COVID-19

• 1. Introduction

  ›

  COVID-19 entered the public record on the 31st of December 2019, when the Wuhan Municipal Health Commission announced a pneumonia outbreak of unknown cause. The announcement confirmed 27 cases, and that was enough to trigger an investigation. The cause turned out to be a contagious disease produced by a coronavirus called SARS-CoV-2. Within weeks it was moving across borders. Many questions followed. Who noticed it first, and what happened to the people who sounded the alarm? Where does a virus like this come from? Why does it devastate some bodies while barely troubling others? And what actually worked against it once the world started to push back?

  25463

• 2. Warnings in Wuhan

  ›

  On the 24th of December 2019, Wuhan Central Hospital sent a bronchoalveolar lavage sample from an unresolved case to a sequencing company called Vision Medicals. On the 27th and the 28th of December, the company reported back to the hospital and to the Chinese CDC. Its result showed a new coronavirus.

  Other clues were arriving at the same time. On the 26th of December, the doctor Zhang Jixian at Hubei Provincial Hospital treated a cluster of pneumonia cases with no known cause. Zhang Jixian passed the news to the Wuhan Jianghan CDC on the 27th of December.

  The 30th of December brought confusion. A test report from the company CapitalBio Medlab, addressed to Wuhan Central Hospital, wrongly stated a positive result for SARS. The error alarmed a group of doctors at the hospital, and they warned colleagues and hospital authorities. That same evening, the Wuhan Municipal Health Commission sent medical institutions a notice about treating pneumonia of unknown cause.

  Raising the alarm carried a price. Eight doctors from this group, including Li Wenliang, were later admonished by the police for spreading false rumours. Li Wenliang was punished on the 3rd of January. Another doctor, Ai Fen, was reprimanded by her superiors for sounding the warning.

  The numbers were already climbing. Hubei had 60 cases by the 20th of December and at least 266 by the 31st. In the early outbreak, cases doubled roughly every seven and a half days. That clock was ticking while the Chinese New Year migration approached.

  11181921

• 3. Around the World

  ›

  In early and mid-January 2020, the virus left Hubei. The Chinese New Year migration helped it along, as did Wuhan's role as a transport hub and a major rail interchange.

  On the 20th of January, China reported nearly 140 new cases in a single day, including two in Beijing and one in Shenzhen. Official data later showed that 6,174 people had already developed symptoms by that date. The same day, the WHO and Chinese authorities confirmed that the virus passed from person to person. Four days later, a report in The Lancet pointed to human transmission and called testing essential because of the virus's "pandemic potential". On the 30th of January, the WHO declared a Public Health Emergency of International Concern. By then the outbreak had grown by a factor of 100 to 200.

  Italy confirmed its first cases on the 31st of January 2020, in two tourists from China. On the 19th of March, Italy overtook China in the number of deaths. By the 26th of March, the United States had passed both countries for the most confirmed cases. Genome research indicated that most cases in New York came from European travellers, not directly from China or elsewhere in Asia.

  Later evidence pushed the timeline back. Retesting of old samples found a person in France carrying the virus on the 27th of December 2019. It also found a person in the United States who died of the disease on the 6th of February 2020. Wastewater samples collected in Milan and Turin on the 18th of December 2019 also appeared to contain the virus. The source warns that sewage studies of this kind are not yet optimised, and many lack peer review or risk false positives.

  Reuters later estimated that worldwide deaths had passed five million. The emergency designation for COVID-19 finally ended on the 5th of May 2023, by which time everyday life in most countries had returned to how it was before the pandemic.

  2021222717

• 4. Naming the Virus

  ›

  During the first outbreak in Wuhan, people spoke of "coronavirus" and "Wuhan coronavirus", and the illness was sometimes called "Wuhan pneumonia". Place names have a long history in medicine. The Spanish flu, Middle East respiratory syndrome and Zika virus all carry one.

