# Sustained Increase in Pediatric Mastoiditis in the Post-COVID-19 Era: A 9-Year Interrupted Time-Series Analysis Based on National Data

Apolline Furgier, Romain Basmaci, Zaba Valtuille, Inès Fafi, Zein Assad, Léa

Lenglart, Natacha Teissier, Charlotte Benoit, Emilien Chebib, Aurélie

Bourmaud, et al.

► To cite this version:

Apolline Furgier, Romain Basmaci, Zaba Valtuille, Inès Fafi, Zein Assad, et al. Sustained Increase in Pediatric Mastoiditis in the Post-COVID-19 Era: A 9-Year Interrupted Time-Series Analysis Based on National Data. The Journal of Pediatrics, 2026, 289, 10.1016/j.jpeds.2025.114835. hal-05503428

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# Sustained Increase in Pediatric Mastoiditis in the Post-COVID-19 Era: A 9-Year Interrupted Time-Series Analysis Based on National Data

Apolline Furgier, MD¹,², Romain Basmaci, MD, PhD¹,³,⁴, Zaba Valtuille, PhD¹,³,⁵, Inès Fafi, MD¹,²,⁵, Zein Assad, MD¹,³,⁶, Léa Lenglart, MD¹,³,⁷, Natacha Teissier, MD, PhD⁸, Charlotte Benoit, MD⁸, Emilien Chebib, MD⁸, Aurélie Bourmaud, MD, PhD⁵, François Angoulvant, MD, PhD⁹, Pierre Alex Crisinel, MD¹⁰, André Birgy, MD, PhD¹,¹¹, Naïm Ouldali, MD, PhD¹,²,³,#, and Manon Jaboyedoff, MD¹,¹⁰,†

**Objective** To assess the impact of COVID-19 pandemic-related non-pharmaceutical interventions (NPI) on the incidence of mastoiditis cases, causative pathogens, and associated complications in children.

**Study design** We conducted a population-based interrupted time-series analysis using national surveillance data from France between January 2016 and December 2024. All hospitalized mastoiditis cases among individuals younger than 18 years in France were included. The main outcome was the monthly incidence of mastoiditis cases, analyzed using quasi-Poisson regression models, accounting for seasonality.

**Results** We included 7390 hospitalized cases of mastoiditis in children. Following a decrease in the incidence of mastoiditis by 58.9% (95% CI: 68.2% to 46.9%, *P* < .001) during the strict NPI period, we observed an increase of 71.7% (95% CI: 26.4% to 133.3%, *P* < .001) in the post-NPI period compared with the expected trend without NPI. The proportions of complicated cases and those requiring surgery remained stable over time. By pathogen, the most important increase in the post-NPI period was observed among mastoiditis caused by *Streptococcus pyogenes* (+627.8%, 95% CI: +269.1% to +1335.0%, *P* < .001), followed by *Streptococcus pneumoniae* (+135.6%, 95% CI: +20.5% to +360.6%, *P* = .012) and *Haemophilus influenzae* (+124.3%, -17.0% to +506.0%, *P* = .111).

**Conclusions** In this 9-year population-based national study, we observed a sustained increase in the incidence and etiology of mastoiditis in children during the post-COVID-19 period. We hypothesize that these changes, associated with NPI during the pandemic and lifting postpandemic, reflect consequences that should be considered in the management of future pandemics. (J Pediatr 2026;289:114835).

acute mastoiditis is a severe complication of acute otitis media (AOM) in children.¹,² An estimated 780 000 cases of mastoiditis occur each year globally, complicating about 0.20% of the 391 million global episodes of AOM.¹,³ The main pathogens involved in acute mastoiditis include *Streptococcus pneumoniae*, *Streptococcus pyogenes*, *Haemophilus influenzae*, *Staphylococcus aureus*, and *Fusobacterium necrophorum*.⁴,⁵ Severe complications occur in 10%-20% of mastoiditis cases, including meningitis, facial palsy, intracranial abscesses, thrombosis, labyrinthitis, and hearing loss.⁶,⁷

During the COVID-19 pandemic, non-pharmaceutical interventions (NPI) led to major shifts in the epidemiology of infectious diseases worldwide, with a marked reduction in both localized infections such as AOM⁸⁻¹⁰ and invasive bacterial infections.¹¹,¹² The post-NPI period was marked by an unprecedented increase in pediatric infectious diseases possibly explained by an immunity gap.¹³,¹⁴ Population-level incidence and etiology of mastoiditis in the post-COVID-19 years have not been assessed in national studies, existing studies being based on small case series and short timeframes.¹⁵⁻¹⁸

This study aimed to assess the impact of NPI implementation and lifting on the incidence of mastoiditis, its causative pathogens, and associated complications.

