When Noopur Raje’s husband fell critically ill with Covid-19 in mid-March, she did not suspect that she too was infected with the virus.
Raje, an oncologist at Massachusetts General Hospital in Boston, had been caring for her sick husband for a week before driving him to an emergency centre with a persistently high fever. But after she herself had a diagnostic PCR test – which looks for traces of the Sars-CoV-2 virus DNA in saliva – she was astounded to find that the result was positive.
“My husband ended up very sick,” she says. “He was in intensive care for a day, and in hospital for 10 days. But while I was also infected, I had no symptoms at all. I have no idea why we responded so differently.”
It took two months for Raje’s husband to recover. Repeated tests, done every five days, showed that Raje remained infected for the same length of time, all while remaining completely asymptomatic. In some ways it is unsurprising that the virus persisted in her body for so long, given that it appears her body did not even mount a detectable immune response against the infection.
When they both took an antibody test earlier this month, Raje’s husband showed a high level of antibodies to the virus, while Raje appeared to have no response at all, something she found hard to comprehend.
“It’s mind-blowing,” she says. “Some people are able to be colonised with the virus and not be symptomatic, while others end up with pretty severe illness. I think it’s something to do with differences in immune regulation, but we still haven’t figured out exactly how this is happening.”
Epidemiological studies are now revealing that the number of individuals who carry and can pass on the infection, yet remain completely asymptomatic, is larger than originally thought. Scientists believe these people have contributed to the spread of the virus in care homes, and they are central in the debate regarding face mask policies, as health officials attempt to avoid new waves of infections while societies reopen.
But the realisation that asymptomatic people can spread an infection is not completely surprising. For starters, there is the famous early 20th century case of “Typhoid Mary”, a cook who infected 53 people in various households in the US with typhoid fever despite displaying no symptoms herself. In fact, all bacterial, viral and parasitic infections – ranging from malaria to HIV – have a certain proportion of asymptomatic carriers. Research has even shown that at any one time, all of us are infected with between eight and 12 viruses, without showing any symptoms.
From the microbe’s perspective, this makes perfect evolutionary sense. “For any virus or bacteria, making people infectious but not ill is an excellent way to spread and persist in populations,” says Rein Houben, an infectious diseases researcher at the London School of Hygiene and Tropical medicine.
However, when Covid-19 was identified at the start of the year, many public health officials both in the UK and around the world failed to account for the threat posed by asymptomatic transmission. This is largely because they were working on models based on influenza, where some estimates suggest that only 5% of people infected are asymptomatic. As a result, the large scale diagnostic testing regimes required to pick up asymptomatic Covid-19 cases were not in place until too late.
“I warned on 24 January to consider asymptomatic cases as a transmission vehicle for Covid-19, but this was ignored at the time,” says Bill Keevil, professor of environmental healthcare at the University of Southampton. “Since then, many countries have reported asymptomatic cases, never showing obvious symptoms, but shedding virus.”
Finding the real number of asymptomatic patients
The first identified case of asymptomatic transmission of Covid-19 occurred in early January, when a traveller from Wuhan passed on the virus to five family members in different parts of the city of Anyang. After testing positive, she then remained asymptomatic for the entire 21-day follow-up period.
While scientists still don’t know whether asymptomatic people are as contagious as those who display symptoms, there are still many ways in which they can pass on Covid-19. “We know that you don’t need to be coughing to transmit a respiratory infection like Sars-CoV-2,” says Houben. “Talking, singing, even blowing instruments like a vuvuzela – in the past all of those have been shown to transmit respiratory viruses in some way.”
Since January, the race has been on to try and identify just how many asymptomatic cases are out there, with varying findings. One study in the Italian town of Vo reported that 43% of the town’s cases of Covid-19 were asymptomatic, while initial reports from the US Centers for Disease Control and Prevention investigation into the spread of Covid-19 on the Theodore Roosevelt aircraft carrier in March, suggest that as many as 58% of cases were asymptomatic. Some 48% of the 1,046 cases of Covid-19 on the Charles de Gaulle aircraft carrier proved to be asymptomatic while, of the 712 people who tested positive for Covid-19 on the Diamond Princess cruise ship, 46% had no symptoms.
“Almost all evidence seems to point to a proportion of asymptomatic infections of around 40%, with a wide range,” says Houben. “The proportion is also highly variable with age. Nearly all infected children seem to remain asymptomatic, whereas the reverse seems to hold for the elderly.”
Houben points out that, because most asymptomatic people have no idea they are infected, they are unlikely to be self-isolating, and studies have shown this has contributed to the rampant spread of the virus in facilities such as homeless shelters and care homes. He says this means there is a need for regular diagnostic testing of almost all people in such closed environments, including prisons and psychiatric facilities.
“When it comes to controlling Covid-19, this really shows that we cannot rely on self-isolation of symptomatic cases only,” he says. “Going forwards we need trace and test approaches to account for individuals who are not reporting any symptoms.”
Following Korea’s example
Since February, the country that has arguably had the greatest success in suppressing asymptomatic spread of Covid-19 is South Korea. Armed with a rigorous contact tracing and diagnostic testing regime, which involved dozens of drive-through testing centres across major cities enabling tests to be carried out at a rate of one every 10 minutes, they put specific policies in place to offset the threat of asymptomatic carriers from the moment the virus began to spread out of control in Daegu.
“Once identified, all asymptomatic people are asked to self quarantine in their house until they test negative, with health service officials checking on them twice daily, and monitoring their symptoms,” says Eunha Shim, an epidemiologist at Soongsil University in Seoul.
As Korea attempts to prevent a second wave of infections while reopening schools and allowing people to return to offices, preventing asymptomatic spread is one of their main priorities. This is being done by a mass public health campaign advocating the wearing of masks at all times outside the home. In Seoul, it is not possible to access the subway without a mask.
Many scientists are increasingly calling for this policy to be officially introduced in the UK, especially as more and more people resume commuting in the coming months. Keevil says: “There is a strong case to be made for the public wearing appropriate face covers in confined areas such as stations, trains, metro carriages and buses, where it is extremely difficult to maintain the two-metre gap, considered essential to allow respiratory droplets from infected people to fall down before making contact with other people.
“The argument is that face covers may not protect the wearer, but might significantly reduce transmission of virus particles to adjacent people in the closed environment. If there is any benefit to be gained, then everyone should wear a mask, which is why some countries are fining people who do not wear a mask and preventing them travelling.”
Some have argued that masks may pose a risk of harm to the wearer because of their potential to become an infectious surface, but Keevil says this can be avoided through proper cleaning.
“There would need to be policies such as, when arriving at work, place the mask immediately in a plastic bag and wash your hands,” he says. “And then, when returning home, carefully take off the mask and place it immediately in a washing machine for a 60C wash and wash your hands.”
It remains to be seen whether the UK government endorses this as an official recommendation, but a recent study across Barts NHS Trust hospitals in London has illustrated how regular testing and social distancing combined with use of facial protection – in this case PPE – can prevent asymptomatic spread of the virus. Researchers James Moon and Charlotte Manisty said they found that the rate of asymptomatic infection among hospital staff fell from 7% to 1% between the end of March and early May.
For Raje, understanding why asymptomatic patients like her respond the way they do to the virus, will have some critical implications for all of us over the coming months, for example in determining whether vaccines turn out to be effective.
“The big question I have after my experience, is whether a vaccine will really work in all people,” she says. “The vaccination approach is to create an immune response, which then protects you. But if asymptomatic people are not producing a normal antibody response to the virus, what does that mean? Because it’s these people who are the vectors and the carriers of this virus, I think we can’t get away from social distancing until we have some of these answers out there.”