Shifts in the pathogen spectrum and epidemiology of respiratory tract infections in the post-COVID-19 era: A study from Quzhou, Eastern China

This study of 2,800 respiratory specimens in Quzhou, China, from late 2023 to mid-2024 reveals that influenza virus, *Streptococcus pneumoniae*, and adenovirus are the dominant pathogens causing acute respiratory infections, with infection rates varying significantly by age, season, and region, thereby highlighting the need for continuous multi-pathogen surveillance and integrated prevention strategies in the post-pandemic era.

The Gist

Imagine the human respiratory system (your nose, throat, and lungs) as a busy, bustling city square. Before the pandemic, this square had a predictable rhythm: certain "visitors" (germs) would show up in the winter, others in the spring, and the crowd knew how to handle them because they had seen them before.

Then came the pandemic. Everyone stayed home, wore masks, and washed hands. The city square went quiet. The usual visitors stopped coming. But because they didn't visit, the city's "security guards" (our immune systems), especially the young ones, forgot how to recognize them. This is what scientists call "immunity debt."

Now, the pandemic restrictions are gone, and the square is open again. This study from Quzhou, China, is like a security camera report from that square, looking at who showed up between late 2023 and mid-2024. Here is what they found, translated into everyday terms:

1. The "Big Three" Invaders

When the researchers looked at 2,800 people with coughs, fevers, or sore throats, they found that 6 out of 10 people were actually infected with something. The top three "criminals" causing trouble were:

• The Flu Virus: The most common troublemaker (about 23% of cases).
• Pneumococcus (a bacteria): The second most common (about 13%). Think of this as a bacteria that loves to hide in the nose and attack when defenses are low.
• Adenovirus: The third most common (about 8%). This is a virus that often causes colds and eye infections.

2. The "Double Trouble" (Co-infections)

Sometimes, the city square gets hit by two invaders at once. About 1 in 6 of the infected people had a "double infection" (two different germs attacking at the same time). It's like a burglar breaking in while a fire alarm is already going off—it makes the situation much messier and harder to fix.

3. Who Got Hit the Hardest?

• The Little Kids (Under 5): They were the most vulnerable. Nearly 8 out of 10 sick kids tested positive for a germ. Why? Because their immune systems are still learning the ropes, and they missed the "practice rounds" during the pandemic lockdowns.
• The Seniors (Over 65): They had the lowest infection rate (about 35%). The study suggests this might be because the local government gave free flu shots to everyone over 60, acting like a strong shield.
• Teens and Adults: They were in the middle, but the Flu was still their biggest enemy.

4. The Seasonal Dance

The study watched how the germs moved over time, like tracking the weather:

• Winter (Nov-Jan): The Flu virus was the king, dominating the scene.
• Early Spring (Feb-Mar): The Flu took a break, but other viruses like SARS-CoV-2 and Adenovirus started dancing.
• Late Spring (Apr-May): Adenovirus had its moment in the spotlight.
• Summer: The activity slowed down, but the germs never fully disappeared.

5. Mild vs. Severe Cases

The researchers compared people with mild symptoms (just a fever and cough, called ILI) to those who were so sick they had to be hospitalized (SARI).

• Mild cases were mostly driven by the Flu and Rhinovirus (the common cold).
• Severe cases in the hospital had a higher mix of other bacteria and viruses, suggesting that while the Flu is common, other germs are more likely to knock someone down hard enough to need a hospital bed.

The Big Takeaway

The main lesson from this study is that the rules have changed. We can no longer assume that only the Flu is dangerous in the winter. The "enemy" is now a mix of many different viruses and bacteria, and they are attacking the young and the old with different patterns than before.

What should we do?
Just like a city needs a diverse security team, our health system needs to keep an eye on all these germs, not just the Flu. We need to keep vaccinating, keep testing for multiple bugs at once, and remember that our immune systems, especially in children, need a little extra help to remember how to fight these old enemies again.

In short: The pandemic paused the party, but now the music is back on, and the dance floor is crowded with a mix of old and new partners. We need to stay alert to keep everyone safe.

Technical Summary

1. Problem Statement

Following the relaxation of strict non-pharmaceutical interventions (NPIs) for COVID-19 in China (early 2023), the transmission dynamics of respiratory pathogens have shifted significantly. While global data suggests a resurgence of endemic viruses and potential "immunity debt" (particularly in children), there is a scarcity of regional epidemiological data from medium-sized cities in Eastern China regarding the post-pandemic pathogen landscape. Understanding these shifts is critical for optimizing diagnostic strategies, guiding empirical treatment, and formulating targeted prevention policies.

