Despite advances in perinatal medicine, sepsis remains a major cause of mortality and morbidity in newborns, particularly in developing countries (Al-Matary et al., 2019). Neonatal sepsis is classified into early-onset sepsis (EOS), occurring within 72 hours of birth, and late-onset sepsis (LOS), which manifests thereafter. Factors such as premature birth, low birth weight (LBW), prolonged premature rupture of membranes, mechanical ventilation, and central venous catheter use increase the risk of sepsis in newborns (Ba-Alwi et al., 2022; Yu et al., 2022).

In response to the COVID-19 pandemic, extensive non-pharmaceutical interventions (NPIs) altered lifestyles, hospital operations, and clinical care worldwide, including travel restrictions, event cancellations, social distancing, mask mandates, and lockdowns. These measures have impacted hospital protocols, leading to tightened infection-control practices and changes in medical care delivery such as deprogramming of elective surgeries and restricting of physical visits. For instance, social distancing has been linked to reduced bacteremia, while endogenous infection cases such as hospital-diagnosed bacteremia associated with the NPIs have risen (Brueggemann et al., 2021; Cauhape et al., 2023).

The impact of the COVID-19 pandemic on neonatal intensive care units (NICUs) has been complex and multifaceted. A study conducted in an Italian NICU showed a reduction in colonization by multiresistant organisms among infants, attributed to strengthened infection-control measures post-COVID-19 outbreak (Pezzotta et al., 2021). In contrast, there was an increase in the incidence of central-line associated bloodstream infections during the pandemic, linked to shortages of alcohol-based hand rubs (Kharrat et al., 2021). Additionally, a retrospective, observational, multi-center study involving four Italian NICUs aimed to assess the indirect effects of pandemic-related measures on very-low-birthweight (VLBW) infants. Their findings indicated that the implementation of enhanced NICU hygiene policies likely reduced the occurrence of LOS in these high-risk settings (Indrio et al., 2022).

Despite China being the first country to confront COVID-19 and implement NPIs, there is a lack of reports assessing how these measures have affected neonatal sepsis. In the current study, we analyzed clinical data from two distinct periods at a tertiary pediatric hospital to compare neonatal sepsis cases before (January 2016 to December 2019, Phase I) and during the pandemic (January 2020 to December 2022, Phase II). Our aim was to assess the indirect effects of pandemic-related measures on the epidemiology and antimicrobial resistance of neonatal sepsis.

Out of 734 neonates with culture-proven neonatal sepsis, 507 were included in the study after excluding 227 for not meeting the criteria during the study period. Of the 227 sepsis episodes in these excluded 227 neonates, the reasons for exclusion were as follows: 12 episodes were excluded due to age at onset being outside the criteria, 52 episodes were excluded because of the absence of abnormal clinical manifestations, 150 episodes were excluded because the blood culture showed only a single positive result for CoNS or other common contaminants and was considered contaminated, 4 episodes were excluded due to malignancy, congenital malformation, or autoimmune disease, and 9 episodes were excluded due to incomplete or missing records. The analysis identified 525 sepsis episodes in 507 infants, including 343 in Phase I and 182 in Phase II. EOS occurred in 92 episodes (19.4%), and LOS in 432 episodes (80.6%) ( Figure 1 ). Of the 525 episodes, 443 underwent lumbar puncture (84.3%), yielding 59 positive CSF cultures (13.3%). Among these, 28 were from neonates with negative blood cultures, while the remaining 31 had matching organisms in both blood and CSF.

The annual birth rate in Suzhou city has declined since 2021, rather than since 2020 when the pandemic began ( Figure 2 , https://tjj.suzhou.gov.cn/sztjj/ndjb/nav_list.shtml). Concurrently, the incidence of EOS decreased starting in 2020, calculated based on both the birth population in Suzhou city and hospitalized infants at the Neonatal Department ( Figure 2 ).

