Pandemic

So How Do We Develop A Plan Of Treatment?

Before we get into potential treatment modalities, let’s all realize that there are some unique features and as yet unknown characteristics about this virus that make projections about it’s future course difficult to make. For example, we know that this virus can be deadly in some cases, but a relatively mild illness in others. In fact, it is turning out that the vast majority of individuals who acquire this virus are asymptomatic or only mildly ill.  So why is it that some people have a severe life threatening illness  whereas others are mildly ill or not ill at all?  Sure, people who have “predisposing conditions” like diabetes, heart disease, pulmonary disease, advanced age or debilitation are for one reason or other more likely to be at greater risk.  However, the same is true for any illness, so why is that we are also occasionally seeing young previously healthy individuals succumbing to this Coronavirus? Some of this has to do with the fact that we are not all built the same way. Some of us have a different immune response to an infection. In others words, some of us respond to this infection, or any infection for that matter, differently than others. You might have heard the term “cytokine storm” used in describing the overwhelming inflammatory response that this viral infection triggers in some people leading to severe pneumonia, respiratory failure, renal failure, blood clots and a whole host of other deadly reactions. This does not happen to everyone who has Covid-19. In fact, it happens to a relatively small percentage, but it is not a unique situation occurring only in patients who have Covid-19. This type of thing happens in other infections as well. There are differing immune factors in any given individual that determine what the response will be to that infection.  This is obvious, but it bears discussing because the media sometimes seems to create an aura of  panic and mystery around this virus that may not warranted. From a medical point of view  it is important to realize that an individual’s inflammatory response to the virus may be what really needs to be treated particularly in severely ill patients.  Another issue to consider regarding this virus and how to deal with it is the fact that it, like other viruses such as the influenza virus, may mutate periodically making it necessary to change vaccines periodically.

There needs to be a four pronged approach

The first prong has to do with developing medications that impair the ability of the virus to either replicate itself in the cell or penetrate the cell.  One such medication is remdesivir. This drug produced by Gilead has received a lot of attention recently. It seems to shorten the time to recovery by a few days (by about 31%) and lower mortality a bit, but it is really not a “game changer”. In fact, a recent Chinese study showed no real improvement in a remdesivir treated group of patients.  This drug presumably works by interfering with viral replication. Hydroxychloroquine and azithromycin have received a lot of attention in the past. A number of studies around the world early on in the pandemic reported a remarkable improvement in patients treated with the combination. However, more recent studies have been less supportive of its use and have pointed out some potential side effects. Although azithromycin is an antibiotic designed to be used against bacteria and not viruses, it has been shown to have some antiviral activity though it’s mechanism of action against viruses is not clear.  Interestingly, hydroxychloroquine’s effectiveness against coronavirus, if any, may not be so much related to antiviral properties per se, but rather it’s anti inflammatory effects as an immune modulator.  Some antiviral medications used to treat HIV may also have some effect on the coronavirus, but these drugs are in trial at this point. Tamiflu, an antiviral medication used to treat influenza, has not been shown to be of much help. There are a number of other anti-viral medications that are currently being investigated that either impair the ability of the virus to replicate or prevent it from attaching itself to the cell so that it can’t enter the cell and begin replicating.  Immune globulin therapy, an old modality in dealing with infections, may also turn out to be very helpful in preventing the virus from penetrating the cells and initiating the infection. With this technique the immune globulins of people who have experience the disease are harvested from their blood, purified and injected into individuals acutely ill with Covid-19. These antibidies attach to the virus and prevent it from entering into the recipient’s cells giving the recipient time to mount his or her own antibody response.

The second prong has to do with developing medications to treat the “Cytokine Storm”.  Once the virus enters the cell and begins to replicate it can, in some instances, trigger an overwhelming immune response known as a “cytokine storm” which is likely responsible for a large proportion of the the deaths associated with this virus. This “storm” causes a sort of autoimmune response that can result in irreparable damage to the lungs, kidneys, heart and other organ systems. Drugs like Acetemra which is an immune modulating drug have been used with some success in the “cytokine storm” phase of Covid-19. The down side of drugs like Acetemra is that they can also weaken the the body’s ability to fight off an infection. An older anti-inflammatory drug, colchicine, is also being studied to see if it has any effect against “cytokine storm.”

The third prong has to do with the development of vaccines that are effective against this virus. However, if this virus is anything like the influenza virus which in many respects it resembles, then we can expect mutations in the coronavirus which will limit the effectiveness of a vaccine.  Mutations in the influenza virus are why we need to get a new vaccine every year and that’s also one of the reasons why the influenza vaccine may be effective in only about 45% of the population depending on whose statistics are reviewed and how accurate the surveillance is.  We can expect the same with the same with the Sars-Cov-2 virus.  None the less, vaccine development will be crucial in limiting the spread of the illness. A number of companies are now working on developing a vaccine depending on which components of the virus are used in the process.

The fourth prong has to do with the evolution of so called “herd immunity.”  Herd immunity occurs when so many people in a community become immune to a contagious disease that it stops spreading. Statistics vary regarding this,  but herd immunity may go into effect when as little as  40 percent of the people in a population become immune to the disease either due to prior infection or through vaccination.  However, some authorities feel that 80 to 95 percent of the population must be immune to the disease to stop its spread. The difficulty in achieving herd immunity naturally; i.e., without vaccination, is the risk it poses in causing severe illness and death in a large number of people. In the case of Covid-19 herd immunity will occur slowly over time as more people either acquire the disease or develop immunity through vaccination. How long this will take is unclear, but having adequate and accurate testing for the virus and for the antibodies against the virus will go a long way in helping us to identify who may be immune and who may be at risk so we can take precautions to isolate those who are are risk and those who are carriers of the virus. By doing so we may be more easily able to open up society again and speed up return to normal.