  In January 2020, the WHO recommended the interim names 2019-nCoV and 2019-nCoV acute respiratory disease. That followed 2015 guidance against naming diseases after places or groups of people, to prevent social stigma. The official names arrived on the 11th of February 2020. COVID-19 is shorthand for "coronavirus disease 2019", and SARS-CoV-2 names the virus itself.

  The virus did not stay the same. Once enough mutations pile up, a subtype counts as a variant, and the most worrying ones received Greek letters such as Alpha, Beta and Delta. The Alpha variant, labelled B.1.1.7, first appeared around autumn 2020. By the end of that year, Gamma (P.1) had appeared in Brazil and Beta (B.1.351) in South Africa. Alpha came to dominate the Northern Hemisphere, Gamma South America and Beta Africa.

  The Delta variant, B.1.617.2, was first seen in India around the same time and came to dominate globally in 2021. Omicron emerged at the end of 2021 with a large number of mutations compared with earlier variants. Within about seven weeks, it rose from 1% of global cases to 95% by January 2022. After the WHO named Omicron in November 2021, it stopped assigning Greek letters to new variants of concern. Scientists now rely on the Pango system, which labels JN.1 for a variant active in 2024 and XFG for one in 2025.

  Variants differ in how well they spread, how severe they are, and how well they evade vaccine protection. Omicron seems to cause milder illness than earlier strains but slipped past the original vaccines more easily.

  2325383963

• 5. Hunting the Origin

  ›

  A joint study by China and the WHO in early 2021 concluded that the virus descended from a coronavirus carried by wild bats. It most likely reached people through an intermediary wildlife host. Investigations into the exact origin of the pandemic are still ongoing.

  In July 2022, articles in Science argued for two spillover events in November 2019, probably linked to the live wildlife trade at the Huanan wet market in Wuhan. Doubts about those conclusions mostly concern the precise site of the spillover. Earlier phylogenetic work put the virus's emergence in October or November 2019, and one algorithm suggested it may have circulated in Guangdong before Wuhan.

  The genetic evidence points toward bats. Every structural feature of the virus particle occurs in related coronaviruses in nature, particularly in Rhinolophus sinicus, the Chinese horseshoe bat. At the whole genome level, the virus is 96% identical to a bat coronavirus sample called BatCov RaTG13. It was first isolated from three people with pneumonia tied to the Wuhan cluster.

  The Intergovernmental Panel on Climate Change said climate change, destruction of natural ecosystems and wildlife trade all raised the odds of such a spillover. One study supported by the European Union found that climate change increased the likelihood of the pandemic by shifting the distribution of bat species.

  A minority of scientists, and some members of the US intelligence community, believe the virus may have leaked unintentionally from a laboratory such as the Wuhan Institute of Virology. US intelligence has mixed views, but broadly agrees that the virus was not built as a biological weapon and is unlikely to have been genetically engineered. There is no evidence that SARS-CoV-2 existed in any laboratory before the pandemic.

  The market itself remains a puzzle. In May 2020, George Gao, the director of the Chinese CDC, said animal samples from the Huanan market had tested negative. He concluded that the market was the site of an early superspreading event, not the place the outbreak began. A study of the first 41 confirmed cases, published in The Lancet in January 2020, gave the earliest symptom onset as the 1st of December 2019. Official WHO publications gave the 8th of December.

  The traffic can also run the other way. Cats and ferrets can catch the virus from infected humans, and tigers and lions in zoos have been infected through contact with people. Minks are in the same family as ferrets, and they can spread the virus back to humans. Denmark, a major producer of mink pelts, ordered the slaughter of all its minks over fears of viral mutations after an outbreak known as Cluster 5.

  1215163637

• 6. Inside the Body

  ›

  The virus gets into cells through a receptor for the enzyme ACE2, which is most abundant on type II alveolar cells in the lungs. It latches on with a surface protein called the spike. The spike has two subunits. S1 determines which hosts and cells the virus can infect, while S2 fuses the virus to the cell membrane. Many effective vaccines target spike protein expression.