According to our findings, the COVID-19 pandemic and the response measures significantly altered the incidence and characteristics of neonatal sepsis at our institution, a tertiary children’s hospital in East China. The incidence of EOS showed a notable decrease during the pandemic period compared to the pre-pandemic era, a trend partially corroborated by a prior study in India (Dutta et al., 2022). However, the proportion of neonates experiencing any culture-positive sepsis, as indicated in this Indian report, demonstrated a decrease primarily attributed to a significant decline in Acinetobacter baumannii sepsis and sepsis caused by multi-drug resistant/extreme drug resistant/pan drug resistant organisms during the lockdown compared to the pre-lockdown period, which contrasts with our findings. EOS, typically resulting from microorganisms transmitted from mother to child before or during delivery (Schrag et al., 2016), saw a marked decrease during Phase II (2020–2022) compared to Phase I (2016–2019) in our study. This decline coincided with a reduction in maternal intrapartum fever, which may be partly attributable to the enhanced hygiene practices implemented in response to the pandemic. These measures, including maintaining social distancing, universal use of personal protective equipment, restricted patient movement and visitor policies, and rigorous cleaning protocols in the obstetrics department, likely played crucial roles. Such precautions could have reduced the transmission of infectious agents, thereby decreasing the incidence of conditions conducive to EOS. Understanding these connections is vital for developing strategies to prevent neonatal sepsis beyond the current pandemic context, suggesting that some of these enhanced hygiene practices could be beneficial if sustained in the long term.

We noted a statistically significant increase in the proportion of LOS cases from 79% (271/343) in Phase I to 89% (162/182) in Phase II. The decline in EOS may contribute to the escalation in the proportion of LOS. Furthermore, prominent risk factors for LOS include premature birth and need for intensive medical interventions such as intubation, mechanical ventilation, central catheter insertion, poor nutrition, and surgical procedures due to LBW (Pan et al., 2020; Kostlin-Gille et al., 2021). Some studies show a decrease in the premature birth rate of newborns during the COVID-19 period (Been et al., 2020; Bian et al., 2021), while conversely, other studies indicate that during the COVID-19 pandemic, the rates of premature births and low birth weight have increased (Charles et al., 2023; Gholami et al., 2023). In our findings, neonates with neonatal sepsis in Phase II presented with smaller GAs and lower BWs compared to those in Phase I, correlating with an increased proportion of LOS. Additionally, the use of endotracheal tubes also increased, though not significantly (p < 0.1). These conditions, more prevalent among preterm infants who typically require more complex care, likely contributed to the higher proportion of LOS observed during the pandemic. Indrio and his colleagues enrolled infants with VLBW and/or GA between 22 and 29 weeks from four Italian NICUs in their study. They found a decreased incidence of LOS during the pandemic period compared to the pre-pandemic period (Indrio et al., 2022), which is inconsistent with the results of our study. This discrepancy may be related to differences in GA and BW of the populations included.

In our study, clinical manifestations such as mottled skin, severe anemia and thrombocytopenia were more frequent in Phase II, coinciding with a higher rate of complications. Notably, the incidence of NEC significantly increased during this phase (p < 0.05), as did the occurrence of neonatal meningitis, though less significantly (p < 0.1). These conditions are major contributors to morbidity and mortality from neonatal sepsis, suggesting greater severity of illness during the pandemic compared to the pre-pandemic period.

Pathogen analysis revealed that CoNS, E. coli, K. pneumoniae, and GBS were the most prevalent, with E. coli and K. pneumoniae being primarily responsible for neonatal deaths and NEC cases in our center. This pathogen distribution aligns variably with global reports, reflecting regional differences in pathogen prevalence (Jiang et al., 2016; Al-Matary et al., 2019; Ba-Alwi et al., 2022). For instance, while E. coli and K. pneumoniae showed substantial susceptibility to amikacin, gentamicin, carbapenems, and quinolones in our study, research by Kumar et al (Kumar et al., 2023). indicated high resistance to amikacin and gentamicin among these pathogens. Such discrepancies can often be attributed to local antibiotic usage patterns, environmental conditions, and healthcare practices. Furthermore, our comparative analysis between phases revealed a significant decrease in the proportion of K. pneumoniae in Phase II. Despite this reduction, there was a marked increase in antibiotic resistance for both E. coli and K. pneumoniae during the same period.

