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. 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. 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). 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. Innovation Fund Denmark and Rigshospitalets Forskningsfond.

Objective To evaluate the implementation of switch from intravenous-to-oral antibiotic therapy with amoxicillin in neonates with early-onset infection (EOI). Design, setting and patients A population-based multicentre cohort study. All term-born neonates with EOI were prospectively included between 1 December 2018 to 30 November 2020. Intervention Intravenous-to-oral switch antibiotic therapy in clinically stable neonates. Main outcome measures The primary outcome was readmission due to infection. Secondary outcomes were days of hospitalisation and antibiotic use in the pre-implementation versus post implementation period. Results During 2 years, 835 neonates commenced antibiotics for EOI (1.5% (95% CI 1.4% to 1.6%)) of all term live births). Of those, 554 (66%) underwent a full course of treatment. There were 23 episodes of culture-proven infection (0.42 per 1000 term live births (95% CI 0.27 to 0.63)). A total of 478 of 531 (90%) neonates with probable infection underwent switch therapy. None was readmitted due to infection. The median duration of hospitalisation was 3.0 days (IQR 2.5–3.5) and 7.4 days (IQR 7.0–7.5) in the switch and intravenous therapy groups, respectively. According to antibiotic surveillance data, 1.2% underwent a full course of treatment following implementation of oral switch therapy (2019–2020), compared with 1.2% before (2017–2018). Conclusion In clinical practice, switch therapy was safe and used in 9 of 10 neonates with probable EOI. Knowledge of the safety of antibiotic de-escalation is important as home-based oral therapy ameliorates the treatment burden for neonates, caregivers and healthcare systems. Despite the ease of oral administration, implementation of switch therapy did not increase the overall use of antibiotics.

Multisystem inflammatory syndrome in children (MIS-C) is a severe disease that emerged during the COVID-19 pandemic. Although recognized as an immune-mediated condition, the pathogenesis remains unresolved. Furthermore, the absence of a diagnostic test can lead to delayed immunotherapy. Using state-of-the-art mass-spectrometry proteomics, assisted by artificial intelligence (AI), we aimed to identify a diagnostic signature for MIS-C and to gain insights into disease mechanisms. We identified a highly specific 4-protein diagnostic signature in children with MIS-C. Furthermore, we identified seven clusters that differed between MIS-C and controls, indicating an interplay between apolipoproteins, immune response proteins, coagulation factors, platelet function, and the complement cascade. These intricate protein patterns indicated MIS-C as an immunometabolic condition with global hypercoagulability. Our findings emphasize the potential of AI-assisted proteomics as a powerful and unbiased tool for assessing disease pathogenesis and suggesting avenues for future interventions and impact on pediatric disease trajectories through early diagnosis.

Objective To estimate the incidence of neonatal herpes simplex virus (HSV) infection and the number of neonates with suspected invasive bacterial infection (IBI) needed to treat (NNT) with acyclovir to ensure prompt treatment of invasive HSV infections. Design A nationwide population-based cohort study. Setting All neonatal and paediatric emergency departments in Denmark from 1 January 2010 to 31 December 2019. Patients Neonates aged 0–28 days with HSV infection. Main outcome measures The main outcome measures were incidence and NNT. The NNT was calculated based on neonates with invasive HSV infection whose onset symptoms resembled IBI and the estimated number of Danish neonates who received antibiotics for suspected IBI. Results Fifty-four neonates with HSV infection were identified, that is, an incidence of 9 per 100 000 live births. Twenty presented with symptoms resembling IBI, all within the first 14 days of life. Of 18 (78%) neonates, 14 had elevated C reactive protein, 14 of 19 (74%) had elevated alanine aminotransferase and 11 of 17 (65%) had thrombocytopaenia. The estimated NNTs with empiric acyclovir at postnatal ages 0–3, 4–7 and 8–14 days were 1139 (95% CI 523 to 3103), 168 (95% CI 101 to 726) and 117 (95% CI 48 to 198), respectively. Conclusions The incidence of neonatal HSV infection was higher than in previous decades; however, the estimated NNT with empiric acyclovir was high. Therefore, we propose not to treat all neonates suspected of IBI with empiric acyclovir, as current European guidelines suggest. However, HSV should be considered in neonates with signs of infection, especially after the third postnatal day and in neonates with high alanine aminotransferases and thrombocytopaenia.

Background: Neonatal herpes simplex virus (HSV) infection is life-threatening, with a mortality of up to 70–80% when disseminated, often due to vague symptoms and delayed treatment. Neonatal screening using dried blood spot (DBS) samples is among the most impactful preventative health measures ever implemented, but screening for HSV has not been investigated. Methods: We investigated high throughput multiplexed proteomics on DBS samples collected on days 2–3 of life from a nationwide cohort of neonates with HSV infection (n = 53) and matched controls. We measured 2941 proteins using the Olink Explore 3072 panels and proximity extension assays, followed by differential protein expression by Analysis of Variance with post-hoc correction and functional annotation. Results: Here, we show distinct protein profiles in neonates with disseminated HSV disease, with differences in 20 proteins compared to controls. These proteins are associated with innate and adaptive immune responses and cytokine activation. Conclusions: Our findings indicate the potential of neonatal screening for disseminated HSV disease to ensure early treatment and reduce the high mortality.