 90 days of initial diagnosis.

### Statistical analysis

Univariate and multivariate logistic regression analyses identified predictors of outcomes. Variables with *p* < 0.10 in univariate analysis were included in multivariate models. Mean and median values were compared using t-tests or Mann-Whitney U tests, as appropriate. Kaplan-Meier survival curves were generated to compare 90-day mortality between groups, with differences assessed by log-rank tests. Statistical significance was set at *p* < 0.05.

All statistical calculations were performed using Jamovi software version 2.3.28 and GraphPad Prism 9.1.1 for figures.
## Ethics

The present work is part of the SUPERFLUOUS study, which was originally designed to evaluate the risk of superinfection among viral agents during the fall-winter season [13]. Study design was approved by the ethical and scientific committee for health research, studies and evaluation (CESREES) and by the Commission Nationale Informatique et Libertés (CNIL) under the number 921,061. Patients provided written informed consent for the SUPERFLUOUS study.

## Results

### Baseline characteristics

A flowchart of patient inclusion and exclusion criteria is provided in Fig. 1.

Overall, 347 patients were included, 234 had influenza A and 113 had influenza B.

Patients' characteristics for influenza A and B are detailed in Table 1. Overall, mean age ± standard deviation (SD) was 69 ± 19 years.

A higher proportion of influenza A patients received oseltamivir (43.5% (102/234) vs. 29.2% (33/113), *p* = 0.01). The median (min-max) delay before oseltamivir initiation was 2 (1–4) days from the time of admission for both groups (*p* = 0.15), reflecting a consistent treatment approach. Radiological findings were also similar between groups, with 26.5% (62/234) and 23.0% (26/113) of influenza A and B patients, respectively, showing alveolar consolidation (*p* = 0.51).

### Predictors of hospitalization

Age ≥65 years strongly predicted hospitalization in both A&B infections (adjusted odds ratio (aOR), 4.78 [95% confident interval (CI), 1.46–15.67]). Chronic respiratory disease (CRD) was associated with an increased risk of hospitalization in univariate analysis but did not retain

<table><caption>**Table 1**

Characteristics of patients between influenza type A and B.</caption><thead><tr><th></th><th>Influenza type A<br>(n = 234)</th><th>Influenza type B<br>(n = 113)</th><th>p-value</th></tr></thead><tbody><tr><td>Mean age ± SD (years)</td><td>69 (±20)</td><td>70 (±17)</td><td>0.37</td></tr><tr><td>Male gender, n (%)</td><td>119 (50.8)</td><td>55 (48.6)</td><td>0.73</td></tr><tr><td>Chronic respiratory disease<br>(CRD) <sup>a</sup>, n (%)</td><td>52 (24.8)</td><td>24 (21.2)</td><td>0.89</td></tr><tr><td>Inhaled corticosteroids among<br>CRD, n (%)</td><td>34 (58.6)</td><td>9 (37.5)</td><td>0.08</td></tr><tr><td>Smoking cessation among<br>smokers, n (%)</td><td>57 (67.8)</td><td>31 (86.1)</td><td>0.59</td></tr><tr><td>Immunosuppression <sup>b</sup>, n (%)</td><td>44 (18.8)</td><td>27 (11.5)</td><td>0.32</td></tr><tr><td>Influenza vaccination, n (%)</td><td>53 (22.6)</td><td>21 (18.5)</td><td>0.41</td></tr><tr><td>Pneumococcus vaccination, n<br>(%)</td><td>26 (11.1)</td><td>7 (6.2)</td><td>0.17</td></tr><tr><td>Charlson Comorbidity Index ≥5,<br>n (%)</td><td>131 (55.9)</td><td>56 (47.5)</td><td>0.31</td></tr><tr><td>Documented superinfection, n<br>(%)</td><td>25 (10.6)</td><td>12 (10.6)</td><td>0.99</td></tr><tr><td>Polymorphonuclear cell count<br>≥7000/mm3, n (%)</td><td>69 (29.5)</td><td>36 (31.8)</td><td>0.71</td></tr><tr><td>Eosinophil count = 0/mm3, n<br>(%)</td><td>81 (34.6)</td><td>49 (43.3)</td><td>0.12</td></tr><tr><td>Lymphocyte count ≤800/mm3,<br>n (%)</td><td>115 (49.1)</td><td>52 (46.0)</td><td>0.65</td></tr><tr><td>Radiological abnormalities</td><td></td><td></td><td></td></tr><tr><td>Alveolar syndrome, n (%)</td><td>62 (26.5)</td><td>26 (23.0)</td><td>0.51</td></tr><tr><td>Interstitial syndrome, n (%)</td><td>3 (1.3)</td><td>2 (1.8)</td><td>0.66</td></tr><tr><td>Bilateral involvement, n (%)</td><td>17 (7.2)</td><td>9 (7.9)</td><td>0.83</td></tr><tr><td>Oseltamivir treatment, n (%)</td><td>102 (43.5)</td><td>33 (29.2)</td><td>0.01</td></tr></tbody></table>

