# Influenza and pneumococcal vaccine coverage among adults hospitalised with acute respiratory infection in France: a prospective cohort study

Simon Rolland, Lb Luong Nguyen, A Descamps, Florence Galtier, X Duval, Philippe Vanhems, F Lainé, Pierre Tattevin, R Bauer, O Launay

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## ► To cite this version:

Simon Rolland, Lb Luong Nguyen, A Descamps, Florence Galtier, X Duval, et al.. Influenza and pneumococcal vaccine coverage among adults hospitalised with acute respiratory infection in France: a prospective cohort study. International Journal of Infectious Diseases, 2025, 153, pp.107811. 10.1016/j.ijid.2025.107811. hal-04975787

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Submitted on 4 Mar 2025

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# Influenza and pneumococcal vaccine coverage among adults hospitalized with acute respiratory infection in France: A prospective cohort study

<figure><img src="image_3.png" /></figure>

Simon Rolland<sup>1,2,*</sup>, LB. Luong Nguyen<sup>1</sup>, A. Descamps<sup>1</sup>, F. Galtier<sup>3,4</sup>, X. Duval<sup>4,5</sup>, P. Vanhems<sup>4,6</sup>, F. Lainé<sup>4,7</sup>, P. Tattevin<sup>4,8</sup>, R. Bauer<sup>9</sup>, O. Launay<sup>1,4,10</sup>, for the FLUVAC study group<sup>#</sup>

## ARTICLE INFO

**Article history:**

Received 26 October 2024

Revised 12 December 2024

Accepted 27 January 2025

**Keywords:**

Influenza

Streptococcus pneumoniae

Vaccination coverage

France

Adults

## ABSTRACT

**Objectives:** This study aimed to estimate influenza and pneumococcal vaccination coverage among adults hospitalized with severe acute respiratory infections in France from 2016 to 2022 and to analyze factors associated with vaccination.

**Methods:** We analyzed data from a prospective multicenter study involving adults hospitalized with severe acute respiratory infections. Descriptive and comparative analyses of influenza and pneumococcal vaccination coverage were conducted along with multivariate logistic regression to identify the factors associated with vaccination.

**Results:** We included 4,614 patients; 88% (4,080/4,614) had an indication for influenza vaccination. Among them, 2,181/4,080 (53%) were vaccinated against influenza. Factors associated with vaccination included age ≥65 years (adjusted odds ratio [aOR] 3.05; 95% confidence interval [CI] 2.63-3.55) and chronic respiratory diseases (aOR 1.38; 95% CI 1.20-1.59). Pneumococcal vaccination status was available for 90% (4,142/4,614) of patients, of whom 71% (2,920/4,142) had an indication for vaccination. Pneumococcal vaccination coverage was 19% (551/2,920). The factors associated with vaccination were chronic respiratory disease (aOR 2.74; 95% CI 2.22-3.40) and immunocompromised conditions other than malignancies. The vaccination coverage for each vaccine did not increase over time. Among the 3,247 patients eligible for both vaccines, 13% received both vaccines.

**Conclusions:** In this high-risk population, the vaccination coverage was low, particularly with pneumococcal vaccines. Therefore, improved vaccination recommendation strategies and communication are required.

© 2025 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

<footnote n="1"><sup>1</sup>INSERM, CIC 1417; AP-HP, Cochin Hospital, CIC Cochin Pasteur, Paris, France</footnote>

<footnote n="2"><sup>2</sup>Infectious and Tropical Diseases Department, Cavale Blanche Hospital, Brest University Hospital, Brest, France</footnote>

<footnote n="3"><sup>3</sup>INSERM, CIC 1411, Saint-Éloï Hospital, Montpellier University Hospital, Montpellier, France</footnote>

<footnote n="4"><sup>4</sup>INSERM, F-CRIN, I REIVAC, Paris, France</footnote>

<footnote n="5"><sup>5</sup>INSERM CIC 1425, AP-HP, Bichat Hospital, Paris, France</footnote>

<footnote n="6"><sup>6</sup>Hygiene, Epidemiology, Infectious vigilance and Prevention Department, Hospices Civils de Lyon, Lyon, France</footnote>

<footnote n="7"><sup>7</sup>INSERM CIC 1414, Rennes, France</footnote>

<footnote n="8"><sup>8</sup>Infectious Diseases and Intensive Care Departement, Pontchaillou Hospital, Rennes University Hospital, Rennes, France</footnote>

