Clustering Cases of Chlamydia psittaci Pneumonia in Coronavirus Disease 2019 Screening Ward Staff

Abstract

We describe 4 cases of Chlamydia psittaci pneumonia among medical staff in a coronavirus disease 2019 (COVID-19) screening ward, as well as the experience of dealing with this nosocomial infection event. Atypical pneumonia, in addition to COVID-19, should be considered when clustering cases occur, even during a COVID-19 pneumonia pandemic.

Chlamydia psittaci, COVID-19, nosocomial infection, differential diagnosis, epidemic prevention and control

The coronavirus disease 2019 (COVID-19) pandemic is spreading globally [1]. When clustering pneumonia occurs among medical staff, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection should be excluded, and other atypical pneumonias should be considered [2, 3]. Although most of the common or atypical pathogens related to respiratory infection can be confirmed using popular etiological detection methods, etiological detection of Chlamydia psittaci cannot be performed in most hospitals, and physicians are not vigilant enough about this infection [2, 4, 5]. Facing the worldwide COVID-19 pandemic, a misdiagnosis of C. psittaci pneumonia in COVID-19 is possible.

In May 2020, clustering C. psittaci pneumonia occurred among 4 medical staff in the COVID-19 screening ward of the 2nd Xiangya Hospital. Two doctors and 2 nurses were infected almost simultaneously. Their symptoms and lung computed tomography (CT) changes were very similar to those of COVID-19 cases. Metagenomic next-generation sequencing (mNGS) revealed the presence of C. psittaci in their bronchoalveolar lavage fluid (BALF).

METHODS

The clinical courses, diagnosis, and treatment of the 4 cases, as well as the experience in dealing with such a nosocomial infection event, are reported. The study was approved by the Ethics Committee of the hospital.

RESULTS

Clinical Features of the Cases

The first case was a 29-year-old female doctor. She had continuous fever and mild cough with a small amount of white phlegm starting on 24 May 2020 that were accompanied by headache, fatigue, myalgia, and loss of appetite. Thereafter, a 36-year-old male doctor, a 26-year-old male nurse, and a 32-year-old female nurse developed similar symptoms on 27 May, 28 May, and 29 May, respectively. Lung CT scans revealed inflammatory infiltration and consolidation in their lower lung lobes that were similar to those of the first patient.

All patients were quarantined and started on empirical antibiotic therapy with ceftriaxone, piperacillin, amoxicillin, or cefoperazone. When their symptoms were not alleviated, moxifloxacin therapy was combined. Their fevers subsided within 2–4 days, and the other symptoms disappeared gradually. On 3 June, C. psittaci pneumonia was confirmed by the presence of sequence reads of C. psittaci in all BALF specimens by mNGS. Their antibiotic therapeutic regimes were adjusted to combination therapy with doxycycline and moxifloxacin.

By 4 June, all patients had maintained normal body temperature for more than 3 days, and lung CT examinations showed markable infiltrate absorption and consolidation remission. The patients were then allowed back home with continuous oral moxifloxacin and doxycycline treatment, strict quarantine in single rooms, and instructions to wear a mask to keep respiratory tract fluids away from their families. On 19 June, follow-up lung CT scans showed that pulmonary consolidation had disappeared and that inflammation was almost completely gone. Moxifloxacin treatment was discontinued, while doxycycline treatment was kept until the fourth week to prevent recurrence.

Routine laboratory test results are shown in Table 1. It is noted that many results were similar to those for COVID-19 patients, except that the patients’ peripheral blood lymphocyte counts were within the reference ranges throughout, without hypolymphocytemia.

Table 1.

