Detection of viable SARS-CoV-2 in deep respiratory specimens despite negative nasopharyngeal SARS-CoV-2 RT-PCR: Occult COVID-19 as an unsuspected cause of pulmonary infiltrates in immunocompromised patients

尽管鼻咽 SARS-CoV-2 RT-PCR 检测结果为阴性,但在深呼吸道标本中检测到 SARS-CoV-2 活体:隐匿性 COVID-19 可能是免疫功能低下患者肺浸润的未知原因

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作者:Liang En Wee, Jing Yuan Tan, Karrie Kwan-Ki Ko, Wei Yee Wan, Deborah Chooi Mun Lai, Lynette Lin Ean Oon, Alfonso Tan-Garcia, Joe Poh Sheng Yeong, Angela Maria Takano Pena, Tony Kiat Hon Lim, Edwin Philip Conceicao, Indumathi Venkatachalam, Limin Wijaya, Thuan Tong Tan

Background

Prolonged shedding/relapse of COVID-19 infection has been reported, particularly in patients who received anti-CD20 agents (eg. rituximab). However, cases of occult COVID-19, in which SARS-CoV-2 persistence in lung parenchyma is diagnosed despite clearance from nasopharyngeal (NP) specimens, are uncommon. Case summary: We describe two cases of occult COVID-19 in immunocompromised patients. Both patients had received rituximab previously. Both cases initially presented as ground-glass infiltrates on lung imaging; the diagnosis was originally not suspected due to repeated demonstration of negative SARS-CoV-2 from NP specimens, and alternative etiologies were originally considered. Persistence of SARS-CoV-2 in lung parenchyma, however, was demonstrated on bronchoalveolar lavage (BAL) specimens; additionally, isolation of viable SARS-CoV-2 virus and detection of SARS-CoV-2 nucleocapsid and spike-protein antigen in lung tissue on immunohistochemistry close to 3-months from primary infection strongly suggested ongoing viral persistence and replication as a driver of the lung parenchymal changes, which resolved after antiviral treatment.

Discussion

Occult COVID-19 can be a cause of unexplained ground-glass infiltrates on lung imaging; negative NP samples do not rule out SARS-CoV-2 persistence and invasive sampling must be considered. The unsuspected presence of viable virus on BAL, however, highlights that procedurists perfoming aerosol-generating-procedures during an ongoing pandemic wave must also practise appropriate infection-prevention precautions to limit potential exposure.

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