Introduction
Managing the coronavirus disease 2019 (COVID-19) pandemic has been challenging particularly in the setting of immunocompromised patients. In the field of haematology where immunocompromised patients are common, there is concern that COVID-19 infection may complicate patient management through a prolonged and severe infection.
B-cell haematological malignancies and autoimmune disorders commonly utilize anti-CD20 antibody-based B-cell-depleting strategies, such as rituximab which has been shown to efficiently eliminate normal and malignant B cells in blood and lymphoid organs[
1]. It has also been shown to weaken COVID-19 vaccine responses in patients with haematological malignancies[
2]. Consequently, patients undergoing rituximab treatment face an increased risk of severe disease, typically defined as COVID-19 resulting in death or necessitating intensive care[
3]. Mortality rates are up to 40% among hospitalized patients with haematologic malignancies[
4,
5].
Several monoclonal antibody agents have proven effective for both pre- and post-exposure prophylaxis against pre-Omicron variants[
6,
7] and have also shown benefit when given early in the course of infection[
8,
9]. However, there are limited data on the use of monoclonal antibody therapy during the critical stage of COVID-19 pneumonia. This case report describes a unique instance of prolonged COVID-19 pneumonia in a patient with lymphoma on maintenance rituximab, successfully treated with monoclonal antibody therapy during intubation as a rescue intervention.
Case presentation
We present a case of a 72-year-old Chinese gentleman with intermediate risk, stage III, low-grade follicular lymphoma on maintenance rituximab. He was also unvaccinated against COVID-19. The patient was admitted to the hospital on September 16, 2021 (day 1), with a one-week history of cough and dry throat. The COVID-19 PCR cycle threshold (Ct) value was 19.10 on admission. His vital signs were generally stable, and physical examination revealed no significant abnormalities. He exhibited no signs of respiratory distress and a chest radiograph revealed no signs of consolidation. Subsequently, he developed his first documented fever of 38.1 °C, and the decision was made to initiate intravenous piperacillin/tazobactam due to febrile neutropenia (ANC < 0.5). Blood cultures taken on days 5 and 7 of admission were negative. A bronchoscopy and bronchoalveolar lavage showed no significant microbiological isolates. A computed tomography (CT) scan of the thorax, abdomen, and pelvis showed patchy ground-glass changes and consolidation in both lungs in keeping with the given history of COVID-19 infection. There was no evidence of acute inflammation or infection in the abdomen or pelvis. The COVID-19 PCR Ct value was 26.11 on day 11 of admission. His fever recurred the next day at 39.0 °C with desaturation to 88% on room air requiring 2 litres via nasal prongs. The patient was started on remdesivir and dexamethasone.
On day 14 of admission, COVID-19 PCR Ct value was 21.30. The patient desaturated despite escalation to a non-rebreather mask, and was transferred to the outbreak intensive care unit (OICU) for a trial of non-invasive ventilation (Optiflow). The chest radiograph revealed predominantly unchanged consolidation in both lungs. He then experienced another desaturation episode and was subsequently intubated. The chest radiograph indicated a slight worsening of bilateral lung opacities, with no significant pleural effusion observed.
In view of his poor immune response to COVID-19 despite treatment with remdesivir, the medical team decided to administer the combined monoclonal antibodies casirivimab/imdevimab (standard dose of REGEN-COV[
7]) as an off-label therapyon day 29 of admission. Following casirivimab/imdevimab administration, repeat COVID-19 PCR Ct value increased to 32.20 and 35.16 on days 37 and day 43 of admission, respectively, suggesting virological clearance. Clinically, his condition improved, and he was successfully extubated after 22 days of intubation. On day 64 of admission, repeat chest radiograph showed stable bilateral diffuse patchy airspace opacities. The patient subsequently stepped down from the OICU to the general ward, and then to the subacute medical ward for rehabilitation, prior to discharge home. Figure 1 illustrates the correlation between clinical events since hospital admission and COVID-19 PCR Ct values.
Discussion
This is a challenging case involving the management of COVID-19 infection in an immunocompromised patient with follicular lymphoma on maintenance rituximab therapy.