AOM Acute otitis media

ICD-10 Tenth Revision of the International Classification of Diseases

iGAS Invasive Streptococcus pyogenes infections

NPI Non-pharmaceutical interventions

PCV13 Pneumococcal conjugate vaccination targeting 13 serotypes

From the ¹Paris Cité University, Infection, Antimicrobials, Modelling, Evolution (IAME) Research Unit, Paris, France; ²Department of General Pediatrics, Pediatric Infectious Disease and Internal Medicine, Robert Debré University Hospital, Assistance Publique - Hôpitaux de Paris, Paris Cité Université, Paris, France; ³Groupe de Pathologie Infectieuse Pédiatrique (GPIP), Paris, France; ⁴Pediatric Emergency Department and General Pediatrics Department, Louis Mourier University Hospital, Assistance Publique - Hôpitaux de Paris, Paris Cité Université, Paris, France; ⁵Center of Clinical Investigations, INSERM CIC 1426, Robert Debré University Hospital, Paris, France; ⁶Department of Pediatrics, French Guiana University, Cayenne Hospital, Cayenne, France; ⁷Pediatric Emergency Department, Robert Debré University Hospital, Assistance Publique - Hôpitaux de Paris, Paris Cité University, Paris, France; ⁸Department of Pediatric Otolaryngology, Robert Debré Hospital, Assistance Publique - Hôpitaux de Paris, Paris Cité University, Paris, France; ⁹Department Women-Mother-Child, Service of Pediatrics, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland; ¹⁰Department Women-Mother-Child, Unit of Pediatric Infectious Diseases and Vaccinology, Service of Pediatrics, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland; and ¹¹Department of Microbiology, Robert Debré Hospital, Assistance Publique - Hôpitaux de Paris, Associated National Reference Center for Escherichia coli, Paris, France

#N.O. and M.J. contributed equally to this study.

0022-3476/© 2025 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). https://doi.org/10.1016/j.jpeds.2025.114835
# Methods

## Study Design

We conducted a retrospective population-based interrupted time-series analysis over 9 years, from January 1, 2016, to December 31, 2024, using national data from the hospital-based French national surveillance system.

## Data Source

Data were extracted from the French Program for the Medicalization of Information Systems, a comprehensive national medico-administrative database that includes all inpatients stays in both public and private hospitals in France. Data collected are anonymized and include demographic information, diagnoses related to hospitalization and coded according to the International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10), and surgical procedures coded according to the national Common Classification of Medical Procedures.¹⁹ All diagnoses and procedures follow national coding guidelines as established by the Technical Agency for Hospital Information.²⁰ A subset of 223 mastoiditis cases hospitalized between 2021 and 2024 was previously described in a French single-center study.²¹

Age-specific French population data, provided by the National Institute of Statistics and Economic Studies, were used as the denominator to calculate the incidence of mastoiditis for each year of the study.²²

## Study Periods

We defined four time periods based on stringency of NPI implemented. Levels of NPI stringency were defined according to the Oxford COVID-19 Government Response Tracker which attributed a daily score on a scale of 0 to 100, higher score indicating stricter NPI.²³ The periods were defined as follows: (1) pre-NPI period, from January 1, 2016, to March 30, 2020; (2) strict NPI period, from April 1, 2020 to July 31, 2021, with an average stringency index of 75; (3) light NPI period, from August 1, 2021, to August 31, 2022, with an average stringency index of 43; and (4) the post-NPI period, from September 1, 2022, to December 31, 2024.

## Inclusion and Exclusion Criteria

We included all cases of hospitalized mastoiditis in children under 18 years of age occurring during the study period. Cases were identified using the corresponding ICD-10 codes recorded as the primary or related diagnosis during hospitalization (Supplementary Appendix; available at www.jpeds.com). To account for potential patient transfers between hospitals, hospitalizations occurring within 2 months of an initial case were considered part of the same case and were counted once.

## Outcomes

The primary outcome was the monthly incidence of hospitalized mastoiditis per 100 000 children younger than 18 years.

Secondary outcomes were: (1) the incidence of hospitalized mastoiditis cases by age groups (<2 years, 2 to 4 years, 5 to 9 years, and 10 to 17 years); (2) by pathogen (S. pneumoniae, S. pyogenes, S. aureus, H. influenzae, and anaerobes); (3) by the proportion of complicated cases of mastoiditis defined as the presence of a concomitant diagnosis of meningitis, intracranial abscess or thrombosis; and (4) by the proportion of hospitalized mastoiditis associated with surgery (mastoidectomy or neurosurgery). Pathogen, complications, and surgery were identified with corresponding ICD-10 and procedures' codes (Supplementary Appendix; available at www.jpeds.com). To explore potential bias due to hidden cointerventions, the evolution of the national incidence of hospitalized urinary tract infections in children younger than 18 years over the same period was analyzed as a control outcome. The proportion of microbiologically undocumented cases was used as a control outcome to explore potential changes in microbiological documentation practices.

