The last year has seen the tragedy of the Corona Virus pandemic where a virus new to humans has infected vast numbers of people and caused widespread illness and many deaths world-wide. While not identical to the Influenza pandemic of 1918-1920, there are many parallels between this pandemic and the current Corona virus pandemic. For example, the importance of using masks in a respiratory virus pandemic was graphically demonstrated in cities such as San Francisco in 1918. Unlike 1918, there has been not only a rapid demonstration that we are dealing with a virus, but the gene structure of the virus was uncovered quickly. An explosion of research on all aspects of the virus and the infection led to the rapid development of diagnostic tests, therapeutics and vaccines.
Scientifically there have been two major challenges. The first has been to understand why some people develop severe lung and systemic infections, which in some cases leads to death. The second is a delayed worsening, usually in the second week after onset of symptoms and notable for high fever, and systemic symptoms. The mystery of both of these has been partly unraveled.
Until 2019 there were 4 Corona viruses known to infect humans. They accounted for about 20% of colds. Last year the SARS-CoV-19 Corona virus jumped from wild animals (probably from bats) to humans as a result of a new mutation in the virus surface protein (spike protein) which allowed this virus to enter human cells very efficiently. The virus surface (this is the spike protein) binds on to a receptor on the surface of lung cells, which is why major respiratory infection can result.
We make a family of proteins called Interferons whose function is to fight off viral infections. One of these is particularly important to counteract the Corona virus. An important effect of the SARS-CoV-19 Corona virus infection is to shut off production of this particular Interferon; which allows the virus to overcome human resistance to the infection. This is one reason why we see so many severely infected people and why there are more deaths than we see, for instance, in Influenza. Rare cases exist where this Interferon is not made at all because of a mutated and defective gene. In this instance, the infection is often fatal. There are also a number of functional gene variations for components of Interferon signaling pathways in cells which may reduce the biological effectiveness of Interferon – and these variations also lead to more severe disease. And an unknown autoimmune disease affecting men was discovered in which antibodies against the cell surface receptor for interferon blocks its action on cells. Here again more severe and potentially fatal disease is seen. We have now learned that steroid treatment can save lives of individuals with this disease by suppressing production of this antibody.
An unanticipated genetic finding has recently been uncovered which explains why people of Bangladeshi origin have more severe Corona virus infections. A series of genes lined up on a segment of DNA shows strong inheritance particularly in people who originate from Bangladesh. The gene sequence itself was derived from a subgroup of Neanderthals and was incorporated into human genes, mostly in Asia but to a lesser extent in Europe and the Americas. One or more of the genes in this region is thought to contribute to the increased severity of disease.
Individuals at high risk for poor outcomes from Corona infection often develop a delayed and damaging inflammatory response called a macrophage activation syndrome or cytokine storm syndrome. The interferon we make to fight the virus is largely made by the Innate immune system. This is a rapid response system which allows more specific immune responses (Adaptive immune system) to come into play in time. The Corona virus can suppress the Innate immune system excessively in certain individuals. As a result, less Interferon is made but other inflammatory proteins called pro-inflammatory cytokines are produced instead. These cytokines initiate accelerated inflammation and poor outcomes. The pro-inflammatory cytokines are suppressed by dexamethasone which now has an established role in suppressing the cytokine storm syndrome. Certain monoclonal antibodies against some of these cytokines may also have a therapeutic role.
The central nervous system can be affected directly by Corona virus infection or by inflammation triggered by the infection. Generally, there is little direct infection although the olfactory (nasal) mucosa can be infected and spread the virus to the frontal lobe of the brain. Other cases of infectious Meningoencephalitis have been seen. Inflammation of the nervous system can occur in Corona virus infection such as Acute Disseminated Encephalomyelitis and immune-mediated areas of inflammation. Strokes are seen when the Corona infection triggers inflammatory initiated clotting in blood vessels. And inflammation of peripheral nerves can cause Guillain-Barre syndrome.
Once the gene sequences of the Corona virus were known modern technology enabled very rapid production of vaccines. The spike protein on the surface of the Corona virus elicits much of our immune response to the virus. This is why the RNA for the protein or the protein itself have been used to develop vaccines. There are two major approaches to producing Corona virus vaccines. Messenger RNA is copied from DNA and it is then used as a template to produce protein. The viral messenger RNA for the spike protein can be synthesized; and when inserted in a capsule of either fatty molecules or the shell from Adenoviruses (human or chimpanzee respiratory viruses) it can be injected into muscle. The capsule carries the RNA into the cytoplasm of cells where the spike protein is made and then released. When the immune system sees the foreign protein, we make antibodies, which then block the virus from entering cells; and we train T cells to recognize and kill viral infected cells. An alternative strategy is to introduce the viral messenger RNA into cells in tissue culture. These then make and release the spike protein which can be purified and used to inject as a vaccine.
So how does all of this affect someone with MS?
There have been a number of clinical studies which show that overall individuals with MS have the same degree of susceptibility to the SARS-CoV-19 infection as the general population, with some exceptions. The proportion of mild, moderate and severe cases does not differ from the general population. Individuals with MS with co-morbidities such as obesity, diabetes and lung and heart conditions have the expected increased risk. African American and Latinx patients with MS also carry a higher risk for more severe disease. Individuals with more severe disability from MS do carry greater risk for more severe disease. There is no obvious link between MS and the genetic syndromes discussed above. Likewise, MS and the autoimmune disease against Interferon receptors do not co-exist.
The MS therapies by and large do not adversely affect resistance to the Corona virus. There may even be some protection from the injected interferons. It is likely the Alemtuzumab and stem cell transplantation will worsen outcomes but there is insufficient data to establish this. There was concern that Ocrelizumab treatment increases risk but this has not been confirmed in a large review of all MS patients treated with this monoclonal antibody.
Finally, there is no evidence that the vaccines affect MS, with one exception. The vaccine made by the University of Oxford and Astra Zeneca might have the potential to either trigger MS or MS relapses. One case of MS and a few cases of Transverse Myelitis, a spinal cord inflammation which can develop into MS seem to be more common after this vaccine is administered. The reason for this is not clear. It is possible that the high rate of MS in the UK may have resulted in this signal. Alternatively, the vaccine could have activated the immune system to trigger demyelination because of its composition. One specific concern is that the capsule used to transfer the messenger RNA is derived from the Chimpanzee. This could be seen as foreign by the immune system, and in the case of MS or MS susceptibility it could have triggered inflammation and demyelination.
However, we have increasing vaccine choices. It is extremely important for someone with MS to get vaccinated to maintain good health.