Aetiology of severe community acquired pneumonia in adults identified by combined detection methods: a multi-centre prospective study in China

Figures & data

Figure 1. Screening, Eligibility, and Enrolment of Adult Patients with Severe Community-Acquired Pneumonia. SCAP stands for severe community-acquired pneumonia. ER stands for emergency room. HAP stands for hospital acquired pneumonia. AIDS stands for acquired immune deficiency syndrome.

Table 1. Baseline Characteristics, Clinical Manifestation and Radiographic Findings of Adult Patients with Severe Community-Acquired Pneumonia in the Study on Admission.

Characteristics On Admission	All Patients
Age – yr – median (IQR)	61(49-69)
18–64 yr	170/275(61.8%)
65–79 yr	78/275(28.4%)
≥ 80 yr	27/275(9.8%)
Male – no. (%)	199/275(72.4%)
Any underlying Disease – no. (%)	166/275(60.4%)
COPD	20/275(7.3%)
Diabetes Mellitus	54/275(19.6%)
Hypertension	59/275(21.5%)
Chronic renal disease	11/275(4.0%)
Malignant	18/275(6.5%)
Chronic heart disease	25/275(9%)
Cerebrovascular disease	13/275(4.7%)
Current Smoker – no. (%)	124/275(45.1%)
Current Alcoholic – no. (%)	58/275(21.1%)
Duration from illness onset to admission – days – median (IQR)	5(3-7)
Clinical manifestation – no. (%)
Fever	235/275(85.5%)
Cough	234/275(85.1%)
Dyspnoea	183/275(66.5%)
Tiredness, dizziness or headache	68/275(24.7%)
Shiver	64/275(23.3%)
Myalgia	35/275(12.7%)
Sore throat	30/275(10.9%)
Nausea	18/275(6.5%)
Haemoptysis	17/275(6.2%)
Emesis	14/275(5.1%)
Diarrhoea	13/275(4.7%)
Abdominal pain	8/275(2.9%)
Abnormal auscultation	223/275(81.1%)
White phlegm	106/275(38.5%)
Purulent respiratory secretion	87/275(31.6%)
Cyanosis	11/275(4%)
Rash	7/275(2.5%)
Highest temperature – °C	39.0 (38.3–39.5)
Pulse rate – per min	98(86-115)
Respiration rate – per min	26(20-31)
CURB-65 Score – no. (%)
0–1	82/275(29.8%)
2	86/275(31.3%)
3–5	107/275(38.9%)
Pneumonia Severity Index
Median	110
Interquartile range	80–136
Risk class – no. (%)
1–3	92/275(33.5%)
4	104/275(37.8%)
5	79/275(28.7%)
Radiographic finding – no. (%)
Consolidation	194/275(70.6%)
Ground-glass opacity	179/275(65.1%)
Pleural effusion	121/275(44%)

Abnormal auscultation including rale or consolidation sign. COPD stands for chronic obstructive pulmonary disease. The CURB-65 severity score measures confusion, urea, respiratory rate, and blood pressure at age 65 years or older. The pneumonia severity index is based on sex, age, nursing home status, mental status, heart rate, respiratory rate, blood pressure, temperature, selected underlying medical conditions, laboratory values, and the presence or absence of pleural effusion.

Figure 2. Responsible Pathogen identified in Adult Patients with Severe Community-Acquired Pneumonia. Figure 2 shows the numbers (above the bars) and percentages (y-axis) of specific pathogens detected. A total of 222 pathogens were detected in 275 patients, of which 198 patients got positive aetiology results. The big pie chart in the middle shows the proportions of bacterial only, viral only, other pathogens only (including fungi, mycoplasma, Chlamydia Psittaci and Leptospira), not detected and co-infection. The small pie chart on the left shows the detailed proportions of co-infection.

Figure 3. Comparison of Pathogen Detected in Different Regions and Seasons. Panel A shows the proportions of a specific pathogen in southern (177 patients) and northern China (98 patients), which are geographically divided from the Qinling-Huaihe Line. Panel B shows the number of patients in whom influenza virus, S. pneumoniae, Enterobacteriaceae, Chlamydia Psittaci and Leptospira were detected according to month and year. Panel C shows the number of patients in whom influenza virus was detected according to month and geography. SCAP denotes severe community-acquired pneumonia.

Figure 4. Performance of Different Diagnostic Tools. Panel A shows the presume positive rate with different detection methods combination. Only used traditional culture detected 14.4% (43 of 299) pathogens. Culture, antigen test and PCR detected 40.8% (122 of 299). Culture, antigen test, PCR and NGS detected 74.2% (222 of 299). Note all 278 patients enrolled were used combined methods and 24 were detected for two pathogens responsible. PCR stands for a polymerase chain reaction. NGS stands for next-generation sequencing. Panel B shows in-hospital mortality of patients with or without positive aetiology results. Venn diagrams in Panel C show specific pathogens detected according to different detected methods. Green for molecular detection methods, including PCR and mNGS. Red for traditional culture. Blue for antigen tests. The numbers in the circles stand for cases.

Table 2. Laboratory Findings on Admission.