<footnote n="9"><sup>9</sup>INSERM, SC10-US19, Villejuif, France</footnote>

<footnote n="10"><sup>10</sup>Université Paris Cité; Paris, France</footnote>

<footnote>* Corresponding author: Tel.: +33.2.30.33.76.74.</footnote>

<footnote>E-mail address: simon.rolland@chu-brest.fr (S. Rolland).</footnote>

<footnote># FLUVAC Study group. Includes: S. Amour, A. Arulananthan, R. Bauer, A. Bourgeois, F. Cerret, H. Chevassus, Y. Costa de Beauregard, L. Crantelle, C. Del-Signore, J. Dira, C. Durier, X. Duval, V. Foubert, V. Foulongne, L. Gallais, P. Géraud, S. Henry, N.</footnote>

<footnote>Houho, R. Kafi, S.M. Keita, AS. L'Honneur, G. Lagathu, F. Lainé, B. Lefeuvre, B. Lina, LB. Luong Nguyen, L. Meyer, C. Merle, E. Nyiramigisha, B. Robin, Y. Saidi, P. Tattevin, M. Zerrouki.</footnote>
## Introduction

Influenza viruses and *Streptococcus pneumoniae* are the major causes of severe acute respiratory infections (SARI) and lower respiratory tract infections (LRTIs). *S. pneumoniae* was identified as the leading cause of LRTIs, accounting for 197 million cases and more than one million deaths in 2016 [1], whereas influenza accounted for more than 54 million LRTIs, resulting in approximately 145,000 associated deaths in 2017 [2]. In high-income countries, LRTIs predominantly affect older adults, individuals with chronic medical conditions (especially pulmonary or cardiovascular diseases), and those with immunocompromised conditions, with a higher incidence and poorer outcomes for both infections [1,3-6]. Thus, influenza and pneumococcal vaccines are instrumental in mitigating this burden [7,8], and many countries recommend both vaccines to at-risk individuals [9,10].

In France, recommendations for seasonal influenza vaccination target adults aged ≥65 years, as well as those aged <65 years with chronic medical conditions (i.e., chronic respiratory or cardiac disease, diabetes, chronic renal failure, body mass index ≥40 kg/m², chronic liver disease, sickle cell disease, neurologic and muscular disorders, history of stroke, paraplegia, and tetraplegia) or immunocompromised diseases [11]. Influenza vaccination campaigns include broad communication using mass media, vouchers sent directly to eligible patients (as identified by the French National Health Insurance), and vaccines that can be directly prescribed and administered by different health care professionals (medical doctors, nurses, midwives, and pharmacists). In contrast, pneumococcal vaccination recommendations are not based on age but target adults with specific chronic medical conditions (i.e., chronic respiratory or cardiac disease, diabetes, chronic renal failure, chronic liver disease, and adults with an osteomeningeal breach or a cochlear implant) or acquired immunocompromised conditions. Until recently, the vaccination regimen involved a combination of two vaccines: a first dose of a pneumococcal 13-valent conjugate vaccine (PCV13) and a second dose of a non-conjugated 23-valent polysaccharide vaccine (PPSV23) at least 8 weeks later, with a booster dose of PPSV23 5 years later. In the context of the evolving landscape of available vaccines against infectious agents that cause SARIs, this study aimed to describe influenza and pneumococcal vaccine coverage among adults hospitalized with SARI between the 2016 and 2022 seasons and their determinants in a surveillance network of five French referral hospitals.

## Matériel and methods

### Study overview

We analyzed data from patients enrolled between the 2016 and 2022 seasons in the FLUVAC study, a prospective, multicenter, test-negative design study conducted in five French referral hospitals, measuring seasonal influenza vaccine effectiveness against hospitalized flu [12-14]. Before 2020, the inclusion period lasted during the influenza season from October to May, as defined by the French Public Health Agency (Santé Publique France). Due to the COVID-19 pandemic, patients were included year-round from November 2020 to 2022. The inclusion criteria were age ≥18 years, hospitalization for at least 24 hours with SARI (identified according to the European Centre for Disease Prevention and Control case definition, see Supplementary Methods 1), and symptoms onset <14 days before swabbing. The exclusion criteria were as follows: contraindications to influenza vaccination, previous laboratory-confirmed influenza in the current influenza season, use of influenza antiviral medication between symptom onset and swabbing, lack of French social security affiliation, and residence in a long-term care facility.

