Mycoplasma pneumoniae incidence, phenotype, and severity in children and adolescents in Denmark before, during, and after the COVID-19 pandemic: a nationwide multicentre population-based cohort study

Kia H S Dungu; Mette Holm; Ulla Hartling; Lise H Jensen; Allan Bybeck Nielsen; Lisbeth S Schmidt; Lise B Toustrup; Lotte H Hansen; Kathrin W Dahl; Kirstine T Matthesen; Anne C Nordholm; Søren Uldum; Hanne-Dorthe Emborg; Maren J H Rytter; Ulrikka Nygaard

doi:10.1016/j.lanepe.2024.101103

Mycoplasma pneumoniae incidence, phenotype, and severity in children and adolescents in Denmark before, during, and after the COVID-19 pandemic: a nationwide multicentre population-based cohort study

Lancet Reg Health Eur. 2024 Oct 18:47:101103. doi: 10.1016/j.lanepe.2024.101103. eCollection 2024 Dec.

Authors

Kia H S Dungu¹, Mette Holm², Ulla Hartling³, Lise H Jensen^{4

5}, Allan Bybeck Nielsen⁶, Lisbeth S Schmidt^{5

7}, Lise B Toustrup², Lotte H Hansen⁸, Kathrin W Dahl⁹, Kirstine T Matthesen¹⁰, Anne C Nordholm¹¹, Søren Uldum¹², Hanne-Dorthe Emborg¹¹, Maren J H Rytter^{5

13}, Ulrikka Nygaard^{1

5}

Affiliations

¹ Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet, Denmark.
² Department of Paediatrics and Adolescent Medicine, Aarhus University Hospital, Denmark.
³ Department of Paediatrics and Adolescent Medicine, Hans Christian Andersen Children's Hospital, Odense, Denmark.
⁴ Department of Paediatrics and Adolescent Medicine, Zealand University Hospital, Roskilde, Denmark.
⁵ Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
⁶ Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital, Hvidovre, Denmark.
⁷ Department of Paediatrics and Adolescent Medicine, Herlev University Hospital, Herlev, Denmark.
⁸ Department of Paediatrics, University Hospital of Southern Denmark, Aabenraa, Denmark.
⁹ Department of Paediatrics and Adolescent Medicine, Hillerød University Hospital, Hillerød, Denmark.
¹⁰ Department of Paediatrics and Adolescent Medicine, Aalborg University Hospital, Aalborg, Denmark.
¹¹ Department of Infectious Disease Epidemiology and Prevention, Statens Serum Institut, Copenhagen, Denmark.
¹² Department of Bacteria, Parasites & Fungi, Statens Serum Institut, Copenhagen, Denmark.
¹³ Department of Paediatrics and Adolescent Medicine, Slagelse Hospital, Denmark.

Abstract

Background: Mycoplasma pneumoniae infections resurged globally in 2023-2024 after a three-year decline during the COVID-19 pandemic. We explored the incidence and severity of M pneumoniae infections in children and adolescents before, during, and after the pandemic.

Methods: This nationwide, population-based cohort study included all Danish children and adolescents aged 0-17 years with a positive M pneumoniae PCR test from May 1, 2016, to April 30, 2024. We obtained clinical details for patients hospitalised for 24 h or more. Risk ratios for infections, hospitalisations, and disease manifestations in 2023-2024 versus pre-COVID-19 seasons were calculated using Fisher's exact and Pearson's χ² tests. A season was defined from May 1 to April 30.

Findings: Among the Danish population of 1,152,000 children and adolescents, 14,241 with a positive PCR test for M pneumoniae were included. In 2023-2024, children and adolescents with a positive PCR rose 2.9-fold (95% CI 2.8-3.1; p < 0.0001) compared to the pre-COVID-19 seasons, and hospitalisations rose 2.6-fold (95% CI 2.0-3.3; p < 0.0001). M pneumoniae-induced rash and mucositis increased 5.3-fold (95% CI 1.8-15.3; p = 0.0007). In 2023-2024 compared to the pre-COVID-19 seasons, there was no difference in the proportion of hospitalisation (360 [4%] of 8165 versus 230 [4%] of 6009; p = 0.09), the median duration of hospital stay (3 days [IQR 2-5] versus 3 days [IQR 2-5]; p = 0.84), or paediatric intensive care unit admission (14 [4%] of 360 versus 9 [4%] of 230 p = 1.00).

Interpretation: In Denmark, M pneumoniae infections and hospitalisations increased three-fold in 2023-2024 compared with the pre-COVID-19 seasons, indicating an immunity debt caused by the decline in M pneumoniae during the COVID-19 pandemic. While the severity of M pneumoniae infections did not change in 2023-2024, the five-fold increase in M pneumoniae-induced rash and mucositis in children and adolescents highlights M pneumoniae as an important pathogen causing mucocutaneous eruptions.

Funding: Innovation Fund Denmark and Rigshospitalets Forskningsfond.

Keywords: COVID-19; Corticosteroids; MIRM; Mycoplasma; Mycoplasma induced rash and mucositis; Mycoplasma pneumoniae; Mycositis; RIME; Reactive infectious mucocutaneous eruptions; Resurgence.