Results of Laboratory Tests of the 4 Chlamydia psittaci Pneumonia Cases

			Case 1: Female, Aged 29 Years		Case 2: Male, Aged 36 Years		Case 3: Male, Aged 26 Years		Case 4: Female, Aged 32 Years
Detection Index	Unit	Reference Range	Date	Result	Date	Result	Date	Result	Date	Result
C-reactive protein	mg/L	<10.00	26 May	31.87	31 May	12.17	30 May	58.01	30 May	50.55
			28 May	89.50			1 June	52.27	1 June	40.03
			22 June	1.81	22 June	<0.5	18 June	<0.5	18 June	<0.5
Procalcitonin	ng/mL	0–0.050			1 June	0.087	30 May	0.136	31 May	0.127
Routine blood test
White blood cell, leukocytes	109/L	3.50–9.50	26 May	10.07	1 June	10.43	29 May	10.53	30 May	11.70
			28 May	7.55	18 June	6.70	1 June	6.22	31 May	10.69
			1 June	5.58			18 June	6.36	1 June	13.11
			22 June	7.84					18 June	8.47
Neutrophils	109/L	1.80–6.30	26 May	6.61	1 June	7.57	29 May	8.41	30 May	8.66
			28 May	5.02	18 June	2.95	1 June	4.37	31 May	8.37
			1 June	2.82			18 June	3.96	1 June	11.00
			22 June	4.29					18 June	4.45
Neutrophils	%	40.00–75.00	26 May	65.70	1 June	72.50	29 May	79.90	30 May	74.00
			28 May	66.50	18 June	44.00	1 June	70.20	31 May	78.30
			1 June	50.60			18 June	62.20	1 June	83.80
			22 June	54.60					18 June	52.60
Lymphocytes	109/L	1.10–3.20	26 May	2.33	1 June	2.04	29 May	1.11	30 May	2.21
			28 May	1.73	18 June	3.14	1 June	1.21	31 May	1.50
			1 June	2.35			18 June	1.94	1 June	1.57
			22 June	2.93					18 June	3.51
Lymphocytes	%	20.00–50.00	26 May	23.10	1 June	19.60	29 May	10.50	30 May	18.90
			28 May	22.9	18 June	46.90	1 June	19.50	31 May	14.00
			1 June	42.10			18 June	30.50	1 June	12.00
			22 June	37.40					18 June	41.40
Platelets	109/L	125–350	26 May	249	1 June	369	29 May	193	30 May	241
			28 May	213	18 June	255	1 June	141	31 May	242
			1 June	287			18 June	232	1 June	231
			22 June	236					18 June	353
Serum tests
Alanine aminotransferase	U/L	7.0–40.0	29 May	14.8	1 June	30.1	30 May	8.3
			22 June	16.6	22 June	54.8	22 June	22.6	22 June	24.3
Aspartate aminotransferase	U/L	13.0–35.0	29 May	25.6	1 June	23.0	30 May	19.7
			22 June	19.7	22 June	30.7	22 June	21.6	22 June	24.3
Albumin	g/L	40.0–55.0	29 May	35.7	1 June	38.1	30 May	38.0
			22 June	45.2	22 June	44.4	22 June	45.2	22 June	42.6
Globulin	g/L	20.0–40.0	29 May	30.0	1 June	34.4	30 May	28.3
			22 June	32.4	22 June	33.1	22 June	30.0	22 June	34.9
Total bilirubin	μmol/L	3.4–17.1	29 May	6.8	1 June	13.0	30 May	11.1
			22 June	10.4	22 June	13.6	22 June	18.9	22 June	5.3
Direct bilirubin	μmol/L	0–6.0	29 May	2.9	1 June	5.1	30 May	4.6
			22 June	3.8	22 June	5.3	22 June	7.2	22 June	2.1
Total bile acids	μmol/L	0–10.0	29 May	5.0	1 June	2.7	30 May	4.0
			22 June	3.8	22 June	7.1	22 June	1.0	22 June	7.7
Creatine kinase	U/L	40.0–200.0	29 May	179.9	1 June	57.0	30 May	231.9
Creatine kinase-myocardial band isoenzyme	U/L	0–24.0	29 May	9.7	1 June	8.0	30 May	15.4
Urea nitrogen	mmol/L	2.90–7.14	29 May	1.47	1 June	4.68	30 May	3.16
			22 June	3.29	22 June	3.93	22 June	3.62	22 June	2.90
Creatinine	μmol/L	44.0–133.0	29 May	55.2	1 June	89.7	30 May	91.4
			22 June	56.1	22 June	83.5	22 June	75.2	22 June	51.1
Uric acid	μmol/L	155.0–357.0	29 May	274.4	1 June	262.1	30 May	224.0
			22 June	262.6	22 June	335.3	22 June	360.5	22 June	183.7
Serum immunoglobulin M antibodies against 9 common respiratory pathogens a			1 June	Neg	1 June	Neg	1 June	Neg	31 May	Neg
Isothermal amplifying tests on gene chips of nucleic acids of 13 respiratory pathogens in BALF b			31 May	Neg	31 May	Neg	31 May	Neg	31 May	Neg
Chlamydia psittaci sequence reads reported by BALF metagenomic next-generation sequencing c		DNA reads	31 May	2 d	31 May	274	31 May	254	31 May	82
		RNA reads	31 May	3 d	31 May	249	31 May	99	31 May	80

