Background Neonates are at major risk of sepsis, but data on neonatal sepsis incidence are scarce. We aimed to assess the incidence and mortality of neonatal sepsis worldwide. Methods We performed a systematic review and meta-analysis. 13 databases were searched for the period January 1979–May 2019, updating the search of a previous systematic review and extending it in order to increase data inputs from low-income and middle-income countries (LMICs). We included studies on the population-level neonatal sepsis incidence that used a clinical sepsis definition, such as the 2005 consensus definition, or relevant ICD codes. We performed a random-effects meta-analysis on neonatal sepsis incidence and mortality, stratified according to sepsis onset, birth weight, prematurity, study setting, WHO region and World Bank income level. Results The search yielded 4737 publications, of which 26 were included. They accounted for 2 797 879 live births and 29 608 sepsis cases in 14 countries, most of which were middle-income countries. Random-effects estimator for neonatal sepsis incidence in the overall time frame was 2824 (95% CI 1892 to 4194) cases per 100 000 live births, of which an estimated 17.6% 9 (95% CI 10.3% to 28.6%) died. In the last decade (2009–2018), the incidence was 3930 (95% CI 1937 to 7812) per 100 000 live births based on four studies from LMICs. In the overall time frame, estimated incidence and mortality was higher in early-onset than late-onset neonatal sepsis cases. There was substantial between-study heterogeneity in all analyses. Studies were at moderate to high risk of bias. Conclusion Neonatal sepsis is common and often fatal. Its incidence remains unknown in most countries and existing studies show marked heterogeneity, indicating the need to increase the number of epidemiological studies, harmonise neonatal sepsis definitions and improve the quality of research in this field. This can help to design and implement targeted interventions, which are urgently needed to reduce the high incidence of neonatal sepsis worldwide.

Background: Sepsis is one of the most frequent causes of death worldwide, but the recording of population-based epidemiology is challenging, which is why reliable data on sepsis incidence and mortality are only available in a few, mostly highly-resourced countries. Objective: The aim of this narrative review is to provide an overview of sepsis epidemiology worldwide and in Germany based on current literature, to identify challenges in this research area, and to give an outlook on future developments. Materials and methods: Selective literature review. PubMed and Google Scholar were searched for current literature. The results were processed narratively. Results: Based on modeling studies or meta-analyses of prospective studies, global annual sepsis incidence was found to be 276–678/100,000 persons. Case fatality ranged from 22.5 to 26.7%. However, current data sources have several limitations, as administrative data of selected individual countries—mostly with high income—were used as their basis. In these administrative data, sepsis is captured with limited validity. Prospective studies using clinical data often have limited comparability or lack population reference. Conclusion: There is a lack of reliable data sources and definitions to monitor the epidemiology of sepsis and collect reliable global estimates. Increased policy efforts and new scientific approaches are needed to improve our understanding of sepsis epidemiology, identify vulnerable populations, and develop and target effective interventions.

Purpose Sepsis contributes considerably to global morbidity and mortality, while reasons for its increasing incidence remain unclear. We assessed risk adjusted secular trends in sepsis and infection epidemiology in Germany. Methods Retrospective cohort study using nationwide German hospital discharge data. We assessed incidence, outcomes and trends of hospital-treated sepsis and infections between 2010 and 2015. Sepsis was identified by explicit ICD-10 sepsis codes. As sensitivity analysis, results were compared with sepsis cases identified by implicit sepsis coding (combined infection and organ dysfunction codes). Results Among 18 664 877 hospital admissions in 2015, 4 213 116 (22.6%) patients had at least one infection code. There were 320 198 patients that had explicit sepsis codes including 136 542 patients with severe sepsis and septic shock; 183 656 patients were coded as sepsis without organ dysfunction. For patients with explicitly coded sepsis (including severe sepsis), or with severe sepsis alone, mortality rates over the period 2010–2015 decreased from 26.6 to 23.5%, and from 47.8 to 41.7%, respectively. Conclusions Sepsis and infection remain significant causes of hospital admission and death in Germany. Sepsis-related mortality is higher and has declined to a lesser degree than in other high-income countries. Although infection rates steadily increased, the observed annual increase of sepsis cases seems to result, to a considerable degree, from improved coding of sepsis.