### Study population and data collection

We collected sociodemographic characteristics, chronic medical conditions, usual treatments, pneumococcal vaccination details within 5 years before hospitalization (type of vaccine, number of doses, and date of vaccination), and influenza vaccination before hospitalization during the inclusion season from medical records and interviews with patients or their families, and if necessary, patients' general practitioners or pharmacists. HIV infection and/or organ/hematopoietic cell transplantation were recorded as single variables without distinction or further detail. No information regarding osteomeningeal breaches, cochlear implants, or candidates for cochlear implants was available.

### Data analysis

We defined eligibility for influenza and pneumococcal vaccination in accordance with the National Guidelines during the study period [11] (see Supplementary Methods 2). We considered participants as vaccinated against influenza if they received the vaccine before hospitalization during the ongoing season and against pneumococcus if they received any pneumococcal vaccines during the last 5 years before hospitalization. Among patients vaccinated against pneumococcus, we described the pneumococcal vaccine schedule received (either a non-conjugated polysaccharide vaccine alone, a conjugate vaccine alone, or a combination of the two) when the vaccine schedule could be identified. The vaccination status was self-reported or collected from medical records or interviews with family members or health care professionals (physicians and pharmacists).

To identify factors associated with influenza and pneumococcal vaccination, multivariate analysis was conducted based on the univariate analysis used for selecting variables of interest. All covariates with a P-value <0.2 in a multivariable model were tested using a backward stepwise logistic regression model. The results were expressed as adjusted odds ratios (aOR) with a 95% confidence interval (CI). In the final model, a P-value ≤0.05 was considered statistically significant.

All statistical analyses were performed using STATA 15.1 and R software version 4.3.1 (R Foundation for Statistical Computing) in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines for reporting observational studies (see Supplementary Methods 3).

## Results

### Population characteristics

We included 4,614 patients between December 15, 2016 and September 28, 2022. Among them, 49% (2,242/4,614) were included in 2020/2021 and 2021/2022. The median age was 72 years (interquartile range 58-83 years), and 65% (3,011/4,614) of the patients were aged ≥65 years. Overall, 85% (3,921/4,614) of the patients had at least one chronic disease, mostly chronic respiratory disease (38%, 1,744/4,614). Among the study population, 33% (1,504/4,584) were immunocompromised, mostly due to solid or hematologic malignancies (50%, 751/1,504) (Table 1). In addition, 88% (4,080/4,614) of the patients had at least one indication for seasonal influenza vaccination, 71% (3,265/4,614) were eligible for pneumococcal vaccination, and 70% (3,248/4,616) were eligible for both influenza and pneumococcal vaccinations.

### Seasonal influenza vaccination eligibility and coverage

Among the 4,080 patients with at least one indication for the seasonal influenza vaccine, 26% (1,069/4,080) were aged <65 years
<caption>**Table 1**</caption>

Patients' characteristics according to influenza season/year of enrollment, FLUVAC study, 2016-2022, France.

<table><thead><tr><th></th><th>Overall<br>N = 4,614</th><th>2016/2017<br>N = 511</th><th>2017/2018<br>N = 705</th><th>2018/2019<br>N = 714</th><th>2019/2020<br>N = 442</th><th>2020/2021<br>N = 1,293</th><th>2021/2022<br>N = 949</th><th>P-value<sup>a</sup></th></tr></thead><tbody><tr><td><strong>Baseline characteristics</strong></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Age</td><td>72 (58-83)</td><td>74 (62-86)</td><td>72 (60-83)</td><td>72 (60-82)</td><td>73 (59-83)</td><td>69 (56-82)</td><td>73 (61-83)</td><td>&lt;0.001</td></tr><tr><td>Women</td><td>2,106 (46)</td><td>250 (49)</td><td>313 (44)</td><td>320 (45)</td><td>229 (52)</td><td>570 (44)</td><td>424 (45)</td><td>0.047</td></tr><tr><td><strong>At least one chronic disease</strong></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Chronic respiratory disease</td><td>3,921 (85)</td><td>454 (89)</td><td>633 (90)</td><td>625 (88)</td><td>389 (88)</td><td>1,020 (79)</td><td>800 (84)</td><td>&lt;0.001</td></tr><tr><td>Chronic heart disease</td><td>1,744 (38)</td><td>245 (48)</td><td>334 (47)</td><td>332 (46)</td><td>169 (38)</td><td>323 (25)</td><td>341 (36)</td><td>&lt;0.001</td></tr><tr><td>Renal disease</td><td>720 (16)</td><td>87 (17)</td><td>113 (16)</td><td>49 (7)</td><td>33 (8)</td><td>101 (8)</td><td>79 (8)</td><td>&gt;0.9</td></tr><tr><td>Diabetes</td><td>1,074 (23)</td><td>126 (25)</td><td>149 (21)</td><td>145 (20)</td><td>106 (24)</td><td>310 (24)</td><td>238 (25)</td><td>0.4</td></tr><tr><td>Solid tumor or hematologic<br>malignancy</td><td>751 (16)</td><td>92 (18)</td><td>118 (17)</td><td>144 (20)</td><td>73 (17)</td><td>175 (14)</td><td>149 (16)</td><td>0.005</td></tr><tr><td>Splenic disease</td><td>340 (7)</td><td>41 (8)</td><td>54 (8)</td><td>45 (6)</td><td>37 (8)</td><td>98 (8)</td><td>65 (7)</td><td>0.7</td></tr><tr><td>Immunosuppressive<br>treatment</td><td>704 (15)</td><td>80 (16)</td><td>148 (21)</td><td>128 (18)</td><td>53 (12)</td><td>133 (11)</td><td>162 (17)</td><td>&lt;0.001</td></tr><tr><td>HIV infection or organ<br>transplant</td><td>246 (5)</td><td>29 (6)</td><td>54 (8)</td><td>49 (7)</td><td>22 (5)</td><td>35 (3)</td><td>57 (6)</td><td>&lt;0.001</td></tr></tbody></table>