## Statistical Analysis

Outcomes were analyzed using a quasi-Poisson regression model, accounting for seasonality by using periodic B-splines of month with 4 degrees of freedom, allowing the model to account for the cyclical nature of seasonal patterns across the year.²⁴ The time unit was set to 1 month. Incidence per 100 000 children was calculated by dividing the monthly number of cases by the number of children under 18 years old living in France during the corresponding year and adjusted to cases per 100 000. The observed monthly incidence of hospitalized mastoiditis was fitted by the model for each month of the study period, with NPI implementation and lifting included as explanatory categorical variables. Incidences observed during the reference (pre-NPI) period were used to estimate the expected incidence without NPI. The incidence of hospitalized mastoiditis cases following NPI implementation (strict and light) and NPI lifting was compared with the expected values based on the pre-NPI reference period. The validity of the quasi-Poisson regression models was assessed by visual inspection of correlograms and residuals analysis.

To assess the robustness of results, we performed several sensitivity analyses for the main outcome: (1) a quasi-Poisson regression model accounting for seasonality by including harmonic terms (sines and cosines with 12-, 6-, and 3-month periods); (2) a segmented linear regression model; (3) a segmented linear regression using an additive model to remove seasonality; (4) a negative binomial regression model; (5) a quasi-Poisson regression model with mastoiditis coded only as principal diagnosis (instead of principal or related diagnoses); and (6) a quasi-Poisson regression model with a single NPI period defined from March 2020 to August 2022, encompassing both strict and light periods of intervention.

All statistical tests were two-sided with *P* < .05 considered statistically significant. Analyses were performed using R Statistical Software version 4.2.2 (www.R-project.org; R Core Team 2021).
## Ethics

The data collection was approved by the National Commission on Information and Liberty. Access to the French Program for the Medicalization of Information Systems was granted by the National Commission on Information and Liberty. As part of a continuous public health surveillance mission using anonymized, aggregated data, this study did not require ethical committee approval or written informed consent in accordance with the French Data Protection Act.

## Results

Between January 1, 2016, and December 31, 2024, 8821 cases of mastoiditis were assessed for eligibility. After exclusion of 1341 cases occurring within 2 months of the initial case, 7390 cases were included in the analysis. Median age at diagnosis was 2 years (IQR: 1–6). Male-to-female ratio was 1.4. Most cases were microbiologically undocumented (n = 6095, 82.5%). When present, the most frequent associated pathogens were *S. pyogenes* (n = 521, 7.1%), *S. pneumoniae* (n = 486, 6.6%), *S. aureus* (n = 186, 2.5%), *H. influenzae* (n = 147, 2%), and anaerobes including *Fusobacterium spp.* (n = 38, 0.5%). There were 970 cases (13.1%) of complicated mastoiditis, including 148 cases of meningitis, 475 of intracranial abscess, and 627 of thrombosis. Surgery (mastoidectomy or neurosurgery) was performed in 1336 cases (18.1%), and myringotomy in 763 cases (10.3%) (Table I).

The implementation of NPI in March 2020 was associated with a marked reduction in the incidence of hospitalized cases of mastoiditis (strict NPI period: -58.9%, CI 95%: -68.2% to -46.9%, *P* value < .001). During the partial NPI lifting period, the incidence of mastoiditis was similar to the pre-NPI period (light NPI period: -14.2%, 95% CI: -34.0% to +11.6%, *P* value 0.254), yet total NPI lifting was associated with a marked increase in mastoiditis incidence, exceeding the pre NPI trend (post-NPI period: +71.7%, 95% CI: +26.4% to +133.3%, *P* value 0.001, compared with the expected trend without NPI) (Table II and Figure 1). Analyses of correlograms and residuals indicated a satisfactory fit of the final model.

The decrease in the incidence of mastoiditis during the strict NPI period was of the same magnitude across all age groups (Table II and Figure 2). The increase observed in the post-NPI period was most pronounced in children younger than 5 years and was not statistically significant in children aged 10 to 17 years.

The most pronounced decrease during the NPI period followed by the most important increase during the post-NPI period was observed for mastoiditis caused by *S. pyogenes* (strict NPI period: -84.3%, 95% CI: -94.2% to -57.4%, *P* value <.001; post-NPI period: +627.8%, 95% CI: +269.1% to +1335.0%, *P* value <.001, Table II and Figure 3). The incidence of mastoiditis caused by *S. pneumoniae* remained stable during both NPI periods but