  Outside the body, the virus is fragile. Household soap bursts its protective bubble, and alcohols, heat, povidone-iodine and ultraviolet-C light also disinfect surfaces.

  Autopsies of people who died of COVID-19 found diffuse alveolar damage in the lungs. On CT scans, infected lungs showed white patches of fluid called ground-glass opacity. These patches tended to match a clear jelly liquid that pathologists found in the lungs at autopsy. One hypothesis in medical research is that hyaluronic acid could drive the jelly, in what might be a hyaluronic storm alongside the cytokine storm.

  The loss of smell comes from infection of the support cells in the olfactory epithelium, which then damages the olfactory neurons. In a study of people who had been infected, most with mild cases, brain regions connected to smell had lost an extra 0.2% to 2% of tissue. On average, that matched at least one extra year of normal ageing. These people also scored lower on several cognitive tests. Later research found that every variant studied, including Omicron, killed brain cells, though the exact cells varied by variant. Whether the damage lasts is unknown.

  In Wuhan, acute cardiac injury was found in 12% of infected people admitted to hospital. People moved to intensive care showed a high incidence of thrombosis and venous thromboembolism. The kidneys suffered too. Early reports from China and New York found that up to 30% of hospitalised patients had some kidney injury, including people with no earlier kidney problems.

  Much of the severe damage comes from the immune system overreacting. Severe cases show signs of systemic hyperinflammation and a cytokine storm, which is linked to worse prognosis and higher fatality. Interferon alpha plays a Janus-faced role. It helps remove infected cells, but it also raises ACE2 expression, which makes it easier for the virus to enter cells.

  Some people may start with a head start. Among healthy adults never exposed to SARS-CoV-2, about 35% have CD4+ T cells that recognise the spike protein. Researchers suggest this reflects cross-reactivity from earlier common colds caused by other coronaviruses.

  4841424635

• 7. Who Falls Ill

  ›

  Symptoms can start one to fourteen days after exposure to the virus. They often include fever, fatigue, cough, breathing difficulties, and loss of smell and taste. At least a third of infected people never develop noticeable symptoms. Among those who do, 81% have mild to moderate illness, 14% have severe symptoms and 5% become critically ill.

  Age is the strongest dividing line. A December 2020 meta-analysis estimated the infection fatality rate at 0.002% at age 10 and 0.01% at age 25. It rose to 0.4% at age 55, 1.4% at age 65, 4.6% at age 75 and 15% at age 85. The same study found first-wave rates of about 0.5% to 1% in France, the Netherlands, New Zealand and Portugal. It found 1% to 2% in Australia, England, Lithuania and Spain, and above 2% in Italy. Most of those differences came from the age makeup of each population. For the same reason, the case fatality rate was lower in India than in the US.

  Pre-existing illness matters too. The Italian Istituto Superiore di Sanità examined medical charts for 8.8% of deaths. Of those, 96.1% had at least one comorbidity, and the average person had 3.4 diseases. Hypertension appeared in 66% of deaths, type 2 diabetes in 29.8% and ischaemic heart disease in 27.6%.

  Men fared worse in many places. The Chinese Center for Disease Control and Prevention reported a death rate of 2.8% for men and 1.7% for women. In Europe as of February 2020-57% of infected people were men, and 72% of those who died were men. Reviews pointed to smoking, earlier onset of hypertension and immune differences. Later reviews in June 2020 found no significant gender difference in susceptibility or case fatality.

  In the US, a greater proportion of deaths occurred among African Americans and other minority groups. Crowded housing and essential jobs such as grocery work, public transit and custodial work made distancing harder. A US health policy non-profit reported that 34% of non-elderly American Indian and Alaska Native adults were at risk of serious illness, compared with 21% of non-elderly white adults. In the UK, a greater share of deaths occurred among people of Black, Asian and other ethnic minority backgrounds.

