# Comparison of patients presenting to emergency departments infected with respiratory syncytial virus versus influenza virus: A retrospective cohort study

Karine Alamé, Quentin Le Hingrat, Pierre Catoire, Richard Chocron, Xavier Eyer, Christelle Hermand, Judith Gorlicki, Sarah Addou, Ségolène Brichler, Maud Salmona, et al.

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Karine Alamé, Quentin Le Hingrat, Pierre Catoire, Richard Chocron, Xavier Eyer, et al. Comparison of patients presenting to emergency departments infected with respiratory syncytial virus versus influenza virus: A retrospective cohort study. Journal of Clinical Virology, 2025, 177, pp.105775. 10.1016/j.jcv.2025.105775. hal-05006594

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# Comparison of patients presenting to emergency departments infected with respiratory syncytial virus versus influenza virus: A retrospective cohort study

Karine Alamé<sup>a</sup>, Quentin Le Hingrat<sup>b,c</sup>, Pierre Catoire<sup>d</sup>, Richard Chocron<sup>e</sup>, Xavier Eyer<sup>f</sup>, Christelle Hermand<sup>g</sup>, Judith Gorlicki<sup>h</sup>, Sarah Addou<sup>i</sup>, Ségolène Brichler<sup>j</sup>, Maud Salmona<sup>k</sup>, David Veyer<sup>l</sup>, Stéphane Marot<sup>m</sup>, Aurélie Schnuriger<sup>n</sup>, Yonathan Freund<sup>a</sup>, Donia Bouzid<sup>b,o,*</sup>

## ARTICLE INFO

### Keywords:

RSV

Influenza

Respiratory viruses

## ABSTRACT

**Objective:** In recent years, there has been increased awareness of the impact of respiratory syncytial virus (RSV) on adult health, especially in elderly patients. Unlike influenza infection, its presentation and patient outcomes are not well studied. The aim of this study was to compare clinical outcomes in emergency department patients infected by RSV vs influenza.

**Methods:** This was a multicenter retrospective study in seven emergency departments (ED) in France. Patients with a laboratory-confirmed RSV or influenza infection in the ED were included between January 2017 and December 2022. The primary endpoint was in-hospital mortality truncated at day 28. Secondary endpoints included one year occurrence of thrombo-embolic event, acute coronary syndrome, and stroke.

**Results:** 3397 patient charts were screened, and 3224 were analyzed. Of these, 551 (17 %) patients had RSV-positive PCR, and 2673 (83 %) had influenza-positive PCR. Patients with RSV were older (median age 73 vs. 68; difference, -5.00 % points [CI, -4.0 to -6.0 % points])), and had more comorbidities (15.0 % vs 22.0 % difference, -6.92 % points [CI, -10.6 to -3.21 % points))), compared to those with influenza. There was no significant difference in in-hospital mortality rate at day 28: 3.82 % for influenza vs. 4.72 % for RSV (adjusted OR 0.93, 95 %CI [0.59-1.46] p = 0.73). There was no significant difference in the occurrence of the secondary endpoints.

**Conclusions:** In this large study of ED patients, although RSV patients were more fragile, no significant differences were found in in-hospital mortality or the occurrence of cardiovascular or thromboembolic events between RSV and influenza infections.

<footnote><sup>a</sup> AP-HP, Emergency Department, Pitié Salpétrière University Hospital, Sorbonne Université, Paris, France</footnote>

<footnote><sup>b</sup> Université Paris Cité, INSERM UMR1137, IAME, F-75018 Paris, France</footnote>

<footnote><sup>c</sup> AP-HP, Virology, Bichat-Claude Bernard University Hospital, Université Paris Cité, Paris, France</footnote>

<footnote><sup>d</sup> Bordeaux University, Inserm, Bordeaux Population Health Research Center, Bordeaux, France</footnote>

<footnote><sup>e</sup> AP-HP, Emergency Department, Georges Pompidou European Hospital, Université Paris Cité, Paris, France</footnote>

<footnote><sup>f</sup> AP-HP Nord, Emergency Department, Lariboisière Hospital, Université Paris Cité, Paris, France</footnote>

<footnote><sup>g</sup> AP-HP, Emergency Department, Saint Antoine University Hospital, Sorbonne Université, Paris, France</footnote>

<footnote><sup>h</sup> AP-HP, Emergency Department, Avicenne University Hospital, Université Sorbonne Paris Nord, Bobigny, France</footnote>

<footnote><sup>i</sup> AP-HP Nord, Emergency Department, Saint Louis University Hospital, Université Paris Cité, Paris, France</footnote>