<table><caption>Table I. Characteristics of Mastoiditis Cases in France by Time Period</caption><thead><tr><th rowspan="3">Characteristics</th><th rowspan="2">Total number of<br/>mastoiditis cases</th><th>Pre-NPI period</th><th>Strict NPI period</th><th>Light NPI period</th><th>Post-NPI period</th></tr><tr><th>January 1, 2016 to<br/>March 30, 2020,</th><th>April 01, 2020 to<br/>July 31, 2021,</th><th>August 01, 2021 to<br/>August 31, 2022,</th><th>September 01, 2022 to<br/>December 31, 2024,</th></tr><tr><th>n = 7390</th><th>n = 3060</th><th>n = 408</th><th>n = 716</th><th>n = 3206</th></tr></thead><tbody><tr><td>Age at admission: median<br/>(IQR) - year</td><td>2 (1-6)</td><td>3 (1-6)</td><td>3 (1-8)</td><td>2 (1-6)</td><td>2 (1-5)</td></tr><tr><td>0-1 year: no (%)</td><td>2989 (40.4)</td><td>1210 (39.5)</td><td>168 (41.2)</td><td>288 (40.2)</td><td>1323 (41.3)</td></tr><tr><td>2-4-year-old: no (%)</td><td>2031 (27.5)</td><td>780 (25.5)</td><td>74 (18.1)</td><td>203 (28.4)</td><td>974 (30.4)</td></tr><tr><td>5-9-year-old: no (%)</td><td>1454 (19.7)</td><td>640 (20.9)</td><td>86 (21.1)</td><td>127 (17.7)</td><td>601 (18.7)</td></tr><tr><td>10-17-year-old: no (%)</td><td>916 (12.4)</td><td>430 (14.1)</td><td>80 (19.6)</td><td>98 (13.7)</td><td>308 (9.6)</td></tr><tr><td>Sex assigned at birth: no M/<br/>no F (ratio)</td><td>4286/3104 (1.38)</td><td>1776/1284 (1.38)</td><td>236/172 (1.37)</td><td>416/300 (1.39)</td><td>1858/1348 (1.38)</td></tr><tr><td>Complications: no (%)</td><td>970 (13.1)</td><td>366 (12.0)</td><td>39 (9.6)</td><td>107 (14.9)</td><td>458 (14.3)</td></tr><tr><td>Meningitis</td><td>148 (2.0)</td><td>53 (1.7)</td><td>8 (2.0)</td><td>23 (3.2)</td><td>64 (2.0)</td></tr><tr><td>Intracranial abscess</td><td>475 (6.4)</td><td>164 (5.4)</td><td>23 (5.6)</td><td>48 (6.7)</td><td>240 (7.5)</td></tr><tr><td>Thrombosis: no (%)</td><td>627 (8.5)</td><td>247 (8.1)</td><td>18 (4.4)</td><td>69 (9.6)</td><td>293 (9.1)</td></tr><tr><td>Surgical care: no (%)</td><td>1336 (18.1)</td><td>568 (18.6)</td><td>55 (13.5)</td><td>127 (17.7)</td><td>586 (18.3)</td></tr><tr><td>Mastoidectomy</td><td>1332 (18.0)</td><td>566 (18.5)</td><td>55 (13.5)</td><td>126 (17.6)</td><td>585 (18.2)</td></tr><tr><td>Neurosurgery</td><td>12 (0.2)</td><td>5 (0.2)</td><td>0</td><td>2 (0.3)</td><td>5 (0.2)</td></tr><tr><td>Myringotomy: no (%)</td><td>763 (10.3)</td><td>328 (10.7)</td><td>48 (11.8)</td><td>72 (10.1)</td><td>315 (9.8)</td></tr><tr><td>Pathogens: no (%)</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Streptococcus pyogenes</td><td>521 (7.1)</td><td>185 (6.0)</td><td>6 (1.5)</td><td>15 (2.1)</td><td>315 (9.8)</td></tr><tr><td>Streptococcus<br/>pneumoniae</td><td>486 (6.6)</td><td>175 (5.7)</td><td>34 (8.3)</td><td>65 (9.1)</td><td>212 (6.6)</td></tr><tr><td>Staphylococcus aureus</td><td>186 (2.5)</td><td>76 (2.5)</td><td>11 (2.7)</td><td>18 (2.5)</td><td>81 (2.5)</td></tr><tr><td>Haemophilus influenzae</td><td>147 (2.0)</td><td>52 (1.7)</td><td>3 (0.7)</td><td>11 (1.5)</td><td>81 (2.5)</td></tr><tr><td>Anaerobes (including<br/>Fusobacterium spp.)</td><td>38 (0.5)</td><td>20 (0.7)</td><td>2 (0.5)</td><td>5 (0.7)</td><td>11 (0.3)</td></tr><tr><td>None of the five previous<br/>groups</td><td>6095 (82.5)</td><td>2576 (84.2)</td><td>354 (86.8)</td><td>612 (85.5)</td><td>2553 (79.6)</td></tr></tbody></table>
<table><caption>**Table II.** Estimated Changes in the Incidence of Mastoiditis During and After the NPI Period Compared to the Pre-NPI Period</caption><thead><tr><th rowspan="2">Analyses</th><th colspan="2">Strict NPI period</th><th colspan="2">Light NPI period</th><th colspan="2">Post-NPI period</th></tr><tr><th>Estimated change in incidence, % (CI - 95%)</th><th>P</th><th>Estimated change in incidence, % (CI - 95%)</th><th>P</th><th>Estimated change in incidence, % (CI - 95%)</th><th>P</th></tr></thead><tbody><tr><td>Main analysis</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Incidence of mastoiditis</td><td>-58.9 (-68.2; -46.9)</td><td>&lt;.001</td><td>-14.2 (-34.0; +11.6)</td><td>.254</td><td>+71.7 (+26.4; +133.3)</td><td>.001</td></tr><tr><td>Subgroup analyses</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Incidence of mastoiditis by age group</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>0-1 year</td><td>-55.5 (-68.2; -37.7)</td><td>&lt;.001</td><td>-8.9 (-35.5; +28.6)</td><td>.597</td><td>+79.3 (+20.2; +167.4)</td><td>.004</td></tr><tr><td>2-4 years old</td><td>-70.0 (-80.0; -55.1)</td><td>&lt;.001</td><td>+0.2 (-30.3; +44.1)</td><td>.991</td><td>+112.3 (+38.7; +225.1)</td><td>.001</td></tr><tr><td>5-9 years old</td><td>-60.8 (-72.5; -44.3)</td><td>&lt;.001</td><td>-31.5 (-53.0; -0.2)</td><td>.049</td><td>+55.6 (+0.9; +139.7)</td><td>.045</td></tr><tr><td>10-17 years old</td><td>-50.0 (-65.5; -27.5)</td><td>&lt;.001</td><td>-34.3 (-57.2; +0.8)</td><td>.054</td><td>-3.2 (-42.1; +61.8)</td><td>.902</td></tr><tr><td>Incidence of mastoiditis by causative pathogen</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td><em>Streptococcus pyogenes</em></td><td>-84.3 (-94.2; -57.4)</td><td>&lt;.001</td><td>-40.5 (-72.4; +28.1)</td><td>.184</td><td>+627.8 (+269.1; +1335.0)</td><td>&lt;.001</td></tr><tr><td><em>Streptococcus pneumoniae</em></td><td>-26.8 (-56.5; +23.2)</td><td>.241</td><td>+65.6 (-3.9; +185.2)</td><td>.069</td><td>+135.6 (+20.5; +360.6)</td><td>.012</td></tr><tr><td><em>Staphylococcus aureus</em></td><td>-65.9 (-84.2; -26.5)</td><td>.006</td><td>-42.8 (-74.4; +27.8)</td><td>.174</td><td>-0.3 (-61.4; +157.2)</td><td>.995</td></tr><tr><td><em>Haemophilus influenzae</em></td><td>-82.1 (-94.6; -40.8)</td><td>.005</td><td>-26.0 (-69.8; +81.6)</td><td>.512</td><td>+124.3 (-17.0; +506.0)</td><td>.111</td></tr><tr><td>Anaerobes (including <em>Fusobacterium spp.</em>)</td><td>-83.6 (-97.1; +9.1)</td><td>.039</td><td>-64.3 (-92.6; +73.4)</td><td>.202</td><td>-78.6 (-97.0; +55.0)</td><td>.127</td></tr><tr><td>None of the five previous groups</td><td>-59.4 (-68.4; -47.9)</td><td>&lt;.001</td><td>-17.7 (-36.4; +6.4)</td><td>.137</td><td>+51.0 (+11.6; +104.4)</td><td>.008</td></tr><tr><td>Control outcome</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Urinary tract infection</td><td>-3.4 (-7.4; +0.8)</td><td>.108</td><td>-6.7 (-11.5; -1.5)</td><td>.012</td><td>-7.3 (-13.3; -0.9)</td><td>.025</td></tr></tbody></table>