	Reference Range	On Admission
Blood Routine (n = 275)
Red blood cell count - ×10^12/L	4.09–5.74 × 10^12/L	4.07 (3.5–4.54)
White blood cell count - ×10^9/L	3.97–9.15 × 10^9/L	9.58 (5.57–14.01)
Neutrophil count - ×10^9/L	2.00–7.00 × 10^9/L	7.9 (4.31–12.52)
Lymphocyte count - ×10^9/L	0.80–4.00 × 10^9/L	0.7 (0.48–1.09)
Platelet count - ×10^9/L	85–303 × 10^9/L	152 (105–223)
Haemoglobin - g/L	131–172 g/L	125 (104–139)
Neutrophil percentage - %	50.0%–70.0%	86.1 (77.2–91.2)
Lymphocyte percentage - %	20.0–40.0	8.1 (5–14)
Eosinophil percentage - %	0.5%–5.0%	0 (0–0.4)
Basophilic granulocyte percentage - %	< 1.0	0.1 (0–0.2)
Monocyte percent - %	3.0%–10.0%	4.5 (2.4–6.6)
Blood biochemistry (n = 275)
Alanine transaminase - IU/L	10–64IU/L	36 (23–63)
Aspartate aminotransferase - IU/L	8–40IU/L	50 (26–89)
Total bilirubin - μmol/L	4.7–24 μmol/L	12.3 (8.5–19.8)
Direct bilirubin - μmol/L	0–6.8 μmol/L	5.1 (3.3–10.3)
Lactate dehydrogenase - IU/L	98–192IU/L	430 (251–698)
Blood Urea Nitrogen - mmol/L	2.5–7.1 mmol/L	7.7 (4.9–11.7)
Serum creatinine - μmol/L	62–115 μmol/L	61 (8–89)
Serum albumin - g/L	35–55 g/L	30 (27–34)
Blood sodium - mmol/L	130–147 mmol/L	137 (134–140)
Blood potassium - mmol/L	3.50–5.10 mmol/L	3.75 (3.43–4.2)
Blood chlorinum - mmol/L	96–108 mmol/L	103 (99–106)
Blood phosphorus - mmol/L	0.80–1.60 mmol/L	0.92 (0.69–1.13)
Blood glucose - mmol/L	3.90–6.10 mmol/L	7.49 (6–10.6)
Creatine kinase - IU/L	22–269IU/L	136 (50–367)
D-dimer - mg/L	<0.55 mg/L	3.64 (1.68–21)
Fibrinogen - g/L	1.8–3.5g/L	5.4 (3.9–7.9)
Prothrombin time - s	10.0–16.0 s	13.8 (12.3–15.4)
Activated partial thromboplastin time - s	22.3–38.7 s	35.9 (30.9–43.1)
C-reactive protein - mg/L	< 10 mg/L	90 (19–152)
Procalcitonin - ug/L	< 0.5 ug/L	1.2 (0.3–9)
T cell Percentage (n = 177)
CD3^+ T cell percentage - %	64.0–76.0%	62.5 (51.4–73.3)
CD3 ^+CD4^+ T cell percentage - %	30.0–40.0%	36.8 (28.2–46)
CD3 ^+CD8^+ T cell percentage - %	21.0–29.0%	20.2 (15–28.2)
Arterial blood gas (n = 270)
pH	7.35–7.45	7.43 (7.38–7.47)
PaO2 - mmHg	80–100 mmHg	71 (60–86)
PaCO2 - mmHg	35–45 mmHg	35 (31–41)
HCO3^- - mmol/L	22.0–27.0 mmol/L	23.2 (20.4–25.9)
BE - mmol/L	−3–3 mmol/L	0 (−4-3)
Urine routines - no. (%)
Haematuria		116/275 (42.2%)
Proteinuria		133/275 (48.3%)

Table 3. Clinical Outcomes and Medical Cost.

Variables	(N = 275)
Length of hospital stay - days - median (IQR)	14 (9–22)
Length of ICU stay - days - median (IQR)	7 (2–14)
Non-invasive mechanical ventilation - no. (%)	43/275 (15.6%)
Length of non-invasive mechanical ventilation - days - median (IQR)	7 (2–12)
Invasive mechanical ventilation - no. (%)	81/275 (29.4%)
Length of invasive mechanical ventilation - days - median (IQR)	10 (5–14)
Extracorporeal membrane oxygenation - no. (%)	7/275 (2.5%)
Length of ECMO - days - median (IQR)	10 (2–15)
30-day mortality - no. (%)	52/275 (18.9%)
In-hospital mortality - no. (%)	63/275 (22.9%)
Medical cost - US dollar per patient - median (IQR)	7064 (3804–13904)

ICU denotes for intensive care unit.

Figure 5. Pathogen-Specific Outcome in Adult Patients with Severe Community-Acquired Pneumonia.The tree map in Panel A shows the proportions of specific pathogen in non-survived patients. The area stands for the quantity of hospital death patients the specific pathogen caused. The Sankey diagram in Panel B shows the different outcomes of specific pathogens. The width of the arrows is proportional to the flow rate (survived in blue or non-survived in red). The numbers above are cases. Panel C shows the in-hospital mortality (%) of pathogens.