As evidenced by negative COVID-19 serology on day 27 of admission, the use of maintenance rituximab in this patient has resulted in an inability to mount an appropriate immune response to the infection, despite prolonged exposure to the virus. There are no established treatment protocols for immunocompromised patients, and some with haematological malignancies remain refractory to standard therapy with prolonged viral shedding. Reported cases include two patients treated with extended or repeated courses of remdesivir[
10,
11] and another treated with remdesivir plus nirmatrelvir/ritonavir[
12]. A case series similarly documented four cases of patients with B-cell-depleted non-Hodgkin lymphoma who received rituximab therapy and later contracted COVID-19 infection. These cases showed a prolonged clinical course, with transient clinical improvement after standard steroid and remdesivir treatment followed by subsequent early relapse or exacerbation of symptoms[
13].
Remdesivir is an antiviral agent that has been demonstrated to possess potent antiviral activity against SARS-CoV-2[
14]. However, antiviral treatment proved inadequate as our patient continued to experience further deterioration. Hence, he subsequently received monoclonal antibodies casirivimab/imdevimab on day 29 of admission, alongside a second cycle of remdesivir. The patient’s condition improved and was eventually stable enough to be extubated and transferred to the general ward.
In our case presentation, it is of significance to note that casirivimab/imdevimab potentially played a pivotal role in the patient’s recovery, as it was administered during the period of intubation, coinciding with subsequent gradual clinical improvement and rising Ct values observed thereafter. Casirivimab/Imdevimab are laboratory-made monoclonal antibodies developedto mimic the body’s immunity for the treatment and prevention of COVID-19[
15]. We encountered a limited number of publications available for discussion regarding the use of monoclonal antibodies as a rescue therapy in patients with haematological malignancies and severe COVID-19 infection. In a retrospective descriptive analysis of 40 lymphoma-patients with COVID-19[
16], 35 were on maintenance rituximab and all were treated with remdesivir, with four receiving monoclonal antibodies tixagevimab/cilgavimab as treatment. Although 40.9% required oxygen or invasive ventilation, it was unclear whether these included the 4 patients or whether the antibodies were used as a rescue therapy. All patients in the analysis survived.
Combining antiviral agents with monoclonal antibodies may offer an advantage by enhancing efficacy through their distinct antiviral mechanisms, as inhibiting viral replication alone may be insufficient for viral clearance in patients lacking humoral immunity[
17,
18]. Several case series[
19,
20], and observational cohort studies[
21–
23] have described successful use of combination therapy involving antivirals and monoclonal antibodies.
Other studies primarily focus on monoclonal antibodies use as a prophylactic treatment. A retrospective, observational study on the early use of casirivimab/Imdevimab, Bamlanivimab/Etesevimab, Bamlanivimab, and Sotrovimab in paucisymptomatic patients[
24] reported decreased time to viral clearance compared to a control group of patients with haematological malignancies not treated with monoclonal antibodies. Another systematic review also demonstrated that prophylactic treatment with tixagevimab/cilgavimab exhibited clinical effectiveness against coronavirus in immunocompromised patients in terms of COVID-19-related hospitalisations, intensive care admissions and mortality[
25].
To the best of our knowledge, there have been no publications at the time of writing, regarding the administration of combined monoclonal antibodies casirivimab/imdevimab as a treatment during significant deterioration while the patient was intubated, as in our case report. Our case suggests that the use of casirivimab/imdevimab as a form of salvage therapy may contribute to COVID-19 viral clearance and clinical recovery in patients with severe COVID-19 receiving B-cell depleting immunosuppressive therapy. However, this is a single case report of monoclonal antibodies use, confounded by a second-cycle remdesivir and dexamethasone, and the emergence of SARS-CoV-2 variants and potential monoclonal antibody resistance may limit the generalisability of the findings.
This case report seeks to highlight a major complication of long-term immunosuppressive therapy in patients with follicular lymphoma. It suggests that a single agent such as remdesivir may be insufficient as monotherapy in immunocompromised individuals. Our case demonstrates the potential role of monoclonal antibodies in managing prolonged and severe COVID-19 infections in patients with haematological malignancies.
The Author(s) 2026. This article is published with open access at journal.hep.com.cn.
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