A clinical support technician extracts viruses from swab samples so that the genetic structure of covid-19 can be analysed and identified. Photo / Getty Images
New York Times journalists summarise some of the most critical things that scientists and public health officials have yet to understand.
In the time since the world's scientists and public health officials first became widely aware of the new coronavirus in January, they've had six months to learn about it. They've reached many conclusions about the virus and the illness it causes, from the importance of wearing masks to contain it to the unusual range of symptoms it provokes.
But there are major gaps in scientific knowledge about the virus. In the half-year that journalists of the health and science desk of The New York Times have been reporting on SARS-CoV-2, we have recounted some of the enduring uncertainties they have identified. How scientists resolve some of these mysteries will shape our future with the coronavirus.
One of the epidemic's great unknowns is how many Americans have been infected so far.
Only about 1.9 million Americans had tested positive as of May 28, according to the Centers for Disease Control and Prevention — or perhaps only about 1.7 million according to the Johns Hopkins Center for Health Security, which produces a frequently cited map of world cases.
Statisticians believe the actual number of cases is higher, but it is not clear by how much.
They have more confidence in the accuracy of data produced by states that do the most testing. On that score, New York state is a leader; it has tested about 9.6 per cent of its population, which is almost double the national average. (Rhode Island tested 13 per cent of its people, beating New York, but its population is small.)
New York has also done tens of thousands of antibody tests for surveillance purposes. On May 22, Governor Andrew Cuomo announced that, according to these tests, about a fifth of all New York City residents have had the virus, as had about 27 per cent of thousands of black and Hispanic New Yorkers who were tested at their local churches.
If that same pattern were assumed to hold in other hard-hit big cities like Chicago, New Orleans, Detroit and Miami, it is likely that somewhere between 3 and 4 million urban Americans were infected.
Even if that figure was doubled or tripled — which is probably generous — to account for Americans infected all around the country before the lockdowns, that would still be only 9 million to 12 million people.
That is in line with the low end of estimates made in mid-April, before antibody testing began; different modellers predicted then that between 3 per cent and 10 per cent of the country was infected.
In any case, since this is a country of 330 million, a mere 10 million or even 20 million infected would be a drop in the bucket. As the country comes out of lockdown, the vast majority of Americans remain vulnerable to the virus.
Nor will the country be able to spot all of those who get it. The CDC's "best estimate," according to the pandemic scenarios it issued May 22, is that about 35 per cent of those infected have no symptoms.
Currently, about 21,000 Americans are getting infected each day. If a third of them show no symptoms, almost 210,000 "silent spreaders" are created each month.
It seems impossible to imagine that any contact-tracing program, no matter how large, will be able to keep up with that.
- DONALD G. MCNEIL JR.
There are many crucial unresolved questions about children and Covid-19. Finding the answers is not only important for them and their families, but for society at large, as communities plan to reopen schools, day care centers, playgrounds and other places children frequent.
One puzzle is what role children play in spreading the virus. They seem less likely to become seriously ill than adults, making up about 2 per cent of confirmed American coronavirus cases. There are different theories about whether that is because children are less likely to become infected to begin with, or whether the virus infects them just as easily but mostly causes few or no symptoms.
Either way, a growing body of evidence suggests that infected children can transmit the virus, possibly as easily as adults. And one recent study suggests that when children attend school, they come in contact with three times as many people as average adults do, providing more opportunities for children to become infected and infect others.
Although far fewer children than adults have experienced severe symptoms, some children have become devastatingly ill and there have been at least 20 deaths of children from Covid-19 in the United States and elsewhere. Reports from hospitals suggest that the children most vulnerable to the respiratory failure adults develop are those who already have a serious medical condition. Some studies also suggest that infants and preschoolers may be more vulnerable than older children.
But a small number of other children, including teenagers, who did not have any symptoms when they were first infected, have developed a newly identified inflammatory syndrome that can cause serious heart problems. The syndrome, which seems to occur weeks after infection and to result from a revved-up immune response to the virus, has been reported Europe and throughout the United States and has caused several deaths. Doctors are urgently trying to understand what causes the syndrome, why it afflicts some children and not others, and how to best treat or prevent it.
- PAM BELLUCK
The notion of a single patient zero is both theatrical and real: In any new epidemic, some unlucky soul seeds the first infection, several links of which are fated to seed chains of their own and spark a viral Big Bang.
By analysing the genetic material of people who test positive, scientists can trace the lineage of each virus back to a common ancestor and often to an individual carrier. The first confirmed coronavirus case in the United States was a man who landed at Seattle-Tacoma Airport on January 15 from China. Other introductions came in February, and scientists are now closing in on who, exactly, set off the outbreak in Washington state.
New York confirmed its first case on March 1. Scientists have found genetic signatures on the viruses studied so far linking them to Europe, probably brought in by some of the millions of the arrivals in New York in February; it is likely that there were multiple introductions that spread widely: patients zero, plural.
