The underpinning biology relating to multiple sclerosis disease modifying treatments during the COVID-19 pandemic

Abstract

Background: SARS-CoV-2 viral infection causes COVID-19 that can result in severe acute respiratory distress syndrome (ARDS), which can cause significant mortality, leading to concern that immunosuppressive treatments for multiple sclerosis and other disorders have significant risks for both infection and ARDS.

Objective: To examine the biology that potentially underpins immunity to the SARS-Cov-2 virus and the immunity-induced pathology related to COVID-19 and determine how this impinges on the use of current disease modifying treatments in multiple sclerosis.

Observations: Although information about the mechanisms of immunity are scant, it appears that monocyte/macrophages and then CD8 T cells are important in eliminating the SARS-CoV-2 virus. This may be facilitated via anti-viral antibody responses that may prevent re-infection. However, viral escape and infection of leucocytes to promote lymphopenia, apparent CD8 T cell exhaustion coupled with a cytokine storm and vascular pathology appears to contribute to the damage in ARDS.

Implications: In contrast to ablative haematopoietic stem cell therapy, most multiple-sclerosis-related disease modifying therapies do not particularly target the innate immune system and few have any major long-term impact on CD8 T cells to limit protection against COVID-19. In addition, few block the formation of immature B cells within lymphoid tissue that will provide antibody-mediated protection from (re)infection. However, adjustments to dosing schedules may help de-risk the chance of infection further and reduce the concerns of people with MS being treated during the COVID-19 pandemic.

Fig. 1

The protective and destructive immune response against the SARS-CoV-2 virus. Immune cells target the SARS-CoV-2 virus that initially involves the innate immune response, which is then supplemented with anti-viral cytotoxic T cell responses and neutralizing and binding antibodies.

Fig. 2

Removal of the SARS-CoV-2 virus occurs before a significant anti-viral antibody response is generated. Rhesus macaques were infected with coronavirus and the viral titre was assessed using nasal swabs. Animals were re-infected one month later. The results show the responses of two individual (blue and orange) monkeys, as seen in two additional monkeys, relating to viral titre and anti-viral antibody response. A.U. arbitrary units. Adapted from Bao et al. 2020. DoI.org/10.1101/2020.03.13.990226