COVID-19

4. What makes it lethal; why do some people die and others have minimal symptoms

COVID-19 disease is much more complicated than ‘flu. COVID-19 can be asymptomatic, or can result in mild to severe symptomatic disease. Furthermore, developing COVID-19 is significantly more fatal than, say, H1N1 swine ‘flu: the fatality rate for H1N1 was 0.02% of the infections (or 1 out of every 5,000). Although control measures and reports vary between different countries, the latest estimates  of rate of COVID-19 fatalities from South Korea, who are likely to be the more accurate due to them having among the highest levels of population testing for SARS-CoV-2, is between 1-2% [Latest data: https://coronavirus.jhu.edu/map.html]. This section will explore what is happening and why this is the case.

As discussed, all viruses bind to cells via interaction between two proteins: one on the virus, and one on the surface of the host cell. In SARS-CoV-1 and 2 the virus attaches to cells via the angiotensin-converting enzyme 2 (ACE2) receptor: what is striking is that ACE2 is abundantly present in humans in the nasopharynx, the epithelia of the lungs, and vascular endothelium more generally, which explains some of the significant early symptoms such as loss of taste and/or smell, and why the virus predominantly attacks the lungs [Ref: doi.org/10.1002/path.1570]. MERS, by way of contrast, attached to DPP4 (dipeptidyl peptidase IV) receptors, which is rarely detected in the surface epithelium of the nasopharynx, and marginally in distal airways, which explains why it was harder to spread – due to a lack of virus binding in the upper airway.

The open question, however, is why does the virus cause major symptoms in some people, and not in others? We don’t yet have all of the answers for this, especially as there is still uncertainty regarding confounding risk factors, however older age (>65 years old) is consistently associated with a severe COVID-19 reaction; other factors include: male sex, hypertension, diabetes and cardiovascular disease [Ref: doi.org/10.1101/2020.04.05.20054155].

Another factor to consider is that of secondary infection. Some studies have found that one in seven patients hospitalized with COVID-19 had acquired a secondary bacterial infection, 50% of which died. It is important to appropriately treat secondary bacterial infection, ensuring that problems such as antimicrobial resistance are not exacerbated. Secondary lung infections may also obfuscate diagnosis of COVID-19, which will be covered elsewhere in this resource.