Anti-CD52 Therapy for Multiple Sclerosis: An Update in the COVID Era

Figures & data

Figure 1 Effects of anti-CD52 on immune system. Administration of anti-CD52 causes depletion of circulating CD52⁺ cells, which are T cells, B cells, and immature myeloid dendritic cells (DCs). Depletion is due to complement-dependent cytolysis (CDC) and antibody-dependent cellular cytotoxicity (ADCC). In the periphery, after CD52⁺-cell depletion, a transient increase in TNFα and IFNγ is observed. Repopulation of depleted cells occurs from the thymus and bone-marrow population of cells, taking in human 3–6 months for B cells and up to 61 months for T cells. Fast repopulation of regulatory T and B cells is observed, which creates an immunotolerant environment. After depletion in the periphery, CD52⁺-cell infiltration into the CNS is decreased. This further decreases cell aggregates in the CNS and increases levels of anti-inflammatory cytokines, and decreased levels of proinflammatory cytokines are observed. Increased levels of neurotrophic factors are also noted.

Abbreviations: BDNF, brain-derived neurotrophic factor; CNTF, ciliary neurotrophic factor.

Table 1 Alemtuzumab treated MS patients with COVID-19 described in the literature

	Case 1	Case 2	Case 3	Case 4	Case 5	Case 6	Case 7
Literature	Carandini et al^Citation63	Matias-Guiu et al^Citation67	Matias-Guiu et al^Citation67	Guevara et al^Citation65	Fernandez-Diaz et al^Citation64	Fernandez-Diaz et al^Citation64	Fiorella and Lorna^Citation66
Sex/age (years)	Female/25	Female/54	Female/51	Male/35	Male/43	Female/30	Female/24
Comorbidities	None	None	None	None	None	Ex-smoker	None
MS course	Relapsing–remitting	Relapsing–remitting	Relapsing–remitting	Relapsing–remitting	Relapsing–remitting	Relapsing–remitting	Relapsing–remitting
Alemtuzumab dosing
Year 1	Feb 2019	not clearly stated	not clearly stated	Dec 2018	Apr 2018	Mar 2019	Jan 2019
Year 2	Feb 2020	Feb 2019	Feb 2019	Feb 2020	Apr 2019	Mar 2020	Feb 2020
COVID-19 data
Onset	28 Feb 2020	May 2020	May 2020	May 2020	Mar 2020	Mar 2020	May 2020
Diagnostic method	PCR SARS-CoV2 (nasopharyngeal swab)	No	No (positive IgG one month after)	PCR SARS-CoV2 (nasopharyngeal swab)	PCR SARS-CoV2 (nasopharyngeal swab)	PCR SARS-CoV2 (nasopharyngeal swab)	PCR SARS-CoV2 (nasopharyngeal swab)
Maximum lymphopenia (cells/µL)	90	1000	500	210	200	0	930
Severe disease	No	No	No	No	No	No	No
Hospitalization	No	No	Yes	No	No	Yes	Yes
Treatment type duration	Acetaminophen No data	No data	No data	No data	Lopinavir–ritonavir Hydroxychloroqine Amoxicillin 10 days	Hydroxychloroquine Ceftriaxone–cefditoren 9 days	Acetaminophen Levodropropizine 7–8 days
Outcome	Recovery	Recovery	Recovery	Recovery	Recovery	Recovery	Recovery

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Fernández-Díaz E, Gracia-Gil J, García-García JG, Palao M, Romero-Sánchez CM, Segura T. COVID-19 and multiple sclerosis: a description of two cases on alemtuzumab. Mult Scler Relat Disord. 2020. doi:10.1016/j.msard.2020.102402

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Matías-Guiu J, Montero-Escribano P, Pytel V, Porta-Etessam J, Matias-Guiu JA. Potential COVID-19 infection in patients with severe multiple sclerosis treated with alemtuzumab. Mult Scler Relat Disord. 2020. doi:10.1016/j.msard.2020.102297

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