<sup>a</sup> Chronic respiratory disease included COPD, asthma, bronchiectasis and other underlying lung disease.

<sup>b</sup> Immunosuppression was defined as conditions or treatments impairing immune function, including autoimmune diseases requiring immunosuppressants, active cancer therapy, organ/stem cell transplantation, HIV with CD4+ <200 cells/mm³, congenital immunodeficiencies, or asplenia.

<figure><img src="image_8.png" /><figcaption>**Fig. 1.** Flowchart of study participant selection.</figcaption></figure>
significance in multivariate models. Radiological alveolar consolidation also emerged as a significant factor in univariate analysis (3.45 [1.41–8.42]; Table 2). Of note, superinfection was not assessed in out-patients due to the delay required for microbiological confirmation. Additionally, oseltamivir was not offered to outpatients and could therefore not be taken into consideration.

## Admission rates and hospital stay

Admission rates were high in both groups, with 76.5% (179/234) of influenza A patients and 70.8% (80/113) of influenza B patients ($p = 0.29$) requiring hospitalization. The mean length of stay (LOS) ($\pm$ SD)

<table><caption>**Table 2**
Potential predictors of hospital admission among included patients ($n = 347$).</caption><thead><tr><th rowspan="2">Variables</th><th colspan="2">Univariate model</th><th colspan="2">Multivariate model</th></tr><tr><th>OR [95% CI]</th><th>p value</th><th>aOR [95% CI]</th><th>p value</th></tr></thead><tbody><tr><td>Age ≥ 65 years</td><td>4.67 [2.79 -7.81]</td><td>&lt;0.001</td><td>4.78 [1.46 -15.67]</td><td>0.01</td></tr><tr><td>Male gender</td><td>0.77 [0.48 -1.26]</td><td>0.31</td><td>-</td><td>-</td></tr><tr><td>Chronic Respiratory Disease (CRD) <sup>a</sup></td><td>1.55 [0.84 -2.85]</td><td>0.16</td><td>-</td><td>-</td></tr><tr><td>Inhaled corticosteroids among CRD</td><td>2.28 [0.93 -5.6]</td><td>0.07</td><td>1.50 [0.38 -5.80]</td><td>0.55</td></tr><tr><td>Smoking cessation</td><td>2.26 [0.85 -5.95]</td><td>0.11</td><td>-</td><td>-</td></tr><tr><td>Immunosuppression <sup>b</sup></td><td>1.10 [0.59 -2.04]</td><td>0.75</td><td>-</td><td>-</td></tr><tr><td>Type of influenza type A</td><td>Reference</td><td>0.25</td><td>-</td><td>-</td></tr><tr><td>type B</td><td>0.74 [0.45 -1.24]</td><td>-</td><td>-</td><td>-</td></tr><tr><td>Lack of influenza vaccination</td><td>0.55 [0.28 -1.10]</td><td>0.09</td><td>0.99 [0.34 -2.88]</td><td>0.9</td></tr><tr><td>Lack of pneumococcus vaccine</td><td>0.60 [0.25 -1.45]</td><td>0.26</td><td>-</td><td>-</td></tr><tr><td>CCI≥5 <sup>c</sup></td><td>3.65 [2.18 -6.13]</td><td>&lt;0.001</td><td>1.40 [0.48 -4.02]</td><td>0.53</td></tr><tr><td>Laboratory values PMN > 7000 (/mm³)</td><td>2.84 [1.45 -5.56]</td><td>0.002</td><td>2.70 [0.74 -9.81]</td><td>0.13</td></tr><tr><td>Eosinophil count (/mm³) > 50</td><td>Reference</td><td>0.52<br>0.64</td><td>-</td><td>-</td></tr><tr><td>0 - 50</td><td>0.79 [0.38 -1.63]</td><td>-</td><td>-</td><td>-</td></tr><tr><td>0</td><td>1.19 [0.56 -2.55]</td><td>-</td><td>-</td><td>-</td></tr><tr><td>Lymphocytes ≤ 800 (/mm³)</td><td>0.78 [0.46 -1.33]</td><td>0.36</td><td>-</td><td>-</td></tr><tr><td>Radiological abnormalities None</td><td>Reference</td><td>0.007<br>0.02</td><td>Reference</td><td>0.56<br>0.27</td></tr><tr><td>Alveolar consolidation</td><td>3.45 [1.41 -8.42]</td><td>-</td><td>1.52 [0.36 -6.32]</td><td>-</td></tr><tr><td>Bilateral involvement</td><td>11.9 [1.59 -89.3]</td><td>-</td><td>3.41 [0.38 -30.90]</td><td>-</td></tr></tbody></table>

