Tuesday, April 07, 2020. Author FitnessGenes
Tuesday, April 07, 2020. Author FitnessGenes
We hope you are keeping safe during these challenging times imposed by the current COVID-19 pandemic.
There is an overwhelming amount of information about COVID-19 at the moment, and much of it can appear complicated, or, unfortunately, even be misleading. The aim of this explainer article is to distil lots of the existing scientific research and studies into one place.
When reading this article, please bear in mind that, due to the rapidly-evolving nature of the pandemic, and with new studies and data coming out all the time, some of the information below (particularly the figures and statistics) is liable to change. The article is based on studies available up to the time of writing (6th April 2020).
Also note that there isn’t always necessarily a scientific consensus on certain topics. For example, different modelling systems will generate different estimates of fatality rates caused by COVID-19.
Nevertheless, all facts and figures cited here are based on published epidemiological studies and official statistics from organisations such as WHO (World Health Organisation), CDC (Centers for Disease Control and Prevention) and the NHS (National Health Service).
Coronaviruses are a family of related viruses that are known to cause disease in humans, mammals and birds.
Coronaviruses are so called because the virus particles are characterised by club-shape spikes projecting from their surface, which resemble a crown (“corona” is Latin for crown).
Examples of coronaviruses that can affect humans include:
The specific coronavirus responsible for the current COVID 19 pandemic is called SARS-CoV-2.
COVID-19 is the name of the respiratory disease caused by the SARS-CoV-2 virus.
Breaking down the term COVID-19: “COVI” stands for coronavirus; “D” stands for disease; and “19” corresponds to 2019 – the year when the disease first emerged (in Wuhan, China).
COVID-19 mainly affects the respiratory tract.
Mild cases tend to be restricted to the upper respiratory tract (which includes the nasal cavity, pharynx and larynx [voice box]).
More severe cases can affect the lower respiratory tract (trachea [windpipe], bronchi, bronchioles [small airways] and alveoli (air sacs of the lung).
The main symptoms of COVID-19 include:
Other common symptoms include:
More rarely, people with COVID-19 may experience:
Recent reports also suggest that a loss of smell and taste are symptoms of COVID-19.
According to figures from WHO, 81% of COVID cases are mild and uncomplicated. People with mild COVID-19 tend to recover without requiring hospital admission or any special treatment.
More severe cases of COVID-19 result in severe pneumonia, which is caused by infection and acute inflammation of the bronchioles and alveoli. Severe pneumonia is characterised by symptoms such as fever (above 37.8 C) and severe shortness of breath (breathing rate above 30 per min). This may progress to Acute Respiratory Distress Syndrome (ARDS), sepsis and septic shock (described in the next section).
Figures from WHO suggest 14% of COVID-19 cases require hospitalisation and oxygen therapy. The same figures state that 5% of cases require admission to an intensive care unit (ICU).
Inflammation is one of the body’s defense mechanisms against infection. While inflammation can help get rid of pathogens (i.e. disease-causing agents such as viruses), excessive, widespread and dysregulated inflammation can damage our tissues and impair the function of vital organs. This can be life-threatening and requires support from intensive care units (ICU).
WHO figures suggest 5% of COVID-19 cases require admission to intensive care units.
Severe cases of COVID-19 can cause acute inflammation of the small airways (bronchioles) and air sacs (alveoli) in the lung – known as pneumonia.
In severe pneumonia, the extent of inflammation can impair the ability of the lungs to effectively oxygenate the blood. Consequently, levels of oxygen in the blood become low (termed hypoxemia) and oxygen supply to tissues becomes compromised (termed hypoxia).
People with severe pneumonia will therefore require admission to hospital to receive oxygen therapy.
Severe pneumonia may also develop into a condition known as Acute Respiratory Distress Syndrome (ARDS).
In ARDS, inflammation causes the linings of alveoli (air sacs) as well as the linings of blood vessels surrounding alveoli to become increasingly permeable. As a result, fluid moves into the alveoli, preventing them from filling with air. Furthermore, cells in alveoli become damaged and no-longer produce surfactant (a substance that reduces surface tension inside alveoli). As a result of increased surface tension, alveoli collapse and are unable to inflate.
Consequently, people who develop ARDS require admission to intensive care units for mechanical ventilation, which helps push air and oxygen into the lungs. Ventilators also help to apply a small pressure within the alveoli, known as PEEP (Positive end expiratory pressure), which prevents alveoli from collapsing.
