Respiratory pathogen spectrum and coinfection patterns in acute respiratory infection patients during and post-COVID-19 pandemic from 2021 to 2025

Technical Summary: Respiratory Pathogen Spectrum and Coinfection Patterns in Acute Respiratory Infection Patients (2021–2025)

Problem Statement
The global implementation of non-pharmaceutical interventions (NPIs) during the COVID-19 pandemic significantly altered the transmission dynamics of respiratory pathogens. Following the relaxation of these measures in China, there was a need to understand the epidemiological shifts, pathogen spectra, and coinfection patterns in Acute Respiratory Infection (ARI) patients. Specifically, the study addresses the challenges posed by the resurgence of ARI, the increasing incidence of coinfections (virus-virus, virus-bacteria, bacteria-fungus), and the rising prevalence of drug-resistant bacteria, which complicate diagnosis and treatment strategies in both general wards and Intensive Care Units (ICU).

Methodology
This study is a retrospective analysis conducted at Hebei General Hospital involving 9,674 patients admitted with ARI between January 2021 and December 2025.

• Cohort Definition: Patients were categorized into Upper Respiratory Tract Infection (URTI) and Lower Respiratory Tract Infection (LRTI) based on clinical symptoms and imaging (CT/MRI). A subset of 79 patients admitted to the ICU for severe LRTI was analyzed separately.
• Pathogen Detection: All patients underwent testing for 13 specific respiratory pathogens using fluorescence PCR combined with capillary electrophoresis (mPCR). The panel included Influenza A (subtypes H1N1, H3N2, etc.) and B, Parainfluenza virus, Adenovirus, Rhinovirus, Metapneumovirus, Respiratory Syncytial Virus, Coronaviruses (229E, OC43, NL63, HKU1), Mycoplasma pneumoniae, Chlamydia, and Bocavirus.
• Microbiology: ICU patients underwent standard bacterial and fungal culture and identification, including drug sensitivity testing.
• Statistical Analysis: Data were analyzed using SPSS 26.0. Chi-square tests were used for categorical data, and Mann-Whitney U or t-tests for continuous variables, with significance set at p < 0.05.

Key Contributions

• Longitudinal Epidemiological Tracking: The study provides a comprehensive five-year dataset (2021–2025) capturing the transition from strict NPI enforcement to post-pandemic normalization, documenting the "suppression-resurgence" trend of ARI.
• Differentiation of URTI vs. LRTI: It systematically contrasts pathogen detection rates and coinfection patterns between upper and lower respiratory tract infections, highlighting distinct etiological profiles.
• ICU-Specific Profiling: The research offers a detailed etiological and resistance profile of severe LRTI cases in the ICU, focusing on the high burden of multidrug-resistant (MDR) bacteria and fungal coinfections.
• Coinfection Dynamics: It quantifies the prevalence of single versus multiple infections (double/triple) and identifies specific high-risk pathogen combinations.

Results

• Epidemiological Trends: ARI incidence and pathogen positivity rates were suppressed during 2021–2022 (positivity rates ~24–27%) due to NPIs. A significant resurgence occurred in 2023 (positivity rate 34.62%), peaking in 2024 (54.84%), before declining in 2025.
• URTI vs. LRTI Disparities:
  • Prevalence: LRTI cases (54.67%) outnumbered URTI cases (45.33%).
  • Detection Rates: Pathogen detection was significantly higher in LRTI (55.57%) compared to URTI (15.44%).
  • Dominant Pathogens: Mycoplasma pneumoniae (MP) was the leading pathogen in LRTI (18.08%), whereas Rhinovirus (RV) predominated in URTI (5.12%).
  • Coinfection: Multiple infections were significantly more common in LRTI (8.09%) than in URTI (1.66%).
• ICU Severe Cases (n=79):
  • Demographics: The cohort was predominantly elderly (median age 69) and male (73.42%), with 86.08% having underlying conditions.
  • Pathogens: Influenza A (51.90%) and Rhinovirus (16.46%) were the primary viral drivers.
  • Coinfections: 91.14% of ICU cases exhibited bacterial coinfections. Notably, 51.90% involved multidrug-resistant or resistant strains, primarily Carbapenem-Resistant Acinetobacter baumannii (CRAB) and Carbapenem-Resistant Klebsiella pneumoniae (CRE).
  • Fungal Infections: Present in 16.46% of cases, primarily Candida species.
  • Outcomes: The mortality rate was 8.86% (7/79), with all fatal cases involving virus-bacteria mixed infections. Patients with MDR bacterial or fungal coinfections had significantly longer hospital stays (26 and 25 days, respectively) compared to those without (19 and 17 days).

Significance and Claims
The authors claim that the study provides an evidence-based foundation for optimizing the management of ARI in the post-pandemic era. Key implications include:

1. Diagnostic Strategy: The high detection rate of pathogens in LRTI and the prevalence of coinfections necessitate the use of multi-pathogen detection technologies (e.g., mPCR) rather than single-target testing.
2. Treatment Challenges: The high incidence of drug-resistant bacteria and fungal coinfections in severe LRTI cases, particularly among the elderly, increases the difficulty of treatment and necessitates optimized antimicrobial stewardship.
3. Immunity Debt: The resurgence of infections and the shift in age distribution (with school-age children showing high LRTI positivity) suggest that prolonged NPIs may have led to a decline in population-level immune memory, resulting in a "resurgence" pattern that requires sustained vigilance.
4. Clinical Management: The findings underscore the need for early detection of coinfections (viral, bacterial, and fungal) in ICU settings to improve outcomes and reduce hospital length of stay.

The paper concludes that while the overall disease burden has receded from its 2023 peak, the persistently elevated rates of multiple infections and ICU admissions highlight the ongoing need for precise regional diagnosis and control strategies.