Coronavirus Disease 2019 (COVID-19) is a respiratory disease that has caused scores of people around the globe to fall severely ill or die. While the race to discover a treatment and vaccine that will curb the infection rates and dampen down the impact of the virus on human health continues, it helps to understand the science behind what causes COVID-9 to be such a serious threat to life and what treatment options could be available for people. Key aspects worth considering here are, i) what the virus does to the body upon infection, ii) how the body’s immune system responds to viral infection and iii) what are the consequences on overall health.
1. Impact of viral infection
Once the coronavirus enters the body (commonly through the lungs) it infects the cells and replicates (makes several copies of itself) within them – the virus cannot replicate on its own without infecting host cells. After several copies of the virus are made, they are released and free to infect more and more cells and make further copies of the virus. The virua can negatively impact the normal functioning of the infected cells and tissues of the lungs often causing serious breathing issues and, in severe cases, lung failure and even death.
2. Impact of immune system activation
The entry of foreign pathogens such as viruses to the human body will elicit an immune response, the extent to which depends on the type of pathogen. COVID-19 virus causes intense activation of the immune system associated with a marked rise in levels of inflammatory cytokines (messenger molecules that drive orchestration of immune responses). This so-called “cytokine storm” causes severe inflammation that can destroy normal body cells, even posing a threat to organ function and ultimately life. It is thought that the tissue injury caused by immune system overdrive is the main cause for the serious health complications that follow infection with coronavirus.
3. Impact on overall health
The intense activation of the immune system that occurs with coronavirus infection can overwhelm the immune system and engender a state of fighter immune immune cell exhaustion that could leave us more vulnerable to opportunistic infection with other pathogens, causing further health complications.
It is worth noting that elderly people or those with compromised organ function or immune system health are more likely to experience severe illness following infection compared to young, healthy people. However, differences between individuals also exist (e.g. genetics, lifestyle, fitness) so it is hard to predict with certainly the outcome of infection with the virus for any one person.
So what treatment options are there for COVID-19?
In terms of therapy, and based on our understanding of how the COVID-19 virus works, the following are the two main categories of treatment being explored today to combat the disease:
1. Inhibition of viral infection: The aim here is to weaken the virus and curb the cycle of infection; this is done through the use of drugs that stop virus replication (e.g. the anti-viral drug remdesivir) or antibodies that directly stick to the virus to neutralise it and block its ability to infect cells (e.g. REGN-COV2 antibody cocktail). Both of these types of treatment have shown efficacy in early stages of infection in mild or moderate cases but benefit in severe cases of disease when patients are hospitalised have been modest.
2. Modulation of immune system activity: This approach aims to reduce the degree of local and systemic (body-wide) inflammation and the cytokine storm associated with coronavirus infection. This may seem counter-intuitive as an active immune system is required to keep infections in check, but it is its heightened state of alert that needs to be re-balanced in order to avoid the dangerous potentially life-threatening consequences on health. Drugs that are relevant here and already used in the treatment of other inflammatory conditions include the anti-inflammatory glucocorticoid dexamethasone, which has been shown to reduce death in severe COVID-19 patients (the RECOVERY study), and antibodies targeted at the inflammation-promoting cytokine IL-6 (e.g. tocilizumab and sarilumab).
As of October 22, 2020, remdesivir is the first and only drug that has been FDA approved for COVID-19 patients, specifically those requiring hospital admission.
Given the multiple steps and mechanisms invoked following COVID-19 infection, it is conceivable that early access to treatment will be critical for minimising the overall impact of infection on patients’ recovery and long term health. It is also clear that different therapies will be more relevant at different stages /severity of the disease (e.g. late vs early, mild vs severe). Furthermore, a cocktail approach with drugs targeting different processes may be warranted provided the drugs that are administered together do not interfere with each other’s efficacy (minimal drug-drug interaction) and have a compatible safety profile.
Further information on the approaches being investigated for COVID-19 treatment, including treatment recommendations are available on the NIH COVID-19 Treatment Guidelines website.