<footnote><sup>j</sup> AP-HP, Virology, Avicenne University Hospital, Université Sorbonne Paris Nord, Bobigny, France</footnote>

<footnote><sup>k</sup> AP-HP, Virology, Saint Louis University Hospital, Université Paris Cité, Paris, France</footnote>

<footnote><sup>l</sup> AP-HP, Virology, Georges Pompidou European Hospital, Université Paris Cité, Paris, France</footnote>

<footnote><sup>m</sup> AP-HP, Virology, Pitié Salpétrière University Hospital, Sorbonne Université, Paris, France</footnote>

<footnote><sup>n</sup> AP-HP, Virology, Saint Antoine University Hospital, Sorbonne Université, Paris, France</footnote>

<footnote><sup>o</sup> AP-HP Nord, Emergency Department, Bichat-Claude Bernard University Hospital, Université Paris Cité, Paris, France</footnote>

<footnote>* Correspondence to: Bichat-Claude Bernard University Hospital, Emergency Department, 46 rue Henri Huchard, 75018 Paris, France.
E-mail address: donia.bouzid@aphp.fr (D. Bouzid).</footnote>
# 1. Introduction

Respiratory syncytial virus (RSV) is a leading cause of viral respiratory infection in all age groups, particularly affecting young children and older adults [1]. Transmitted through respiratory droplets and contaminated surfaces, RSV has a distinct seasonal pattern in temperate climates, typically appearing from late September to April, with a peak incidence in December or January, preceding the influenza season. Following a significant decline in global RSV cases since 2019 [2], recent data suggests a return to pre-pandemic levels of seasonal activity [3].

In response to the ongoing threat posed by RSV, both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) approved the use of RSV vaccines for active immunisation of persons aged 60 years and older in 2023 to reduce the incidence of RSV-associated lower respiratory tract disease [4-7].

A pre-COVID-19 study of adults aged 60 years and older hospitalised with either RSV or influenza infection showed a higher prevalence of congestive heart failure and chronic obstructive pulmonary disease (COPD) in RSV patients compared with those with influenza [8]. Both RSV and influenza infections have been associated with cardiovascular complications. Kwong et al. reported a significantly increased risk of acute myocardial infarction (AMI) within seven days of viral detection for both influenza and RSV [9]. Furthermore, a crossover cohort analysis showed significantly increased odds of AMI and venous thromboembolism (VTE) in the 30 days after hospital discharge compared with the 30 days before respiratory viral infection, independent of the specific virus type [10].

This study aimed to compare mortality rates between emergency department (ED) patients infected with RSV and those infected with influenza and examine the occurrence of thromboembolic and cardiovascular events in these populations.

# 2. Methods

## 2.1. Study design

We performed a retrospective chart review from January 2017 to December 2022.

This retrospective observational multicenter study included seven E. D.s in the Paris metropolitan area, France. All centers are academic hospitals belonging to the "Assistance Publique – Hôpitaux de Paris" network.

The study was approved by the ethics committee of Sorbonne Université (Comité d'éthique de la recherche de Sorbonne Université, Paris, France). Due to its retrospective nature on de-identified data, informed consent was waived, and the study was excluded from the legal requirements applicable to research involving humans within the provisions of the French Public Health Code.

## 2.2. Objective and outcomes

The primary objective of this study was to assess the in-hospital mortality of adult patients visiting the E.D. with an RSV infection compared to influenza infection.

The primary endpoint was in-hospital mortality, truncated at day 28. The secondary objective was to compare the one-year occurrence of cardiovascular and thromboembolic events infection among those patients. Secondary endpoints included thrombo-embolic events (pulmonary embolism or deep venous thrombosis), acute coronary syndrome, stroke, and any of these three events.

## 2.3. Patients

Patients were included if they visited one of the participating E.D.s between January 2017 and December 2022 and presented an RSV, influenza A or influenza B infection, confirmed through a molecular

assay. In each hospital, patients with a laboratory-confirmed RSV, influenza A, or B infection were identified through the laboratory information management system (Glims, Clinisys, Paris, France).

In cases of multiple E.D. visits during the inclusion period, only the first one was included and analyzed.

Patients with documented co-infections were excluded from the analysis.

## 2.4. Data collection

The recommendations for reducing bias in retrospective chart review studies were followed. These included a priori definition of baseline characteristics, exposure and outcomes, formal coding of the case report form, and remote training for abstractors. A standardized data collection instrument with clear criteria (categorical or quantitative variables) was shared. All data were collected on the integrated electronic patient record of the APHP trust (Orbis, AGFA Healthcare). We could not retrieve medical charts if the patients visited a hospital outside the APHP trust.

