As one comedian remarked about lockdown, ‘it is perfectly possible that in nine months’ time, there might be a baby boom… we will call them the Coronials’! Many of us will remember the daily government briefings on COVID-19 and those eternal catch phrases such as ‘guided by the science’ for many years to come (and ‘I took my wife and child for an hour’s test drive to test my eyesight’) . But even the science did not necessarily initially anticipate what was coming. We have learned in a few short months what we normally learn in 100 years for other diseases. I have also covered pandemics in another article and COVID-19 was not an anticipated event. As our understanding increases, it is now evident that COVID-19 was much more than an acute respiratory infection and it is a disease of alarming complexity. After 5.7 million reported cases worldwide (and counting) it is now evident that COVID-19 affects our kidneys, livers, gastrointestinal systems, central nervous system and even our sensory organs. Significantly it also affects key blood clotting factors which add extra layers of complication.
Not only are the symptoms unusual but who it affects is also much more complicated than originally thought. It affects different demographics such as the Black, Asian and Minority ethnicities (BAME), genders, then of course health status and age in contrasting ways. Spare a thought as the pandemic currently reaches its peak in other countries lacking in healthcare infrastructure such as Brazil. Controversially Brazil’s indigenous people are dying at alarming rate with little help in sight. According to the advocacy group Articulation of the Indigenous Peoples of Brazil (AIPB) their mortality rate is 12.6% compared to the national average of 6.4%. Meanwhile in the UK the pandemic appears past it speak. The Office of National Statistics (ONS) has now collated much of the data since the first coronavirus death on March 2nd and there are some interesting observations.
Statistics on Mortality Rates in the First Two Months of March & May
Between 1st March and 5th May 2020 in England and Wales there were 33,841 registered deaths. Of these, 32,143 (95.0%) had COVID-19 assigned as the underlying cause of death. This is equivalent to all the deaths combined due to chronic lower respiratory diseases for the whole of 2018. Of the deaths involving COVID-19 there was at least one pre-existing condition in 90.4% of cases.
Males had a significantly higher rate of death due to COVID-19; for males in England this was 781.9 deaths per 100,000 compared with 439.0 deaths per 100,000 females; in Wales, these figures were 630.6 and 363.2 per 100,000, respectively. Dementia and Alzheimer’s disease were the most common main pre-existing conditions found among deaths involving COVID-19, involving 6,887 deaths (20.4% of all deaths involving COVID-19). These sad statistics reflect those age groups most vulnerable to COVID-19 and reflect why the government has asked 12.5 million people to self-isolate.
As lockdown restrictions are lifted it is important to remember that what is remarkable about COVID-19 is that for most age groups the chances of dying seems to mirror our chance of dying anyway. For example, an average person aged 40 has around a one-in-1,000 risk of not making it to their next birthday as an annual risk and an almost identical risk of not surviving a coronavirus infection. Clearly however the point of social distancing is to protect the vulnerable and at-risk age groups as any one of us can be a carrier.
So far three children have died under the age of 15 years old and this compares to about 50 children who are killed in road traffic accidents each year. However as most of us know at this point this disease preys on our frailties.
General Complexities of COVID-19 & ACE 2 Receptors
Generally, the hallmark symptoms of a primarily respiratory virus are a sore throat, temperature, headache, progressive tightening of the chest. The strange thing about COVID-19 is that it is much more than this. For the vulnerable and at-risk age groups COVID-19 can generate an aggressive inflammatory response by stimulating an overproduction of key immune factors called cytokines in what is known as a ‘cytokine storm’. This generates persistent and severe inflammation in the lungs (hence the term severe acute respiratory syndrome or SARS) and other organs leading to multiple organ failure. Even the effects on the respiratory system are unusual. Under normal circumstances severe pneumonia sufferers require mechanical ventilation for a week but many COVID-19 patients are ventilated for a much longer timeframe. Conversely it also appears that some people may test positive for the virus yet appear to be function normally with alarmingly low levels of oxygen saturation (60-80%) for reasons that yet remain unclear.
The main point of entry for COVID-19 is a cell receptor called ACE2 (or angiotensin-converting enzyme 2). This cell receptor is mainly expressed by epithelial cells of the lung, intestine, kidney, and blood vessels. There are also ACE2 receptor on the mucosal lining of our mouths, granting the virus easy access to a new susceptible host. One possible theory for the greater prevalence of COVID-19 amongst BAME communities is for instance that they could be genetically predisposed to have more ACE-2 receptors (although this is unproven).
