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

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 speci-mens, 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 immuno-histochemistry 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 po-tential exposure.

Automated summary

This study describes two cases of occult COVID-19 in immunocompromised patients who had previously received rituximab treatment. Lung imaging showed ground-glass infiltrates, but nasopharyngeal samples were negative for SARS-CoV-2, leading to initially ruling out COVID-19. However, bronchoalveolar lavage specimens confirmed the persistence of SARS-CoV-2 in lung parenchyma, and viral isolation and immunohistochemistry further supported ongoing viral persistence and replication.