Medical files of patients that were transferred to another hospital from the APHP trust were available, reducing the risk of loss to follow-up.

Baseline characteristics included demographic data, past medical history, vaccination status, physiological variables at E.D. presentation, inflammatory biological markers (leukocytes, C-reactive protein (CRP)), and oxygen supplementation in the E.D. Discharge disposition and hospital course were also recorded, including ward admission, ICU admission, mechanical ventilation, length of stay in the hospital and length of stay in the ICU, and in-hospital mortality.

## 2.5. Statistical analysis

Patient characteristics were summarized using counts and percentages for categorical variables, and medians with interquartile ranges for numerical variables. The impact of virus type on 28-day mortality was assessed using both univariable and multivariable analyses, applying a logistic mixed model with a random intercept for the center. Variable selection for the multivariable analysis was conducted using the purposeful selection algorithm [11]. Clinically relevant confounding factors, based on experts' judgment (including chronic respiratory disease, obesity and immunodeficiency) were maintained in the model even if they were excluded from the purposeful algorithm. As blood pressure and pulse oximetry can be considered as mediators (both consequence of virus type, and causing death), they have been excluded from confounding factors [12]. Secondary outcomes were analyzed using the same multivariable mixed model applied to the primary outcome. To handle missing data, multiple imputations by chained equations were performed with pooling according to Rubin's rule. Missing values are detailed in Table 1. An effect was considered significant if the p-value for the parameter estimate was less than 0.05.

All analyses were conducted using R software, version 4.4.0 [R4.4.0] [13], utilizing the lme4 and mice packages [lme4, mice] [14,15].

# 3. Results

## 3.1. Baseline characteristics at ED admission

Of the 3397 patient charts reviewed, 28 patients with RSV and influenza coinfection and 145 with missing data were excluded. A total of 3224 patients were included. Of these, 2673 (83 %) had a positive PCR for influenza A/B, including 2232 (69.2 %) with Influenza A and 441 (13.6 %) with influenza B, and 551 (17 %) had a positive PCR for RSV (Fig. 1).

Patients with RSV were more frequently female (54.80 % vs. 49.64 %, difference, -5.16 % points [CI, -9.73 to -0.60 % points]) and older than those with influenza (median [IQR], 73 [60-86] years vs. 68 [48-81] years; difference, -5.00 % points [CI, -4.00 to -6.00 %
<table><caption>**Table 1**

