On 31 December 2019, about a cluster of 鈥渧iral pneumonia鈥� cases of unknown cause in the city of Wuhan. Two years later, the coronavirus now known as SARS鈥慍oV-2 has resulted in at least 5.3 million deaths. As the world awaits the full impact of the new variant omicron, New 杏吧原创 looks back at the phenomenal scientific endeavour across the pandemic, and at how much we now know about the virus and how to fight it.
Where did covid-19 come from?
In March 2021, a group tasked by the WHO to investigate covid-19鈥檚 origins concluded that SARS-CoV-2 is most likely to be an animal virus that moved into humans through contact with an animal host, either at the Huanan Seafood Wholesale Market, a live animal market in Wuhan, or at another step in the trade of wildlife.
The WHO group hedged its bets because the first person reported to have become ill with covid-19 on 8 December 2019 had no link with the market. , however, suggests that this individual actually developed symptoms on 16 December, and聽only visited a hospital on 8聽December for dental problems.
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This means the earliest known case may indeed have had ties to聽the market: a seafood vendor . A third of the 168聽people later identified as having had the virus聽in December 2019 had connections to the market.
The mounting evidence for a market origin weakens the case for a lab leak, a premise that couldn鈥檛 be ruled out by an investigation commissioned by US president Joe聽Biden in 2021. Since these investigations, coronaviruses that are have been discovered in bats in Laos, says at Erasmus University Medical Centre in the Netherlands, who was part of the WHO鈥檚 investigation team. Certain features of these wild viruses were聽the same as those that some聽researchers claimed could only have arisen during 鈥済ain of function鈥� tests in a lab, in which an聽organism is genetically altered to enhance certain characteristics.
adds further support to聽the market origins story. The authors were serendipitously surveying markets in the Wuhan area that were selling wild animals for food or pets between May 2017 and November 2019. They discovered many animal welfare and exploitation issues with 鈥渃onsiderable implications for food hygiene鈥�. The animals traded are capable of hosting a wide range of infectious diseases, they say.
Some early covid鈥�19 cases were聽linked to an area of Huanan market where wild animals such as raccoon dogs were kept. These animals can be infected and display few symptoms, boosting the idea that animals in the market acted as an intermediate reservoir for the virus, says Koopmans.
In response to covid-19, China聽temporarily prohibited all wildlife trade until the pandemic concludes and permanently banned the eating and trading of聽non-livestock animals for food.
How does the coronavirus spread?
Back in January 2020, researchers urgently needed to understand the nature of the virus and how it聽was spreading. On 3 January, at Fudan University in Shanghai, China, was聽given a box containing swabs from people with the mysterious pneumonia sweeping Wuhan. By聽5聽January, having worked two nights straight, Zhang鈥檚 team had sequenced the virus and identified it as a coronavirus. That same day,聽Zhang uploaded the genome to the US National Center for Biotechnology Information. By comparison, in 2003, scientists took two months to identify the聽cause of an international outbreak of a new disease, SARS, as聽a coronavirus.
It soon became clear that SARS鈥慍oV-2 spread easily and could cause severe disease, particularly in older age groups or in those with underlying health issues. By聽the end of February, its death count had surpassed those caused by the coronaviruses responsible for the SARS outbreak and MERS, a聽disease that emerged in 2012.
The WHO declared the covid-19 outbreak a pandemic on 11聽March 2020. Working out how to minimise transmission was key, but from early on, there was disagreement among experts. At聽first, the focus was on surface transmission聽鈥� infected people contaminating surfaces that were聽then touched by others. Swabs from hospitals found the virus lurking everywhere, from stethoscopes to reading glasses. .
Other researchers concentrated on transmission via large droplets spread as an infected person coughs or sneezes near others. Droplets are heavy and fall from the air within seconds, rarely travelling more than 2 metres.
Social distancing and face聽coverings were widely implemented as a way to help prevent this type of spread. But聽rigorous evidence on the effectiveness of face coverings was聽slow to appear and often contested. The WHO initially only recommended them for people who were actively coughing or caring for those with covid-19.
Today, we know that all face聽coverings help cut the risk of聽catching and transmitting the聽virus to a certain extent.
Then, there is the issue of aerosols. These tiny particles hang聽in the air and so can travel further than 2 metres, but many researchers initially disregarded this route of spread. The WHO stated at a press conference on 27聽March 2020 that 鈥渢ransmission of covid鈥�19 is through droplets, it聽is not airborne鈥�.
