key: cord-0960916-9owyfybf authors: Mei, Federico; Bonifazi, Martina; Menzo, Stefano; Di Marco Berardino, Alessandro; Sediari, Michele; Paolini, Luca; Re, Antonina; Gonnelli, Francesca; Grilli, Martina; Vennarucci, Giacomo Spurio; Latini, Maria Agnese; Zuccatosta, Lina; Gasparini, Stefano title: First detection of SARS-CoV-2 by real-time reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assay in pleural fluid date: 2020-06-11 journal: Chest DOI: 10.1016/j.chest.2020.05.583 sha: dac3d94e149ab10696c27799cb0c94d1e1773e60 doc_id: 960916 cord_uid: 9owyfybf Abstract COVID-19 is a pandemic infection due to a novel coronavirus (SARS-CoV-2) spreading, resulting in a wide range of clinical features, from asyntomatic carriers to acute respiratory distress syndrome. The gold standard for diagnosis is nucleic acid detection by real-time reverse-transcriptase–polymerase-chain-reaction (RT-PCR) in naso-pharyngeal swabs, but, due to limitations in its sensitivity, thoracic imaging plays a crucial, complementary role in diagnostic work-up and it allows also to reveal atypical findings and potential alternative target for sampling, such as pleural effusion. Although not common, pleural involvement has been described in a minority of patients. Here, we describe the first case of SARS-CoV-2 RT-PCR detection in pleural fluid obtained by means of ultrasound-guided thoracentesis and report its main characteristics. Pleural effusion is not a common finding in COVID-19 infection, but a prompt recognition of this potential localization may be useful to optimize diagnostic work-up as well as management of these patients. In December 2019, an outbreak of novel coronavirus disease (COVID-19, 2019-nCoV or SARS-CoV-2) occurred in Wuhan, China, and, thereafter, it has dramatically spread worldwide. The cornerstone of diagnosis in this context is nucleic acid detection by real-time reverse-transcriptasepolymerase-chain-reaction (RT-PCR) in naso-pharyngeal swabs. However, a not negligible false negative rate has been reported in the literature for this technique, 1, 2 as sensitivity seems to be influenced by several factors, including selected "intrinsic" patients' characteristics (i.e. stage of disease, viral load) as well as technical aspects in collecting and managing specimens. 3, 4 Thoracic imaging, in particular computed tomography (CT) scan and thoracic ultrasound (TUS) technique, plays a complementary, key role in diagnostic work-up of COVID-19. Both these procedures allow to increase the likelihood of disease in the proper clinical setting and to reveal further atypical features as well as potential target for sampling, such as pleural effusions. 1, 2, 5, 6 Although less common, pleural involvement has been described in a substantial minority of cases (pleural thickening 32%, pleural effusion 5%) 7 and it has been significantly associated with a worse prognosis. 8 Pleural fluid characteristics in these patients have never been described and there are no reports on RT-PCR detection in pleural samples. Here, we describe the first case of SARS-CoV-2 RT-PCR detection in pleural fluid obtained by means of TUS-guided thoracentesis and report its main characteristics. On March 25, 2020, a 72-year-old man was admitted to our Pulmonology Unit with a 5-day history of dry cough, fever up 39°C, fatigue, and positive RT-PCR assay for SARS-CoV-2 in naso-pharyngeal swabs, demonstrating a high viral load (174000000 copies/ml of swab solution). He was a nonsmoker and his medical history was unremarkable apart from mild hypertension. The physical examination revealed a body temperature of 38.7°C, blood pressure of 124/76 mm Hg, pulse of 115 beats per minute, respiratory rate of 23 breaths per minute, and oxygen saturation of 93% on oxygen mask at 50% of fraction inhaled oxygen. Chest radiography showed bilateral infiltrates, with prevalent distribution on the right side and CT scan confirmed bilateral, multilobar ground-glass opacities with multifocal consolidations, predominantly in the lower lobes and small bilateral pleural effusion; contrast-enanched CT was negative for pulmonary embolism. (Fig. 1 A- Due to the worsening of respiratory symptoms and gas exchanges, CT scan and TUS evaluations were repeated after 6 days and both showed persistence of lung consolidations, mainly in the right lower lobes, and significant right pleural effusion (Fig. 2 A-B-C) . Therefore, TUS-guided thoracentesis was performed, removing 600 ml of clear yellow pleural fluid, that was sent for differential cell counts, (Table 2) . After plural fluid removal, dyspnea and respiratory failure progressively improved and no recurrence of pleural effusion was observed at TUS daily assessment over the following days. Current diagnostic approach to COVID-19 disease mainly relies on positive RT-PCR assay for SARS-CoV-2 in nasopharyngeal swabs, although sensitivity of this technique is limited, especially in later stages with predominant involvement of lower respiratory tract. For this reason, RT-PCR assay is currently performed on other biological materials, such as broncho-alveolar lavage fluid and stool, 10 but, to the best of our knowledge, this is the first case of SARS-CoV-2 detection in pleural fluid. In our case, the recognition of a significant pleural effusion was also essential for optimizing patient prognosis, as fluid removal substantially contributed to improve respiratory dynamics, leading to a better lung expansion, especially during ventilatory positive pressure support. A further relevant message of this case is the key role of TUS longitudinal evaluation, as it offers the advantage of being low cost, non ionisinig and available at bedside, leading to reduced risk of transmission for health-workers during patient transportation and to avoid to sanitize larger areas of equipment (just the probe instead of the whole radiological suite). Pleural effusion is not a common finding in COVID-19 infection, but clinicians should be aware of this potential disease localization, as its prompt recognition may be useful to optimize diagnostic work-up in patients with negative upper respiratory tract RT-PCR, as well as management of these patients. Sensitivity of Chest CT for COVID-19: Comparison to RT-PCR Correlation of Chest CT and RT-PCR Testing in Coronavirus Disease 2019 (COVID-19) in China: A Report of 1014 Cases Stability issues of RT-PCR testing of SARS-CoV-2 for hospitalized patients clinically diagnosed with COVID-19 Potential false-negative nucleic acid testing results for Severe Acute Respiratory Syndrome Coronavirus 2 from thermal inactivation of samples with low viral loads The Role of Chest Imaging in Patient Management during the COVID-19 Pandemic: A Multinational Consensus Statement from the Fleischner Society Our Italian Experience Using Lung Ultrasound for Grading and Serial Follow-up of Severity of Lung Involvement for Management of Patients with COVID-19 Radiological findings from 81 patients with COVID-19 China: a descriptive study The Clinical and Chest CT Features Associated with Severe and Critical COVID-19 Pneumonia Pleural effusions: the diagnostic separation of transudates and exudates Detection of SARS-CoV-2 in Different Types of Clinical Specimens Footnotes : RT-PCR: reverse transcription real-time polymerase chain reaction