key: cord-0995451-4l3g6pyc
authors: Aviv, Rachel; Weber, Andrew; Anzum, Tarif; Federbush, Matthew; Horowitz, Diane; Singas, Effie
title: Prolonged COVID-19 Disease in a Patient with Rheumatoid Arthritis on Rituximab Therapy
date: 2021-05-08
journal: J Infect Dis
DOI: 10.1093/infdis/jiab248
sha: d7f3ec2dd06a21c093a16e582c068e00964b36b9
doc_id: 995451
cord_uid: 4l3g6pyc

nan

M a n u s c r i p t We read with interest a brief report by Helleberg et al which describes the fascinating case of a Caucasian male in his fifties who had received treatment with rituximab and developed a prolonged coronavirus disease 2019 (COVID-19) infection [1] . Treatment with 2 courses of remdesivir temporarily abrogated his symptoms; however, after convalescent plasma (CP) treatment on day 58, his symptoms abated 2 days later, and he was discharged with disease resolution. This brief report and the concept of combined antiviral and antibody treatment has influenced our management for patients who are B-cell depleted with COVID-

Here we report a 50-year-old female being treated with rituximab for rheumatoid arthritis (RA) who also developed a prolonged course of COVID-19. She responded well to a treatment regimen of remdesivir and CP. We review the current literature for CP use in COVID-19 and argue for its use in B-cell depleted patients with prolonged symptoms.

A 50-year-old female with RA presented in July 2020 with persistent fevers and malaise for 4 months. She had been receiving rituximab injections regularly. In March, she developed fever, anosmia, ageusia, fatigue, decreased appetite, diarrhea and myalgias. In April, she tested positive for COVID-19 on nasopharyngeal reverse transcription polymerase chain reaction (NP-RT-PCR). She presented twice to the emergency department in April, was not hypoxemic, and was discharged.

In May, she was admitted for persistent fevers and dyspnea. Computed Tomography (CT) chest demonstrated patchy lower lobe opacities (Figure 1 ). She improved initially after A c c e p t e d M a n u s c r i p t receiving antibiotics and was discharged home; however, she required readmission in June for persistent fever and malaise. CT chest showed new areas of ground glass opacities. An extensive workup for fever of unknown origin was unrevealing (see Supplementary Table 1) .

Laboratory analysis demonstrated hypogammaglobulinemia, and absent CD-19 cells. She was treated with intravenous immunoglobulin and oral methylprednisolone and discharged after fever resolution.

Two-weeks later, her symptoms returned, and she was readmitted for further evaluation. NP-RT-PCR and serum antibodies were negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and inflammatory markers were elevated (see Supplementary Table 2 

The use of CP to treat patients with SARS-CoV-2 has remained inconsistent and guidance in the immunocompromised is scarce. A recent trial compared 228 people who received CP to 105 who received placebo, revealing no differences in clinical status or mortality [2] . Only 6 patients in the treatment group (2.6%) and 3 in the placebo group (2.9%) were prescribed immunosuppressants. Another trial testing CP with high IgG titers in older adult patients within 72-hours after the onset of mild COVID-19 symptoms showed A c c e p t e d M a n u s c r i p t decreased disease progression [3] . Patients with immunosuppressant use were excluded from randomization.

Immunocompromised patients can have a prolonged disease course when infected with SARS-CoV-2. Successful and safe treatment strategies are crucial to guide clinicians as it is unlikely that there will be large, randomized control trials examining optimal therapeutic strategies for patients with a lack of humoral protection. The American Society of Hematology (ASH) recently published a proof-of-concept study in which 17 B-cell depleted patients with prolonged COVID-19 were treated with CP. All but 1 patient had symptom improvement within 48 hours [4] , consistent with the findings from Helleberg et al., and our experience.

As of March 9, 2021, the Food and Drug Administration reissued authorization for continued use of CP under Emergency Use Authorization (EUA), allowing use of high titer COVID-19 CP for hospitalized patients early in the disease course, or for those who are hospitalized with impaired humoral immunity [5] . This EUA permits CP use outside of the IDSA guidelines [6] , allowing for the innovative and successful treatment seen in the original brief report by Helleberg et al., our patient, and the case series published by ASH. Future clarification of CP guidelines is needed regarding the use of combined remdesivir and CP in patients with B-cell depletion who have prolonged symptoms.

Persistent COVID-19 in an Immunocompromised Patient Temporarily Responsive to Two Courses of Remdesivir Therapy

A Randomized Trial of Convalescent Plasma in Covid-19 Severe Pneumonia

Early High-Titer Plasma Therapy to Prevent Severe Covid-19 in Older Adults

Convalescent plasma therapy for B-cell-depleted patients with protracted COVID-19

Convalescent Plasma Emergency Use Authorization Letter of Authorization

Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19

A c c e p t e d M a n u s c r i p t