Clinical Characteristics of Chlamydia psittaci Infection Diagnosed by Metagenomic Next-Generation Sequencing: A Retrospective Multi-Center Study in Fujian, China

Figures & data

Table 1 Demographics and Clinical Characteristics of Patients with C. psittaci Infection

Variables	All Patients (n=74)	Severe Group (n=39)	Non-Severe Group (n=35)	p value
Age (years), median (IQR)	64.5 (55.7, 74.0)	66.0 (53.0, 74.0)	62.0 (56.0, 73.0)	0.729
Men, n (%)	51 (68.9%)	27 (69.2%)	24 (68.6%)	0.951
Live in rural area, n (%)	66 (89.2%)	36 (92.3%)	30 (85.7%)	0.464
Exposure history, n (%)	34 (46.0%)	24 (61.5%)	10 (28.6%)	0.004
History of contact with avian, n (%)	9 (12.2%)	4 (10.3%)	5 (14.3%)	0.727
History of contact with poultry, n (%)	25 (33.8%)	20 (51.3%)	5 (14.3%)	0.001
Samples for mNGS
BALF, n (%)	71 (96.0%)	37 (94.9%)	34 (97.1%)	1.000
Blood samples, n (%)	4 (5.4%)	4 (10.3%)	0 (0.0%)	0.117
Tracheal aspirate, n (%)	1 (1.4%)	0 (0.00%)	1 (2.9%)	0.473
CSF samples, n (%)	1 (1.4%)	1 (2.6%)	0 (0.0%)	1.000
No underlying diseases, n (%)	40 (54.1%)	18 (46.2%)	22 (62.9%)	0.150
Hypertension, n (%)	20 (27.0%)	12 (30.8%)	8 (22.9%)	0.444
Diabetes, n (%)	14 (18.9%)	8 (20.5%)	6 (17.1%)	0.712
Malignancy, n (%)	4 (21.6%)	1(2.6%)	3 (8.6%)	0.339
Chronic liver disease, n (%)	2 (2.7%)	1(2.6%)	1 (2.9%)	1.000
SOFA, median (IQR)	2 (1, 5)	5 (3, 7)	1 (0, 2)	<0.001
APACHE II, median (IQR)	11 (8, 14)	13.7±4.6	8.1±3.9	<0.001
CURB-65, mean (SD)	1.9±1.6	3.1±1.2	0.5±0.6	<0.0001
CRB-65, mean (SD)	1.0±1.1	1.7±1.04	0.2±0.5	<0.0001
Time from illness onset to hospital admission (days), median (IQR)	5.5 (2.7, 7)	4 (3, 7)	6 (2, 10)	0.249
Time from illness onset to confirmed diagnosis (days), median (IQR)	9.5 (8, 12.3)	9 (8, 11)	10 (8, 15)	0.064
Time from admission to confirmed diagnosis (days), median (IQR)	4 (3, 6)	4 (3, 6)	5 (3, 6)	0.155
Symptoms
Productive cough n (%)	37 (50.0%)	22 (56.4%)	15 (42.9%)	0.244
Dry cough, n (%)	28 (37.8%)	16 (41.0%)	12 (34.3%)	0.551
High Fever n (%)	64 (86.5%)	35 (89.7%)	29 (82.9%)	0.502
Moderate Fever n (%)	7 (9.5%)	4 (10.3%)	3 (8.6%)	1.000
Low fever, n (%)	3 (4.1%)	0 (0.0%)	3 (8.6%)	0.101
Dyspnea n(%)	38 (51.4%)	31 (79.5%)	7 (20.0%)	<0.0001
Hemoptysis n (%)	5 (6.8%)	3 (7.7%)	2 (5.7%)	1.000
Chill, n (%)	18 (24.3%)	10 (25.6%)	8 (22.9%)	0.780
Myalgia, n (%)	8 (10.8%)	5 (12.8%)	3 (8.6%)	0.714
Chest pain, n (%)	21 (28.4%)	13 (33.3%)	8 (22.9%)	0.318
Fatigue, n (%)	39 (52.7%)	31 (79.5%)	8 (22.9%)	<0.0001
Headache, n (%)	10 (13.5%)	6 (15.4%)	4 (11.4%)	0.740
Delirium, n (%)	15 (20.3%)	13 (33.3%)	2 (5.7%)	0.003
Nausea, n (%)	4 (5.4%)	3 (7.7%)	1 (2.9%)	0.617
Vomit, n (%)	3 (4.1%)	3 (7.7%)	0 (0.0%)	0.242
Abdominal pain, n (%)	4 (5.4%)	3 (7.7%)	1 (2.9%)	0.617
Diarrhea, n (%)	5 (6.8%)	3 (7.7%)	2 (5.7%)	1.000
Pharyngalgia, n (%)	4 (5.4%)	2 (5.1%)	2 (5.7%)	1.000
Signs
Relative bradycardia	38 (51.4%)	22 (56.4%)	16 (45.7%)	0.358
Moist rale, n (%)	47 (63.5%)	30 (76.9%)	17 (48.6%)	0.011
Dry rale, n (%)	8 (10.8%)	3 (7.7%)	5 (14.3%)	0.464

Figure 1 Cumulative hospital admissions of psittacosis per month.

