Multiple Sclerosis and SARS-CoV-2: Has the Interplay Started?

Abstract

Current knowledge on Multiple Sclerosis (MS) etiopathogenesis encompasses complex interactions between the host’s genetic background and several environmental factors that result in dysimmunity against the central nervous system. An old-aged association exists between MS and viral infections, capable of triggering and sustaining neuroinflammation through direct and indirect mechanisms. The novel Coronavirus, SARS-CoV-2, has a remarkable, and still not fully understood, impact on the immune system: the occurrence and severity of both acute COVID-19 and post-infectious chronic illness (long COVID-19) largely depends on the host’s response to the infection, that echoes several aspects of MS pathobiology. Furthermore, other MS-associated viruses, such as the Epstein-Barr Virus (EBV) and Human Endogenous Retroviruses (HERVs), may enhance a mechanistic interplay with the novel Coronavirus, with the potential to interfere in MS natural history. Studies on COVID-19 in people with MS have helped clinicians in adjusting therapeutic strategies during the pandemic; similar efforts are being made for SARS-CoV-2 vaccination campaigns. In this Review, we look over 18 months of SARS-CoV-2 pandemic from the perspective of MS: we dissect neuroinflammatory and demyelinating mechanisms associated with COVID-19, summarize pathophysiological crossroads between MS and SARS-CoV-2 infection, and discuss present evidence on COVID-19 and its vaccination in people with MS.

Preserved T cell responses to SARS-CoV-2 in anti-CD20 treated multiple sclerosis

“…Remarkably, in three of five patients infected with SARS-CoV-2 before anti-CD20 therapy, first symptoms of MS developed few months after symptoms of SARS-CoV-2 infections, similar to previously described cases. 32 The relatively frequent detection of SARS-CoV-2 infections in pwMS before anti-CD20 therapy in our cohort could, therefore, also be due to potential triggering of the first clinical manifestation of MS by SARS-CoV-2 infections in these three patients. 33 Limitations of this observational study include lack of data on total lymphocyte and B cell counts at the time of SARS-CoV-2 vaccinations precluding evaluations of these parameters as potential risk factors for low vaccine immunogenicity.…”

“…Remarkably, in three of five patients infected with SARS-CoV-2 before anti-CD20 therapy, first symptoms of MS developed few months after symptoms of SARS-CoV-2 infections, similar to previously described cases. 32 The relatively frequent detection of SARS-CoV-2 infections in pwMS before anti-CD20 therapy in our cohort could, therefore, also be due to potential triggering of the first clinical manifestation of MS by SARS-CoV-2 infections in these three patients. 33 …”

Does COVID-19 increase the long-term relapsing-remitting multiple sclerosis clinical activity? A cohort study

“…Earlier case studies [ 6 – 9 ] and some population-based studies were able to confirm a positive short-term association between COVID-19 and exacerbation of relapsing-remitting MS (RRMS) [ 10 – 13 ]. Although this confirmation was not achieved in a study contributed by the current authors [ 14 ], the mentioned association between COVID-19 and MS disease activity could be well-explained by our current knowledge of their pathophysiology [ 15 ]. Still, the effect of COVID-19 on longer-term MS activity remains unclear.…”

Multiple Sclerosis Patients and Disease Modifying Therapies: Impact on Immune Responses against COVID-19 and SARS-CoV-2 Vaccination

“…Neutralizing Abs, particularly anti-RBD antibodies, can play a role in the clearance of SARS-CoV-2 primary infection [9,20,21,23]. The higher ratios of anti-S1 or anti-RBD domains IgG antibodies compared to the nucleocapsid protein contribute to the milder COVID-19 disease showing the importance of these antibodies.…”

“…Today, vaccination seems to be the most effective way to prevent COVID-19 infection, disease, or transmission [9,25]. By the end of February 2021, more than 40 countries and regions have been working on COVID-19 vaccine development and in total, 256 COVID-19 vaccine candidates have been developed based on different approaches, including live attenuated or inactivated vaccines (8.2%), non-replicating viral vector vaccines (13.3%), replicating viral vector vaccines (9.8%), recombinant protein-based vaccines (protein subunit vaccines (35.9%), virus-like particles (VLP)), and nucleic acid vaccines (DNA-(10.2%) and mRNA-based (12.1%) vaccines) (Table 1) [1,3,9,23,25,26]. As S protein is critical for the entrance of virus to the host cell, many COVID-19 candidate vaccines were designed based on the whole or a fragment of SARS-CoV-2 spike protein [1,3,11,23,27,28].…”