Six months of coronavirus: the mysteries that scientists are still struggling to solve
From immunity to the role of genetics, prestigious science journal Nature discusses five pressing questions about COVID-19 that researchers are addressing
In late December 2019, reports of a mysterious pneumonia emerged in Wuhan, China, a city of 11 million people in the southeast province of Hubei. The cause, Chinese scientists quickly determined, was a new coronavirus distantly related to the SARS virus that had emerged in China in 2003, before spreading globally and killing nearly 800 people.
Six months and more than ten million confirmed cases later, the COVID-19 pandemic has become the worst public health crisis in a century. More than 500,000 people have died worldwide. It has also catalyzed a revolution in research as scientists, doctors, and other academics have worked at breakneck speed to understand COVID-19 and the virus that causes it: SARS-CoV-2.
They have learned how the virus enters and hijacks cells, how some people fight it, and how it eventually kills others. They have identified drugs that benefit the sickest patients, and many more potential treatments are being prepared. They have developed nearly 200 potential vaccines, the first of which could be proven effective by the end of the year.
But for every COVID-19 idea, more questions arise and others persist. This is how science works. To commemorate six months since the world first learned of the disease responsible for the pandemic, the scientific journal Nature discusses some of the key questions for which researchers still have no answers.
One of the most striking aspects of COVID-19 is the marked differences in the experiences of the disease. Some people never develop symptoms, while others, some apparently healthy, have severe or even fatal pneumonia. “The differences in clinical outcome are dramatic,” says Kári Stefánsson, geneticist and CEO of DeCODE Genetics in Reykjavik, whose team is looking for variants of human genes that can explain some of these differences.
That search has been hampered by the relatively small number of cases in Iceland. But last month, an international team that analyzed the genomes of approximately 4,000 people from Italy and Spain discovered the first strong genetic links to severe COVID-19. People who developed respiratory failure were more likely to carry one of two particular genetic variants than people without the disease.
A variant lies in the region of the genome that determines the ABO blood type. The other is close to several genes, including one that encodes a protein that interacts with the receptor that the virus uses to enter human cells, and two others that encode molecules linked to the immune response against pathogens. The researchers are part of the COVID-19 Host Genetics Initiative, a global consortium of groups that are pooling data to validate the findings and uncover more genetic links.
The variants identified so far seem to play a modest role in the outcome of the disease. A team led by Jean-Laurent Casanova, an immunologist at Rockefeller University in New York City, is looking for mutations that have a bigger role.
To find them, his team is combining the complete genomes of people under the age of 50 who are otherwise healthy and who have experienced severe cases of COVID-19, he says, like “the guy who runs a marathon in October and now five months. later, he is in the ICU, intubated and ventilated. ” Extreme susceptibility to other infections, such as tuberculosis and the Epstein-Barr virus, a generally harmless pathogen that sometimes causes serious illness, has been attributed to mutations in individual genes. Casanova suspects that the same will be true for some cases of COVID-19.
Immunologists are working feverishly to determine what immunity to SARS-CoV-2 might look like and how long it could last. Much of the effort has focused on “neutralizing antibodies,” which bind to viral proteins and directly prevent infection. Studies have found that levels of neutralizing antibodies to SARS-CoV-2 remain high for a few weeks after infection, but then begin to decrease.
However, these antibodies can remain at high levels for longer in people who have particularly severe infections. “The more viruses, the more antibodies and the longer they last,” says immunologist George Kassiotis of the Francis Crick Institute in London. Similar patterns have been observed with other viral infections, including SARS (severe acute respiratory syndrome). Most people with SARS lost their neutralizing antibodies after the first few years. But those who actually had it severely still had antibodies when they were retested 12 years later.
Researchers do not yet know what level of neutralizing antibody is needed to combat SARS-CoV-2 reinfection, or at least to reduce COVID-19 symptoms in a second disease. And other antibodies may be important for immunity. Virologist Andrés Finzi, from the University of Montreal in Canada, for example, plans to study the role of antibodies that bind to infected cells and mark them for execution by immune cells, a process called antibody-dependent cellular cytotoxicity, in response to SARS-CoV -2.
Ultimately, a full picture of immunity to SARS-CoV-2 is likely to extend beyond the antibodies. Other immune cells called T cells are important for long-term immunity, and studies suggest that SARS-CoV-2 is also calling them to arms. “People equate antibodies with immunity, but the immune system is such a wonderful machine,” explains Finzi. “It is much more complex than just the antibodies.”
Because there is as yet no clear, measurable marker in the body that correlates with long-term immunity, researchers must reconstruct the mosaic of immune responses and compare it with responses to infections with other viruses to estimate how long it could last. protection. Studies of other coronaviruses suggest that “sterilizing immunity,” which prevents infection, could last only a few months. But protective immunity, which can prevent or alleviate symptoms, could last longer than that, says Shane Crotty, a virologist at the La Jolla Institute of Immunology in California.
All viruses mutate as they infect people, and SARS-CoV-2 is no exception. Molecular epidemiologists have used these mutations to track the global spread of the virus. But scientists are also looking for changes that affect their properties, for example, making some lineages more or less virulent or transmissible. “It is a new virus; if it got more severe, that’s something I wish I knew, “says David Robertson, a virologist at the University of Glasgow, UK, whose team is cataloging SARS-CoV-2 mutations. Such mutations also have the potential to decrease the effectiveness of vaccines, by altering the ability of antibodies and T cells to recognize the pathogen.
But most mutations will have no impact, and choosing the worrisome ones is a challenge. Versions of the coronavirus identified at the start of outbreaks in hot spots such as Lombardy in Italy or Madrid, for example, might appear more deadly than those found in later stages or elsewhere. But such associations are likely spurious, says William Hanage, an epidemiologist at Harvard University’s TH Chan School of Public Health in Boston, Massachusetts: Health officials are more likely to identify serious cases in the early, uncontrolled stages of an outbreak. The wide spread of certain mutations could also be due to “founding effects,” in which lineages that emerge early in transmission centers such as Wuhan or northern Italy have a mutation that is transmitted when outbreaks spread elsewhere.
Researchers are debating whether the widespread prevalence of a virus spike protein mutation is the product of a founder effect, or an example of a consequent change in the biology of the virus. The mutation appears to have first emerged around February in Europe, where most circulating viruses now carry it, and is now found in all regions of the world. A number of preprint studies have suggested that this mutation makes the SARS-CoV-2 virus more infectious to cultured cells, but how this property translates into human infections is unclear.