OR, Odds ratio; aOR, adjusted Odds ratio; CI, confidence interval.

<sup>a</sup> Chronic respiratory disease included COPD, asthma, bronchiectasis and other underlying lung disease.

<sup>b</sup> Immunosuppression was defined as conditions or treatments impairing immune function, including autoimmune diseases requiring immunosuppressants, active cancer therapy, organ/stem cell transplantation, HIV with CD4+ <200 cells/mm³, congenital immunodeficiencies, or asplenia.

<sup>c</sup> CCI, The Charlson Comorbidity Index ≥ 5 reflects patient's fragility; PMN, polymorphonuclear neutrophils; Multivariate logistic regression was used for variables with a $p < 0.10$ in univariate analysis. The adequacy test used is an adjustment by Hosmer and Lemeshow.

was $11 \pm 0.8$ days for influenza A patients and $12 \pm 1.2$ days for influenza B patients ($p = 0.67$).

## Short-Term outcomes and ICU admission

Short-term favourable outcomes were observed in younger patients ($\le 65$ years, aOR 3.14 [1.24–7.98]) and those with influenza B (aOR 2.52 [1.15–5.51]). CRD inversely correlated with favorable outcomes (aOR 0.34 [0.12–0.93]) as a high Charlson Comorbidity Index (CCI) ≥ 5 (aOR 0.25 [0.11–0.60]) as detailed in Table 3.

Key predictors of ICU admission included bilateral radiological involvement (aOR 19.4 [6.32–59.7]) and polymorphonuclear cell count >7000/mm³ at admission (aOR 2.18 [1.04–4.55]). Patients with documented superinfection showed a trend towards higher ICU admission risk (aOR 2.56 [0.94–6.99]). Age <65 years was also a significant predictor of being admitted in ICU (aOR 3.18 [1.22–8.28]; Table 4).

## Mortality

By 90 days, 24/179 (13.4%) influenza A and 7/80 (8.7%) influenza B patients had died, respectively ($p = 0.30$). Fig. 2 depicts the Kaplan-Meier survival curve.

## Discussion

This study provides a comprehensive comparison of clinical outcomes between influenza A and B during seasonal epidemics in the pre-COVID-19 era. While influenza B patients experienced better short-term ($\le 5$ days) outcomes, overall they experienced more hospitalizations, ICU admissions, and mortality than expected. These findings warrant further investigation to determine contributing factors. Indeed, despite the fact that influenza B has historically received less attention due to the dominance of influenza A pandemics, recent surveillance suggests that its disease burden may be greater than previously recognized, warranting increased focus in the post-COVID era.