Characteristics and Management of patients presenting to the ED with RSV versus Influenza infections.</caption><thead><tr><th>Demographics</th><th>Observ<sup>a</sup></th><th>All patients<br>N = 3224</th><th>Influenza A/B<br>N = 2673</th><th>RSV<br>N = 551</th><th>p-value</th></tr></thead><tbody><tr><td>Age (years) med, IQR</td><td>3224</td><td>69(51-82)</td><td>68(48-81)</td><td>73(60-86)</td><td>&lt;0.0001</td></tr><tr><td>&nbsp;&nbsp;&nbsp;&nbsp;&lt; 65 years, %</td><td></td><td>1358(42.12)</td><td>1182(44.22)</td><td>176(31.94)</td><td>&lt;0.0001</td></tr><tr><td>&nbsp;&nbsp;&nbsp;&nbsp;65-75 years, %</td><td></td><td>593(18.39)</td><td>481(17.99)</td><td>112(20.33)</td><td>0.22</td></tr><tr><td>&nbsp;&nbsp;&nbsp;&nbsp;75-90 years, %</td><td></td><td>903(28.01)</td><td>734(27.46)</td><td>169(30.67)</td><td>0.14</td></tr><tr><td>&nbsp;&nbsp;&nbsp;&nbsp;&gt; 90 years, %</td><td></td><td>370(11.48)</td><td>276(10.33)</td><td>94(17.06)</td><td>&lt;0.0001</td></tr><tr><td>Female, %</td><td>3224</td><td>1629(50.53)</td><td>1327(49.64)</td><td>302(54.80)</td><td>0.03</td></tr><tr><td><strong>Comorbidities</strong></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>BMI &gt; 30 kg/m<sup>2</sup>, %</td><td>3220</td><td>353(10.95)</td><td>269(10.06)</td><td>84(15.25)</td><td>0.0005</td></tr><tr><td>Hypertension, %</td><td>3220</td><td>1447(44.88)</td><td>1155(43.21)</td><td>292(52.99)</td><td>&lt;0.0001</td></tr><tr><td>Diabetes, %</td><td>3220</td><td>681(21.12)</td><td>547(20.46)</td><td>134(24.32)</td><td>0.04</td></tr><tr><td>Chronic lung disease, %</td><td>3220</td><td>737(22.86)</td><td>558(20.88)</td><td>179(32.49)</td><td>&lt;0.0001</td></tr><tr><td>Chronic kidney disease, %</td><td>3220</td><td>407(12.62)</td><td>319(11.93)</td><td>88(15.97)</td><td>0.01</td></tr><tr><td>Immunodeficiency, %</td><td>3220</td><td>628(19.48)</td><td>501(18.74)</td><td>127(23.05)</td><td>0.02</td></tr><tr><td>Nb of comorbidities, %</td><td>3220</td><td></td><td></td><td></td><td></td></tr><tr><td>&nbsp;&nbsp;&nbsp;&nbsp;None</td><td></td><td>946(29.34)</td><td>841(31.46)</td><td>105(19.06)</td><td>&lt;0.0001</td></tr><tr><td>&nbsp;&nbsp;&nbsp;&nbsp;One</td><td></td><td>1016(31.51)</td><td>852(31.87)</td><td>164(29.76)</td><td>0.36</td></tr><tr><td>&nbsp;&nbsp;&nbsp;&nbsp;Two</td><td></td><td>739(22.92)</td><td>578(21.62)</td><td>161(29.22)</td><td>0.0001</td></tr><tr><td>&nbsp;&nbsp;&nbsp;&nbsp;Three or more</td><td></td><td>523(16.22)</td><td>402(15.04)</td><td>121(21.96)</td><td>&lt;0.0001</td></tr><tr><td><strong>Vaccination status</strong></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Influenza</td><td>1718</td><td>556(17.25)</td><td>445(16.65)</td><td>111(20.15)</td><td>0.06</td></tr><tr><td>RSV</td><td>3224</td><td>0(0.00)</td><td>0(0.00)</td><td>0(0.00)</td><td></td></tr><tr><td><strong>ED presentation</strong></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Heart rate (bpm), med, IQR</td><td>3129</td><td>95(82-110)</td><td>95(82-110)</td><td>95(81-109)</td><td>0.36</td></tr><tr><td>SystBP (mmHg), med, IQR</td><td>2418</td><td>131(115-147)</td><td>130(114-147)</td><td>135.5(118-152)</td><td>0.01</td></tr><tr><td>SystBP &lt; 90 mmHg, %</td><td>2418</td><td>56(1.74)</td><td>45(1.68)</td><td>11(2.00)</td><td>0.73</td></tr><tr><td>SpO2(%), med, IQR</td><td>3055</td><td>95(92-98)</td><td>96(92-98)</td><td>94(90-97)</td><td>&lt;0.0001</td></tr><tr><td>SpO2 &lt; 92%, %</td><td>3055</td><td>709(21.99)</td><td>541(20.24)</td><td>168(30.49)</td><td>&lt;0.0001</td></tr><tr><td>Symptom onset, med, IQR</td><td>3003</td><td>3(2-5)</td><td>3(2-5)</td><td>3(2-7)</td><td>&lt;0.0001</td></tr><tr><td>Temperature &gt; 38 °C, %</td><td>3224</td><td>2076(64.39)</td><td>1801(64.38)</td><td>275(49.91)</td><td>&lt;0.0001</td></tr><tr><td><strong>Laboratory results</strong></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>WBC (G/l), med, IQR</td><td>2729</td><td>7.60(5.5-10.3)</td><td>7.40(5.4-10.0)</td><td>9.03(6.5-11.8)</td><td>&lt;0.0001</td></tr><tr><td>CRP (mg/l), med, IQR</td><td>1579</td><td>40.0(18.0-89.0)</td><td>40.0(17.0-88.0)</td><td>44.0(20.0-95.0)</td><td>0.25</td></tr><tr><td><strong>ED management</strong></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Oxygen therapy, %</td><td>3224</td><td>1264(39.21)</td><td>968(36.21)</td><td>296(53.72)</td><td>&lt;0.0001</td></tr><tr><td>Oxygen (l/min), med, IQR</td><td>3224</td><td>0.0(0.0-2.0)</td><td>0.0(0.0-2.0)</td><td>0.0(1.0-3.0)</td><td></td></tr><tr><td>HFNC, %</td><td>3224</td><td>8(0.25)</td><td>6(0.22)</td><td>2(0.36)</td><td>0.90</td></tr><tr><td>Mechanical ventilation, %</td><td>3224</td><td>25(0.78)</td><td>18(0.67)</td><td>7(1.27)</td><td>0.23</td></tr><tr><td><strong>ED Diagnosis</strong></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>LRTI, %</td><td>3224</td><td>1678(52.05)</td><td>1355(50.69)</td><td>323(58.62)</td><td>0.0008</td></tr><tr><td>COPD exacerbation, %</td><td>3224</td><td>356(11.04)</td><td>248(9.28)</td><td>108(19.60)</td><td>&lt;0.0001</td></tr><tr><td>Congestive heart failure, %</td><td>3224</td><td>334(10.36)</td><td>231(8.64)</td><td>103(18.69)</td><td>&lt;0.0001</td></tr><tr><td>Pulmonary embolism, %</td><td>3224</td><td>21(0.65)</td><td>13(0.49)</td><td>8(1.45)</td><td>0.02</td></tr><tr><td><strong>ED discharge disposition, %</strong></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Discharged to residence, %</td><td>3224</td><td>1189(36.88)</td><td>1056(39.51)</td><td>133(24.14)</td><td>&lt;0.0001</td></tr><tr><td>Hospital admission, %</td><td>3224</td><td>2035(63.12)</td><td>1617(60.49)</td><td>418(75.86)</td><td>&lt;0.0001</td></tr><tr><td>ICU admission, %</td><td>3224</td><td>206(6.39)</td><td>166(6.21)</td><td>40(7.26)</td><td>0.41</td></tr></tbody></table>

