key: cord-0939310-8r1j3nuy authors: Lei, Jian-Hua; Xu, Yun; Jiang, Yong-fang; Shi, Zhi-hui; Guo, Tao title: Clustering cases of Chlamydia psittaci pneumonia in COVID-19 screening ward staff date: 2020-11-05 journal: Clin Infect Dis DOI: 10.1093/cid/ciaa1681 sha: 5251b436dac32306e5cceaf65c864781e3986e39 doc_id: 939310 cord_uid: 8r1j3nuy Four medical staff cases of Chlamydia psittaci pneumonia in a COVID-19 screening ward, as well as the experience in dealing with such a nosocomial infection event, were described. It reminds that atypical pneumonia except for COVID-19 should also be considered when clustering cases occurred even during a COVID-19 pneumonia pandemic. A c c e p t e d M a n u s c r i p t The coronavirus disease 2019 (COVID-19) pandemic is spreading globally [1] . When clustering pneumonia occurred in the medical staff, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection should be excluded. Meanwhile, other atypical pneumonia should also be considered [2] [3] . Although most of the common or atypical pathogens related to respiratory infection can be confirmed by popular etiological detection methods, etiological detection of Chlamydia psittaci can't be carried out in most hospitals and physicians are not vigilant enough about its infection [2, [4] [5] . Facing worldwide pandemic of COVID-19, misdiagnosis of Chlamydia psittaci pneumonia for COVID-19 is possible. In May 2020, clustering Chlamydia psittaci pneumonia occurred in 4 medical staff in the COVID-19 screening ward of the 2nd Xiangya Hospital. Two doctors and two nurses were attacked 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 presence of Chlamydia psittacis in their bronchoalveolar lavage fluids (BALF). The clinical courses, diagnosis and treatment of the four cases, as well as the experience in dealing with such a nosocomial infection event, were reported. The study was approved by the Ethics Committee of the hospital. The first case was a 29-year-old female doctor. She had continuous fever and mild cough with a little white phlegm since May 24, 2020, accompanied with headache, fatigue, myalgia, and loss of appetite. Thereafter, a 36-year-old male doctor, a 26-year-old male nurse and a M a n u s c r i p t 32-year-old female nurse developed similar symptoms on May 27, May 28 and May 29, respectively. Lung CT scan examinations revealed similar inflammatory infiltration and consolidation in their lower lung lobes. They were quarantined and were started on empirical antibiotic therapy with ceftriaxone, piperacillin, amoxicillin or cefoperazone, respectively. However, their symptoms were not alleviated, then moxifloxacin therapy was combined, and their fever subsided within 2-4 days, with the other symptoms disappearing gradually. On June 3, Chlamydia psittaci pneumonia was confirmed by presence of sequence reads of Chlamydia psittaci in all of their BALF specimens by mNGS. Their antibiotic therapeutic regimes were adjusted to combination therapy by doxycycline and moxifloxacin. By June 4, all patients had maintained normal body temperature for more than 3 days, and the lung CT examinations showed markable infiltrate absorption and consolidation remission. Then they were allowed to be back home with continuous oral moxifloxacin and doxycycline treatments, strict quarantine in single rooms and wearing masks to keep respiratory tract isolation from their families. The follow-up lung CT scans on June 18 showed disappearance of pulmonary consolidation and almost thorough absorption of inflammation. Then moxifloxacin treatment was discontinued while doxycycline was kept till the fourth week to prevent recurrence. Till July 31, no similar cases had been found in their family members, in their hospital colleagues and other close contacts. Their routine laboratory test results were shown in Table 1 . It could be found that many examination results were similar to those of COVID-19 patients, except that their peripheral blood lymphocyte counts were within the reference ranges throughout, without hypolymphocytemia. A c c e p t e d M a n u s c r i p t Nucleic acid of SARS-CoV-2 in throat swab and BALF specimens were repeatedly detected by real time RT-PCR assay in each patient. Plasma IgM or IgG antibodies against SARS-CoV-2 were repeatedly tested by ELISA at admission and two weeks later. Besides, routine cultures of BALF, blood and sputum samples, indirect immunofluorescence tests of serum specific IgM antibodies against common respiratory pathogens (Table 1) , isothermal amplifying 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 carried out. None of the above tests reported positive results. reported that considerable number of sequence reads of Chlamydia psittaci were found in all of their BALF specimens (Table 1) . Although the four staff had been working in the emergency COVID-19 screening ward for several months, all of them and their family members definitely had not contacted with confirmed cases of COVID-19 within half a month before the onset of the disease，nor had they closely