A notable finding in our study is the significant higher use of oseltamivir in influenza A patients compared to influenza B, despite similar hospitalization and mortality rates. This may reflect clinicians' perception of greater severity in influenza A, as supported by previous studies [17,18], given its higher circulation [19]. However, given the comparable ICU admission and mortality rates between influenza A and B, our findings suggest that oseltamivir could also benefit influenza B patients, particularly those with severe disease or risk factors for complications. Oseltamivir has been shown to improve outcomes of influenza-B related pneumoniae [20], and early administration reduces complications and ICU admissions, especially within 48 h of symptom onset [21]. Notably, a recent meta-analysis found no benefit of oseltamivir in preventing admissions among outpatients [22], in contrast with previous findings [23].

Interestingly, influenza B patients in our study achieved better short-term outcomes, despite significantly lower oseltamivir use, while other patient characteristics were comparable. While some studies link influenza B with severe outcomes in certain populations [4,5,7], our findings are consistent with research suggesting a milder clinical course for influenza B in some settings [6]. This discrepancy warrants further investigation, given influenza B's global burden and healthcare impact. Although a trend toward higher mortality in influenza A patients was observed, it was not statistically significant, aligning with studies associating influenza A with severe outcomes [6,24] even with differences between A/H 1N1 and H3N2 subtypes in obesity-related outcomes [25]. Likewise, Lytras et al. [26] found early oseltamivir reduced mortality in critically ill patients with influenza A/H3N2 but not in A/H 1N1 or influenza B, emphasizing the need for further research into antiviral therapies' impacts.

Our study confirms predictors of adverse outcomes, including age $\ge 65$ years and high CCI scores, consistent with evidence linking older
<caption>**Table 3**</caption>

Potential predictors of short-term favourable outcome, defined as recovery to pre-infection status within five days with apyrexia, stable vital signs, and no oxygen requirement, among admitted patients (n = 259).