2. Methodology

• Study Design & Setting: A retrospective cross-sectional surveillance study conducted in Quzhou City, Zhejiang Province, from November 2023 to July 2024.
• Population: A total of 2,800 acute respiratory infection (ARI) cases were enrolled:
  • 1,960 Influenza-like Illness (ILI) cases from outpatient/emergency departments.
  • 840 Severe Acute Respiratory Infection (SARI) cases from inpatient departments.
• Inclusion Criteria:
  • ILI: Fever (≥38°C) with sore throat or cough.
  • SARI: Fever onset within 10 days, accompanied by cough/sore throat, requiring hospitalization.
• Specimen Collection: Respiratory samples (throat/nasopharyngeal swabs, bronchoalveolar lavage fluid, etc.) were collected within 3 days of symptom onset.
• Laboratory Analysis: All samples underwent multiplex fluorescence quantitative PCR to detect 13 common respiratory pathogens:
  • Viruses: Influenza A/B (Flu), SARS-CoV-2, RSV, Adenovirus (AdV), Human Metapneumovirus (HMPV), Rhinovirus (RV), Parainfluenza (HPIV), Coronavirus (HCoV), Bocavirus (HBoV), Enterovirus (EV).
  • Bacteria/Atypicals: Streptococcus pneumoniae (SP), Mycoplasma pneumoniae (MP), Chlamydia pneumoniae (CP).
• Statistical Analysis: Data were analyzed using SPSS 21.0. Chi-square tests ($\chi^2$) were used to compare rates across groups (sex, age, case type, region, time). A $P$-value < 0.05 was considered statistically significant.

3. Key Results

A. Overall Epidemiology

• Positivity Rate: The overall pathogen detection rate was 59.28% (1,660/2,800).
• Case Type Differences: ILI cases had a significantly higher positivity rate (64.39%) compared to SARI cases (47.38%) ($P < 0.01$).
• Demographics:
  • Gender: No significant difference in detection rates between males and females ($P = 0.545$).
  • Age: A strong inverse correlation was observed between age and positivity. Children ≤5 years had the highest rate (78.00%), while adults ≥65 years had the lowest (34.53%). This trend is attributed to "immunity debt" in children and high influenza vaccination coverage in the elderly (60+).
• Co-infections: Single infections accounted for 73.55% of positive cases, while co-infections (≥2 pathogens) accounted for 26.45% of positives, resulting in an overall co-infection rate of 15.68%.

B. Pathogen Spectrum

The top three pathogens detected were:

1. Influenza Virus (Flu): 23.21% (Dominant in ILI and across most age groups >5 years).
2. Streptococcus pneumoniae (SP): 13.14% (Highest in children ≤5 years at 20.00%).
3. Adenovirus (AdV): 8.39%.

• Age-Specific Patterns:
  • Children (≤5 yrs): High prevalence of SP, Flu, and AdV.
  • Adolescents/Adults (6–64 yrs): Flu was the dominant pathogen.
  • Elderly (≥65 yrs): Flu remained dominant, but overall detection rates were lower.
• Temporal Trends:
  • Nov–Dec 2023: Peak activity driven by Influenza A.
  • Jan–Feb 2024: Peak for Influenza B and SARS-CoV-2.
  • Mar–May 2024: Peak for Adenovirus.
  • April 2024: All 13 pathogens were detected simultaneously.
• Geographic Variation: Significant differences existed across counties. Kaihua County had the highest positivity rate (72.47%), while Changshan County had the lowest (40.55%).

C. ILI vs. SARI Comparison

• Higher in ILI: Flu, SP, SARS-CoV-2, and RV were significantly more prevalent in ILI cases.
• Higher in SARI: RSV, HPIV, HBoV, CP, and MP showed higher detection rates in severe cases, suggesting these pathogens are more likely to progress to severe disease or that SARI patients had received prior treatment reducing viral loads for other pathogens.

4. Key Contributions

• Post-Pandemic Baseline: Provides the first comprehensive multi-pathogen surveillance data for a medium-sized Eastern Chinese city in the post-2023 relaxation era.
• Pathogen Spectrum Shift: Identifies a shift where Streptococcus pneumoniae has emerged as the second most prevalent pathogen overall, highlighting the importance of bacterial surveillance alongside viral monitoring.
• Co-infection Dynamics: Quantifies the significant burden of co-infections (15.68%), suggesting that single-pathogen testing may be insufficient for accurate diagnosis.
• Age-Stratified Insights: Confirms the "immunity debt" hypothesis in young children (highest positivity) while noting the protective effect of vaccination in the elderly.

5. Significance and Implications

• Public Health Strategy: The findings underscore the need for continuous, multi-pathogen surveillance rather than focusing solely on influenza or SARS-CoV-2.
• Clinical Guidance: Clinicians should consider broader differential diagnoses, including bacterial pathogens (SP) and co-infections, especially in pediatric and severe cases.
• Prevention: The data supports targeted vaccination campaigns for children (who showed the highest susceptibility) and reinforces the success of elderly vaccination programs.
• Limitations & Future Work: The study is limited by its retrospective nature, a specific 13-pathogen panel, and a relatively short surveillance window. Future research should include genetic sequencing, longer-term monitoring, and integration of clinical outcome data to refine prevention strategies.

Conclusion: The post-COVID-19 era in Quzhou is characterized by a complex circulation of multiple respiratory pathogens with distinct seasonal and age-specific patterns. Effective control requires integrated strategies that address both viral and bacterial etiologies and account for the high susceptibility of young children.