<figure><img src="image_3.png" /><figcaption>**Figure 1.** Incidence of mastoiditis per 100 000 children per month in France across pre-NPI, NPI, and post-NPI periods. The grey line shows the observed data. The red line shows the fitted model, with shaded area showing the 95% confidence intervals. The yellow line shows the expected incidence based on data before NPI implementation, with shaded area showing the 95% confidence intervals. The vertical lines show the limit between periods (pre-NPI, NPI, post-NPI).</figcaption></figure>
<figure><img src="image_4.png" /><figcaption>**Figure 2.** Age-specific incidence of mastoiditis per 100 000 children per month in France across pre-NPI, NPI, and post-NPI periods. The grey line shows the observed data. The red line shows the fitted model, with shaded area showing the 95% confidence intervals. The yellow line shows the expected incidence based on data before NPI implementation, with shaded area showing the 95% confidence intervals. The vertical lines show the limit between periods (pre-NPI, NPI, post-NPI). **A** = children aged 0 to 1 year; **B** = children aged 2 to 4 years old; **C** = children aged 5 to 9 years old; **D** = children aged 10 to 17 years old.</figcaption></figure>

significantly increased after NPI lifting (Table II and Figure 3). Those caused by *H. influenzae* significantly decreased during the strict NPI period and showed a trend towards an increase in the post-NPI period, although not significant. The incidence of mastoiditis caused by *S. aureus* significantly decreased during the strict NPI period and was stable in the post-NPI period compared with the expected trend without NPI (Table II and Figure 3).