For numerical variables, data are expressed in median(med) and interquartile range (IQR): second quartile (first quartile-third quartile), along with the difference in range(diff) and its 95 % confidence interval(95 %CI).

For categorical variables, data are expressed in n/N (%) along with the difference in percentage (diff) and its 95 % confidence interval(95 %CI), where n represents the number of events and N represents the total number of observations or the overall subpopulation.

Statistical significance of Mann-Whitney, t-Student or Khi2 tests is: p < 0.05 and p < 0.001.

Abbreviations: COPD, Chronic Obstructive Pulmonary Disease; CRP, C-Reactive Protein; ED, Emergency Department; HFNC, High Flow Nasal Cannula; ICU, Intensive Care Unit; LRTI, Lower Respiratory Tract Infection; WBC, White Blood Cells; SystBP, Systolic Blood Pressure.

a Observ = Observations represents the total number of observations, without missing data.

points]). RSV patients had more comorbidities (15.04 % vs 21.96 % difference, -6.92 % points [CI, -10.6 to -3.21 % points), such as BMI above 30 kg/m² (15.25 % vs. 10.06 %; difference, -5.18 % points [CI, -8.39 to -1.97 % points), hypertension (52.99 % vs. 43.21 %; difference, -9.78 % points [CI, -14.4 to -5.21 % points) and chronic respiratory disease (32.49 % vs. 20.88 %; difference, -11.61 % points [CI, -15.8 to -5.21 % points). RSV patients had higher rates of dyspnea (70.6 % vs. 51.0 %) and cough (77.6 % vs. 70.7 %) compared to influenza patients, while influenza patients more commonly reported shivering (21.2 % vs. 16.0 %) and myalgia (26.5 % vs. 13.6 %). Significant differences in these symptoms highlight varying clinical presentations (p < 0.05) (Supplementary Table 1). RSV patients were also more likely to require oxygen therapy in the ED (53.72 % vs. 36.21 %; difference, -17.51 % points [CI, -22.1 to -12.96 % points) and were more likely to be admitted to the hospital after ED management (75.86 % vs. 60.49 %; difference, -15.37 % points [CI, -19.39 to -11.34 % points]). 556 patients (17.25 %) were vaccinated against influenza and none were vaccinated against RSV (Table 1).

## 3.2. Primary endpoint: In-hospital mortality for RSV and influenza patients truncated at day 28

RSV patients exhibited a 4.72 % (n = 26) in-hospital mortality rate truncated at day 28, compared to 3.82 % (n = 102) for influenza patients. However, after adjusting for confounding variables, no significant difference in hospital mortality at day 28 was identified between the groups (adjusted odds ratio 0.93, 95 % CI 0.59-1.46). Age, chronic respiratory failure and chronic kidney disease were independently associated with increased in-hospital mortality, with adjusted odds ratios of 1.05 (95 % CI: 1.04-1.07), 1.13 (95 % CI: 0.75-1.72) and 1.63
<figure><img src="image_3.png" /><figcaption>**Fig. 1.** Flowchart of the study. Abbreviations: ED, Emergency department; NA, missing values; RSV, Respiratory Syncytial Virus. * in-hospital deaths truncated at day 28.</figcaption></figure>

(95 % CI: 1.06–2.53) respectively. The results of the multivariable mixed model are detailed in Tables 2 and 3.

