SARS-CoV-2

• 1. Introduction

  ›

  SARS-CoV-2, the coronavirus that causes COVID-19, is almost impossibly light. Each particle measures between 60 and 140 nanometres across. Scientists have estimated that every copy in every human body on Earth, added together, would weigh somewhere between 0.1 and 10 kilograms. Yet this tiny passenger set off a pandemic that began in late 2019 and stayed an international emergency until 2023. How did something so small cross the world so fast? Why did it need several names before it settled on one? Where did it come from, and why is that question still argued over? And what exactly does it do when it meets a human cell? The answers lead through a stubborn name, an odd little piece of genetic code, a cruise ship, and a mink farm.

  3621

• 2. A Name Under Revision

  ›

  In January 2020, with the outbreak centred on the city of Wuhan, the World Health Organization recommended a provisional label: 2019 novel coronavirus, or 2019-nCoV. Until then, people had used loose phrases such as the coronavirus or the Wuhan coronavirus. The provisional label followed guidance the organization issued in 2015. That guidance warns against baking places, animal species or groups of people into the names of diseases and viruses. On the 11th of February 2020, the International Committee on Taxonomy of Viruses adopted the formal name severe acute respiratory syndrome coronavirus 2, shortened to SARS-CoV-2. The formal name created a new worry, because it sounded like the disease SARS. So in public health messages, the organization sometimes says the COVID-19 virus instead. Some research papers used the label HCoV-19. The phrase Wuhan virus carries real costs. WHO officials called it dangerous, and many journalists and academics called it xenophobic. The organization had declared the outbreak a public health emergency of international concern on the 30th of January 2020. It did not lift that status until the 5th of May 2023.

  6064676968

• 3. Anatomy of a Virion

  ›

  Four proteins, labelled S, E, M and N, make up the basic hardware of every SARS-CoV-2 particle. The N protein holds the genetic material. The S, E and M proteins together form the outer envelope. The S protein, called spike, has been imaged at the atomic level with cryogenic electron microscopy. It has two working parts. The S1 portion handles attachment to a host cell, and the S2 portion handles fusion with the cell's membrane. Inside the particle sits a single strand of RNA, about 30,000 bases long. That is long even for a coronavirus, and coronaviruses already carry the biggest genomes of any RNA family. Almost all of it codes for proteins. The letters are lopsided. Uracil makes up 32.2 percent, adenine 29.9 percent, guanine 19.6 percent and cytosine 18.3 percent. The virus appears to shed pairings of cytosine and guanine for two reasons. One is to dodge a cellular defence called the zinc finger antiviral protein. The other is that adenine and uracil join with two hydrogen bonds, where cytosine and guanine need three, so the strand unbinds with less energy. One more feature stands out: a short insertion that a cellular enzyme called furin can cut. Its closest relatives lack that insertion, and no other member of its subgenus has it. The sequence resembles one found in a feline coronavirus.

  5546424020

• 4. Inside the Cell

  ›

  By the 22nd of January 2020, two teams had independently shown how the virus gets in. One team in China worked from the full genome, and one in the United States used reverse genetics. Both found that the human protein ACE2 can act as its doorknob. Measurements show that SARS-CoV-2 grips human ACE2 more tightly than the original SARS virus does. The virus may also use a protein called basigin, and a host protein called neuropilin 1 may help it along. Before entry can happen, an enzyme named TMPRSS2 must prime the spike by cutting it open. That exposes a fusion peptide in the S2 portion. After fusion, the cell wraps the virion in an endosome, a bubble that walls it off. The virion escapes when the bubble turns more acidic or when a host enzyme called cathepsin cuts it free. Then the RNA spills out, and the cell is forced to build and release more copies. A team from the University of North Carolina found that the nasal cavity seems to be the main first site of infection, with the virus later drawn down into the lungs. Few drugs reliably stop this cycle. Masitinib cut viral levels in the lungs and nose of mice more than 200-fold, but it is not approved for COVID-19 in people. In December 2021, the United States granted emergency authorisation to the combination nirmatrelvir and ritonavir, and one study found it reduced the risk of hospitalisation and death by 88 percent. A separate open-science effort, COVID Moonshot, began in March 2020 and aims at an un-patented oral antiviral.

  5547262928

• 5. How It Travels

  ›

  Human-to-human spread of SARS-CoV-2 was confirmed on the 20th of January 2020. At first, experts assumed it moved mainly in droplets from coughs and sneezes, falling within about 1.8 metres. Laser light scattering experiments then suggested that plain speech also launches the virus, and that indoors with little airflow it can go far. Other studies point to aerosols, the finer mist of breathing. Between 200 and 800 infectious virions are thought to start a new infection. Aerosols matter to laboratories too, since working with emerging viruses can release them without anyone noticing. Surfaces are a possible route as well. Early research found the virus viable on plastic and stainless steel for up to three days. It lasted no more than one day on cardboard and four hours on copper. Soap destroys it by breaking down its fatty outer layer. Viral RNA has also turned up in stool and semen. Cats, ferrets, hamsters, minks, raccoon dogs, rabbits and several other animals can catch the virus, so some institutions advise infected people to limit contact with pets. A meta-analysis from November 2020 put the number of new infections per case between 2.39 and 3.44 in an unprotected, non-immune community. Behaviour shifts the figure. One study found about 3.5 in Sweden, Belgium and the Netherlands, against 5.9 in Spain and 6.4 in the United States.