a Kruskal-Wallis rank sum test; Pearson's chi-squared test.

Continuous data are reported as medians with first and third quartiles (Q1-Q3); categoric data as numbers and percentage.

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

Influenza and pneumococcal vaccine coverages according to influenza season/year of enrollment, FLUVAC study, 2016-2022, France.

<table><thead><tr><th></th><th>Total<br>N = 4,614</th><th>2016/2017<br>N = 511</th><th>2017/2018<br>N = 705</th><th>2018/2019<br>N = 714</th><th>2019/2020<br>N = 442</th><th>2021<br>N = 1,293</th><th>2022<br>N = 949</th><th>P-value<sup>a</sup></th></tr></thead><tbody><tr><td><strong>Influenza vaccination, n (%)</strong></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Vaccination indication</td><td>4,080/4,614 (88)</td><td>482/511 (94)</td><td>654/705 (93)</td><td>655/714 (92)</td><td>400/442 (91)</td><td>1,038/1,293 (80)</td><td>851/949 (90)</td><td>&lt;0.001</td></tr><tr><td>Age ≥65 years ± medical condition</td><td>3,011/4,080 (74)</td><td>360/482 (75)</td><td>475/654 (73)</td><td>467/655 (71)</td><td>292/400 (73)</td><td>760/1,038 (73)</td><td>657/851 (77)</td><td>0.15</td></tr><tr><td>Age &lt;65 years with medical condition</td><td>1,069/4,080 (26)</td><td>122/482 (25)</td><td>179/654 (27)</td><td>188/655 (29)</td><td>108/400 (27)</td><td>278/1,038 (27)</td><td>194/851 (23)</td><td></td></tr><tr><td>Vaccination coverage</td><td>2,181/4,080 (53)</td><td>275/482 (57)</td><td>327/654 (50)</td><td>391/655 (60)</td><td>252/400 (63)</td><td>526/1,038 (51)</td><td>410/851 (48)</td><td>&lt;0.001</td></tr><tr><td>Age ≥65 years ± medical condition</td><td>1,805/3,011 (60)</td><td>224/360 (62)</td><td>277/475 (58)</td><td>304/467 (65)</td><td>203/292 (70)</td><td>444/760 (58)</td><td>353/657 (54)</td><td>&lt;0.001</td></tr><tr><td>Age &lt;65 years with medical condition</td><td>376/1,069 (35)</td><td>51/122 (42)</td><td>50/179 (28)</td><td>87/188 (46)</td><td>49/108 (45)</td><td>82/278 (30)</td><td>57/194 (29)</td><td>&lt;0.001</td></tr><tr><td><strong>Pneumococcal vaccination, n (%)</strong></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Vaccination indication</td><td>3,265/4,614 (71)</td><td>401/511 (78)</td><td>549/705 (78)</td><td>540/714 (76)</td><td>336/442 (76)</td><td>775/1,293 (60)</td><td>664/949 (70)</td><td>&lt;0.001</td></tr><tr><td>Immunocompromised condition alone</td><td>472/3,265 (14)</td><td>55/401 (14)</td><td>74/549 (13)</td><td>86/540 (16)</td><td>49/336 (15)</td><td>113/775 (15)</td><td>95/664 (14)</td><td>0.7</td></tr><tr><td>Specific medical condition alone</td><td>1,761/3,265 (54)</td><td>225/401 (56)</td><td>290/549 (53)</td><td>276/540 (51)</td><td>193/336 (57)</td><td>427/775 (55)</td><td>350/664 (53)</td><td></td></tr><tr><td>Immunocompromised and specific<br>medical condition</td><td>1,032/3,265 (32)</td><td>121/401 (30)</td><td>185/549 (34)</td><td>178/540 (33)</td><td>94/336 (28)</td><td>235/775 (30)</td><td>219/664 (33)</td><td></td></tr><tr><td>Vaccination coverage<sup>b</sup></td><td>551/2,920 (19)</td><td>84/372 (23)</td><td>106/506 (21)</td><td>130/502 (26)</td><td>71/307 (23)</td><td>73/681 (11)</td><td>87/552 (16)</td><td>&lt;0.001</td></tr><tr><td>Immunocompromised condition alone</td><td>57/417 (14)</td><td>9/51 (18)</td><td>9/72 (13)</td><td>13/79 (16)</td><td>7/43 (16)</td><td>10/99 (10)</td><td>9/73 (12)</td><td>&lt;0.001</td></tr><tr><td>Specific medical condition alone</td><td>260/1,587 (16)</td><td>44/206 (21)</td><td>44/268 (16)</td><td>61/257 (24)</td><td>40/181 (22)</td><td>34/377 (9)</td><td>37/298 (12)</td><td>&lt;0.001</td></tr><tr><td>Immunocompromised and specific<br>medical condition</td><td>234/916 (26)</td><td>31/115 (27)</td><td>53/166 (32)</td><td>56/166 (34)</td><td>24/83 (29)</td><td>29/205 (14)</td><td>41/181 (23)</td><td>&lt;0.001</td></tr></tbody></table>

