Coronaviruses: SARS, MERS and SARS-CoV-2
Coronaviruses are a family of enveloped RNA viruses that cause about a third of common colds in humans, and serious disease when one jumps from animals to humans, as SARS, MERS and SARS-CoV-2 each did after passing from bats through another animal. By May 2020, how SARS-CoV-2 spreads, how its spread is stopped and why some people fall more ill than others were partly known and partly still open.
The coronavirus family and its structure
Human coronaviruses cause about a third of all common colds and are usually quite benign. Coronaviruses are mostly found in animals, where they can cause serious disease, and they cause serious disease in humans when a jump from animals to humans occurs.
Coronavirus strains differ slightly in structure but share the same main components. A positive-sense single-stranded RNA genome, encoding around 27 to 30 proteins, is protected by the nucleocapsid or N protein, and around it sits an envelope carrying the envelope or E protein. The other key proteins are the membrane or M protein and the spike or S protein. S is the largest, gives the family its crown appearance and is the most antigenic, although M can also induce an immune response. S is also the protein that first interacts with the host cell.
SARS
Severe acute respiratory syndrome, SARS, first appeared in Guangdong province in China in 2002, with about 8,000 reported cases and a mortality rate of approximately 10%. Its mortality rate and its early effect on the Chinese economy made the outbreak severe, and it mobilised the scientific community. Soon after, scientists at the Centers for Disease Control in Atlanta and in Hong Kong announced that a new coronavirus had been isolated from patients with SARS, which established that a coronavirus causes SARS, and shortly afterwards genome sequences from two isolates were published simultaneously. The sequencing studies also pinpointed the virus's origin: coronaviruses with a very high sequence similarity in the S protein were isolated in Guangdong from palm civets and from bats, so the likely route ran from bats to palm civets, which are regarded there as a delicacy.
SARS mostly affected China, and the outbreak might never have reached the global news. It made headlines as a spreading disease when an American businessman travelling back to the United States through Hong Kong died of it. The outbreak was generally handled well: the rapid response of the World Health Organization is credited with containing it, and a year later there were barely any cases.
Because SARS was handled relatively well, it was in a way seen as a dodged bullet, and the possibility of a recurrence was largely ignored, although several papers warned of one. A 2007 review called the large reservoir of SARS-CoV-like viruses in horseshoe bats, together with the culture of eating exotic animals in southern China, a time bomb, and urged preparedness. SARS was thought of instead as a freak accident, and no health system was going to be planned around a pandemic that might come every 50 or 100 years.
MERS
Middle East respiratory syndrome, MERS, first appeared in Saudi Arabia in 2012, with about 2,500 cases and a very high mortality of 34%. It spread somewhat, but most deaths occurred in Saudi Arabia and in hospitals, which suggested that it affected particular populations and the immunocompromised. Sequencing identified a North African bat as its source, and the missing link between North Africa and the Middle East turned out to be camels, which are traded between the two regions. The camels were presumably infected with viruses from the bats and eventually passed them to humans through saliva or another route, and whether they first hosted the viruses for a very long time is not known.
SARS-CoV-2 and its origin
The novel coronavirus was first called 2019-nCoV and then SARS-CoV-2, and the disease it causes is coronavirus disease 2019. At the end of January 2020 there were about 1,300 confirmed cases and about 41 deaths linked to the disease in China, numbers that by May 2020 seemed very low.
By May 2020, sequencing pointed again to bats, which transmitted the virus to pangolins. Pangolins can be eaten but are valued chiefly for their scales, which are used in traditional medicine. Other, more controversial theories of the virus's source exist. There is clear evidence that the virus was not artificially generated, although a similar virus studied in a laboratory could have escaped.
Why the outbreaks come from bats
The coronaviruses behind the recent outbreaks all originated in bats, and one reason is that bats have a very strong immune system, which makes them a great reservoir for viruses. They produce a lot of interferons, molecules that generate a cellular antiviral response. Humans have interferons too, and interferons can also cause inflammation, but bats apparently deal with that inflammation much better. So a bat virus that jumps species and acquires a mutation that makes it viable in another host is extremely virulent, because it has evolved methods of fighting a much stronger immune system. Studies show about 500 different coronavirus types circulating in bats, so the potential for mutation and a species jump is large. This potential, the wet markets that are a big part of China's economy, travel that is easier and more frequent than when SARS struck in 2002, with flights now often cheaper than train tickets, and the neglect of studies warning of further mutations and epidemics may together have resulted in the recent outbreaks.
How SARS-CoV-2 spreads
SARS-CoV-2 appears to be shed mostly in aerosol droplets, the main route of spread confirmed by May 2020. Infection through the mouth and nose is therefore the more direct route, and it carries a much higher concentration of virus, which makes it the most dangerous route and, from the virus's point of view, the most effective. The virus has also been found to a lesser extent in faeces and in the semen of some men, so it spreads in the body somehow, possibly through viraemia, which had not yet been fully demonstrated.
Why some people are super-spreaders may have no scientific explanation, and super-spreading is probably mostly a matter of behaviour: whether a person wears a mask, coughs into the air or touches everything. A carrier of a higher viral load does shed more virus, and depending on their immune system some people may carry a higher viral load with the same symptoms as others.
How the spread of SARS-CoV-2 is stopped
Washing hands works because SARS-CoV-2 is an enveloped virus: detergent soaps are designed to insert themselves into lipid layers and break the envelope apart, and without the envelope the virus has no S protein to bind the receptors on the cell. Hand washing works in the same way against other enveloped viruses, including influenza. It is good practice even without a pandemic.
By May 2020 enough studies showed that avoiding contact and wearing masks are important, because aerosolised droplets carry much of the spread. It is not certain whether air-conditioning filters, such as those on aircraft, retain the virus. The virus is about 100 nanometres in diameter, so a filter would have to be finer than that, and aircraft filters probably are not. Most masks do not filter out the virus either, but a mask catches whole aerosol droplets, which reduces the radius of spread around the wearer.
SARS-CoV-2 has been described as a Schrödinger's virus: a person should act as though they have it, so as not to spread it to others, and at the same time as though they have no antibodies, so as not to fall ill. Quarantine works very well.
Who becomes severely ill
Among people without comorbidities, some have more severe disease than others, and the reasons are hard to pin down because many people do not know what predispositions they have. With obvious predispositions such as heart conditions or existing breathing problems, more severe disease is to be expected, since the virus infects the alveoli. But because it was not yet fully known how the virus functions or which tissues it affects, it was not known which predispositions to look for. Chance also plays a part. Women appear to cope better than men with coronavirus infections, as with influenza, and there may be a biological reason for it.
Small children appeared to be largely unaffected, though by May 2020 there were reports and counter-reports. One hypothesis, which makes sense but has not been proven, is resistance to superinfection: a cell already infected by certain viruses resists entry by a related virus, and children frequently carry one of the benign coronaviruses, so SARS-CoV-2 may be unable to enter their cells.