history of covid-19
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SARS‐CoV‐2 is not the first coronavirus to cause outbreaks of respiratory infection in humans. Six others have been identified so far, all believed to have originated in animals.6, 7 The four coronaviruses that are now endemic in humans cause 10–15% of common colds, mostly peaking between December and April in temperate climates.8 NL63 and 229E probably came from bats; OC43 and HKU1 seem to have originated in rodents. Each of these causes mild symptoms, though OC43 has ancestry as a bovine coronavirus that may have caused a pandemic at the end of the 19th century.
Two non‐endemic coronaviruses have caused serious disease. SARS‐CoV was the first to be recognised, occurring first in November 2002 in China (though not known at the time) and coming to the attention of WHO early in 2003 in Viet Nam.9 The outbreak was largely over by July, and the last cases were reported in China in April 2004. This virus was responsible for Severe Acute Respiratory Syndrome (SARS), a flu‐like illness, though diarrhoea was common. It could progress to pneumonia and respiratory failure in two weeks and 25% of people infected required intensive care. A total of 8098 cases and 774 deaths were notified.10 SARS‐CoV appears to have originated in horseshoe bats and possibly transmitted to humans via palm civet cats, traded in China for their meat.
The second serious infection due to a coronavirus was Middle Eastern Respiratory Syndrome (MERS). The MERS‐CoV virus was first identified as the cause of a fatal infection in Saudi Arabia in 2012.11 It spread to 27 countries. Unlike SARS, MERS is still prevalent and, as of November 2019, 2494 infections had been notified, of which 858 proved fatal.12 Like SARS, MERS causes a flu‐like illness with symptoms ranging from mild (with about one‐quarter of people also having diarrhoea) to severe pneumonia, acute respiratory distress syndrome, septic shock and multiorgan failure. MERS‐CoV is believed to have reached humans via dromedary camels, which appear to be a reservoir in several Middle East states. The original source species is not known, but bats are the most likely.
SARS‐CoV‐2 more closely resembles the bat wild virus than it does either SARS‐CoV or MERS‐CoV, strongly suggesting that it is a novel coronavirus in humans.5 The coronavirus spike protein – the structure that binds the virus to the target receptor and mediates cell entry – requires six amino acids: SARS‐CoV‐2 shares only one of these with SARS‐CoV. This spike protein confers high affinity for angiotensin‐converting enzyme 2 (ACE2), the host receptor in humans (and many other species, including pigs, primates and cats).13 The second major structural difference from SARS‐CoV is a unique subunit of the spike protein that determines viral infectivity and host range. It may have been a mutation of this feature during human infection that led to the rapid spread of COVID‐19 in humans. There is currently no evidence that any of the mutations identified since SARS‐CoV‐2 virus emerged in humans have altered the key characteristics of COVID‐19.8
How do major respiratory viral infections compare?
Outbreaks of MERS‐CoV now occur mostly due to animal‐to‐human transmission (probably during the camel calving season).14 Person‐to‐person spread seems to depend on close contact, such as providing care to an infected person or within a hospital setting. In all, 40% of confirmed cases have been acquired nosocomially – on one day in May 2015, an individual with MERS visited several hospitals in Korea and infected 186 people.11
SARS‐CoV is transmitted via droplets in respiratory aerosol, contact with surfaces and possibly via faecal‐oral contact.10 Within one month of 55 index cases being recognised in Hong Kong, Hanoi and Singapore, a total of 3000 cases had been confirmed globally with a peak reporting rate of 200 new cases per day.15 At the time, this was described as devastating. For comparison, one month after 5 January when the first 59 cases of COVID‐19 were recognised, 24,554 cases had been confirmed globally.16
These figures are influenced by the restrictions on travel and lockdown measures recommended by WHO in liaison with governments to control the spread of infection. They are not, therefore, solely an indicator of the natural pathogenicity of the viruses.
The COVID‐19 pandemic has often been compared with global influenza outbreaks in an attempt to put this new threat in an historical context. According to WHO data, seasonal flu causes three to five million cases of severe illness and 290,000–650,000 deaths from respiratory disease each year.17 H1N1, the virus that caused the swine flu pandemic of 2009/10, infected 11–21% of the global population (750 million – 1.4 billion people) and caused around 280,000 deaths from respiratory disease and cardiovascular disorders; about two thirds of those deaths occurred in people aged 18–64 years.18,19 As