a Pearson's chi-squared test.

b Vaccination status could not be determined among 11% (345/3,265) of the patients with indication for pneumococcal vaccination.

with a chronic disease. Overall, influenza vaccination coverage was 53% (2,181/4,080), higher in patients aged ≥65 years (60% vs 35% in those aged <65 years, *P* <0.001) and lower in patients enrolled in 2020/2021 and 2021/2022 compared with previous years (50% vs 57%, respectively, *P* <0.001) (Table 2, Figure 1). Of those vaccinated against influenza, 81% (1,762/2,181) had at least one indication for pneumococcal vaccination, of whom 28% (434/1,543) had received a pneumococcal vaccination (see Supplementary Results).

Among patients aged ≥65 years, those with chronic medical disease had higher influenza vaccination coverage (1,591/2,579, 62%) than those with no chronic medical disease (1,67/316, 53%; *P* = 0.002). Multivariable analysis showed that age ≥65 years (aOR 3.05; 95% CI 2.63-3.55), chronic respiratory diseases (aOR 1.38; 95% CI 1.20-1.59), and the number of chronic diseases were the main factors associated with influenza vaccination (Table 3).

### Pneumococcal vaccination eligibility and coverage

Among the 4,614 patients included, 3,265 (71%) were considered to be at high risk for pneumococcal infection, and following French recommendations for eligibility for pneumococcal vaccination, most had chronic medical conditions without immunosuppression (54%, 1,761/3,265). Pneumococcal vaccination status was obtained for 89% of the patients (2,920). Among those eligi-

ble for pneumococcal vaccination with a known vaccination history, 19% (551/2,920) had received at least one dose of the pneumococcal vaccine over the last 5 years. Coverage was lower in patients enrolled in the 2020/2021 and 2021/2022 seasons (13%, 160/1,073) than in those enrolled previously (27%, 391/1,451, *P* <0.001) (Table 2, Figure 1).