Administrative data are used to generate estimates of sepsis epidemiology and can serve as source for quality indicators. Aim was to compare estimates on sepsis incidence and mortality based on different ICD-code abstraction strategies and to assess their validity for sepsis case identification based on a patient sample not pre-selected for presence of sepsis codes. We used the national DRG-statistics for assessment of population-level sepsis incidence and mortality. Cases were identified by three previously published International Statistical Classification of Diseases (ICD) coding strategies for sepsis based on primary and secondary discharge diagnoses (clinical sepsis codes (R-codes), explicit coding (all sepsis codes) and implicit coding (combined infection and organ dysfunction codes)). For the validation study, a stratified sample of 1120 adult patients admitted to a German academic medical center between 2007–2013 was selected. Administrative diagnoses were compared to a gold standard of clinical sepsis diagnoses based on manual chart review. In the validation study, 151/937 patients had sepsis. Explicit coding strategies performed better regarding sensitivity compared to R-codes, but had lower PPV. The implicit approach was the most sensitive for severe sepsis; however, it yielded a considerable number of false positives. R-codes and explicit strategies underestimate sepsis incidence by up to 3.5-fold. Between 2007–2013, national sepsis incidence ranged between 231-1006/100,000 person-years depending on the coding strategy. In the sample of a large tertiary care hospital, ICD-coding strategies for sepsis differ in their accuracy. Estimates using R-codes are likely to underestimate the true sepsis incidence, whereas implicit coding overestimates sepsis cases. Further multi-center evaluation is needed to gain better understanding on the validity of sepsis coding in Germany.

Sepsis is a disability-inducing event, resulting in considerable financial burden for health care systems.^1-3 An estimated 38 million patients survive sepsis each year,⁴ many of whom experience persisting health problems,^1,5 including new or worsened physical,⁶ psychological,^7,8 and cognitive⁶ impairments. Because of these sequelae, sepsis survivors often need ongoing nursing care and experience increased risk of death.⁹

Background: Sequelae of COVID-19 can be severe and longlasting. We compared frequencies of fatigue, depression and cognitive dysfunction in survivors of SARS-CoV-2-infection and sepsis. Methods: We performed a prospective cohort study of 355 symptomatic post-COVID patients who visited our out-patient clinic for post-COVID-19 care. We compared them with 272 symptomatic patients from the Mid-German Sepsis Cohort, which investigates the long-term courses of sepsis survivors. Possible predictors for frequent clinical findings (fatigue, signs of depression, cognitive dysfunction) in post-COVID were investigated with multivariable logistic regression. Results: Median age of the post-COVID patients was 51 years (range 17–86), 60.0% were female, and 31.8% required hospitalization during acute COVID-19. In the post-COVID patients (median follow-up time: 163 days) and the post-sepsis patients (180 days), fatigue was found in 93.2% and 67.8%, signs of depression were found in 81.3% and 10.9%, and cognitive dysfunction was found in 23.5% and 21.3%, respectively. In post-COVID, we did not observe an association between fatigue or depression and the severity of acute COVID-19. In contrast, cognitive dysfunction was associated with hospitalization (out-patient versus in-patient) and more frequent in post-COVID patients treated on an ICU compared to the MSC patients. Conclusion: In post-COVID patients, fatigue and signs of depression are more common than in sepsis survivors, independent from the acute SARS-CoV-2-infection. In contrast, cognitive dysfunction is associated with hospitalization. Despite the differences in frequencies, owing to the similarity of post-COVID and post-sepsis sequelae, this knowledge may help in implementing follow-up approaches after SARS-CoV-2 infection.