By Dean Willis, Lecturer in Neuroscience, Physiology and Pharmacology, University College London
The major obstacle to fighting COVID-19 is that it is a new disease. Indeed, this was reflected in the initial name given to the virus which causes the disease, novel Coronavirus (nCoV). This was later changed to the less snappy, but more precise, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Since SARS-CoV-2 is new there’s no population herd immunity against it, and vaccines and anti-viral drugs are also not available. All three of these have been put forward as a way out of the current crisis.
By far the most controversial mechanism to overcome the current pandemic is to let herd immunity develop, impeded to different degrees. Herd immunity works by placing a barrier between an infected individual and a non-infected individual. The barrier is other people: individuals who have already had the infection and are therefore, hopefully, immunity against it. If sufficient individuals are immune to the infection then the virus stops spreading because there is no one to infect. This is the natural mechanism by which a virus can be controlled at the population level. The Zika virus scare of 2015 is believed to have finally been brought under control because 63% of individuals in infected areas had already being exposed to the virus by 2017, resulting in herd immunity.
What percentage of the population needs to have been infected before, in theory, herd immunity could protect us from SARS-CoV-2? Here the maths gets tricky. Critical to the calculations is a value called R0. R0 is a number which indicates how contagious an infectious agent is. Current information suggests that SARS-CoV-2 as a R0 of about 2. Simply put, 1 infected individual, infects 2 others. If this is the case we would require around 50% of the population to have immunity against SARS-CoV-2 for herd immunity to work. However, it is by no means certain that SARS-CoV-2 has a R0 value of 2. It may be much higher.
This is important because if R0 increases the percentage of the population required for herd immunity to work will also increase. Measles with a R0 of 12 requires at least 90% of the population to have immunity against the measles virus for herd immunity to work.
So if the herd immunity is a viable option to contain the current pandemic, why are governments around the world enforcing distancing measures which would actually slow down the development of herd immunity? The problem is that while most individuals develop a relatively mild form of COVID-19, others can develop a serve form of the disease which requires hospitalization and can be life-threatening. Distancing measures reduce the rate that vulnerable members of the population get infected with SARS-CoV-2 and therefore prevent the health systems from being overwhelmed with severe cases of COVID-19. In addition, it’s also not absolutely certain that, once infected, an individual will develop good immunity against SARS-CoV-2.
When used widely, vaccinations also contribute towards herd immunity. Vaccinations provides an individual with some immunity against an infection. Currently at least 10 different vaccine programmes against SARS-CoV-2 are in development. These take a variety of approaches including the use of a weakened live virus, the use of virus protein subunits and a new type of vaccine based on RNA. The big question is how long will these vaccines take to develop.
In 2003, cases of a new type of severe respiratory infection broke out in Asia. This disease was shown to be caused by a coronavirus which was named Severe Acute Respiratory Syndrome Coronavirus SARS-CoV, and renamed SARS-CoV-1. Further outbreaks of SARS-CoV-1 occurred in 2015 and 2018. To combat this coronavirus, which is related to SARS-CoV-2, various vaccine programmes were initiated. As yet no vaccine is available against SARS-CoV-1.
Will this be different for a vaccine against SARS-CoV-2? Certainly the resources and new innovations being poured into vaccine development for SARS-CoV-2 are unprecedented, with estimates of a new vaccine being available in 12-18 months. But these vaccines must still pass regulatory and safety hurdles, and this is by no means certain. Could anti-viral drugs take up the mantle more quickly?
Anti-viral drugs attempt to limit the virus once an individual is infected. Perhaps the biggest success in this area is the use of anti-retroviral drugs for the treatment of HIV. The theory behind anti-viral drugs is relatively simple. Viruses are intracellular parasites, meaning they enter the host cell, copy their genomes, produce new structural proteins, build new viral particles and exit the cell. Because viral genomes are small and only code for relatively few proteins, they hijack some of the biochemical pathways of their host to copy themselves.
To develop a good anti-viral drug, you target only those pathways which the virus requires and not those shared with the host. For example SARS-CoV-2 is a single-stranded RNA virus, which means its genome is made of RNA instead of DNA. To allow it to copy its RNA genome, the virus makes an enzyme, called RNA-dependant RNA polymerase. The host does not have this enzyme for copying RNA.
Therefore, in theory, drugs which target RNA-dependant RNA polymerase would only affect cells which contain the virus, while leaving uninfected cells alone. Importantly, some of these unique viral pathways and proteins are shared amongst different viruses, therefore anti-viral drugs against another virus may work against SARS-CoV-2. This is known as drug repurposing. As with vaccines, a race is now on to develop new anti-viral drugs for SARS-CoV-2. The problem? Typical development of a new drug takes a least 10 years.
Repurposing would be a much quicker option. This is why the anti-malarial drugs chloroquine/hydroxychloroquine and the anti-HIV drugs lopinavir/ritonavir have been gaining a lot of attention as possible treatments for COVID-19. How solid is the evidence that these drugs will be effective in COVID-19? We will explore this in our next blog, so stay tuned.
As the world’s resources have been marshalled against SARS-Cov-2, will herd immunity, vaccination or anti-viral drugs deal the decisive blow against this pandemic? In the end in it may be a combination of all three. The race is on.