Among those who received pneumococcal vaccination, the type of vaccine received could be identified in 80% (439/551) of the patients. During the study period, most patients received a single dose of PPSV23 (233/439, 53%). Throughout the study period, the use of non-conjugated vaccines alone significantly decreased from 79% to 38% (*P* <0.001), whereas that of conjugated vaccines alone or in combination with non-conjugated vaccines increased from 21% to 62% (*P* <0.001) (see Supplementary Results, Table 1). We identified 102 patients who declared a two-dose vaccination schedule (3% of patients with pneumococcal vaccination indications and 23% of patients who received a pneumococcal vaccine). Patients with immunocompromised conditions alone or in combination with other specific medical conditions were more likely to report a two-dose vaccination schedule (33% and 28% vs 17%, *P* = 0.046). Among the patients vaccinated against pneumococcus, 99% (550/551) had at least one indication for influenza vaccination, and 79% (434/550) received the influenza vaccine (see Supplementary Results, Table 2).
<figure><img src="image_4.png" /><figcaption>**Figure 1.** Evolution of vaccination coverage against influenza and pneumococcus among patients included in the FLUVAC study from 2016 to 2022 in France. The proportions of patients vaccinated against influenza and pneumococcal disease are shown for patients with an indication for vaccination and for whom vaccination status was available, according to the season of inclusion. Blue columns represent the proportion of patients who received influenza vaccine in the current season (among patients aged ≥65 years and with chronic medical condition in dark blue, among patients aged ≥65 years without chronic medical condition in medium blue, and among patients aged <65 years in light blue), and green columns represent the proportion of patients who received any pneumococcal vaccine in the last 5 years, with the value at the top of the column.</figcaption></figure>

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

Factors associated with influenza vaccination among eligible adults hospitalized with SARI, FLUVAC study, 2016-2022, France.

<table><thead><tr><th rowspan="2">Characteristics</th><th colspan="3">Univariate analysis</th><th colspan="3">Multivariable model</th></tr><tr><th>OR</th><th>95% CI</th><th>P-value</th><th>Adjusted OR</th><th>95% CI</th><th>P-value</th></tr></thead><tbody><tr><td><strong>Age ≥65 years</strong></td><td>2.76</td><td>2.39-3.19</td><td>&lt;0.001</td><td>3.05</td><td>2.63-3.55</td><td>&lt;0.001</td></tr><tr><td><strong>Number of chronic diseases</strong></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>None</td><td>Ref</td><td>—</td><td>—</td><td>Ref</td><td>—</td><td>—</td></tr><tr><td>One</td><td>1.08</td><td>0.91, 1.28</td><td>0.4</td><td>1.20</td><td>0.99, 1.45</td><td>0.064</td></tr><tr><td>Two or three</td><td>1.31</td><td>1.10, 1.56</td><td>0.002</td><td>1.35</td><td>1.11, 1.65</td><td>0.002</td></tr><tr><td>Four or more</td><td>1.47</td><td>1.11, 1.94</td><td>0.007</td><td>1.61</td><td>1.19, 2.18</td><td>0.002</td></tr><tr><td><strong>Chronic respiratory diseases</strong></td><td>1.31</td><td>1.16, 1.49</td><td>&lt;0.001</td><td>1.38</td><td>1.20, 1.59</td><td>&lt;0.001</td></tr></tbody></table>

CI, confidence interval; OR, odds ratio; Ref, reference.

Log-likelihood = -2693; Pseudo-R² = 0.044; AIC = 5399; BIC = 5437; Deviance = 5387; No. Obs. = 4080.

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

Factors associated with pneumococcal vaccination among eligible adults hospitalized with SARI and with known vaccination status, FLUVAC study, 2016-2022, France.

<table><thead><tr><th rowspan="2">Characteristic</th><th colspan="3">Univariate analysis</th><th colspan="3">Multivariate model</th></tr><tr><th>OR</th><th>95% CI</th><th>P-value</th><th>Adjusted OR</th><th>95% CI</th><th>P-value</th></tr></thead><tbody><tr><td><strong>Age &gt;65 years</strong></td><td>0.88</td><td>0.72, 1.07</td><td>0.2</td><td>1.07</td><td>0.87, 1.32</td><td>0.5</td></tr><tr><td><strong>Chronic respiratory disease</strong></td><td>2.52</td><td>2.07, 3.09</td><td>&lt;0.001</td><td>2.74</td><td>2.22, 3.40</td><td>&lt;0.001</td></tr><tr><td><strong>Immunosuppression</strong></td><td>1.57</td><td>1.26, 1.93</td><td>&lt;0.001</td><td>1.46</td><td>1.15, 1.85</td><td>0.002</td></tr><tr><td><strong>HIV or organ transplant</strong></td><td>2.08</td><td>1.52, 2.82</td><td>&lt;0.001</td><td>1.99</td><td>1.39, 2.83</td><td>&lt;0.001</td></tr><tr><td><strong>Splenic disease</strong></td><td>1.34</td><td>1.00, 1.77</td><td>0.047</td><td>1.54</td><td>1.13, 2.07</td><td>0.005</td></tr></tbody></table>

CI, confidence interval; OR, odds ratio.