The first infected arrivals in a community are not necessarily the ones who light the fuse. In a report published last week, scientists argued that infected people were among both Americans and Europeans in January, but that most of those viruses fizzled out. And French doctors recently reported that a respiratory sample from a man hospitalised near Paris, in late December, tested positive. That virus, too, most likely died out. France's outbreak did not start until weeks later.
The evidence suggests that the world's patient zero, in China, began infecting others late last fall. An analysis of the first 41 confirmed cases, all in people who had visited the same seafood market in Wuhan, indicates that the first hospital admission was on Dec. 16. The patient first noticed symptoms on Dec. 1, so the infection dates back earlier. Several scientists have estimated that the first outbreak began in late or mid-November, and have inferred a probable common viral ancestor.
The level of detective work required to find the actual patient zero might be steeper than it appears. At least one genetic scientist has argued that the virus could have first infected humans — likely from a pangolin — well before last fall in a form that did not cause sickness. It then evolved its pathogenic features over time while circulating. If that's the case, the question "Who came first?" may go without a conclusive answer for some time, perhaps for good.
- BENEDICT CAREY
Are people infected with the coronavirus protected from further infection? And, if yes, for how long?
The answers to these questions have broad implications for reopening the economy and allowing the public to live with less fear of infection in the short term — and for the effectiveness of vaccines in the long term.
Scientists have made steady, if incremental, progress in getting to the answers. When the body encounters any virus, it typically makes antibodies, some of which are powerful enough to neutralise the pathogen and prevent reinfection. It also produces large numbers of immune cells that can kill the virus.
Most tests that look for antibodies to the coronavirus have been flawed. But at least one team with a reliable test reported that most people, including those who were only mildly ill, make powerful antibodies. Data on immune cells has been slower to emerge, but a few studies suggest a robust response from immune cells as well.
What remains unknown is how long this immunity will last. There have been some reports of reinfection, but scientists have said that they are a result either of faulty testing, or of viral remnants that circulate long after the active infection has ended.
They are hopeful that based on other coronaviruses that cause the common cold, SARS or MERS, immunity to the new coronavirus might last at least a year, but it remains a mystery for now.
- APOORVA MANDAVILLI
Covid-19 is a mercurial disease. While some people experience only mild, fleeting symptoms, others are knocked over with a severe flu like illness that can last several weeks. A minority of patients develop life-threatening complications. Death can ensue.
Why do some people sail through the illness, and others develop the severe inflammation and lung damage that are hallmarks of the disease? It is one of the great mysteries of Covid-19.
Experts say the patient's immune response to the viral infection determines the severity of the illness. If the immune system goes into overdrive, it can trigger a cascade of harmful effects, injuring the lungs and other organs.
Immune function declines with age, and elderly people with Covid-19 are among the most vulnerable to poor outcomes, as are those with chronic health conditions like high blood pressure, diabetes and cardiovascular disease. Obesity, which affects 4 in 10 American adults, also appears to exacerbate the illness.
Other susceptibilities are harder to explain. Men are also at greater risk for critical illness and death, a sex disparity that may be explained by women's more robust immune systems, scientists say.
Generally speaking, patients get sicker faster if they are exposed to a large dose of the virus when they are first infected, said Dr. William Schaffner, an infectious disease specialist at Vanderbilt University.
Much scientific inquiry has focused on the role of a receptor called angiotensin-converting enzyme 2, or ACE2, which is the entry way for coronaviruses into the cells. The receptor is found on the outer surfaces of cells in the lungs, blood vessels, intestines and other organs, as well as in the back of the throat and high up in the nasal passage.
When the pandemic started, there was a concern that people taking blood pressure medications like ACE inhibitors could be at greater risk from the coronavirus, but so far studies have not found that to be the case, and doctors are urging patients to continue their medications.
Though the SARS-CoV-2 virus attaches to the receptor in order to penetrate cells, ACE2 also helps regulate blood pressure and inflammation. Some scientists have suggested that children may be less susceptible to infection with COVID-19 because they have fewer of these receptors. ACE2 is also regulated differently in men and women, according to scientists who study sex differences in medicine, and men tend to develop hypertension, or high blood pressure, at younger ages than women. But much is still unknown.
"ACE2 can play two very critical roles, getting the virus into the cell, but also modulating some of the damage that takes place in the blood vessels and the lungs," said Dr. Ankit B. Patel, a nephrologist at Brigham and Women's Hospital in Boston. "So it's a double-edged sword in a sense, and that's made the whole story all the more complicated."
- RONI CARYN RABIN
Written by: The New York Times
Photographs by: Jens Mortensen
© 2020 THE NEW YORK TIMES
Dominique Pelicot had already confessed to the crimes.