This is because doctors have聽traditionally assumed that聽respiratory diseases, like tuberculosis and influenza, are聽spread mainly by droplets聽鈥� 鈥渃oughs and sneezes spread diseases鈥�, says at the University of Oxford. 鈥淚t鈥檚 a mindset that鈥檚 deeply ingrained in聽the infectious disease community.鈥� But more recent research has shown that both and can be spread via aerosols, upending conventional wisdom.
The tide began to turn in July 2020, when 239 scientists from 32聽countries that SARS-CoV-2 was airborne, appealing to the WHO and others聽to acknowledge its impact.聽However, it wasn鈥檛 until May 2021 that the WHO and the changed their guidance, stating that aerosols are the primary route for transmitting the virus, mainly between people in close proximity with each other, and typically 1 to 2 metres apart, or聽in poorly ventilated or crowded indoor environments.
Subsequent research has shown that surface transmission is likely to be a factor in the spread of the virus, but not a primary means. Good ventilation is now seen as a聽vital .
All of this has left some scientists urging a paradigm shift in how we combat respiratory infection. In a call for action , a聽group of more than 30 scientists and doctors pointed to the great disparity in the way in which we聽address different sources of聽environmental infection. While聽governments have long invested in food safety, sanitation and clean drinking water, the group argued that airborne infections haven鈥檛 been targeted strongly enough through changes to regulations, standards and building design that could help prevent their transmission.
How has the virus evolved?
As soon as the coronavirus started spreading, it also began to mutate, leading to new variants. 鈥淥micron should not surprise anyone, it is what viruses do,鈥� said Tedros Adhanom Ghebreyesus, director general of the WHO, at a press conference in December 2021. 鈥淚t鈥檚聽what this virus will continue to do as long as we allow it to continue to spread.鈥�
Each time a virus replicates, it聽has a chance of mutating. Some聽mutations make it better at聽moving through a population. The first new variant to spread widely was alpha, which was sequenced in September 2020 and聽is about 50聽per cent more transmissible than earlier variants. It was first identified in the UK and research suggests that it may have evolved in someone with a weakened immune system. This meant they couldn鈥檛 wipe out聽the virus, encouraging it to evolve and mutate.
Next came beta, which was first spotted in South Africa and was first sequenced in October 2020. Among its mutations is one that alters the shape of a key protein, helping it to evade antibodies that聽are effective against other variants. Recent work suggests it spread quickly because it is 20 per cent better than previous variants at evading the immune response in previously infected people.
In late 2020, another variant, gamma, emerged and caused a surge of cases in Manaus, Brazil. Here, it was estimated that 75 per cent of the population had already been infected with SARS-CoV-2. The new variant had a mutation allowing the virus鈥檚 spike protein to bind more easily to cells, making it more infectious. This protein is the part of the virus that聽recognises host cells, and is the main target of our immune response. Another mutation helped it evade antibodies from past infections.
Then delta swept the world. The variant was sequenced in October 2020 and first detected in India, where it caused a huge wave of infections. At least 50 per cent more transmissible than alpha, delta outcompeted all other variants over the course of 2021, becoming the most common one in the world. Vaccines are still effective against it, but are around 15 per cent worse at preventing infection by delta than by alpha.
Omicron, which emerged in November 2021, has the highest number of mutations so far seen in the spike protein, and we don鈥檛 yet know their full impact. You can聽eyeball the mutations in order聽to work out what effect they聽might have, says at Imperial College London, 鈥渂ut many are new鈥�.
Omicron spread rapidly in South Africa, where a large majority of the population has聽previously been infected but聽only about 25 per cent are fully聽vaccinated.
By 18 December 2021, a total of聽89 countries had detected the presence of omicron. The variant appears to spread much faster than others. A December study of data from South Africa suggested that omicron is in its early stages than delta, and there is some evidence that it may multiply in聽our airways .
The variant also seems to exhibit 鈥渋mmune escape鈥�, to some聽extent evading the immune responses of people who have already had covid-19 or been vaccinated. Lab studies by Pfizer suggest that three doses of the vaccine it developed with BioNTech offer significant protection against infection from omicron, but two doses don鈥檛.
U臒ur 艦ahin, CEO of BioNTech, said in a press statement that a聽component of our immune system, called memory T-cells, generated by the vaccine, may prevent severe disease in those who haven鈥檛 had three shots.
The variant鈥檚 ability to infect the double-vaccinated prompted the UK to open up its booster programme to all adults in December. Infection numbers in the UK have since hit record-breaking highs, but there was some good news in the run-up to Christmas, as preliminary analyses of data from the UK suggested that infection with omicron may be 20 to 70 per cent less likely to result in a hospital visit. In people who haven鈥檛 yet caught covid-19 or been vaccinated, hospitalisation with omicron appears to be about 11 per cent less likely than with delta. However, this is unlikely to be enough to counteract the variant鈥檚 extreme transmissibility, and health systems worldwide are bracing for surges in hospital admissions.
