Persistent SARS-CoV-2 infection in patients with B-cell deficiency: a case series of successful antiviral treatment of four patients

Persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in immunocompromised patients remains a major medical challenge. Diagnosing the syndrome is difficult as symptoms may mimic other diseases and treatment guidelines are lacking. We describe a case series of four patients with persistent SARS-CoV-2 infection that all had an underlying B-cell deficiency due to rituximab treatment (in one case in combination with epcoritamab). In all four patients, it was initially difficult to recognize the persistent disease, leading to a duration of illness between 45 and 242 days. Two patients were only positive for SARS- CoV-2 by polymerase chain reaction (PCR) in the nasopharynx at the beginning of the disease but were later repeatedly negative. However, when bronchoalveolar lavage was performed, a positive SARS-CoV-2 PCR was revealed from the lower airways in both patients. The difficulties establishing diagnosis contributed to these two patients' long disease course. The longest disease duration was in the patient treated with rituximab and epcoritamab, who also responded poorly to single standard antiviral treatment. This patient ultimately cleared the infection after administering a combination treatment with remdesivir and nirmatrelvir/ritonavir. After a confirmed diagnosis, the other three patients cleared the infection when they were finally treated with antivirals. Increasing clinicians' awareness of this condition is important as it might be treatable once diagnosed. Further studies are warranted to define the condition and treatment strategy with greater precision.