Abbreviation: BALF, bronchoalveolar lavage fluid.

^aIndirect immunofluorescence tests of serum-specific immunoglobulin M antibodies against 9 common respiratory pathogens (adenovirus, parainfluenza virus, respiratory syncytial virus, influenza A virus, influenza B virus, Legionella pneumophila, Mycoplasma pneumoniae, Chlamydophila pneumoniae, rickettsia of Q fever) (Autobio Diagnostics Co, Ltd, China).

^bIsothermal amplifying tests on gene chips of nucleic acids of pathogens (Streptococcus pneumoniae, Staphylococcus aureus, methicillin-resistant Staphylococcus, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, Stenotrophomonas maltophilia, Haemophilus influenzae, L. pneumophila, Mycobacterium tuberculosis, M. pneumoniae, and C. pneumoniae) in BALF (Boao Crystal Core Biological Technology Co, Ltd, China).

^cBALF specimen was collected on 31 May in each patient’s quarantine room. A separate aseptic bronchoscope was used for each patient in order to avoid cross-contamination.

^dBy the time BALF was collected on the night of 31 May, case 1 had been treated with moxifloxacin for 3 days, and her body temperature had been normal for 1.5 days.

Etiological Examinations

SARS-CoV-2 nucleic acid was repeatedly detected on throat swabs and BALF specimens using a real-time reverse-transcription polymerase chain reaction assay for each patient. Plasma immunoglobulin (Ig) M or IgG antibodies against SARS-CoV-2 were repeatedly tested using enzyme-linked immunosorbent assay on admission to the hospital and 2 weeks later. In addition, routine cultures of BALF, blood, and sputum samples; indirect immunofluorescence tests of serum-specific IgM antibodies against common respiratory pathogens (Table 1); isothermal amplification tests on gene chips of nucleic acids of common pathogens in BALF (Table 1); galactomannan tests; and 1–3-β-D glucosamine tests in blood were performed. None of the tests results were positive.

On 3 June, BALF mNGS etiologic analysis at the Shenzhen Huada Gene Research Institute showed that a considerable number of sequence reads of C. psittaci were found in all BALF specimens (Table 1).

Epidemiological Investigation

Although the 4 staff had been working in the emergency COVID-19 screening ward for several months, all of them and their family members did not have contact with confirmed cases of COVID-19 within 2 weeks before disease onset, nor had they been in close contact with symptomatic patients who came from COVID-19 epidemic areas since 15 April.

None of the patients and their family members admitted any recent close contact with birds and live poultry within 1 month before disease onset. However, the male doctor noted that there were several pet parrots in his neighbor’s house, and he could not rule out the possibility that the parrots’ droppings and feathers had entered into his house.