How good are the聽vaccines?
The major success story of the pandemic was how fast vaccines were created. Thanks to years of聽research following the SARS and聽MERS outbreaks, researchers had a聽good idea of what aspects of聽SARS鈥慍oV-2 to target. The pandemic also coincided with the聽maturation of mRNA vaccine聽technology.
Traditional vaccines tend to contain weakened or inactivated virus that the body learns to recognise so it is ready to fight the聽virus when next encountered. The new Pfizer/BioNTech and Moderna vaccines introduce an聽mRNA sequence that tells the body to make a harmless part of the coronavirus鈥檚 spike protein, which triggers an immune response. These vaccines can be聽developed faster and more cheaply than traditional ones.
For vaccines of all types, money聽was pumped into trials so聽multiple studies could be run聽at聽the same time, and cash was聽given to manufacturers to increase production capacities.
We now have , and around 135 others in various stages of human trials. There have, of course, been hurdles. The Oxford/AstraZeneca jab was linked to rare blood clotting events, which led to some countries restricting its use.
Still, the vaccine programme has worked so well in high-income nations that covid鈥�19 was referred to as a disease of the unvaccinated by , director of the聽Oxford Vaccine Group at the University of Oxford. in November 2021 that the 鈥渙ngoing horror鈥� of people with covid-19 fighting for聽breath in intensive care units across Britain 鈥渋s now largely restricted to unvaccinated people鈥�.
While we wait to see omicron鈥檚 impact on hospitalisations and deaths, the good news is that if it, or any other variant, undermines the current vaccine programme, scientists are prepared. Pfizer CEO Albert Bourla has said his company could make an updated vaccine . Others are working on variant-specific and multi-variant vaccines.
What treatments do聽we have?
Vaccines aren鈥檛 our only tool against the virus. Steroids, including dexamethasone, the first drug proven to save lives from聽covid-19, have been used by聽medics from the beginning of the pandemic. Doctors reasoned that steroids would help reduce the impact of severe disease by preventing the immune system from going into overdrive and damaging organs. That turned out聽to be true 鈥� a discovery that was unprecedented in its speed, thanks to collaboration across seven clinical trials in 12 countries, coordinated by the WHO.
Three monoclonal antibodies, which are manufactured versions of antibodies that attach to the virus鈥檚 spike protein and make it harder for it to enter human cells, have been given emergency approval by the US Food and Drug Administration (FDA).
The drugs showed promise in聽reducing hospitalisation in infected people at high risk of more severe disease. They also decreased the spread of disease to聽other people in the household when taken prophylactically. However, there are suggestions from recent data that some monoclonal antibody drugs may not be effective against omicron.
Monoclonal antibodies are also expensive and hard to give outside a hospital setting. Oral antivirals that can be taken at home may be聽a better option. One, a drug made by Pfizer called Paxlovid, has shown very promising results. When taken for five days shortly after symptoms start, the drug cut hospital admissions by 89 per cent in adults at high risk of severe illness. The drug appears to work well against omicron, and was on 22 December. President Biden has already ordered enough pills to treat 10 million people.
Another antiviral, molnupiravir from Merck, appears to reduce the risk of hospitalisation or death in at-risk people with mild to moderate covid-19. The UK approved this drug in November 2021.
Other treatments are in human trials. For instance, the cheap oral antidepressant fluvoxamine progressing from a mild case to a severe one in聽those at serious risk.
What do we still not know?
Two years on, several key questions about the virus are yet聽to聽be resolved, including the virus鈥檚 origins. Although evidence suggests it began in a market in China and that it derives from a bat聽coronavirus, it isn鈥檛 clear how it聽spread to humans.
We don鈥檛 know the dose of SARS-CoV-2 needed to transmit infection. To work this out, several , in which volunteers are given聽varying viral doses in controlled conditions.
We also need to identify the level of antibodies needed to prevent infection, which is helpful for assessing how effective vaccines are and also for rapidly deciding whether they need to be聽changed. Researchers met in December 2021 to discuss data on antibodies for all the variants of concern, to reach an agreement on what antibody levels are required to protect people against severe disease. Results are forthcoming.
We don鈥檛 know what future variants might be called, once we聽have run out of Greek letters. The World Health Organization is considering using lesser-known constellations next, says Maria Van聽Kerkhove at the WHO.
And finally, we don鈥檛 know how dangerous future variants may be.