contacted with symptomatic patients coming from the COVID-19 epidemic areas since April 15. None of them and their family members admitted any recent close contact with birds and live poultry within one month before the onset of the disease. However, the male doctor told that there were several pet parrots in his neighbor's house, and he couldn't rule out the possibility that the droppings and feathers of the parrots might fall into his house unawares. A c c e p t e d M a n u s c r i p t The CDC (Center for Disease Control and Prevention) staff investigated the pet parrots' owner and his family members and other neighbors, as well as the family members of the male doctor. None of them had symptoms similar to the four Chlamydia psittaci infected cases. Although the parrots looked healthy, the owner isolated the parrots to an independent space according to the CDC staff's guidance. Although the patient's access to the COVID-19 screening ward was independently set on the other side of the medical building away from the staff's access, and the fresh-air air conditioning system in the isolation area had been closed since January 18, 2020, and all the medical staff working in the building were requested to wear masks and other protective tools in strict accordance with the requirements, the possibility of clustering cases of nosocomial infection in the medical staff still could not be entirely excluded. Therefore, the following measures were promptly taken. 1. To shut down the whole fresh-air air conditioning system of the building. 2. To collect air and environmental specimens for SARS-CoV-2 and other pathogens testing around the working rooms of the staff, especially around the fresh-air outlets, and then to clean and disinfect the air and suspected COVID-19 should be considered when clustering cases occur in the medical staff even during a COVID-19 pneumonia pandemic despite that many clinical features of the four patients were similar to those of COVID-19 patients. Etiological test is essential for differential diagnosis. Due to false positive and false negative 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 pathogen in pneumonia patients is recommended [8] [9] [10] . It discovered sequence reads of Chlamydia psittaci present in all their BALF specimens. Although Chlamydia psittaci infection was not confirmed by a second test, 4 identical cases all positive for Chlamydia psittaci was hard to discount. Their peripheral blood lymphocyte count and percentage kept normal throughout, consistent with the results reported previously [5, [8] [9] and different from common decrease in COVID-19 [11] [12] , which can be of great value in clinical differential diagnosis. A c c e p t e d M a n u s c r i p t Human got infected with Chlamydia psittaci mainly by inhaling ornithic secretions or contaminated aerosols when being in close contact with infected birds or poultry [4] [5] . Person-to-person transmission of psittacosis is possible but rare [5] . The four medical staff working in the same ward got infected almost simultaneously. In view of no similar infection in their family closest contacts and no accompanying activities outside hospital for them, there was little possibility that they were individually infected at home or outside the hospital. It was more likely that the Chlamydia psittaci infection source existed in the environment where they worked together. The various pipelines of the medical building, especially the fresh-air air conditioning system, might be the possible routes from which the Chlamydia psittaci contaminated pollutants came. In fact, when the conditioning system had been closed, cleaned and disinfected, no more similar cases appeared. No evidence of contact with birds or poultry was found in a large proportion of the reported Chlamydia psittaci pneumonia patients [5] . A c c e p t e d M a n u s c r i p t M a n u s c r i p t M a n u s c r i p t World Health Organization. Coronavirus disease (COVID-2019) situation reports Diagnosis and treatment of community-acquired pneumonia in adults: 2016 clinical practice guidelines by the Chinese Thoracic Society, Chinese Medical Association Comparing current US and European guidelines for nosocomial pneumonia Chlamydia psittaci (psittacosis) as a cause of community-acquired pneumonia: a systematic review and meta-analysis Zoonotic Chlamydophila psittaci infections from a clinical perspective Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19): A Review Stability issues of RT-PCR testing of SARS-CoV-2 for hospitalized patients clinically diagnosed with COVID-19 Metagenomic next-generation sequencing in the diagnosis of severe pneumonias caused by Chlamydia psittaci The application of metagenomic next-generation sequencing in diagnosing Chlamydia psittaci pneumonia: a report of five cases Clinical metagenomic next-generation sequencing for pathogen detection Clinical Characteristics of Coronavirus Disease 2019 in China COVID-19, ECMO, and Lymphopenia: A Word of Caution A c c e p t e d M a n u s c r i p t Figure 1