The proportion of mastoiditis cases complicated by either meningitis, intracranial abscess or thrombosis decreased during the strict NPI period but without significant change during the light nor post-NPI periods compared with the expected trend without NPI. Analyzing each complication separately, only the proportion of mastoiditis complicated by thrombosis decreased during the strict NPI period (Table III and Figure 4). The proportion of mastoiditis cases leading to surgery remained stable across all periods (Table III).

The proportion of microbiologically undocumented cases was stable across the study period (Table III). Sensitivity analyses on the main outcome yielded similar results (Table S1, Supplementary Appendix; available at www.

jpeds.com). The incidence of urinary tract infection remained stable throughout the study period (Table II).

## Discussion

In this 9-year population-based national study, we observed a sustained increase in the incidence of cases of mastoiditis over the 28 months in the post-COVID-19 study period compared with the expected trend without NPI. This increase was not associated with changes in the severity of mastoiditis and was driven primarily by the surge in *S. pyogenes* cases (+627.8%).

Mastoiditis, as a complication of AOM, may increase due to: (1) a rise in AOM incidence<sup>25,26</sup>, or (2) a higher proportion of AOM cases progressing to complications such as acute mastoiditis.<sup>16,17,27</sup> Both could be driven by changes in clinical practices, by changes in vaccination schedules, by shift in the microbiological etiology of AOM or by changes in host immunity.

First, there was no change in national guidelines regarding the antibiotic nor surgical management of AOM in France during the study period. The last major update occurred in
<figure><img src="image_5.png" /><figcaption>**Figure 3.** Pathogen-specific incidence of mastoiditis per 100 000 children per month in France across pre-NPI, NPI, and post-NPI periods. The grey line shows the observed data. The red line shows the fitted model, with shaded area showing the 95% confidence intervals. The yellow line shows the expected incidence based on data before NPI implementation, with shaded area showing the 95% confidence intervals. The vertical lines show the limit between periods (pre-NPI, NPI, post-NPI).</figcaption></figure>

A = *Streptococcus pneumoniae*; B = *Streptococcus pyogenes*; C = *Haemophilus influenzae*; D = *Staphylococcus aureus*.

2011 and introduced a watchful waiting approach for children over 2 years of age with AOM, with antibiotic therapy (amoxicillin for 5 days) recommended only if symptoms persist after 48 hours. For children under 2 years, immediate antibiotic treatment is recommended for 10 days. At the same time, the recommended dosage of amoxicillin was increased

in response to rising rates of penicillin-resistant *S. pneumoniae*.²⁸ There was however a transient change in treatment recommendations due to amoxicillin shortage between November 2022 and March 2023 leading to shortened duration of treatment for AOM in children under 2 years of age to 5 days.²⁹ Although this may have contributed to an increased

<table><caption>**Table III.** Estimated Changes in the Proportion of Undocumented Mastoiditis Cases, Complicated Mastoiditis Cases and Mastoiditis Cases Requiring Surgery Compared to the Pre-NPI Period</caption><thead><tr><th rowspan="2"></th><th colspan="2">Strict NPI period</th><th colspan="2">Light NPI period</th><th colspan="2">Post-NPI period</th></tr><tr><th>Estimated change in proportion, % (CI - 95%)</th><th>P</th><th>Estimated change in proportion, % (CI - 95%)</th><th>P</th><th>Estimated change in proportion, % (CI - 95%)</th><th>P</th></tr></thead><tbody><tr><td>Proportion of microbiologically undocumented mastoiditis cases</td><td>-0.2 (-4.3; +4.1)</td><td>.922</td><td>-1.8 (-7.0; +3.6)</td><td>.495</td><td>-7.5 (-13.4; +1.1)</td><td>.22</td></tr><tr><td>Proportion of complicated mastoiditis cases, overall</td><td>-38.9 (-57.2; -12.7)</td><td>.007</td><td>-18.8 (-46.9; +23.9)</td><td>.334</td><td>-34.0 (-61.2; +12.1)</td><td>.124</td></tr><tr><td>Meningitis</td><td>-8.9 (-57.3; +94.4)</td><td>.809</td><td>+39.9 (-43.7; +247.3)</td><td>.469</td><td>-28.7 (-78.6; +137.0)</td><td>.580</td></tr><tr><td>Intracranial abscess</td><td>-32.2 (-60.0; +14.7)</td><td>.148</td><td>-36.8 (-67.3; +22.2)</td><td>.173</td><td>-42.7 (-74.7; +29.4)</td><td>.180</td></tr><tr><td>Thrombosis</td><td>-52.6 (-70.8; -23.0)</td><td>.003</td><td>-9.7 (-46.8; +53.5)</td><td>.707</td><td>-20.4 (-58.8; +54.0)</td><td>.499</td></tr><tr><td>Proportion of mastoiditis requiring surgery</td><td>-18.9 (-39.0; +7.9)</td><td>.151</td><td>+5.1 (-25.5; +48.3)</td><td>.778</td><td>+5.9 (-30.4; +60.9)</td><td>.790</td></tr></tbody></table>
<figure><img src="image_6.png" /><figcaption>**Figure 4.** Monthly proportion of complicated mastoiditis cases in France across pre-NPI, NPI, and post-NPI periods. The grey line shows the observed data. The red line shows the fitted model, with shaded area showing the 95% confidence intervals. The yellow line shows the expected incidence based on data before NPI implementation, with shaded area showing the 95% confidence intervals. The vertical lines show the limit between periods (pre-NPI, NPI, post-NPI). **A** = Proportion of mastoiditis cases with at least one complication; **B** = Proportion of mastoiditis cases complicated by meningitis; **C** = Proportion of mastoiditis cases complicated by intracranial abscess; **D** = Proportion of mastoiditis cases complicated by thrombosis.</figcaption></figure>