Blood Clotting Factors Are Affected
An added complication to the aggressive inflammation caused by COVID-19 is an increased susceptibility to form blood clots. As mentioned, ACE 2 receptors are also found on the lining of blood vessels. When blood vessels are inflamed, our blood has an increased likelihood of clotting. Of course, blood clots also prevent effective circulation to key organs causing serious issues such as pulmonary embolism, heart attacks or strokes. This is because a key blood clotting factors called fibrinogen is adversely affected. Normal levels of fibrinogen should be between 2-4 grams per litre of blood but with COVID-19 this increases to 10-14 grams. Another key blood protein is D-dimer which is normally measured at roughly 500 ng/mL but with COVID-19 these levels rise to somewhere between 60-80,000 ng/ml signalling a vast increase. These unusual issues mean that blood is much more capable of coagulation in both small and even large arteries. Studies suggest that 25% of patients on mechanical ventilating experience significant blood clots. While lack of oxygen perfusion and damage to blood vessels are an important part of the equation assaults other major organs add to the complexity.
COVID-19 & Kidney Injury
Another key factor is that 90% of patients on mechanical ventilation sustain some form of kidney injury. This is according to a study published recently in ‘Kidney International’. This study examined the electronic health records of 5,000 people hospitalised with COVID-19. A total of 36.6% (or 1,830) of these patients acquired acute kidney injuries and of these14% required kidney dialysis to support their kidney function. Dialysis can be an issue in its own right because of the enhanced capacity of the blood to clot during mechanical dialysis, so blood thinners are often required as well; yet another layer of difficulty. It is also worth pointing out than none of the 5,000 patients in the study had any pre-existing kidney condition. The liver, too, also has ACE2 receptors. Over half of people hospitalized for COVID-19 seem to have elevated or lower-than-normal levels of liver enzymes, which could signal that the virus has invaded the organ. Fortunately, current data suggests that COVID-19 infection does not lead to liver failure,
COVID-19 & The Gastrointestinal Tract
ACE2 receptor sites are particularly abundant in our gastrointestinal tracts (GIT). This is significant in terms of controlling spread of infection. COVID-19 can be shed in faecal matter which means that shared bathrooms can be a source of infection. Essentially flushing the toilet can generate a viral aerosol which is why shutting the toilet lid could be a good idea before flushing; a key point that the public have not been made aware of. A study undertaken at Stanford Health Care Centre in the United States of 116 people who tested positive for COVID-19 suggested that 31.9% had GIT symptoms. Most people described their issues as mild with 22 % describing loss of appetite, another 22% had nausea and vomiting and 12% diarrhoea. Another important point is that the GIT system has a significant role in our immune system. This is supported by an article that was published in the ‘American Journal of Gastroenterology’ which found that people with GIT complaints were generally diagnosed later but endured much longer infections.
Anosmia & Skin Rashes
On the 18th May the UK Chief Medical Officers also updated coronavirus symptoms to also include anosmia. Anosmia is the loss of or a change in your normal sense of smell. Your sense of taste can also be affected as the two are intricately linked. There is good quality evidence from South Korea, China and Italy that significant numbers of patients with proven COVID-19 infection have developed anosmia. In Germany it is reported that more than 2 in 3 confirmed cases had anosmia. In South Korea, where testing has been more widespread, 30% of patients testing positive had anosmia as their major presenting symptom in otherwise mild cases. In addition, there have been a rapidly growing number of reports of a significant increase in the number of patients presenting with anosmia in the absence of any other symptoms. This has received some media coverage, but the presence of skin rashes has not.
Skin rashes are also another phenomenon either because the virus may target the skin or do so as biproduct of an aggressive immune system reaction. So far, a wide range of skin-related conditions have been reported including head-to-toe red rashes, hive-like eruptions, blister-like bubbles and even lacy, purply rashes spreading across larger patches of skin. Recently, the lesions that have captured the most attention are red, tender bumps that appear around the toes and heels—dubbed ‘COVID toes’. Another symptom that is worth being aware of.
Hopefully a second wave will be avoided in the UK. Other European countries are a few weeks on the road out of lockdown but they have nevertheless experienced local spikes in coronavirus infections, but all have maintained an overall downward trend in new daily cases of the virus with an R value of less than one.