In highly critical COVID-19 cases, the body’s inflammatory response to the viral infection becomes extremely widespread, and damages and impairs the function of other important organs, including the kidneys and cardiovascular system. This is known as sepsis.
Sepsis may also lead to septic shock, whereby blood pressure falls, meaning vital tissues and organs are not adequately perfused with blood.
People aged 65 years and older, as well as those with underlying health conditions, are at greater risk of the developing the complications described above and requiring admission to ICU.
According to figures from the CDC (based on data between Feb 12th – March 16th, 2020), adults aged 65 and over made up 53% of ICU admissions and 80% of deaths associated with COVID-19 in the USA.
More recent data from the CDC (between Feb 12th and March 28th, 2020), suggests that 78% of people admitted to ICU had one or more underlying health condition or risk factor. The most common underlying health conditions in this group were diabetes mellitus, chronic lung disease and cardiovascular disease.
Nevertheless, people under the age of 65 and without underlying health conditions can still end up in ICU. For example, the previous CDC statistics suggest that 36% of ICU admissions were aged between 45 and 64 years old and 12% were aged between 20 and 44 years old.
The time taken from being exposed to the virus (i.e. infection) to first developing symptoms is known as the incubation period.
Statistics from WHO suggest the average incubation period is 5-6 days.
The WHO state that incubation period ranges from 1-14 days, although there have been cases of longer (>14 days) incubation periods.
A study of 181 COVID-19 cases estimated that of those who develop symptoms, 97.5% will develop symptoms within 11.5 days.
It’s important to remember that a person can transmit the virus to other people in the incubation period, before showing any symptoms. This is known as pre-symptomatic transmission.
Yes. This is known as asymptomatic infection.
It is unclear as to just how many people have asymptomatic infection. One reason for this is that, in several healthcare systems across the world, people without symptoms are not routinely tested to see whether they have the virus.
Another reason is that existing studies have been based on relatively small sample sizes.
A study of 565 Japanese citizens evacuated from Wuhan suggested that 41.6% were likely to be asymptomatic. A recent analysis of 166 new COVID-19 cases in China found that 78% were asymptomatic.
Given that people without symptoms can still spread the SARS-CoV-2 virus, high numbers of asymptomatic infection may be one underlying reason for the rapid spread of COVID-19 in some areas.
This is a complicated question to answer.
Firstly, we need to clarify what we mean by “mortality rate.” When looking at the proportion of people with COVID-19 who will die, there are two main types of figures that we can study:
Case Fatality Ratio (CFR)
The Case Fatality Ratio (CFR) is calculated by taking the number of deaths due to COVID-19 and dividing this by the number of confirmed cases of COVID-19 at a particular point in time.
One of the main drawbacks of this method is that the number of confirmed COVID-19 cases depends on the extent of testing within a particular region. For instance, if lots of people with mild and asymptomatic COVID-19 are not tested, then these will not be reflected in the CFR. Furthermore, testing may be restricted to more severe cases of COVID-19, where people are more likely to die.
This is known as ascertainment bias and tends to overestimate the true death rate of COVID-19.
Conversely, the CFR can also underestimate the true death rate of COVID 19. As there is a delay of several weeks between a person developing symptoms, being tested and then subsequently dying, the number of confirmed deaths due to COVID-19 at one particular point in time does not account for all the deaths that will occur in coming weeks in people who are already infected.
This is known in statistics as right-censoring – it neglects deaths that will happen on the right-hand side (i.e. the future) of a particular point in time.
A study, published in The Lancet, has tried to adjust for these issues and calculate a corrected Case Fatality Ratio. The study estimates the CFR for China at 1.38%.
Bear in mind that this figure is an average across all ages. In reality, COVID-19 is more deadly in older people. The same Lancet study estimates the CFR for people under 60 to be 0.32% compared to 6.38% in those aged 60 years old and over. Focussing on people aged 80 and over, the adjusted CFR is 13.4%.
Another point to note is that, due to differences in testing, reporting, demographics and access to healthcare, figures for CFR vary considerably between different countries. The same Lancet study reports the adjusted CFR for 37 countries outside China to be 2.7%.
Infection Fatality Ratio (IFR)
In contrast to the CFR, the Infection Fatality Ratio (IFR) is calculated by taking the number of deaths due to COVID-19 and dividing this by the total number of people who are infected with the SARS-CoV-2 virus.
As not all people who are infected end up being tested, the number of people infected and therefore the resultant IFR figures are estimates.