Log-likelihood = -1320; Pseudo-R² = 0.062; AIC = 2658; BIC = 2712; Deviance = 2640; No. Obs. = 2920

Pneumococcal vaccine coverage was higher among patients with both an immunocompromised condition and a specific medical condition than those with a single indication (26% vs 14% and 16%, respectively; P <0.001). Multivariable analysis showed that chronic respiratory diseases (aOR 2.74; 95% CI 2.22-3.40) and immunocompromised conditions other than malignancies (HIV infection, organ transplantation, splenic disease, and immunosuppressive treatment) were the main factors positively associated with pneumococcal vaccination when indicated (Table 4).

## Discussion

This study reported that 70% (3,248/4,616) of patients hospitalized with SARI were eligible for both influenza and pneumococcal vaccination. While influenza vaccine coverage reached 64% during the study period, pneumococcal vaccine coverage was much lower

at 19%, with no measurable increase over time. As expected, influenza vaccination coverage was associated with age ≥65 years, respiratory chronic diseases, and the number of chronic diseases, and pneumococcal vaccination coverage was higher in patients with respiratory chronic diseases and immunocompromised conditions. Interestingly, influenza-vaccinated individuals with indications for pneumococcal vaccination had low pneumococcal vaccination coverage.

These results are in line with other studies previously conducted in France. Rouveix et al. [15] reported 58% influenza vaccine coverage among 903 older adults hospitalized in France following the 2010-2011 influenza season, whereas Verger et al. [16] reported 48% influenza vaccine coverage among French National Insurance Fund beneficiaries aged ≥65 years old and between 16% and 29% among those aged <65 years depending on their condition. In French geriatric cohorts, the pneumococcal vaccine coverage
age ranged from 20.5% to 21.9% [17,18]. More recently, analyses us-
ing data from the National Health Data System found lower over-
all influenza and pneumococcal vaccine coverage than our results
[19]. However, these data only cover vaccines delivered by commu-
nity pharmacies and may underestimate vaccine coverage. Finally,
our multivariate model suggests that the increased risk of inva-
sive pneumococcal disease associated with chronic medical condi-
tions other than immunocompromised diseases is underestimated
by both patients and their physicians. This is consistent with previ-
ous studies: Loubet et al. [20] reported that only 36% of at-risk pa-
tients had a relatively clear understanding of what pneumococcal
infection entailed; 41% of patients believed they were up to date
with their pneumococcal vaccination; 64% of patients claimed to
have never received any recommendation or suggestion regarding
pneumococcal vaccination. A study from Calmels et al. [21], among
patients candidates for kidney transplantation, demonstrated a sig-
nificant improvement in vaccine coverage, from 15.8% to 52.6%,
when patients received infectious disease consultations as part of
their pre-transplant check-ups. Tubiana et al. highlighted the com-
plexity of receiving this message in another study [22], in which
a multifaceted intervention for patients aged ≥65 years attend-
ing emergency departments that combined structured information
about pneumococcal and influenza vaccines and three text mes-
sage reminders did not alter the pneumococcal vaccination rate
(6.4% vs 4.6%) within 6 months.

From an international perspective, our influenza vaccination coverage closely relates to that reported in other high-income countries in non-hospitalized adults, such as the USA in 2014 [23] and 11 European countries during the 2006/2007 and 2007/2008 influenza seasons [24]. We found that influenza coverage was significantly lower among those aged <65 years throughout the study period, ranging from 28% to 47%. The lower vaccination coverage at younger ages is consistent with previous studies and may be related to a lack of awareness in this particular population [25]. Conversely, the higher vaccine coverage associated with respiratory diseases may suggest that pneumologists may be more active in vaccinating patients and that the presence of many chronic conditions with many medical encounters decreases the probability of missed opportunities for vaccination. Regarding pneumococcal vaccination coverage, an international comparison suggests that the lower vaccine coverage may be explained by the complexity of French recommendations. Indeed, our findings are comparable with those of other high-income countries with conditional recommendations, such as the United Kingdom or Switzerland [26,27], but much lower than those of the USA, where pneumococci are recommended for all adults aged ≥65 years [28,29].

