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. 1. SARS-Cov-2 and COVID-19 a new pandemic COVID-19 is the pandemic disease caused by severe acute respiratory syndrome (SARS) coronavirus two (SARS-CoV-2) infection (Zhu et al., 2020a; Zhou et al., 2020). About 80% of people infected with SARS-CoV-2 develop a self-limiting illness, 20% require hospitalisation, largely due to cardiovascular issues and about 5% require critical care and potential ventilatory support (Kimball et al., 2020; Day. 2020). The mortality in those requiring ventilatory support is about 40-50% (Weiss and Murdoch 2020; Zhu et al., 2020b). Death from COVID-19 is associated with older age and comorbidities such as cardiovascular disease, smoking, lung disease, obesity and diabetes (Zhu et al., 2020a; Lippi et al., 2020; Richardson et al., 2020). Mortality in young people and those without comorbidities may be related to excessive viral load (Lui et al 2020a; Chen et al., 2020a). Whilst the typical clinical features requiring self-isolation, and potentially hospitalization are fever, dry cough and shortness of breath related to respiratory tract infection, other symptoms such as headache and gastrointestinal symptoms may go unnoticed or under-appreciated leading to spreading of the virus (Zhu et al., 2020b; Richardson et al., 2020; Huang et al., 2020). People shed infective virus days before symptoms occur and continue to shed virus via the lungs and faeces whilst symptoms develo...

COVID-19 vaccine-readiness for anti-CD20-depleting therapy in autoimmune diseases

“…A vaccination programme should help to create herd immunity against the COVID‐19 virus [25]. Therefore, not only is it relevant to determine how disease‐modifying treatments (DMT) influence susceptibility to infection and length of the carrier state, it is also important to consider how DMT may influence immunity to reinfection and potential vaccine responses [20].…”

Adherence to social distancing and use of personal protective equipment and the risk of SARS-CoV-2 infection in a cohort of patients with multiple sclerosis

“…Before lockdown measures were implemented, specific recommendations to not leave their houses were provided by the earliest nationwide government ruling (Decreto del Presidente del Consiglio dei Ministri, March 4th, 2020) to fragile individuals, such as immunosuppressed or elderly people, supposedly more at risk of complications from COVID19. Patients with Multiple Sclerosis (MS), although not specifically mentioned in the DPCM, are considered among people at major risk, considering their neurological disability, comorbidities and immunosuppressive treatments (Baker et al, 2020;Santangelo et al, 2019). All MS patients and their caregivers have therefore been advised by MS centres, patients' association and the media to stay home and take all available measures of prevention from COVID19 infection, including the use of personal protective equipment (PPE) like face masks and gloves (MSIF, 2020).…”

COVID-19 and multiple sclerosis: A description of two cases on alemtuzumab

“…In some pwMS, especially young and otherwise healthy with highly active MS, the risk of a disabling relapse or disease progression might be higher than the risk of severe complications due to SARS-CoV-2 infection (Brownlee et al, 2020). On the other hand, given that innate immunity seems to be essential in the control of the virus (Baker et al, 2020), it is possible that the risk of COVID-19 in our patients is lower than initially expected, since DMT in MS barely affect it. Moreover, a certain degree of immunosuppression might be protective because the severe acute respiratory syndrome (SARS) is related to a dysregulated immune response (Giovannoni et al, 2020).…”