This is a prospective, multicenter observational cohort study involving approximately 2,700 patients, designed to delineate the natural history of pneumonia by tracking the complete clinical course and dynamic multi-omics evolution from the acute phase to recovery; the study aims to quantify severe conversion rates and mortality by comparing baseline characteristics, pathogen distribution, and immune response trajectories between severe and non-severe groups, ultimately revealing the underlying molecular mechanisms of disease progression and optimizing clinical risk stratification strategies.

1. Inclusion and Exclusion Criteria for Pneumonia Patients 1.1 Inclusion Criteria 1) Age ≥ 18 years old; 2) Meeting the diagnostic criteria for pneumonia (acute onset + new infiltrates on imaging); 3) Time from onset to admission ≤ 72 hours; 4) Signed written informed consent. 1.1.1 Inclusion Criteria for Severe Pneumonia Patients A diagnosis of "severe pneumonia" can be made if one of the main criteria or ≥ 3 of the secondary criteria are met.

   Main Criteria:

   ① Requires mechanical ventilation with tracheal intubation

   ② Requires vasopressor drugs after aggressive fluid resuscitation for septic shock

   Secondary Criteria:

   • Respiratory rate ≥ 30 breaths/min

     • PaO₂/FiO₂ ≤ 250 mm Hg

       • Multiple lobe infiltrates

         • Confusion and/or disorientation

           ⑤ Blood urea nitrogen ≥ 20 mg/dL

           ⑥ Leukopenia (WBC < 4×10⁹/L)

           ⑦ Thrombocytopenia (PLT < 100×10⁹/L)

           ⑧ Decreased body temperature (central body temperature < 36 ℃)

           ⑨ Hypotension requiring fluid resuscitation 1.2 Exclusion Criteria

           1. End-stage diseases (such as expected survival < 48 hours);
           2. Long-term immunosuppressive therapy (prednisone > 20mg/d for more than 3 weeks, or neutropenia after chemotherapy);
           3. Pregnant or lactating women. 2. Inclusion and Exclusion Criteria for Patients with Suspected Infection but Negative Pathogen Testing 2.1 Inclusion Criteria
           1. Age ≥ 18 years old;
           2. Having infection-related symptoms or signs (such as fever, cough, sputum production, elevated white blood cells, etc.), clinically suspected of pneumonia;
           3. All pathogen tests are negative within 3 days after admission;
           4. Time from onset to admission ≤ 72 hours;
           5. Signed written informed consent. 2.2 Exclusion Criteria
           1. End-stage diseases (such as expected survival < 48 hours);
           2. Long-term immunosuppressive therapy;
           3. Pregnant or lactating women;

Based on the reported overall hospital mortality rate of pneumonia of 0.80%1, to ensure the accuracy of the estimation of the primary outcome (overall hospital mortality rate), a two-sided significance level of α = 0.05 was set, with an allowable absolute error of δ = 0.6%. Using the single sample rate formula, the minimum sample size N ≈ 2010 cases was calculated. Considering that this study is a real-world observational cohort design and needs to meet requirements such as multi-subgroup analysis, sensitivity testing, and machine learning modeling, the final plan is to include at least 2400 patients with pneumonia. Given that severe pneumonia accounts for approximately 13.58% to 20.05% of pneumonia patients1,2, an epidemiological proportion of 15% (i.e., 1.5:8.5) was taken. It is estimated that there will be approximately 360 patients with severe pneumonia and about 2040 patients with non-severe pneumonia. Additionally, this study also included 300 hospitalized patients with suspected

Due to concerns over patient privacy and confidentiality issues, the individual patient data (IPD) may not be shared.