A tip of the iceberg or not?
I've been searching for studies that might give us a clue of how large the group is that gets the infection but are asymptomatic or who are symptomatic but remain undocumented. The best way would be to test a random sample of the population, but since we don’t have that yet i thought I might highlight some other methods that might give us a rough idea.
1) One method is complex modelling. There’s, for example, this study by Li et al. that was posted here already. The authors looked at the spread of the virus and mobility data and based on those two their model estimates that “86% of all infections were undocumented.” They think that undocumented infections are the infection source for the majority of documented cases.
2) Another method is looking at the secondary attack rate where you zoom in on an affected person, trace all their contacts and then test how many of these were infected. Bi et al. did an analysis of 391 cases and 1,286 of their close contacts. They estimated the household secondary attack rate to be 15%. The interesting thing is that they found that children were as likely to be infected as adults. So that might suggest that the skewed distribution of documented cases in China and Italy are missing a lot of youngsters who had the virus but didn’t get very ill. In the cases that were picked up by their surveillance, 20% were asymptomatic at the time of first clinical assessment and nearly 30% did not have fever. The authors note that “this is consistent with a reasonably high rate of asymptomatic carriage, but less than suggested by some modeling studies.”
The WHO report also commented on this, suggesting that the proportion of truly asymptomatic infections is probably not that high. It writes: “In Wuhan more than 1800 teams of epidemiologists, with a minimum of 5 people/team, are tracing tens of thousands of contacts a day. Between 1% and 5% of contacts were subsequently laboratory confirmed cases of COVID-19. […]The proportion of truly asymptomatic infections is unclear but appears to be relatively rare and does not appear to be a major driver of transmission.”
Bruce Aylward, who leads the WHO mission in China said in March 3 in an interview with VOX: “In Guangdong province, for example, there were 320,000 tests done in people coming to fever clinics, outpatient clinics. And at the peak of the outbreak, 0.47 percent of those tests were positive. People keep saying [the cases are the] tip of the iceberg. But we couldn’t find that. We found there’s a lot of people who are cases, a lot of close contacts — but not a lot of asymptomatic circulation of this virus in the bigger population.”
3) A third method is the data from travellers who returned from affected regions and who got tested, symptomatic or not. Nishiura et al. for example, used information on Japanese nationals that were evacuated from Wuhan, China on chartered flights (n = 566). 4 asymptomatic and 9 symptomatic passengers tested positive forCOVID-19. The asymptomatic ratio was estimated at 30.8%.
4) Finally, there was an outbreak on the Diamond Princess Cruise ship which forms a natural experiment to estimate the spread and fatality of SARS-CoV-2. This is why Ioannidis, the famous scientists, puts so much emphasis on this data even though it’s quite limited in size. 619 of 3700 passengers and crew (17%) tested positive. About half of those patients were asymptomatic, but that might be because they were tested early – they might develop symptoms later on since there’s an incubation period of a couple of days and COVID-19 often develops slowly, many of the asymptomatic. Mizumoto et al. tried to take this into account and estimated the asymptomatic proportion to be 17.9%. This is most likely an underestimation given that the population on board of the cruise ship was substantially older than the general population (most were in their 60s and 70s which are thought to be at higher risk of developing COVID-19) and not everyone on board got tested.
I don't really know what to make of all of this. I suspect there are reasons to think that asymptomatic or undocumented COVID-19 cases with mild symptoms contribute substantially to the spread of the virus, making it very contagious and hard to control. There was this letter recently in the New England that noted:
"The viral load that was detected in the asymptomatic patient was similar to that in the symptomatic patients, which suggests the transmission potential of asymptomatic or minimally symptomatic patients. These findings are in concordance with reports that transmission may occur early in the course of infection5 and suggest that case detection and isolation may require strategies different from those required for the control of SARS-CoV."
If I understand correctly, the first SARS-coronavirus was also quite contagious but people mainly started to infect others when they were having notable symptoms. That makes it easier to contain it cause you know who to isolate. It could be that the main difference with this second SARS-coronavirus is that people often spread it even when they are not notably symptomatic. That's why we all have to isolate.
On the other hand, the estimates of the asymptomatic proportion aren't that big and based on what Aylward saw in China it doesn't seem like there's a tip of the iceberg situation. That might explain why China and other Asian countries were quite successful in reducing the spread of the virus.
Anyone knows of any other methods or studies that estimated the asymptomatic or undocumented proportion of people infected with SARS-CoV-2?
