Is immune suppression safe during COVID?
The COVID pandemic has raised questions about the safety of immune-suppressing treatments for multiple sclerosis. COVID and MS medications work at cross-purposes: infections require a robust immune response whereas disease-modifying therapies (DMT) modify or reduce the abnormal immune response seen in MS. So how can a person maintain control of their MS while remaining protected against COVID?
To address this question, several aspects need to be considered. The first is the effect of DMTs on the immune response. Immunity is determined in part by lymphocytes, which are a type of white blood cell. The key lymphocytes are T cells (which kill infected cells and stimulate a broader immune response) and B cells (which produce antibodies). Immune competence is a numbers game to some degree: fewer lymphocytes mean a less robust immune response. Since T and B cells have been implicated in MS, treatments often target these cells to reduce the risk of inflammatory flare-ups, which appear as relapses and/or lesions on an MRI.
The different DMTs affect lymphocyte numbers to varying degrees. Some treatments, such as the interferons, Copaxone, Aubagio, Tecfidera and Tysabri, generally have minimal effects on lymphocyte numbers (Rommer and colleagues. Front Immunol 2019;10:1564). Others can have profound effects. Mavenclad reduces T cells about 45% and B cells by 70-90%. Gilenya reduces T cells by about 70% but has a lesser effect on B cells. Ocrevus reduces B cells by over 90% but has a lesser effect on T cells. These differences show that reducing immune cells is not entirely necessary to reduce MS disease activity. It is more likely that the benefits are due to reducing certain types of immune activity, or certain types of T and/or B cells. Unfortunately, the ideal effects on T and/or B cell populations to control MS are not known.
A second consideration is how long the immune system is affected since a person may be more susceptible to COVID for the duration of their immune impairment. This duration is also important because you may have to wait for immune function to be restored before getting a COVID vaccine. Most DMTs have continuous effects on the immune response. However, the time to immune recovery varies substantially once treatment is interrupted – from a week or two for the interferons or Tecfidera, to several months for Gilenya or Tysabri. Aubagio remains in the body for many months (or years) so it is best to actively eliminate it with a detox regimen of activated charcoal.
Mavenclad and Lemtrada are given as short courses once a year so they don’t have continuous effects on the immune system. There is some recovery of the immune response about 3-6 months after the last dose. So this “off period” before the next dose is when the COVID risk is likely lower. There is now much discussion about whether the next dose of Mavenclad or Lemtrada (as well as Ocrevus) can be delayed to prolong the “off period” to reduce COVID-related risks.
A more practical way of looking at the issue of DMT safety during COVID is to look at the infection risk with treatments during non-COVID times. There is little to no increased risk of
infections with some DMTs, such as the interferons, Tecfidera, Aubagio and Tysabri (Winkelmann and colleagues. Nature Rev 2016;12: 217-233. Luna and colleagues. JAMA Neurol 2020;77:184-191). With Copaxone, there is a slightly higher risk of some types of infections (e.g. herpes) but a lower risk of other infections (e.g. skin infections). With Gilenya, there is a small risk of respiratory infections, herpes and fungal infections but the risk of serious infections is generally low. Ocrevus and Lemtrada are associated with somewhat higher rates of respiratory infections and some viral infections (Open Forum Infect Dis 2018;5:ofy174).
A number of studies have looked specifically at people with MS who have developed COVID. Some analyses have reported that people taking Ocrevus have a higher risk of catching COVID (Kieseier and colleagues. ECTRIMS 2020; LB1252) or are more likely to require hospitalization (Simpson-Yap and colleagues. ECTRIMS 2020; SS02.04). Other DMTs have not been seen to worsen outcomes in people who develop COVID.
An important finding from these analyses, however, was that people with MS who were taking a DMT appeared to have a lower risk of COVID complications than people who were not treating their MS (Salter and colleagues. ECTRIMS 2020; LB1242). This demonstrates how important it is not to neglect your MS during the pandemic.
The questions raised by COVID-19 – how much immune suppression is needed and for how long – will remain after the pandemic has finally passed. In some cases, treatment regimens may need to be adjusted to allow for a better response to a COVID vaccine. Once the pandemic is lover, it may be that some medications will be used more judiciously, with the more potent agents kept in reserve for people with aggressive or rapidly worsening MS.
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