Severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2) causes the coronavirus disease 2019 (COVID-19) viral infection. This can lead to severe acute respiratory distress syndrome (ARDS), which can cause significant mortality.1

In the face of the COVID-19 pandemic, neurologists are concerned that immunosuppressive treatments for multiple sclerosis (MS) and other disorders have significant risks for both infection and ARDS.1 MS is an immune-mediated neurologic disease that needs long-term treatment with immunotherapies that have been shown to increase the risk of infections.2

Continuous research on clinical features of COVID-19 in the context of MS has been conducted, which have shown that some disease-modifying therapies (DMTs) can lead to an immunocompromised state.3 In the context of the COVID-19 pandemic, clinicians had to make critical decisions on whether to continue, stop, or change the use of DMTs for their patients with MS, based on the DMT's mechanism of action and clinical trial data on infections.4

Additionally, the impact of each DMT agent on the future SARS-CoV-2 vaccine should be carefully examined in treatment decisions.4 For instance, some MS therapies could have beneficial antiviral effects against SARS-CoV-2, whereas others could have advantageous immune-modulating effects against the cytokine storm and hyperinflammatory phase of the disease.3

This review will analyze the immune response against SARS-CoV-2 and a future vaccine based on some of the common mechanisms of action for DMTs as well as their reported infectious adverse effects (AEs).

Current Multiple Sclerosis Disease-Modifying Therapies

Fingolimod (sphingosine-1-phosphate modulators)
Mechanism of action
Sphingosine-1-phosphate modulators prevent T cells from exiting the lymph nodes. Therefore, the number of lymphocytes present in the central nervous system (CNS) and the central inflammation is reduced without lymphocytes being depleted.3

Possible infection risk in relevance to the COVID-19 pandemic
It is still not known whether S1P modulators increase the risk of SARS-CoV-2 infection. It is rather safe to start S1P modulators in patients who have initially been diagnosed with MS during the pandemic; however, its impact on the future SARS-CoV-2 vaccine has yet to be determined.3

Natalizumab
Mechanism of action
Natalizumab is a non-depleting immunomodulator. It acts as an antagonist to alpha-4 integrin, located on the surface of leukocytes, which helps block its interaction with vascular cell adhesion molecules and prevents leukocyte migration to the CNS.3

Possible infection risk in relevance to the COVID-19 pandemic
Since natalizumab is a non-cell-depleting agent, it is less likely to increase the SARS-CoV-2 susceptibility rate. This suggests a mild increase in the susceptibility to respiratory viral infections based on its infectious AEs.

Overall, natalizumab is safe to use as a treatment during the COVID-19 pandemic as well as in infected patients. It is considered the safest effective DMT treatment for patients with active MS during the pandemic.3

Fumarates
Mechanism of action
The mechanism of action of these medications is still not known; however, it is assumed to cause immunomodulation through inhibition of the Nrf-2 protein that eventually inhibits inflammatory responses.3

Possible infection risk in relevance to the COVID-19 pandemic
It has yet to be determined whether fumarates increase the risk of SARS-CoV-2 infection. It is possible that this group of DMT can increase the susceptibility to SARS-CoV-2 in patients who have moderate-to-severe lymphopenia. Therefore, it is appropriate to continue with the treatment unless the absolute lymphocyte count (ALC) is below 800/mm3.3

Also, it is possibly safe to start fumarates in patients newly diagnosed with MS, but ALC monitoring is still necessary after initiating treatment. Based on different vaccine research, the fumarates do not reduce the immune response against viral vaccines and do not influence immunity against the future SARS-CoV-2 viral protein or inactivated vaccine. Compatibility is still unknown with live-attenuated and viral vector vaccines.3

Overall, immune-modulating therapies, such as the fumarates, sphinogosine-1P modulators, and natalizumab, are preferred over the other cell-depleting immunosuppressants during the pandemic.3

The global COVID-19 pandemic is presumed to remain for several months and even years. Clinical neurologists should understand the mechanism of action of each DMT in relation to its effect on the immune response against SARS-CoV-2 and its future vaccine.3

The proper DMT selection has been an important part of modern MS management but the relevance to the COVID-19 pandemic should now be included in the decision-making process.3 Standard injectables possibly have the safest immune description and should be recommended more often in patients with mild MS during the pandemic.

If a future SARS-CoV-2 vaccine becomes available, patients with MS should be advised that some DMTs may inhibit the protective immune response to the developed vaccine.3

In addition, patients should be informed that most MS therapies are contraindicated with live vaccines if a live SARS-CoV-2 vaccine is developed.3

About the Authors
Sadaf Emad-Vaez is a PharmD candidate at Pacific Oregon University-School of Pharmacy, anticipated to graduate in Spring 2021.

Jonathan Ogurchak, PharmD, CSP, is the CEO and co-Founder of STACK, a pharmacy compliance management software, and serves as preceptor for a virtual Advanced Pharmacy Practice Experiential Rotation for specialty pharmacy, during which this article was composed.

References
  1. Bowen, James D et al. “COVID-19 in MS: Initial observations from the Pacific Northwest.” Neurology(R) neuroimmunology & neuroinflammation vol. 7,5 e783. 26 May. 2020, doi:10.1212/NXI.0000000000000783
  2. Barzegar, Mahdi et al. “COVID-19 infection in a patient with multiple sclerosis treated with fingolimod.” Neurology(R) neuroimmunology & neuroinflammation vol. 7,4 e753. 5 May. 2020, doi:10.1212/NXI.0000000000000753
  3. Baker, David et al. “The underpinning biology relating to multiple sclerosis disease modifying treatments during the COVID-19 pandemic.” Multiple sclerosis and related disorders vol. 43 (2020): 102174. doi:10.1016/j.msard.2020.102174
  4. Zheng, Crystal et al. “Multiple Sclerosis Disease-Modifying Therapy and the COVID-19 Pandemic: Implications on the Risk of Infection and Future Vaccination.” CNS drugs, 1–18. 11 Aug. 2020, doi:10.1007/s40263-020-00756-y