Case Presentation: The patient is a 52-year-old male with congestive heart failure, chronic inflammatory demyelinating polyneuropathy (CIDP) on rituximab with last dose 4 months prior, chronic kidney disease, and diabetes mellitus type 2. He was hospitalized 4 times over 2 months for daily fevers, night sweats, 50 lb weight loss, and cough. Ineffective treatment courses included community-acquired pneumonia therapy, pathogen-directed therapy for Ureaplasma (identified on bronchoscopy), and steroids for possible rituximab pneumonitis. During his first and second admissions, nasal COVID PCRs were negative, but the third admission had one positive test out of three. He was treated with remdesivir and prednisone with transient symptom improvement. During his 4th admission, his BAL was positive for SARS-CoV-2 and Pseudomonas. COVID-19 was not treated due to current negative nasal swabs and recent treatment three weeks prior; the positive test on BAL was thought to contain residual inactive viral RNA from his prior infection. Anti-pseudomonal treatment failed to resolve his symptoms and his chest CT continued to evolve, suggestive of organizing pneumonia. However, after he received steroids and failed to improve, his COVID-19 status was re-evaluated. The RT-PCR cycle threshold was 26 on his BAL, indicative of moderate levels of viral RNA, consistent with persistent viral replication. To halt viral replication and treat COVID-19 pneumonia, he was started on Paxlovid. Baricitinib was added and prednisone 60 mg daily was continued to reduce COVID-19-related pulmonary fibrosis. Notably, he had no detectable anti-SARS-CoV-2 IgG, likely secondary to rituximab use, so intravenous immunoglobulin (IV-Ig) was administered to help both with viral clearance and prevention of future infections. Within 2 days of starting this regimen, his fever resolved and his other symptoms promptly improved. It was concluded that the patient had developed prolonged COVID-19 due to the administration of rituximab 4 months ago. He was advised to undergo COVID-19 vaccination one or more months later to help prevent future COVID-19.
Discussion: Rituximab has residual effects on the immune system for 6 to 9 months. Its anti-CD20 effect results in loss of B cells and of humoral (antibody-mediated) immunity, putting patients at risk for viral infections that rely primarily on antibody-mediated protection. Nirmatrelvir/ritonavir dosed for 10-20 days (rather than 5) has been shown to cure immunocompromised patients who develop persistent COVID-191. In this case, discordant nasal and BAL COVID-19 test results led to delayed administration of curative antivirals, which quickly resulted in clinical improvement.
Conclusions: Rituximab use has a higher risk in the COVID-19 era than it did previously, given the high contagiousness and prevalence of COVID-19. Patients using rituximab should be aggressive about self-testing for COVID-19 and should promptly start treatment for this diagnosis as warranted. In some patients, a nasal swab may miss active viral replication in the deep pulmonary parenchyma. Most importantly, persistent COVID-19 results in ongoing pulmonary inflammation that shares many clinical and radiographic features with organizing pneumonia. Given the ubiquitous presence of SARS-CoV-2, patients who receive diagnostic BALs in preparation for possible high-dose steroids should have those samples tested for SARS-CoV-2, and be treated if found to be present at moderate or high levels.