### 3.3. Cardiovascular or thromboembolic events at year one

Within the first year following RSV or influenza infection, there were 55 cardiovascular or thromboembolic events: 1(0.19) within the seven days after discharge, 2(0.39) within the first thirty days after discharge and 13 (2.51 %) within at year-one in the RSV group versus 2(0.08) within the seven days after discharge, 4(0.16) within the first thirty days after discharge and 42 (1.64 %) at year-one in the influenza group. No significant association was found between pulmonary embolism at one year and type of infection, with an adjusted odds ratio (aOR) of 1.62 (95 % CI, 0.89–2.96) for RSV versus influenza. Similarly, no significant associations were observed for acute coronary syndrome (aOR 1.35, 95 % CI, 0.76–2.39) or stroke (aOR 1.28, 95 % CI, 0.68–2.39). These results are detailed in Table 2.

<caption>**Table 3**</caption>

Multivariable logistic regression analysis of in-hospital mortality at day 28 for RSV vs. influenza in Emergency Department Patients.

<table><thead><tr><th></th><th>Estimated Odds-Ratio</th><th>95 %CI</th><th>p-value</th></tr></thead><tbody><tr><td><strong>Virus</strong></td><td></td><td></td><td></td></tr><tr><td>Influenza (Ref)</td><td></td><td></td><td></td></tr><tr><td>RSV</td><td>0.93</td><td>0.59–1.46</td><td>0.73</td></tr><tr><td>Age</td><td>1.05</td><td>1.04–1.07</td><td>&lt;0.05</td></tr><tr><td><strong>Comorbidities</strong></td><td></td><td></td><td></td></tr><tr><td>Chronic kidney disease</td><td>1.63</td><td>1.06–2.53</td><td>0.03</td></tr><tr><td>Chronic resp disease</td><td>1.13</td><td>0.75–1.72</td><td>0.55</td></tr><tr><td>BMI &gt; 30 kg/m<sup>2</sup></td><td>1.39</td><td>0.76–2.56</td><td>0.30</td></tr><tr><td>Immunodeficiency</td><td>1.25</td><td>0.79–1.97</td><td>0.34</td></tr></tbody></table>

Primary outcome: multivariable mixed model assessing the 28-day mortality risk in ED patients with Influenza versus RSV.

Abbreviations: RSV, Respiratory Syncytial Virus; BMI, body mass index.

<caption>**Table 2**</caption>

Primary and Secondary Outcomes of patients presenting to the ED with RSV versus Influenza infections.

<table><thead><tr><th></th><th>All ED patients</th><th>Influenza A/B</th><th>RSV</th><th>Univariable<br>Diff</th><th>95 % CI</th><th>Multivariable<br>aOR</th><th>95 %CI</th><th>p-value</th></tr></thead><tbody><tr><td><strong>Primary outcome</strong></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td><strong>Hospital survival outcome</strong></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>In-hospital mortality truncated at D28</td><td>N = 3224<br>128(3.97)</td><td>N = 2673<br>102(3.82)</td><td>N = 551<br>26(4.72)</td><td>-0.90</td><td>-3.11–-0.78</td><td>0.93</td><td>0.59–1.46</td><td>0.73</td></tr><tr><td><strong>Secondary outcomes</strong></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td><strong>Any adverse event at year-1</strong></td><td>N = 3078<br>55(1.78)</td><td>N = 2560<br>42(1.64)</td><td>N = 518<br>13(2.51)</td><td>-0.87</td><td>-2.66–-0.31</td><td>1.36</td><td>0.72–2.57</td><td>0.346</td></tr><tr><td>Pulmonary embolism</td><td>15(0.48)</td><td>10(0.39)</td><td>5(0.97)</td><td>-0.57</td><td>-1.86–-0.07</td><td>1.62</td><td>0.89–2.96</td><td>0.12</td></tr><tr><td>Coronary artery syndrome</td><td>26(0.84)</td><td>20(0.78)</td><td>6(1.16)</td><td>-0.38</td><td>-1.75–-0.38</td><td>1.35</td><td>0.76–2.39</td><td>0.30</td></tr><tr><td>Stroke</td><td>16(0.52)</td><td>13(0.51)</td><td>3(0.58)</td><td>-0.07</td><td>-1.20–-0.45</td><td>1.28</td><td>0.68–2.39</td><td>0.44</td></tr></tbody></table>

Data are expressed in n/N (%) along with the difference in percentage (diff) and its 95 % confidence interval (95 %CI), where n represents the number of events and N represents the total number of observations or the overall subpopulation.