  78505451

• 6. Hidden Infections

  ›

  On the 1st of February 2020, the World Health Organization said that "transmission from asymptomatic cases is likely not a major driver of transmission". The evidence soon pushed back. One meta-analysis found that 17 percent of infections are asymptomatic, and that those carriers were 42 percent less likely to pass the virus on. A model of the outbreak's start in China suggested that "pre-symptomatic shedding may be typical among documented infections". On a cruise liner that docked at Montevideo, 217 people were aboard. Of 128 who tested positive for viral RNA, only 24 showed symptoms. A study of ninety-four hospital patients first estimated that shedding began two to three days before symptoms. The authors later corrected that to four or five days. Peak viral load in the pharynx comes around four days after infection, and RNA shedding lasts between 3 and 46 days after symptoms start. The scale of hidden spread showed in Wuhan, where a model estimated 75,815 infections on the 25th of January 2020. Only 2,015 cases had been confirmed worldwide that day. Early on, mainland China logged 96,000 confirmed cases, and before the 24th of February 2020 over 95 percent of deaths were in Hubei province. Then came the question of whether anyone is safe afterwards. The first reported reinfection was a 33-year-old man in Hong Kong. He tested positive on the 26th of March 2020 and again on the 15th of August 2020, 142 days later, with genome sequencing showing a different clade. A 25-year-old man in Nevada tested positive on the 18th of April and the 5th of June 2020. His second illness was more severe than the first, and the reason is unknown.

  6169585645

• 7. Roots and Relatives

  ›

  SARS-CoV-2 is the seventh coronavirus known to infect people, after 229E, NL63, OC43, HKU1, MERS-CoV and the original SARS-CoV-1. These viruses range from common cold causes to Middle East respiratory syndrome, which has a fatality rate of roughly 34 percent. SARS-CoV-1 caused the 2002-2004 SARS outbreak, and the International Committee on Taxonomy of Viruses judged the two viruses too similar to count as separate species. Both sit in the subgenus Sarbecovirus. Where the new virus came from remains unclear and disputed. Many early patients worked at the Huanan Seafood Market in Wuhan. Some researchers suggest the market was the source, while others suggest visitors brought the virus in and the market amplified it. A March 2021 report convened by the WHO called a jump through an intermediate animal most likely, and direct spread from bats next most likely. A November 2021 analysis said the earliest-known case had been misidentified and that the cluster of early cases at the market favoured it as the source. Bats are the likeliest natural reservoir. In bats collected in Feuang, Laos, researchers found BANAL-52, which resembles SARS-CoV-2 by 96.8 percent. A virus called RaTG13, from bats in Mojiang, Yunnan, was reported in February 2020 at 96.1 percent. Neither is a direct ancestor. A July 2020 study pointed to pangolins, but seized pangolins in Guangdong carried viruses only 92 percent identical, with poor binding to human ACE2. By the 12th of January 2020, five genomes from Wuhan had been reported, and by the 30th of January there were 42. They differed from a common ancestor by at most seven mutations. That pointed to a first human infection in November or December 2019.

  3233111453

• 8. Variants and Waves

  ›

  In July 2020, scientists reported that a spike variant called G614 had replaced the earlier D614 as the dominant form. It was more infectious, and it was only the beginning. Nextstrain sorts the thousands of variants into five clades, and the GISAID database uses seven. The WHO has named five variants of concern. Alpha emerged in the United Kingdom in September 2020, with R0 of 3.8-5. Beta emerged in South Africa in May 2020, and Gamma in Brazil in November 2020, both carrying the mutations K417N, E484K and N501Y. Delta emerged in India in October 2020, with an R0 near 5.1. Omicron emerged around Botswana in November 2021. Its BA.1 version had an R0 near 9.5. Later BA.4 and BA.5 subvariants were estimated by some studies at around 20, which would exceed measles. Those later versions were far more contagious than the ancestral strain, with an R0 near 2.9. Denmark saw a different path with Cluster 5, which emerged among mink and led to a mink euthanasia campaign that left it virtually extinct. Meanwhile the sequencing effort kept growing: about 7 million genomes were public by early 2022, with 800,000 or so added each month. By September 2023, one database held more than 16 million. In April 2026, the Omicron variant BA.3.2 was reported to be widespread across Europe and the United States. It carries many spike changes, but existing vaccines protected against it.

  1815176622