Interestingly, data from the Diamond Princess cruise ship, which was held in quarantine in Japan in February 2020, has been used for making some IFR estimates. This is because virtually all of its 3,711 passengers and crew were tested.
Using this data to validate their predictions, researchers (including Prof. Neil Ferguson of Imperial College London) publishing in The Lancet, estimated the IFR in China to be 0.66%.
Another study, based on data in Northern Italy between 8th February and 3rd March, suggests that the IFR in Northern Italy is 3.3%.
If the preceding figures highlight anything, it’s that it is difficult to accurately assess the proportion of people infected with the SARS-CoV-2 who will end up dying. More extensive testing to understand just how many people have been infected will shed more light on this.
COVID-19 is spread from person to person primarily via respiratory droplets.
When someone exhales, coughs, or sneezes, they shed virus particles in these respiratory droplets. If another person breathes these droplets in, they can then become infected with the virus.
The risk of person to person transmission is increased the longer and closer two people are in contact with each other.
For this reason, social distancing measures recommend that people stay apart from one another. Currently, both the CDC and Public Health England advise a keeping distance of 2 metres apart to reduce risk of spreading the virus.
A person can also become infected if they touch objects and surfaces that have been contaminated with these respiratory droplets, and then touch their eyes, nose or mouth.
On this note, a study published in the New England Journal of Medicine found that viral particles can remain stable on plastic and stainless steel for up to 72 hours. That said, the amount of virus decays over time, so the chance of infection from these surfaces will also decrease with time.
According to WHO, people are most contagious at the beginning of the disease, within the first three days of having symptoms. During this time, shedding of virus particles in nose and throat is thought to be highest.
As stated before, people who have not yet developed symptoms are still contagious.
Put simply, the reason for lockdowns and enforced social distancing is to slow the spread of the virus.
By slowing the spread of the virus, fewer people will be infected and hospitalised at a particular point in time. This will prevent healthcare systems and intensive care units (ICUs), which have a limited capacity, from being overwhelmed.
This concept is often referred to as flattening the curve.
Using terms from epidemiology, we say that measures such as social distancing, banning mass gatherings, closing schools and universities etc. act to reduce the basic reproduction number of the disease.
Basic reproduction number (R0) refers to the average number of people infected by one person with the disease.
While there are differing estimates of R0 for COVID-19, the majority of studies suggest an R0 of between 2 and 3 in the early stages of epidemic.
This means that each person with the virus will, on average, infect 2-3 other people. Phrased differently, we can say that each COVID-19 case generates 2-3 more cases.
By implementing various social distancing measures, people are less likely to be in contact with others and spread the infection, thereby reducing the reproduction number. When the reproduction number (R0) falls below 1, the disease will stop spreading and the number of cases will drop.
There are several different strategies for reducing the reproductive number, some more drastic than others.
The decision of the UK and areas of the USA to go into lockdown was partly based on a seminal paper published by a team at Imperial College London led by Professor Neil Ferguson.
Using an initial reproduction number (R0) of 2.4, they modelled three basic scenarios:
In the unmitigated epidemic, 81% of UK and US populations would be infected. This would lead to 510,000 and 2.2 million deaths in the UK and US respectively.Unmitigated strategy model.
Mitigation strategy modelled in UK.
In the mitigation strategy, the model showed that while spread of the disease will be slowed slightly, there will still be a rapid rise in cases. (In other words, the reproduction number would still remain above 1 for a significant period of time, leading to spread of disease). This would overwhelm healthcare systems, creating a demand for critical care beds 8 times over capacity. Furthermore, it would lead to 250,000 and 1.1-1.2 million deaths in the UK and US respectively.
In the suppression strategy, the model showed that population-wide social distancing has the largest impact on the spread of the disease. When combined with home quarantine of symptomatic cases and university and school closure, this has the potential to reduce the reproduction number (R0) to below 1, thereby leading to a decline in cases.
Importantly, the model showed the demand for critical care would remain within the capacity of healthcare systems. Therefore, this would prevent deaths caused by the healthcare system being overwhelmed.
One downside of the suppression strategy, however, is that if the social-distancing measures are suddenly lifted, cases will start to rise again.Suppression strategy modelled in the UK. The shaded blue area corresponds to the time measures are implemented.
In addition to social distancing and staying home as much as possible, the CDC currently recommends:
These measures will help to both reduce your risk of infection and lower the risk of spreading infection to others.
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