<table><thead><tr><th rowspan="2">Variables</th><th colspan="2">Univariate model</th><th colspan="2">Multivariate model</th></tr><tr><th>OR [95% CI]</th><th>p value</th><th>aOR [95% CI]</th><th>p value</th></tr></thead><tbody><tr><td>Age &lt; 65 years</td><td>3.30 [1.77 -6.24]</td><td>&lt;0.001</td><td>3.14 [1.24 -7.98]</td><td>0.01</td></tr><tr><td>Male gender</td><td>0.95 [0.54 -1.67]</td><td>0.87</td><td>-</td><td>-</td></tr><tr><td>Chronic Respiratory Disease (CRD) <sup>a</sup></td><td>0.37 [0.17 -0.78]</td><td>&lt;0.01</td><td>0.34 [0.12 -0.93]</td><td>0.04</td></tr><tr><td>Inhaled corticosteroids among CRD</td><td>0.63 [0.26 -1.55]</td><td>0.32</td><td>-</td><td>-</td></tr><tr><td>Smoking cessation</td><td>1.68 [0.53 -5.67]</td><td>0.39</td><td>-</td><td>-</td></tr><tr><td>Immunosuppression <sup>b</sup></td><td>0.92 [0.45 -1.87]</td><td>0.82</td><td>-</td><td>-</td></tr><tr><td>Type of influenza type A</td><td>Reference</td><td>0.07</td><td>Reference</td><td></td></tr><tr><td>type B</td><td>1.72 [0.95 -3.12]</td><td></td><td>2.52 [1.15 -5.51]</td><td>0.02</td></tr><tr><td>Lack of influenza vaccination</td><td>1.49 [0.62 -3.55]</td><td>0.36</td><td>-</td><td>-</td></tr><tr><td>Lack of pneumococcus vaccine</td><td>0.71 [0.19 -2.62]</td><td>0.60</td><td>-</td><td>-</td></tr><tr><td>CCI≥5 <sup>c</sup></td><td>0.23 [0.13 -0.43]</td><td>&lt;0.001</td><td>0.25 [0.11 -0.60]</td><td>0.001</td></tr><tr><td>Documented superinfection</td><td>0.17 [0.04 -0.73]</td><td>0.02</td><td>0.40 [0.08 -2.24]</td><td>0.30</td></tr><tr><td>Laboratory values PMN &gt; 7000 (/mm³)</td><td>0.53 [0.27 -1.02]</td><td>0.05</td><td>0.75 [0.33 -1.61]</td><td>0.42</td></tr><tr><td>Eosinophil count (/mm³) &gt; 50</td><td>Reference</td><td></td><td>Reference</td><td></td></tr><tr><td></td><td></td><td>0.84</td><td></td><td>0.10</td></tr><tr><td></td><td></td><td>0.08</td><td></td><td>0.86</td></tr><tr><td>0 - 50</td><td>0.92 [0.44 -1.95]</td><td></td><td>2.49 [0.83 -7.3]</td><td></td></tr><tr><td>0</td><td>0.50 [0.23 -1.09]</td><td></td><td>1.09 [0.34 -3.4]</td><td></td></tr><tr><td>Lymphocytes ≤ 800 (/mm³)</td><td>0.58 [0.32 -1.04]</td><td>0.07</td><td>0.58 [0.26 -1.26]</td><td>0.17</td></tr><tr><td>Radiological abnormalities None</td><td>Reference</td><td></td><td>Reference</td><td>0.38</td></tr><tr><td></td><td></td><td>0.05</td><td></td><td>0.07</td></tr><tr><td>Alveolar consolidation</td><td>0.43 [0.19 -1.01]</td><td></td><td>0.62 [0.21 -1.84]</td><td></td></tr><tr><td>Bilateral involvement</td><td>0.12 [0.02 -0.95]</td><td></td><td>0.12 [0.01 -1.17]</td><td></td></tr><tr><td>Oseltamivir treatment</td><td>0.82 [0.63 -1.12]</td><td>0.15</td><td>-</td><td>-</td></tr></tbody></table>

OR, Odds ratio; aOR, adjusted Odds ratio; CI, confidence interval.

<sup>a</sup> Chronic respiratory disease included COPD, asthma, bronchiectasis and other underlying lung disease.

<sup>b</sup> Immunosuppression was defined as conditions or treatments impairing immune function, including autoimmune diseases requiring immunosuppressants, active cancer therapy, organ/stem cell transplantation, HIV with CD4+ <200 cells/mm³, congenital immunodeficiencies, or asplenia.

<sup>c</sup> CCI, The Charlson Comorbidity Index ≥ 5 reflects patient's fragility; PMN, polymorphonuclear neutrophils; Multivariate logistic regression was used for variables with a p < 0.10 in univariate analysis. The adequacy test used is an adjustment by Hosmer and Lemeshow.

age and comorbidities to severe influenza, notably hospitalization and mortality [2,3,7,24]. These findings underscore the importance of vaccination campaigns targeting high-risk populations, with quadrivalent influenza vaccines reducing influenza B hospitalizations strategies [7,27]. Indeed, in the present study, only 21% of patients were vaccinated against influenza. This rate is notably lower than the national vaccination coverage for the same seasons in France, where 29% of individuals aged 65 years and below were vaccinated, according to Santé

<caption>**Table 4**</caption>

Potential predictors of ICU admission among admitted patients (n = 259).

