key: cord-0733845-03lw0mao
authors: Gerber, Victor; Velay, Aurélie; Boehn, Louis; Solis, Morgane; Kaeuffer, Charlotte; Rougier, Estelle; Ursenbach, Axel; Hansmann, Yves; Lefebvre, Nicolas; Danion, François; Ruch, Yvon
title: Protracted SARS‐CoV‐2 pneumonia with rituximab treatment: About two cases
date: 2021-03-14
journal: J Med Virol
DOI: 10.1002/jmv.26921
sha: d867bd53c15c981f3dcbad900bdf3834efb7b604
doc_id: 733845
cord_uid: 03lw0mao

Here, we describe two patients, previously treated with rituximab, who presented with a protracted SARS-CoV-2 infection with an atypical course. We hypothesized an incomplete viral clearance with persistent pneumonia due to an impaired or delayed humoral response. This article is protected by copyright. All rights reserved.

To the Editor,

The clinical presentation and course of patients previously treated with immunomodulatory therapeutics, with coronavirus disease 2019 (COVID-19) remain unclear. Rituximab is an anti-CD20 monoclonal antibody used to treat B-cell lymphoid malignancies and autoimmune diseases. There is little data on COVID-19 patients previously treated with rituximab. 1, 2 Here, we present a protracted severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with an atypical course in two patients previously treated with rituximab for autoimmune disease.

The first patient was a 65-year-old man treated with rituximab for 2 years for neuromyelitis optica spectrum disorder. He reported flu-like symptoms for 10 days in June 2020. SARS-CoV-2 infection was confirmed by polymerase chain reaction (PCR) on a nasopharyngeal swab. Seven days after symptom resolution, he experienced fever, asthenia, weight loss, arthromyalgia, and diarrhea, requiring hospitalization on Day 32. He had elevated C-reactive protein at 155 mg/L, no B-cell and hypogammaglobinemia at 4.2 g/L. The chest computed tomography (CT) on 32 days after symptom onset showed bilateral ground-glass opacities (10%-25%), with condensation and air bronchogram ( Figure 1A ). SARS-CoV-2 PCR was negative on the nasopharyngeal swab (Table 1) . Despite broad-spectrum antibiotic therapy, the patient deteriorated with persistent fever and increased oxygen requirements. Bronchoalveolar lavage (BAL) on Day 39, revealed a high SARS-CoV-2 viral load (Table 1 ). There was no virological, bacteriological, fungal, or parasitological co-infection.

Intravenous methylprednisolone at 1 mg/kg daily was started. SARS-CoV-2 PCR was positive in serum on Day 39. On Day 42, the patient was transferred to the intensive care unit due to respiratory distress.

The chest CT showed a significant increase of lung involvement to more than 50% of the parenchyma ( Figure 1A ). The patient received mechanical ventilation for 17 days and corticosteroid therapy for 27 days, improving gradually. He returned home on Day 81. His immunoglobulin A (IgA) anti-SARS-CoV-2 level peaked after more than forty days of evolution, but his immunoglobulin G (IgG) level remained doubtful on Day 68 ( Table 1 ).

The second patient was a 46-year-old man treated with rituximab for 2 years for severe seropositive rheumatoid arthritis.

He was diagnosed with SARS-CoV-2 infection in August 2020.

Due to persistent fever over 39°C with significant weight loss, the patient was hospitalized 34 days after symptom onset, with elevated C-reactive protein at 107 mg/L, absence of B-cell but normal gammaglobulin level at 7.1 g/L. The chest CT showed an increase of ground-glass opacities, to 10%-25% of the parenchyma ( Figure 1B ). On day 34, SARS-CoV-2 PCR was negative on the nasopharyngeal swab, but BAL revealed a high viral load (Table 1) (Table 1) . Five months later, serology was still negative.

Rituximab predisposes patients to a higher risk of infection, especially viral, although it was prescribed with other immunosuppressive agents in most reported cases of infection. 3, 4 Here, we described protracted forms of SARS-CoV-2 infection with persistent fever and late respiratory worsening in two patients treated only with rituximab for autoimmune diseases.

In SARS-CoV-2 infection, over 90% of immunocompetent patients develop immunoglobulin M and/or IgG within the first 14 days. [5] [6] [7] Interestingly, IgG anti-SARS-CoV-2 were never positive in our two patients.

We hypothesized an incomplete clearance of SARS-CoV-2 due to an impaired or delayed humoral response. Previously, seven patients treated with anti-CD20 agents with COVID-19 showed inconsistent seroconversion but a favorable outcome. 1 Our second observation does not allow us to conclude the effectiveness of convalescent plasma, especially since the patient received remdesivir simultaneously. Nevertheless, the patient finally improved after more than 45 days of fever and persistent positive viral loads. regions of the viral RNA-dependent RNA polymerase (RdRp) gene and has the threshold limit of detection of 10 copies per reaction. b SARS-CoV-2 serological diagnostic was performed according manufacturer instructions:

-IgA were detected using the Euroimmun assays (negative: ratio <0.8; doubtful: 0.8-1.1; positive: >1.1).

-IgG were detected using the Abbott architect assay (negative: ratio <0.49; doubtful: 0.49-1.4; positive: >1.4). c Viral load was not available for this sample; the threshold cycle value was 27.

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