key: cord-1017474-g57nndwo
authors: Foerch, Christian; Friedauer, Lucie; Bauer, Boris; Wolf, Timo; Adam, Elisabeth H.
title: Severe COVID-19 infection in a patient with multiple sclerosis treated with fingolimod
date: 2020-05-06
journal: Mult Scler Relat Disord
DOI: 10.1016/j.msard.2020.102180
sha: 2cf504ba3d01dd8500623b8335e1afd7d9d49953
doc_id: 1017474
cord_uid: g57nndwo

Abstract Background : Fingolimod is used for immune therapy in patients with multiple sclerosis. Long-term treatment is associated with a small increase in the risk of herpes virus reactivation and respiratory tract infections. Patients with coronavirus disease 2019 (COVID-19) under Fingolimod treatment have not been described. Methods and results : We report a 57-year old female patient with a relapsing remitting multiple sclerosis under fingolimod treatment who experienced a severe COVID-19 infection in March 2020 (Extended Disability Status Scale: 2.0). Having peripheral lymphopenia typical for fingolimod treatment (total lymphocytes 0.39/nL [1.22-3.56]), the patient developed bilateral interstitial pneumonia with multiple ground-glass opacities on chest CT. Fingolimod medication was stopped. On the intensive care unit, non-invasive ventilation was used to provide oxygen and ventilation support regularly. Over the following two days, oxygenation improved, and the patient was transferred to a normal ward five days after admission. Conclusion : The implications fingolimod has on COVID-19 are complex. As an S1P analogue, fingolimod might enhance lung endothelial cell integrity. In addition, in case of a so-called cytokine storm, immunomodulation might be beneficial to reduce mortality. Future studies are needed to explore the risks and therapeutic effects of fingolimod in COVID-19 patients.

provide oxygen and ventilation support regularly. Over the following two days, oxygenation improved, and the patient was transferred to a normal ward five days after admission.

Conclusion: The implications fingolimod has on COVID-19 are complex. As an S1P analogue, fingolimod might enhance lung endothelial cell integrity. In addition, in case of a so-called cytokine storm, immunomodulation might be beneficial to reduce mortality. Future studies are needed to explore the risks and therapeutic effects of fingolimod in COVID-19 patients.

Fingolimod, a sphingosine 1 phosphate (S1P) analogue, is used for immune therapy in patients with multiple sclerosis. Fingolimod binds to S1P receptors on lymphocytes, leading to receptor internalization and retention of lymphocytes in the lymphoid organs. In consequence, lymphopenia is observed in the T-cell compartment of the peripheral blood.

Under fingolimod treatment, a small increase in the risk of herpes virus reactivation and respiratory tract infections has been described. 1, 2 The severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) causes coronavirus disease 2019 (COVID-19). 3 While most of the patients develop mild symptoms including fever and coughing, severe cases with bilateral interstitial pneumonia and multi organ failure occur. We report the case of a patient potentially at risk for a severe course of COVID-19 due to advanced age, history of multiple sclerosis and ongoing therapy with fingolimod. Informed consent was obtained from the patient.

In 

By end of March 2020, the patient presented to a primary care hospital reporting dyspnea, fever and dry cough that started to occur 7 days ago. Peripheral oxygen saturation (SpO2) was 87% at a respiratory rate of 30/min. Chest CT scan showed bilateral multiple ground- detected. Fingolimod medication was stopped. Non-invasive ventilation was used to provide oxygen and ventilation support regularly. Over the following two days, oxygenation improved. On day four the patient had a normal respiratory rate, and nasal oxygen supply could be reduced to 2L with SpO2 of 96%. Chest X-ray showed regressive peripheral consolidations in the lungs. No other complications occurred. On day five, we transferred the patient to a normal ward.

Our patient had a severe COVID-19 infection with bilateral interstitial pneumonia demanding non-invasive ventilation and ICU care. 3 In addition, the patient combined several risk factors potentially associated with a worse outcome in COVID-19, including age, chronic concomitant disorder and immunomodulatory therapy. Nevertheless, the disease course stabilized rapidly without occurrence of further organ manifestation. The implications fingolimod has on COVID-19 are complex. As an immunomodulatory drug, it retains naïve T cells and central memory T cells within the lymph nodes, thereby preventing autoimmune inflammation in the brain. 4 However, for defending infectious disease antigens, effector memory T cells are pivotal which are less affected by fingolimod treatment. 4 Thus, despite severe lymphopenia, innate and adaptive immune responses to SARS CoV-2 presumably were preserved in our patient. Pathological key-features of COVID-19 in the lung include pulmonary edema and diffuse alveolar damage with cellular fibromyxoid exudates. 5 Interestingly, S1P is a potent angiogenic factor that enhances lung endothelial cell integrity.

It stabilizes vascular permeability and alveolar flooding in preclinical animal models of acute lung injury. 6 Moreover, increased levels of cytokines were measured in COVID-19 infected patients with severe courses of disease. 7 In case of a so-called cytokine storm, immunomodulation is a therapeutic option. Taken together, fingolimod may be of value to control severe respiratory disease, and a clinical trial has been proposed in COVID-19 patients. 8 

Varicella-zoster virus infections in patients treated with fingolimod: risk assessment and consensus recommendations for management

A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis

Clinical Characteristics of Coronavirus Disease 2019 in China

Impact of sphingosine 1-phosphate modulation on immune outcomes

Pathological findings of COVID-19 associated with acute respiratory distress syndrome

Sphingosine-1-phosphate, FTY720, and sphingosine-1-phosphate receptors in the pathobiology of acute lung injury

Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

Chest CT imaging showed bilateral, multiple ground-glass opacities with a peripheral lung and subpleural distribution in the upper and lower lobes