Primary outcome: multivariable logistic model assessing the 28-day mortality risk in ED patients with Influenza versus RSV. Adjusted on the co-variates age and comorbidities (BMI > 30 m²/kg, diabetes, immunodeficiency, chronic lung and kidney disease). The results are presented as aOR with corresponding 95 % confidence intervals (CI 95 %).

Reference level is influenza A/B infection.

Secondary outcomes: logistic models assessing the association between Influenza versus RSV and adverse effects (cardiovascular or thromboembolic disease) or death, at year-one. The results are presented as aOR accompanied by their CI (95 %).

Reference level is influenza A/B infection.

Abbreviations: aOR, Adjusted odds-ratio; ED, Emergency Department; RSV, Respiratory Syncytial Virus.
### 3.4. Pre and post-pandemic analysis

In hospital mortality at day-28 for influenza ranged from 2.41 % to 4.24 % pre-pandemic (2017–2019), dropping to 2.73 % in 2020 and 3.76 % in 2022. For RSV, mortality ranged from 3.00 % to 6.25 %, with a noticeable increase in 2020 (6.25 %) but no significant trends across the years (p > 0.05). Similarly, the occurrence of adverse events at one year, including pulmonary embolism, coronary artery syndrome, and stroke, showed no significant differences between RSV and influenza infections across the years. Although the number of events varied slightly (e.g., RSV: 1.03–6.35 %; influenza: 1.08–3.70 %), these fluctuations were not statistically significant (Fig. 2).

### 4. Discussion

In this retrospective chart review of 3224 adult patients presenting to academic emergency departments in the Paris area before and after the COVID-19 pandemic, 17 % had RSV-positive PCR, and 83 % had influenza A/B-positive PCR. Although RSV infection affects elder patients and result in more hospitalisations, in-hospital mortality rates for RSV and influenza A/B infections are similar. Cardiovascular and thromboembolic events one year after the infection are also comparable between RSV and influenza infection.

Our study confirms previous findings on RSV infection in adults. Patients with RSV are older than those with influenza, with a median age of 73 versus 68 years. They also have a higher prevalence of comorbidities, especially chronic lung disease (32.4 % vs. 20.8 %) [16], and are more likely to be overweight.

Another important finding was that RSV patients were more likely to require oxygen therapy than influenza patients (53.5 % vs. 36.1 %) and more likely to be hospitalised (76 % vs. 60 %). However, there was no significant difference between RSV and influenza patients' need for high-flow nasal cannula (HFNC) or ICU admission. A recent American cohort study showed that RSV patients were more likely to require HFNC and ICU admission compared to patients hospitalised with COVID-19 or influenza. Specifically, the adjusted odds ratio (aOR) for RSV patients requiring HFNC was 2.25 compared to COVID-19 patients and 1.99

compared to influenza patients. The likelihood of ICU admission was higher for RSV patients, with aORs of 1.49 compared to COVID-19 and 1.55 compared to influenza [17].

The observed difference in ICU admissions and HFNC use in our study compared with a previous report is probably because ICU admission criteria became more stringent in our hospitals since the COVID-19 health crisis. This change in admission criteria has resulted in a more selective approach, with the most severe cases being prioritized for intensive care. Consequently, this may explain why our results differ from previous studies, as the threshold for ICU admission and HFNC use has been raised, reflecting evolving healthcare protocols in the post-pandemic landscape [18].

A recent study by Recto and colleagues has reported a similar mortality rate at day 30 between RSV and influenza among older patients (>75 years) (9.6 % vs. 9.7 %, p = 0.973) [19]. Our study also reports similar but lower, in-mortality rates between RSV (4.7 %) and influenza (3.8 %), which is explained by the fact that our cohort included all adults visiting the emergency departments and not only the elderly or those who were hospitalised.

In another work by Surie and colleagues comparing RSV severity to COVID-19 and influenza, the outcome of invasive mechanical ventilation or death was experienced by 12 % of the RSV patients [20].

