Several people have asked me about the variety of R&D approaches to tackling COVID-19, so I thought I would write a quick note about the different types of test development and vaccine/treatment research currently going on (to the best of my knowledge). First, I thought it would help to declutter some of the terminology:

  • A test or diagnostic is a method to determine positive/negative state about some aspect of a disease or illness.
  • A treatment is any sort of approach to help the body remove the existing disease. Some treatments are full cures, and others help manage symptoms until the body is able to take over and cure itself completely.
  • A vaccine is a method of preventing a disease from occurring (i.e. it confers partial or full immunity on the individual against a particular disease or strain of disease).

There are active research projects and trials in all three areas.

Tests/Diagnostics

There are two flavours of tests: one test type, like the one outlined in Appendix 5 in the Public Health England COVID-19 Standard Operating Procedure, determines whether a subject currently has COVID-19 using a technique called real-time Reverse-Transcriptase Polymerase Chain Reaction (or real-time RT-PCR), whereas the second type determines whether a subject has had the disease. Keeping in mind that many cases of COVID-19 are completely asymptomatic, it is important to produce both types of tests to provide better population-level counts about the prevalence of the disease and to determine who needs hospital-based treatment.

For a better understanding of the first test type, please read more about various PCR techniques here. When someone "tests positive" for having the virus, they are subjected to PCR-based tests like this one.

The second type of test is likely to be an antibody-based approach. When a body is infected by a pathogen like COVID-19, it raises antibodies against it to help fight the infection. This process takes several days in the COVID-19 case, and it is during the course of this time that we suffer the symptoms and go through the journey of fighting the disease. Once the body has raised enough antibodies against the pathogen, the immune system can take over to dispose of the viral particles over time. After the illness passes, the antibodies remain in the bloodstream, conferring a level of immunity in case of reinfection. Since antibodies are specific to a virus type, they are a "signature" that can be detected in the body to determine whether the infection existed in the past. The COVID-19 reinfection rate and length of immunity is not fully clear at the moment as the virus is so new, but in general, it should be very difficult to catch an infection of the same or very, very similar strain again after having caught it once. A reinfection would likely also be significantly milder or asymptomatic.

Broad testing and characterisation of the prevalence of the disease, and especially understanding how many people have recovered after having had it, may pave the way for immunity passports to help people return to their normal lives sooner. For those who have not yet caught the disease, such measures could still provide peace of mind for them knowing that their primary coworkers are immune, for instance. However, we need to be careful not to use such methods as tools to ostracise, discriminate, or segregate.

DNA Sequencing

Given my proximity to the DNA sequencing industry, I should call out that sequencing is also being used for testing and characterisation of the virus. Illumina published a metagenomics workflow for characterising COVID-19, and a large consortium has been formed in the UK (COG-UK) to sequence SARS-CoV-2 from positive COVID-19 human samples using a variety of sequencing techniques and platforms. Whilst DNA sequencing is not as fast as the simple positive/negative test, it is vital for broader and deeper understanding, and for devising new strategies to tackle both this virus and future similar pathogens.

As an interesting side note and cautionary tale, however, mutational analysis of COVID-19 can be overinterpreted to skew the truth and promote hysteria without sufficient evidence and due cause.

Treatments

Allopathic treatments fall primarily in the anti-retroviral category. Medicines originally developed for other retroviruses such as HIV, are being tested for their effects against COVID-19. Repurposing medicines in this way, if successful, would be far quicker than trying to find a novel therapy. Here's a decent list of treatments currently in various development stages. There is also a lot of excitement and initiative around repurposing quinine-based antimalarials (sometimes as part of a cocktail with antivirals).

Naturopathic studies are currently focused on the use of intravenous Vitamin C to shorten hospital stays and speed up healing time. The general theory here is that infections like COVID-19 reduce Vitamin C levels in the body, so there is cause to "top up" in any case and determine the downstream effects. I am still unclear on whether the ascorbic acid compound (Vitamin C) itself can directly block viral docking and entry or whether the effect is regulatory, i.e. higher levels of Vitamin C influence other players in the body to slow uptake or replication of the virus. I would welcome any papers or articles that can better explain this.

Vaccines

The vaccine is the Holy Grail of drug discovery and development. It confers partial or complete immunity against a disease, a factor partly influenced by how quickly a pathogen mutates. The reason seasonal influenza vaccines are variable in their effectiveness is because the 'flu virus mutates very quickly, rendering last year's (or even last season's) vaccine useless against the strain of the day. To that end, there is some evidence that SARS-CoV-2 (the pathogen that causes COVID-19) mutates slowly. This implies that a vaccine produced for one strain should be effective not only for other strains, but potentially for a longer term, rather than requiring repeated treatments (like yearly 'flu shots).

Essentially, a vaccine would allow the body to react immediately to a foreign pathogen without requiring the body to go through the process of creating antibodies to fend off the illness. Some vaccine approaches use "dead" virus particles (without the RNA or machinery for it to replicate in the body), whilst others use "live attenuated" viruses, where the virus is alive but heavily impeded. Still other vaccines use parts of the viral structure (proteins or protein subunits) or even viral RNA introduced directly without the protein encasing (the "corona" in SARS-CoV-2). Suffice it to say, there are numerous approaches to vaccines, each with their pros and cons in how quickly the body is able to build a strong and long-lasting immune response (there is often a tradeoff between these two factors).

Still other approaches are exploring temporary immunity or reduction of symptoms through blood or plasma transfusions from healthy individuals who have already had the disease. Whilst not strictly a vaccine in itself, this approach is similar as it effectively floods the patient's bloodstream with antibodies from the healthy individual, potentially allowing the patient's body to very quickly boost its own immune response. There is a small study published on the matter with promising results, but much larger clinical trials are required to determine whether this technique could be reliably applied to reduce the severity of illness in critical patients before attempting treatment (or hopefully future vaccination) methods to "finish the job".

Summary

Hopefully this helps declutter the terminology around the research happening today with COVID-19. Many of my friends have felt disheartened knowing that a vaccine is not yet available, but I wanted to show that a vaccine is not the only marker of success in combating the disease, and importantly, allowing us to move out of lockdown state.

In compiling notes for this article, I found a very helpful infographic outlining the tests, treatments, and vaccines currently in development. This should provide an easy reference dashboard if anyone is interested in manufacturers, technique types, and state of approval from various governing bodies.