  Genes play a role as well. Professor Svante Pääbo and colleagues at the Max Planck Institute for Evolutionary Anthropology and the Karolinska Institutet linked a chromosomal region on chromosome 3 to more severe disease. That region carries Neanderthal heritage, from interbreeding estimated at between 50,000 and 60,000 years ago in Southern Europe. A variant of the DOCK2 gene is a common risk factor in Asian populations but far less common in Europe.

  Children were generally spared the worst. A European multinational study of hospitalised children from June 2020 found that about 8% needed intensive care. Four of the 582 children in the study died, a rate of 0.7%, although milder cases were not counted. The CDC says pregnant women face an increased risk of serious illness, including miscarriage, premature delivery and intrauterine growth restriction.

  For some people, the illness never fully ends. Around 10% to 30% of non-hospitalised people develop long COVID, and over 50% of hospitalised people do. Among hospital patients, up to 98% of CT scans showed lung abnormalities after 28 days. After four weeks, about a third of those investigated showed pulmonary fibrosis or reduced lung function. On the 30th of October 2020, WHO chief Tedros Adhanom warned about these long-term effects. He called a strategy of herd immunity through infection, rather than vaccination, "morally unconscionable and unfeasible".

  149515240

• 8. Holding the Line

  ›

  Before any vaccine existed, the central goal was flattening the curve. Slowing the infection rate meant health services were less likely to be overwhelmed. It also bought time for better care and for effective treatments to arrive.

  Ventilation became a major topic once it was clear that tiny airborne particles can drift over longer distances indoors. The CDC states that avoiding crowded indoor spaces reduces risk. Risk rises in places where people exercise, shout or sing, and prolonged exposure of more than 15 minutes raises it further. Letting in outdoor air and cutting recirculation can reduce transmission.

  Surfaces drew enormous attention. The virus can stay infective for several days on glass, some plastics, stainless steel and skin, and about a week under ideal conditions. On cotton fabric and copper, it usually dies after a few hours. Surprisingly, N95 respirators and surgical masks were among the longest-lasting surfaces tested. Even so, evidence indicates that contact with surfaces is not the main driver of spread. Deep cleaning has been criticised as hygiene theatre, a false sense of security against something spread mainly through the air. The CDC says that in most situations, cleaning with soap or detergent is enough.

  Hand hygiene came with exact rules. The WHO recommends washing with soap and water for at least 20 seconds. Without soap, the CDC recommends an alcohol-based sanitiser with at least 60% alcohol. The WHO also published two formulations for local production, in which ethanol or isopropanol provides the antimicrobial effect.

  Distancing measures included quarantines, travel restrictions, and closing schools, workplaces, stadiums and theatres. In 2020, prisons suffered outbreaks because crowding made distancing impossible. A 2021 Cochrane rapid review gave low-certainty evidence that travel restrictions may help contain spread. It also concluded that a minimum 10-day quarantine may be beneficial, especially when combined with border screening.

  Research moved at remarkable speed. By the end of 2020, hundreds of clinical trials had been under way on every continent except Antarctica, and more than 200 possible treatments had been tested in humans that year. In March 2020, the WHO started its Solidarity trial, testing remdesivir, chloroquine, hydroxychloroquine, lopinavir/ritonavir and interferon-beta. Hydroxychloroquine and chloroquine proved ineffective at best.

  A cheaper drug produced the first clear win. In June, initial results from the UK's RECOVERY Trial showed that dexamethasone reduced mortality by a third for critically ill people on ventilators. For people receiving supplemental oxygen, it cut mortality by a fifth. Because the steroid was well tested and widely available, the WHO welcomed the result. In September 2020, the WHO recommended systemic corticosteroids for severe and critical COVID-19 but not for non-severe cases.

  The first vaccine approval came on the 2nd of December 2020 from the UK medicines regulator MHRA. The US FDA and several other countries then evaluated it for emergency use authorisation.

  6683857270