The Center for Disease Control and Prevention (CDC) staff investigated the parrots’ owner and his family members and other neighbors, as well as the male doctor’s family members. None had symptoms similar to those of the 4 C. psittaci–infected cases. Although the parrots looked healthy, the owner isolated them to an independent space according to the CDC staff’s guidance.

Contingency Plans in Dealing With the Suspected Nosocomial Infection Event

The patients’ access to the COVID-19 screening ward was on the other side of the medical building away from the access of other staff members. Also, the fresh-air air conditioning system in the isolation area had been closed since 18 January 2020. All medical staff who worked in the building were required to wear masks and other personal protective equipment in strict accordance with hospital requirements. Yet, the possibility of clustering cases of nosocomial infection among the medical staff still could not be excluded. Therefore, the following measures were promptly taken. The entire building’s fresh-air air conditioning system was shut down. Air and environmental specimens were collected to test for SARS-CoV-2 and other pathogens from around the staff’s working areas, especially around the fresh-air outlets. The air and suspected contaminated facilities were cleaned and disinfected. Each patient was isolated in a single room for treatment; and a plan to manage the close contacts was made, especially for colleagues who worked in the same ward and their family members. Staff with similar symptoms were isolated immediately and screened for SARS-CoV-2 infection and CT features of pulmonary infection. Those without symptoms were examined voluntarily and were required to reduce or avoid outdoor activities as much as possible until being informed that the isolation measures had been removed. A more detailed epidemiological investigation was conducted on the 4 patients. Stricter disinfection and isolation measures were implemented in the medical building, especially measures and necessary screening examinations to protect the medical staff from nosocomial infections.

As of 31 July, no similar cases had been found among all the staff in the screening ward and their family members, and no nosocomial infection related to the 4 cases occurred in the patients and their contacts who had been in the medical building.

DISCUSSION

This clustering C. psittaci pneumonia is a significant nosocomial infection event that reminds us that atypical pneumonia, in addition to COVID-19, should be considered when clustering cases occur among medical staff. This applies even during a COVID-19 pandemic despite the fact that many of our patients’ clinical features were similar to those of COVID-19 patients.

Etiological testing is essential for a differential diagnosis. Due to false-positive and false-negative results in detecting nucleic acid of and serum antibodies against SARS-CoV-2 virus in COVID-19 cases [6, 7] and difficulty in identifying psittacosis by routine culture and serological methods [2, 4, 5], mNGS for detecting unknown pathogens in pneumonia patients is recommended [8–10]. We found sequence reads of C. psittaci present in all of the patients’ BALF specimens. Although C. psittaci infection was not confirmed by a second test, 4 identical cases that were all positive for C. psittaci could not be ignored. The patients’ peripheral blood lymphocyte count and percentage remained normal throughout the disease course, consistent with the results reported previously [5, 8, 9], and were different from the common decrease seen in COVID-19 [11, 12], which can be of great value in clinical differential diagnosis.

Humans are infected with C. psittaci mainly by inhaling ornithic secretions or contaminated aerosols when in close contact with infected birds or poultry [4–5]. Person-to-person transmission of psittacosis is possible but rare [5]. The 4 medical staff who worked in the same ward were infected almost simultaneously. In view of no similar infection in their family members and close contacts and no contact with suspected infection sources outside of the hospital, it is not likely that they were individually infected at home or outside of the hospital. It is more likely that the C. psittaci infection source existed in the environment where they worked together.

The various pipelines within the medical building, especially the fresh-air air conditioning system, are possible routes for C. psittaci contamination. In fact, after the conditioning system was closed, cleaned, and disinfected, no more new cases occurred. No evidence of contact with birds or poultry was found in a large proportion of the reported C. psittaci pneumonia patients [5].

Notes

Acknowledgments. The Department of Clinical Laboratory and Department of Radiology of the Second Xiangya Hospital provided substantial collaborative assistance. Xiang-ping Chai directed the contingency plans in dealing with the suspected nosocomial infection event.

Financial support. The study was funded by the Second Xiangya Hospital, Central South University.

Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.