Previous studies have shown a significant association between various infections and cardiovascular events [9]. Lower respiratory tract infections, including bacterial pneumonia, influenza, and RSV infections, can exacerbate existing cardiovascular conditions and trigger new adverse cardiovascular events due to the inflammatory response and increased coagulability they induce. Similarly, a previous report showed that patients with respiratory infection are more likely to be readmitted for venous thromboembolism than patients admitted for asthma with aHR 1.28, 95 % CI 1.24–1.33 [10]. In our study, though, we did not observe any difference in the occurrence of such events between RSV and influenza patients.

### 5. Limitation

The main limitation of our study is its retrospective design. Indeed,

<figure><img src="image_4.png" /><figcaption>**Fig. 2.** Disease severity of RSV versus Influenza infections in the ED yearly, before and after the COVID-19 pandemic. Figure highlighting disease severity of RSV versus Influenza infections in the ED, yearly, before and after COVID-19 pandemic. Disease severity includes mortality and day-28 and any adverse event (pulmonary embolism, coronary artery syndrome and stroke) one year after RSV versus influenza infection in ED patients.</figcaption></figure>
some data may not have been recorded, and there was no monitoring of
the data collection method.

Second, we analyzed patients when they presented to the E.D., which incorporates a selection bias to evaluate the overall mortality of RSV and influenza patients. However, our study allows the comparison of characteristics of patients at the time of E.D. presentation and cardiovascular and thromboembolic events in patients who are subsequently hospitalised or discharged from the hospital.

We did not collect any information about influenza treatment nor antibiotic use. However, in a similar work of our team [21], we demonstrated that rapid respiratory syndromic testing significantly patient management, mainly by improving isolation measures. Almost all patients who were tested influenza positive received Oseltamivir treatment (98 %) while 58 % received antibiotic treatment. This highlights the importance of pathogen identification, which could influence treatment choices in this cohort as well.

Finally, it is essential to note that cardiovascular and thromboembolic events were tracked solely through the AP-HP trust system. Consequently, if patients sought E.D. outside the AP-HP network, we could not obtain data on these events. This limitation means that any such incidents occurring at non-AP-HP facilities were not captured in our analysis.

In conclusion, our comprehensive study of emergency department patients showed no significant differences in in-hospital mortality or the incidence of cardiovascular or thromboembolic events between RSV and influenza infections.

## Funding

There was no funding for this study.

## Author contributions

D.B. and Y.F. conceived the study. K.A. and PC coordinated the analyses. D.B. and Q.L. performed the literature search. R.C., XE, CH, S.A., J.G., MS, AS, DV, and SB collected the data. K.A., and D.B. assessed and revised the data. K.A. and D.B. accessed and verified the underlying study data. KA did the statistical analyses. All authors participated in the interpretation of the data. D.B., Y.F., and Q.L. wrote the manuscript, which was revised by all authors. D.B. and Y.F. were responsible for the decision to submit the manuscript. All authors had full access to all the data in the study and had final responsibility for the decision to submit for publication.

## CRediT authorship contribution statement

**Christelle Hermand:** Investigation. **Judith Gorlicki:** Investigation. **Sarah Addou:** Investigation. **Ségolene Brichler:** Investigation. **Maud Salmona:** Investigation. **David Veyer:** Investigation. **Stéphane Marot:** Investigation. **Xavier Eyer:** Investigation. **Aurélie Schnuriger:** Investigation. **Karine Alamé:** Writing – review & editing, Formal analysis, Data curation. **Yonathan Freund:** Writing – review & editing, Validation, Supervision. **Quentin Le Hingrat:** Writing – review & editing, Validation, Investigation. **Donia Bouzid:** Writing – review & editing, Writing – original draft, Validation, Supervision, Methodology, Conceptualization. **Pierre Catoire:** Methodology, Formal analysis. **Richard Chocron:** Investigation.

## 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.

## Acknowledgments

The authors would like to thank Mrs Vanessa Lemaitre for her constant help and support.

## Appendix A. Supporting information

Supplementary data associated with this article can be found in the online version at doi:10.1016/j.jcv.2025.105775.

## Data availability

Data collected for the study, including individual participant data and the data dictionary, will be made available on reasonable request. Data will be provided as de-identified participant data in accordance with French law and will be available after publication of the manuscript. Data requests should be addressed to Donia Bouzid (donia.bouzid@aphp.fr) or Yonathan Freund (yonathan.freund@aphp.fr), who will send the data after approval, after requestors provide a signed data access agreement.

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