<table><thead><tr><th rowspan="2">Variables</th><th colspan="2">Univariate model</th><th colspan="2">Multivariate model</th></tr><tr><th>OR [95% CI]</th><th>p value</th><th>aOR [95% CI]</th><th>p value</th></tr></thead><tbody><tr><td>Age &lt; 65 years</td><td>2.34 [1.29 -4.33]</td><td>0.005</td><td>3.18 [1.22 -8.28]</td><td>0.02</td></tr><tr><td>Male gender</td><td>0.7 [0.41 -1.21]</td><td>0.20</td><td>-</td><td>-</td></tr><tr><td>Chronic Respiratory Disease (CRD) <sup>a</sup></td><td>2.02 [1.12 -3.64]</td><td>0.02</td><td>1.18 [0.46 -3.23]</td><td>0.69</td></tr><tr><td>Inhaled corticosteroids among CRD</td><td>2.06 [1.07 -4.24]</td><td>0.04</td><td>1.03 [0.33 -3.53]</td><td>0.95</td></tr><tr><td>Smoking cessation</td><td>0.82 [0.31 -2.23]</td><td>0.71</td><td>-</td><td>-</td></tr><tr><td>Immunosuppression <sup>b</sup></td><td>1.27 [0.67 -2.40]</td><td>0.47</td><td>-</td><td>-</td></tr><tr><td>Type of influenza type A</td><td>Reference</td><td>0.30</td><td>-</td><td>-</td></tr><tr><td>type B</td><td>1.35 [0.76 -2.38]</td><td>-</td><td>-</td><td>-</td></tr><tr><td>Lack of influenza vaccination</td><td>1.85 [0.82 -4.18]</td><td>0.13</td><td>-</td><td>-</td></tr><tr><td>Lack of pneumococcus vaccine</td><td>2.41 [0.67 -8.51]</td><td>0.17</td><td>-</td><td>-</td></tr><tr><td>CCI≥5 <sup>c</sup></td><td>0.54 [0.31 -0.93]</td><td>0.03</td><td>0.56 [0.24 -1.29]</td><td>0.17</td></tr><tr><td>Documented superinfection</td><td>4.56 [2.21 -9.41]</td><td>&lt;0.001</td><td>2.56 [0.94 -6.99]</td><td>0.07</td></tr><tr><td>Laboratory values PMN &gt; 7000 (/mm³)</td><td>2.14 [1.23 -3.72]</td><td>0.007</td><td>2.18 [1.04 -4.55]</td><td>0.04</td></tr><tr><td>Eosinophil count (/mm³) &gt; 50</td><td>Reference</td><td></td><td>Reference</td><td></td></tr><tr><td></td><td></td><td>0.11</td><td></td><td>0.19</td></tr><tr><td></td><td></td><td>0.09</td><td></td><td>0.29</td></tr><tr><td>0 - 50</td><td>1.97 [0.85 -4.57]</td><td></td><td>2.09 [0.71 -6.25]</td><td></td></tr><tr><td>0</td><td>2.04 [0.89 -4.70]</td><td></td><td>1.77 [0.61 -5.18]</td><td></td></tr><tr><td>Lymphocytes ≤ 800 (/mm³)</td><td>0.98 [0.57 -1.70]</td><td>0.96</td><td>-</td><td>-</td></tr><tr><td>Radiological abnormalities None</td><td>Reference</td><td></td><td>Reference</td><td>0.04</td></tr><tr><td></td><td></td><td>0.004</td><td></td><td>&lt;0.001</td></tr><tr><td>Alveolar consolidation</td><td>2.72 [1.37 -5.41]</td><td></td><td>2.36 [1.02 -5.45]</td><td></td></tr><tr><td>Bilateral involvement</td><td>17.5 [6.56 -46.5]</td><td></td><td>19.4 [6.32 -59.7]</td><td></td></tr><tr><td>Oseltamivir treatment</td><td>2.05 [1.18 -3.56]</td><td>0.01</td><td>2.43 [1.22 -4.83]</td><td>0.01</td></tr></tbody></table>

OR, Odds ratio; aOR, adjusted Odds ratio; CI, confidence interval.

<sup>a</sup> Chronic respiratory disease included COPD, asthma, bronchiectasis and other underlying lung disease.

<sup>b</sup> Immunosuppression was defined as conditions or treatments impairing immune function, including autoimmune diseases requiring immunosuppressants, active cancer therapy, organ/stem cell transplantation, HIV with CD4+ <200 cells/mm³, congenital immunodeficiencies, or asplenia.