The low vaccination coverage identified in this study highlights
the need to consider new strategies to promote influenza vaccina-
tion, particularly pneumococcal vaccination. French recommenda-
tions have recently changed, allowing nurses and pharmacists to
prescribe and administer vaccinations to people aged >11 years,
providing a valuable opportunity to address missed vaccination op-
portunities and collaboratively improve influenza and pneumococ-
cal vaccination coverage. Regarding pneumococcal vaccination in
particular, consideration should be given to including it in the rou-
tine vaccination schedule for those aged ≥65 years, which is in line
with the higher pneumococcal vaccination coverage observed in
the USA. Furthermore, replacing the current two-dose pneumococ-
cal vaccination regimen with a single dose of the 20-valent con-
jugate vaccine may streamline the vaccination process and con-
tribute to higher vaccination rates [30].

This study extends the groundwork laid by the FLUVAC study, a
multicenter, prospective investigation conducted over an extended
period of time. It involved active data collection from both the pa-
tients and their health care providers, which contributed to the

robustness of our research. However, this study had some limita-
tions that must be acknowledged. First, the FLUVAC study design
introduced selection bias by restricting enrollment to referral hos-
pitals and excluding patients residing in long-term care facilities,
a priority group for vaccination, which limits the generalizability
of our results and their comparability with other studies. In addi-
tion, almost half of the patients were enrolled after the COVID-19
pandemic, with an extended enrollment period, which might have
introduced another selection bias and limited the comparability of
vaccination coverage between periods. Moreover, despite proactive
data collection, pneumococcal vaccination status could not be de-
termined in 10% of the patients, and the vaccination schedule re-
mained unknown in 20% of those immunized against S. pneumo-
niae. The significant rate of missing data on pneumococcal vac-
cines highlights the need for a single reliable source of information
on vaccines received throughout life, which could be addressed
through the recent implementation of national electronic vaccina-
tion records. In addition, the FLUVAC did not collect information
on influenza and pneumococcal vaccination during hospitalization
or at hospital discharge, which may have provided additional in-
sights into missed vaccination opportunities. Finally, some clinical
data were not available in the database, which might impact the
identification of patients at risk, mostly for pneumococcal vacci-
nation. However, the most common indications for vaccination are
accounted for, and only minor causes are missing from our data.

In conclusion, this study shows that adults hospitalized for SARI are largely eligible for influenza and pneumococcal vaccination; however, vaccination coverage is suboptimal for influenza and desperately low for pneumococcus among at-risk patients, with no significant improvement over the years. The difference between influenza and pneumococcal vaccination coverage could, in part, be explained by the level of public health authority engagement in influenza vaccination campaigns compared with pneumococcal vaccination campaigns, the readability of vaccine recommendations (age-based vs disease-based), the convenience of vaccine administration, and a lack of knowledge regarding pneumococcal vaccination in the general population. In a period when new prescribers and vaccinators (nurses and pharmacists) have recently been introduced in France, and with the recent approval by the European Medicines Agency of new vaccines against RSV-associated SARIs, there is a pressing need to standardize our vaccination messages to both health care professionals and at-risk populations and streamline the vaccination process to enhance the identification of people eligible for vaccinations and public understanding and acceptance of vaccination. Further studies exploring the drivers and barriers to pneumococcal vaccination could offer actionable public health insights.

Declarations of competing interest

All authors declare no support from any organization for the
submitted work other than that described above, no financial rela-
tionships with any organization that might have an interest in the
submitted work in the previous 3 years, and no other relationships
or activities that could appear to have influenced the submitted
work.

Funding

This study did not receive any funding. However, the study sites
received funding from the I-REIVAC network, part of the DRIVE and
I MOVE programs, and Janssen during the FLUVAC study years. The
vaccine producers played no role in the study design, data analysis,
decision to publish, or manuscript preparation.
## Ethical approval statement

This study was a part of the FLUVAC clinical trial sponsored by the French National Institute of Health and Medical Research (Inserm). It was approved by the local ethics committee or "Comité de Protection des Personnes" in 2013, authorized by French authorities (ANSM, IDRCB: 2013-A01204-41), and registered in a public trial registry (clinicaltrials.gov NCT02027233). All study participants provided informed consent to participate in the study, in line with French ethical guidelines.

## Acknowledgments

The results were presented as a poster at the RICAI Congress in Paris, France, in December 2023.

## Author contributions

Conception and design: OL, FG, XD, PV, LF, and PT. Data acquisition: Fluvac study group. Data analysis and interpretation: SR, LBLN, and OL. Drafting article: SR. Revised article: OL, LBLN, AD, FG, XD, PV, FL, PT and RB. All authors reviewed and approved the final version of the manuscript.

## Access to data

All data associated with this study are available in the main text.

## Supplementary materials

Supplementary material associated with this article can be found, in the online version, at doi:10.1016/j.ijid.2025.107811.

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