risk of mastoiditis in this age group, incidence of mastoiditis remained elevated even after the shortage was resolved and standard treatment durations were restored.

Second, pneumococcal conjugate vaccination targeting 13 serotypes (PCV13) has been recommended since 2010, and vaccination against *H. influenzae* type b has been in place for several decades. Both vaccines have been administered using a 2 + 1 (ie, 2 doses in the first 12 months of life followed by 1 dose after 12 months) schedule since 2013. Although this schedule may have led to a slightly increased risk in invasive *H. influenzae* type b infection, the change occurred prior to our study.³⁰

Third, evolving patterns in the microbiological etiology of AOM may offer more plausible explanations for the sustained increase in mastoiditis incidence.²¹ In our study, mastoiditis caused by *S. pyogenes* showed the most pronounced decline during the NPI periods and the most significant resurgence in the post-NPI period. This trend mirrors the global surge in invasive *S. pyogenes* (iGAS) infections observed during the winter of 2022-2023 following the lifting of NPI, including in France where the rise in iGAS was comparable with the magnitude of the mastoiditis increase re-

ported in our study.³¹ The risk of mastoiditis is higher following AOM caused by *S. pyogenes* than by *S. pneumoniae* or *H. influenzae*, suggesting that the increase in mastoiditis may reflect the overall rise in iGAS incidence.³² However, unlike the broader category of iGAS infections, which largely returned to baseline levels during the 2023–2024 winter season, *S. pyogenes* mastoiditis incidence remained high in our cohort and only began to decline more markedly in the winter of 2024. One hypothesis may be that distinct clones emerged with increased virulence or tropism for middle ear or mastoid tissue. Genomic sequencing of *S. pyogenes* strains involved in mastoiditis could help clarify whether specific lineages or virulence factors are contributing to the prolonged trend, as in the UK where the increase in iGAS in 2022 was predominantly associated with one lineage, M1UK.³³ A similar approach could be applied to *S. pneumoniae*, which post-NPI increase may reflect the involvement of serotypes outside vaccine coverage with a particular tropism for mastoid tissue. This phenomenon was observed in the early PCV7 era in the United States and in Greece, when serotype 19A, not included in the PCV7, became the
predominant strain recovered from children with mastoid-
itis.³⁴,³⁵ We also observed a decrease in *H. influenzae*
mastoiditis during the strict NPI period, followed by a
nonsignificant upward trend post-NPI. However, interpreta-
tion is limited by the absence of strain typing, particularly
regarding the potential role of nontypeable *H. influenzae*,
which was the main driver of invasive *H. influenzae* trends
during the NPI period in England.³⁶ Another possible
contributing factor could be a progressive rise in *H. influen-
zae* resistance to amoxicillin; yet, recent data from France
found no increase in resistance among AOM isolates, making
this explanation unlikely.³⁷ Finally, other pathogens not
identified by ICD-10 codes also may have contributed to
the observed trends, including species of the *Streptococcus an-
ginosus* group, which have been increasingly implicated in se-
vere complications of mastoiditis in children in the
postpandemic period.³⁸ This highlights the importance of
ongoing molecular and antimicrobial resistance surveillance
to better characterize the bacterial populations driving
these trends.

Fourth, beyond pathogen-related factors, changes in host
immunity driven by the reduced exposure to common respi-
ratory pathogens during the NPI period (immunity gap),
likely contributed to the observed rise in mastoiditis inci-
dence in the post-NPI period.<sup>13,39,40</sup> Immunity “gap” or
“debt” describes the reduction in population-level immunity
resulting from the prolonged suppression of a pathogen’s cir-
culation during NPI. This lack of exposure may have led to a
higher proportion of susceptible individuals, particularly
among children born during the pandemic, thereby
increasing vulnerability to infections and their complications
once pathogen circulation resumed. Moreover, decreased
maternal exposure to pathogen may have limited the trans-
placental transfer of protective antibodies, further height-
ening the risk of early-life infections in the youngest age
groups. This temporary shift in population immunity may
have played an important role in amplifying the burden of
post-NPI complications such as mastoiditis.