Our analysis identified several factors associated with complications among neonatal sepsis infants, with the period of the COVID-19 pandemic (Phase II) emerging as an independent risk factor. This association was probably influenced by multiple factors, including smaller GA and lower BW observed during this period, compounded by the broader impacts of the COVID-19 epidemic and related lockdown measures.

Notably, the increased resistance of E. coli and K. pneumoniae to antibiotics during Phase II played a significant role in the complications observed, which aligns with findings from France, where a study reported an uptick in documented monomicrobial bacteremia in 2020 compared to 2019 (Cauhape et al., 2023). Another French study noted not only an increase in bloodstream infections but also a heightened incidence of infections caused by organisms resistant to third-generation cephalosporins (3GC) during the lockdown compared to the corresponding period in 2019 (Amarsy et al., 2022).

The global surge in AMR has been linked to the pandemic, as indicated by Kaba and colleagues who observed an increase in wild phenotypes of several bacterial species, including E. coli and K. pneumoniae during the lockdown periods (Kaba et al., 2021). The challenges to implement stringent antimicrobial stewardship (AS) programs during the pandemic were significant, as evidenced by a study in Ireland where 76% of respondents noted obstacles to effective AS due to COVID-19 (Martin et al., 2021).

Moreover, the pandemic led to increased prescriptions of antibiotics as a preventive measure against bacterial infections, potentially enhancing the selection pressure for resistant bacteria (Tebano et al., 2018). Concurrently, the extensive use of biocidal agents and environmental disinfectants intended to curb the spread of COVID-19 might also have contributed to the rise in AMR (Fahimipour et al., 2018; Pidot et al., 2018).

The COVID-19 pandemic has significantly disrupted neonatal care globally, particularly for the smallest and most critically ill infants (Rao et al., 2021). Breastfeeding has been reported to protect against sepsis (Carbone et al., 2020). SARS-CoV-2 RNA is found in human milk in trace amount, though WHO recommends exclusive breastfeeding in all cases unless contraindicated (Kumar et al., 2022). However, despite continued efforts to promote breastfeeding, it was less prevalent in our department during the pandemic due to stringent control measures. Therefore, there was no discussion on the effects of not breastfeeding on infants. This reduction in breastfeeding may have contributed to the increased incidence of sepsis complications.

The COVID-19 pandemic has been reported to indirectly elevate neonatal mortality within hospitals (Kc et al., 2020). Our hospital experienced about a one-third reduction in neonatal admissions, a decline partly attributable to a shift in the composition of admissions, where more patients presented with severe conditions and bacteremia. The decrease in admissions also reflected the impact of broader pandemic control measures implemented in the city, such as travel restrictions, lockdown, and the closure of public spaces, which likely delayed hospital visits until conditions worsened. This delay, combined with greater concerns about COVID-19 exposure in healthcare settings, resulted in patients presenting at more advanced stages of illness, thereby increasing the severity of complications associated with neonatal sepsis.

The COVID-19 pandemic has profound impact on the epidemiology and characteristics of neonatal sepsis. Certain pandemic-related measures likely influenced hospital processes and social behaviors, contributing to a reduced rate of EOS, an increase in neonatal sepsis-associated complications and antibiotic resistance. It remains uncertain which specific interventions were most impactful, where further research is needed to isolate and analyze the factors. Future studies should focus on delineating the specific elements of pandemic response that affect neonatal health outcomes, facilitating better preparedness and response strategies in facing similar global health crises.

The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding authors.

The studies involving humans were approved by Clinical Trial Ethics Review Committee of Children’s Hospital of Soochow University. The studies were conducted in accordance with the local legislation and institutional requirements. The ethics committee/institutional review board waived the requirement of written informed consent for participation from the participants or the participants’ legal guardians/next of kin because This is a retrospective clinical study.

XY: Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Software, Validation, Visualization, Writing – original draft, Writing – review & editing. LR: Conceptualization, Data curation, Investigation, Methodology, Project administration, Resources, Supervision, Validation, Visualization, Writing – original draft, Writing – review & editing. MG: Data curation, Methodology, Writing – review & editing. YL: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Software, Visualization, Writing – original draft, Writing – review & editing. XD: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Software, Supervision, Writing – original draft, Writing – review & editing.