What treatment is recommended for a patient with Multiple Sclerosis (MS) who tests positive for Coronavirus Disease 2019 (COVID-19)?

Treatment for Multiple Sclerosis Patients with COVID-19

Treat MS patients with COVID-19 using standard symptomatic care and available COVID-19 therapies (remdesivir, neutralizing monoclonal antibodies) based on symptom severity, while temporarily holding most disease-modifying therapies until clinical resolution and RT-PCR clearance. 1

Immediate COVID-19 Management

Antiviral and Immunomodulatory Treatment

• Administer remdesivir or neutralizing monoclonal antibodies for symptomatic COVID-19 infection in MS patients, selecting therapy based on current variant susceptibility and disease severity 1
• Use corticosteroids for COVID-19-associated cytokine release syndrome if hyperinflammation develops 1
• Consider concurrent medications and potential drug-drug interactions when selecting COVID-19 therapies 2

Disease-Modifying Therapy Management During Active COVID-19

Temporarily discontinue disease-modifying therapies until clinical resolution AND RT-PCR clearance 2. This is critical because:

• Most DMTs (interferon, glatiramer acetate, teriflunomide, cladribine) do not significantly affect COVID-19 risk or severity and can generally be continued, but temporary discontinuation during active infection is prudent 1
• Anti-CD20 therapies (rituximab, ocrelizumab) carry substantially higher risk: rituximab is associated with 4-fold increased risk of ICU admission (aOR 4.32) and 6-fold increased need for artificial ventilation (aOR 6.15) 3
• Ocrelizumab shows increased hospitalization risk (aOR 1.75) and ICU admission (aOR 2.55) compared to other DMTs 3

Monitoring for Resolution

• Use RT-PCR clearance as primary endpoint for resuming DMTs 2
• If asymptomatic with persistent positive PCR, use high cycle threshold (Ct) values to assess resolution 2
• Rapid antigen testing can confirm resolution when PCR remains persistently positive 2
• Consult infectious disease specialist if COVID-19 testing remains positive despite clinical improvement 2

Risk Stratification for Severe COVID-19 Outcomes

High-Risk MS Patient Characteristics

MS patients face similar infection risk as general population, but certain factors predict severe outcomes 1, 4:

• Older age is consistently associated with worse COVID-19 outcomes 4, 3
• Progressive MS phenotype (versus relapsing-remitting) increases severity risk 4, 3
• Higher disability scores (EDSS) and non-ambulatory status predict hospitalization and critical illness 1, 4
• Longer MS disease duration correlates with severe outcomes 1
• Presence of comorbidities increases risk similar to general population 4

DMT-Specific Risk Considerations

Low-risk DMTs (continue during COVID-19 with caution):

• Interferon-β may provide early antiviral protection, though SARS-CoV-2 may have developed resistance 5
• Glatiramer acetate appears safe and should not interfere with COVID-19 course 5
• Teriflunomide may display antiviral activity by depleting cellular nucleotides 5
• Dimethyl fumarate may afford protection via Nrf-2 pathway activation 5

High-risk DMTs (require heightened vigilance):

• Rituximab carries highest risk: 2.76-fold increased hospitalization, 4.32-fold increased ICU admission, 6.15-fold increased artificial ventilation need 3
• Ocrelizumab: 1.75-fold increased hospitalization, 2.55-fold increased ICU admission 3
• Fingolimod may paradoxically be beneficial during hyperinflammatory stage by reinforcing endothelial barrier 5

Critical Clinical Pitfalls

Neurological Symptom Recrudescence

• 21.1% of MS patients experience neurological symptom recrudescence preceding or coinciding with COVID-19 infection 4
• This does NOT represent true MS relapse but rather pseudo-exacerbation from infection 4
• COVID-19 infection does not increase susceptibility to actual MS relapses or exacerbate MS progression 1
• Distinguish between infection-related symptom worsening and true relapse before initiating MS-specific treatments

Vaccination Considerations Post-Recovery

• All MS patients should receive COVID-19 vaccination after recovery, particularly those at higher risk for severe outcomes 1, 6
• Vaccination does not trigger relapses, exacerbate MS symptoms, or diminish DMT efficacy 1, 6
• Safety profile includes injection site pain, fatigue, and headache, with relapse rate of only 2.1% after first dose and 1.6% after second dose (similar to non-vaccinated patients) 6
• Complete full primary series and follow national booster guidelines 7

Resuming DMT After COVID-19 Resolution

• Do not delay resumption of high-efficacy DMTs unnecessarily once COVID-19 has resolved, as MS disease activity poses significant risk 1
• For anti-CD20 therapies, balance infection clearance against risk of MS reactivation
• Most DMTs can be safely resumed once RT-PCR negative and symptoms resolved 2