<sup>c</sup> CCI, The Charlson Comorbidity Index ≥ 5 reflects patient's fragility; PMN, polymorphonuclear neutrophils; Multivariate logistic regression was used for variables with a p < 0.10 in univariate analysis. The adequacy test used is an adjustment by Hosmer and Lemeshow.

Publique France. This discrepancy highlights potential gaps in vaccination uptake among at-risk populations, which may contribute to the disease burden observed in hospital settings. Also, radiological abnormalities, particularly bilateral involvement, predicted ICU admission, aligning with studies associating bilateral infiltrates with severe outcomes [28–30]. Early chest imaging may aid in risk stratification and ICU preparedness according to Aviram et al. [31]. Lastly, our findings highlight the importance of managing superinfections, a major contributor to morbidity and mortality [32]. Enhancing diagnostics for
<figure><img src="image_9.png" /><figcaption>**Fig. 2.** Kaplan-Meier survival curves between influenza A and B showing similar outcomes.</figcaption></figure>

bacterial superinfections could improve outcomes, as supported by Verdiet et al. [33], who emphasized reducing their impact on ICU mortality, and by Morens et al. [34], who retrospectively analyzed postmortem samples from the Spanish flu (1918–1919), which was largely complicated by superinfections.

Despite its strengths, our study has limitations. Its retrospective design and reliance on tertiary hospital data may limit generalizability, especially for outpatient settings or regions with different influenza epidemiology. Additionally, influenza A subtypes (H 1N1 vs. H3N2) were not distinguished due to diagnostic constraints. Similarly, our study was initially designed to focus on superinfections in viral respiratory tract infections rather than the specific burden of influenza, which may have led to an underestimation of certain aspects. This could be particularly true for influenza B virus, for which the burden in real-world settings remains poorly defined. Likewise, oxygen level requirement was not specified and would have been relevant in such study. Finally, future studies should validate these findings in diverse populations and settings, especially in the current post-COVID-19 era, where influenza B/Yamagata has disappeared [9] and vaccination strategies have evolved. In this context, recent WHO guidelines recommend trivalent vaccines, including two influenza A strains and one B strain. However, updated epidemiological data may be needed to confirm their efficacy.

## Conclusion

Our findings highlight both shared and distinct challenges posed by influenza A and B in clinical management. Indeed, while influenza B patients experienced better short-term (≤5 days) outcomes, overall they experienced more hospitalizations, ICU admissions, and mortality than expected. Therefore, tailored therapeutic strategies and equitable access to early antiviral administration are warranted to mitigate the seasonal burden of both influenza types. These insights provide valuable evidence for clinical practice and public health strategies, emphasizing the necessity of comprehensive vaccination programs to optimize outcomes in hospitalized patients.

## New study

Influenza B shows higher short-term favorable outcomes than Influenza A, despite similar hospitalization and mortality rates. Oseltamivir use was lower for Influenza B, highlighting potential treatment gaps. Influenza B's clinical impact should not be underestimated. #Influenza #AMR.

## CRediT authorship contribution statement

**Benjamin Davido:** Writing – review & editing, Writing – original draft, Validation, Supervision, Methodology, Investigation, Formal analysis, Data curation, Conceptualization. **Benoit Lemarie:** Writing – original draft, Formal analysis, Data curation, Conceptualization. **Elyanne Gault:** Writing – original draft, Formal analysis, Data curation, Conceptualization. **Karim Jaffal:** Writing – original draft, Formal analysis, Data curation, Conceptualization. **Martin Rottman:** Writing – review & editing, Investigation. **Sebastien Beaune:** Writing – original draft, Formal analysis, Data curation, Conceptualization. **Christel Mamona:** Writing – review & editing, Investigation. **Djillali Annane:** Writing – original draft, Supervision, Conceptualization.

## Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

## Acknowledgements

Authors would like to thank the coordination staff for making this article possible and for their valuable contribution.

## Funding

No funding was provided for this study.

## Supplementary materials

Supplementary material associated with this article can be found, in the online version, at doi:10.1016/j.cmicom.2025.105072.

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