Table 2 Laboratory Findings and Chest CT Findings Upon Hospital Admission with C. psittaci Infection

Variables	Total (n=74)	Severe Group (n=39)	Non-Severe Group (n=35)	p value
White blood cell count (×109/L), median (IQR)	8.3 (5.9, 11.2)	9.1 (6.6, 11.2)	7.7 (5.8, 11.4)	0.530
Neutrophil count (×109/L), median (IQR)	7.1 (4.6, 9.9)	7.8 (5.1, 9.9)	6.6 (4.3, 9.8)	0.148
Lymphocyte count (×109/L), median (IQR)	0.6 (0.4,1.0)	0.5 (0.3, 0.7)	0.8 (0.5, 1.1)	<0.001
Lymphopenia, n (%)	54 (73.0%)	35 (89.7%)	19 (54.3%)	0.001
Platelet count (×109/L), median (IQR)	188.0 (123.8, 252.3)	143.0 (99.0, 240.0)	212.0 (172.0, 256.0)	0.013
Thrombocytopenia, n (%)	12 (16.2%)	10 (25.6%)	2 (5.7%)	0.020
C-reactive protein (CRP, g/L), mean (SD)	180.6±79.2	207.2±74.8	150.9±74.1	0.002
Procalcitonin (ng/mL), median (IQR)	0.8 (0.3, 2.0)	1.6 (0.7, 9.2)	0.36 (0.2, 1.0)	<0.001
Albumin (ALB, g/L), median (IQR)	29.7 (26.3, 33.8)	28.2 (25.0, 30.0)	32.4 (29.6, 36.6)	<0.001
Creatine kinase (CK, U/L), median (IQR)	256.0 (85.0, 831.8)	567.0 (165.0, 1388.0)	107.0 (61.0, 275.0)	<0.001
Lactate dehydrogenase (LDH, U/L), median (IQR)	434.5 (266.3, 685.0)	463.0 (293.0, 879.0)	351.0 (235.0, 551.0)	0.086
D-dimer (μg/L), median (IQR)	1.1 (0.5, 2.7)	1.3 (0.7, 5.0)	0.8 (0.4, 1.7)	0.024
Proteinuria, n (%)	48 (64.9%)	31 (79.5%)	17 (48.6%)	0.005
Hematuresis, n (%)	34 (46.0%)	23 (59.0%)	11 (31.4%)	0.018
Chest CT findings
Bilateral lungs involved, n (%)	48 (64.9%)	29 (74.4%)	19 (54.3%)	0.071
Multiple lobular involved, n (%)	55 (74.3%)	33 (84.6%)	22 (62.9%)	0.032
Consolidation, n (%)	66 (89.2%)	36 (92.3%)	30 (85.7%)	0.464
Ground-glass opacity, n (%)	15 (20.3%)	7 (18.0%)	8 (22.9%)	0.600
Air bronchogram, n (%)	49 (66.2%)	29 (74.4%)	20 (85.7%)	0.118
Pleural effusion, n (%)	57 (77.0%)	32 (82.1%)	25 (71.4%)	0.278
Bilateral pleural effusion, n (%)	32 (43.2%)	22 (56.4%)	10 (28.6%)	0.016
Pericardial effusion, n (%)	5 (6.8%)	3 (7.7%)	2 (5.7%)	1.000
Lesions close to the pleura, n(%)	47 (63.5%)	25 (64.1%)	22 (62.9%)	0.912
Central location, n (%)	9 (12.2%)	3 (7.7%)	6 (17.1%)	0.292
Random distribution, n (%)	18 (24.3%)	11 (28.2%)	7 (20.0%)	0.411

Figure 2 Chest imaging of a 67-yr-old man with C. psittaci infection show multiple consolidations in the right upper and lower lobe, with air bronchogram in the upper lobe.

Figure 3 Chest imaging of a 78-yr-old man with C. psittaci infection before and after treatment. (A) Pre-treatment computed tomography (CT) scan showing bilateral large consolidation with air bronchogram in right lung and bilateral pleural effusion. (B) Follow-up CT scan after combination therapy for 20 days showing the consolidation and pleural effusion disappeared.