Overall, the sustained increase in mastoiditis incidence post-NPI compared with expected trend without NPI is likely driven by a combination of factors, including changes in pathogen dynamics, most notably the rise in *S. pyogenes* infections, and diminished host immunity. Regardless of the underlying causes and its medium-term impact on pathogens, these findings warrant consideration in future epidemic and postpandemic management.

Our study has several limitations. First, we relied on hos-
pital diagnoses, which are not based on standardized criteria,
potentially introducing heterogeneity in case identification.
To address this, we conducted a sensitivity analysis using
mastoiditis coded as the principal diagnosis only, which
should reduce potential heterogeneity in case identification.
This analysis yielded similar results. Second, microbiological
causes were derived from hospital diagnoses rather than
directly from microbiological data, which may have led to
underreporting or misclassification in some cases. Moreover,
we only had access to pathogens identified by ICD-10 codes,

which are not exhaustive; for example, *Moraxella catarrhalis* and *S. anginosus* are not included. Furthermore, mastoiditis is, in any case, a poorly microbiologically documented condition since cultures are typically obtained only for surgically managed, which in France represent the most severe cases. As 82% of cases were not microbiologically documented, we cannot exclude possible changes in practices regarding microbiological documentation. We would therefore not have been able to identify unexpected or emerging pathogens involved in mastoiditis. To explore this potential bias, we conducted a subgroup analysis using the proportion of mastoiditis cases without microbiological documentation as an outcome, which remained stable over time. Third, the lack of genomic data and detailed serotype information, especially for *S. pneumoniae* and *S. pyogenes*, limits our ability to fully understand the epidemiology and evolution of these pathogens during the study period. Molecular studies need to be developed to better understand the mechanisms driving this increase.

The sustained increase in pediatric mastoiditis incidence
during the post-COVID-19 era underscores the complex
interplay of pathogen dynamics and host immunity in
shaping infection patterns. These findings highlight the
importance of ongoing surveillance to better understand
the long-term impacts of the COVID-19 pandemic on severe
pediatric infectious diseases. ■

CRediT authorship contribution statement

**Apolline Furgier:** Writing – original draft, Visualization, Methodology, Formal analysis, Conceptualization. **Romain Basmaci:** Writing – original draft, Supervision, Project administration, Methodology, Conceptualization. **Zaba Valtuille:** Writing – review & editing, Methodology, Data curation, Conceptualization. **Inès Fafi:** Writing – review & editing, Methodology, Conceptualization. **Zein Assad:** Writing – review & editing, Methodology, Conceptualization. **Léa Lenglart:** Writing – review & editing, Methodology, Conceptualization. **Natacha Teissier:** Writing – review & editing, Validation. **Charlotte Benoit:** Writing – review & editing, Validation. **Emilien Chebib:** Writing – review & editing, Validation. **Aurélie Bourmaud:** Writing – review & editing, Validation. **François Angoulvant:** Writing – review & editing, Validation. **Pierre Alex Crisinel:** Writing – review & editing, Validation. **André Birgy:** Writing – review & editing, Validation. **Naïm Ouldali:** Writing – original draft, Supervision, Project administration, Methodology, Conceptualization. **Manon Jaboyedoff:** Writing – original draft, Visualization, Methodology, Formal analysis, Conceptualization.

**Declaration of Competing Interest**

This study was performed with the financial support of the
Fondation de l'Assistance Publique – Hôpitaux de Paris, Laus-
sanne University, Lausanne University Hospital, SICPA
Foundation, Gottfried und Julia Bangerter-Rhyner Founda-
tion. R. B. reports a relationship with Sanofi that includes:
travel reimbursement. R. B. and N. O. report a relationship
with MSD that includes: travel reimbursement. N. O. reports
travel reimbursement from Pfizer and Sanofi. N. O. reports
financial support was provided by Fondation de l'Assistance
Publique Hôpitaux de Paris. A. B. reports a relationship with
JAZZPHARMA that includes: consultation or advisory fees.
If there are other authors, they declare that they have no
known competing financial interests or personal relation-
ships that could have appeared to influence the work re-
ported in this paper. M.J. reports financial support was
provided by Gottfried und Julia Bangerter-Rhyner Founda-
tion, SICPA Foundation.

Submitted for publication Jul 22, 2025; last revision received Aug 21, 2025; accepted Sep 23, 2025.

Reprint requests: Manon Jaboyedoff, MD, Department Women-Mother-Child, Unit of Pediatric Infectious Diseases and Vaccinology, Service of Pediatrics, Lausanne University Hospital, 50, rue du Bugnon, 1011, Lausanne, Switzerland. E-mail: manon.jaboyedoff@chuv.ch

Data Statement

Data sharing statement available at www.jpeds.com.

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