Table 3 Complications, Treatments and Outcomes of Patients with C. Psittaci Infection

Complications	Total (n=74)	Severe Group (n=39)	Non-Severe Group (n=35)	p value
Acute respiratory distress syndrome, n (%)	41 (55.4%)	36 (92.3%)	5 (14.3%)	<0.0001
Mild acute respiratory distress syndrome, n (%)	12 (16.2%)	8 (20.51%)	4 (11.4%)	0.290
Moderate acute respiratory distress syndrome, n (%)	14 (18.9%)	13 (33.3%)	1 (2.9%)	0.001
Severe acute respiratory distress syndrome, n (%)	15 (20.3%)	15 (38.5%)	0 (0.0%)	<0.0001
Time from admission to ARDS (hours), median (IQR)	24.0 (12.5, 48.0)	24.0 (7.5, 42.0)	36 (24.0, 66.0)	0.148
Type I respiratory failure, n (%)	39 (52.7%)	33 (84.6%)	6 (17.1%)	<0.0001
Type II respiratory failure, n (%)	3 (4.1%)	3 (7.7%)	0 (0.0%)	0.242
Acute cardiac injury, n (%)	18 (24.3%)	17 (43.6%)	1 (2.9%)	<0.0001
Acute heart failure, n (%)	16 (21.6%)	14 (35.9%)	2 (5.7%)	0.002
Acute on chronic heart failure, n (%)	5 (6.8%)	3 (7.7%)	2 (5.7%)	1.000
Acute kidney injury (AKI), n (%)	13 (17.6%)	12 (30.8%)	1 (2.9%)	0.002
Anemia, n (%)	19 (25.7%)	14 (35.9%)	5 (14.3%)	0.034
Rhabdomyolysis, n (%)	5 (6.8%)	5 (12.8%)	0 (0.0%)	0.056
Disseminated intravascular coagulation, n (%)	5 (6.8%)	5 (12.8%)	0 (0.0%)	0.056
Gastrointestinal bleeding, n (%)	3 (4.1%)	2 (%)	0 (0.0%)	0.495
Acute liver injury, n (%)	31 (41.9%)	20 (51.3%)	11 (31.4%)	0.084
Secondary infection, n (%)	20 (27.0%)	17 (%)	3 (8.6%)	<0.0001
Septic Shock, n (%)	12 (16.2%)	12 (%)	0 (0.0%)	<0.0001
Multiple organ dysfunction syndrome (MODS), n (%)	18 (24.3%)	18 (46.2%)	0 (0.0%)	<0.0001
Time from admission onset to MODS (hours), median (IQR)	36.0 (24.0, 48.0)	36.0 (24.0, 48.0)	–	–
Treatment
Doxycycline, n (%)	54 (73.0%)	28 (71.8%)	26 (74.3%)	0.810
Azithromycin, n (%)	7 (9.5%)	5 (12.8%)	2 (5.7%)	0.435
Moxifloxacin, n (%)	54 (73.0%)	30 (76.9%)	24 (68.6%)	0.419
Combination therapy, n (%)	38 (51.4%)	25 (64.1%)	13 (37.1%)	0.021
Empirical antibiotic coverage for atypical pathogens, n (%)	43 (58.1%)	19 (48.7%)	24 (68.6%)	0.084
Using broad-spectrum antibiotics, n (%)	36 (48.6%)	24 (61.5%)	12 (34.3%)	0.019
Glucocorticoid therapy, n (%)	20 (27.0%)	14 (35.9%)	6 (17.1%)	0.070
Fluid resuscitation, n (%)	10 (13.5%)	10 (25.4%)	0 (0.0%)	0.001
Vasoactive drugs, n (%)	11 (14.9%)	11 (28.2%)	0 (0.0%)	0.001
Respiratory Support at highest level
Nasal cannula oxygen therapy, n (%)	10 (13.5%)	0 (%)	10 (28.6%)	<0.0001
Mask oxygen therapy, n (%)	14 (18.9%)	2 (5.1%)	12 (34.3%)	0.001
Non-invasive ventilation, n (%)	18 (24.3%)	10 (25.6%)	8 (22.9%)	0.780
High-flow nasal cannula, n (%)	16 (21.6%)	11 (28.2%)	5 (14.3%)	0.146
Invasive mechanical ventilation, n (%)	16 (21.6%)	16 (41.0%)	0 (0%)	<0.0001
Duration of invasive mechanical ventilation (hours)	212.0 (166.5, 240.0)	212.0 (166.5, 240.0)	–	–
ECMO, n (%)	1 (1.4%)	1 (2.6%)	0 (0.0%)	1.000
Initial respiratory support failure (%)
NIV failure, n /total (%)	10/29 (%)	9 (43.4%)	1 (10%)	0.015
HFNC failure, n/total (%)	8/23 (%)	8 (44.4%)	0 (0.0%)	0.006
IMV failure, n /total (%)	6/17 (%)	6 (35.3%)	0 (0.0%)	0.026
Continuous renal replacement therapy, n (%)	4 (5.4%)	4 (10.3%)	0 (0.0%)	0.117
Outcome
Death, n (%)	6 (8.1%)	6 (15.4%)	0 (0.0%)	0.026
ICU length of stay (days), median (IQR)	7.0 (0.0, 10.0)	7.0 (0.0, 10.0)	–	–
Hospitalization duration (days), median (IQR)	14.0 (10.0, 18.3)	17.0 (11.0, 21.0)	13.0 (9.0, 14.0)	0.001

Data Sharing Statement

The datasets generated and analyzed during the current study are available from the corresponding author upon reasonable request.