26th April 2020, Dr Chee L Khoo
Although the Covid-19 pandemic seems to be under some control, we are still in danger of a second wave if we relaxed the social distancing rules too much too quickly. One of the big unknowns is what is the proportion of people with SARS-COV-2 who are asymptomatic? These are the people we are not testing. If we only test symptomatic people which is what we do by and large, we may be missing a proportion of cases. How big that proportion is remains uncertain.
Part of the problem we have is the data collected so far on how many people are infected and how the epidemic is evolving are utterly unreliable. What is collected across countries are totally heterogenous and it is farcical to try to compare data from different countries. There is tremendous selection bias because of the limited testing capacity. Some countries have the capacity to test “everyone (including asymptomatic people) while others (including Australia) only test those with a symptoms suggestive of having Covid-19. You can imagine how that will affect the proportion of people with Covid-19 are deemed to be asymptomatic. Let’s look at what data we have, however bias or unreliable they may be.
Carl Heneghan, Jon Brassey and Tom Jefferson from the Centre for Evidence-Based Medicine, University of Oxford analysed 21 studies that looked at the proportion of people with Covid-19 who are asymptomatic (1). They found that between 5-80% people tested were asymptomatic. Why is there such a big range? Well, the studies weren’t much of studies as such. They were more like case reports. Nonetheless, it’s worthwhile looking at some of those reports.
Diamond Princess (2)
Shortly after arriving in Yokohama, Japan, the Diamond Princess was placed under quarantine orders on 5 February 2020, after a former passenger had tested positive for Covid-19. During and after the 2 week quarantine period, out of 3711 passengers and crew, 630 tested positive for Covid-19. Out of the 630 people who tested positive, 320 (50.8%) of them were asymptomatic. Now, these are not random people from the general population. Most of those on board the cruise were older and they tend to be more symptomatic than younger people.
Follow up of diagnosed patients in Shanghai (3)
In March 2020, 328 patients diagnosed with Covid-19 who were admitted to the Shanghai Public Health Centre were studied and followed up. 13 (4%) were asymptomatic at admission and had no symptoms within 2 weeks of admission. These patients were admitted within 48 hours of testing positive for Covid-19. 3 patients who were initially asymptomatic developed symptoms after admission. 10 remained asymptomatic throughout the follow up period in hospital (range 3-19 days). Amongst all the 13 patients, twelve had radiographic abnormalities typical of Covid-19. One patient had no symptoms and no radiographic abnormalities.
Japanese nationals evacuated from Wuhan (4)
In February 2020, 563 Japanese nationals were evacuated from Wuhan. All of them were tested for Covid-19 and followed up for 30 days. 13 tested positive. Of the 13, 4 (30.8%) were asymptomatic while 9 were symptomatic.
“Universal” testing in Iceland (5)
Iceland has a population of 364,000. The University Hospital of Iceland tested anyone with symptoms or who has return from risk areas while the Icelandic medical research company deCODE Genetics, tested any9one who wanted to be tested. By April 10, 10% of the population has been tested. About 0.5-0.8% tested positive for Covid-19. Interestingly, it has been reported that 50% of those who tested positive were asymptomatic (6).
Screening of pregnant women in New York (7)
Between March 22 and April 4, 2020, a total of 215 pregnant women delivered infants at the New York–Presbyterian Allen Hospital and Columbia University Irving Medical Center. All the women were screened on admission for symptoms of Covid-19. 4 women had fever on admission and all tested positive for Covid-19. Of the remaining 211 women, 29 tested positive. In other words, 87% who tested positive were asymptomatic at presentation. Of the 29 who were asymptomatic at presentation and tested positive for Covid-19, 3 later developed fever while in hospital. 2 were thought to have endometritis while 1 did not have a localising cause for the fever.
One woman who were asymptomatic and initially tested negative, later became symptomatic and tested positive.
It is not surprising that there are mild cases of Covid-19. It is not inconceivable that the symptoms are so mild that it is asymptomatic. When an asymptomatic patient test positive initially and later become symptomatic, these patients are more pre-symptomatic rather than asymptomatic. Some of these patients are truly asymptomatic and remain asymptomatic until they test negative. They should be regarded as subclinical infection. On the other hand, some of these asymptomatic patients may remain positive for a long time. Perhaps, this group may be chronic carriers.
What proportion of patients infected by the SARS-Cov2 virus is symptomatic is unknown. We don’t have reliable data to even guess how common these asymptomatic people are.
References:
- Carl Heneghan, Jon Brassey, Tom Jefferson. COVID-19: What proportion are asymptomatic? https://www.cebm.net/covid-19/covid-19-what-proportion-are-asymptomatic/
- Mizumoto K, Kagaya K, Zarebski A, et al. Estimating the asymptomatic proportion of coronavirus disease 2019 (COVID-19) cases on board the Diamond Princess cruise ship, Yokohama, Japan, 2020. Euro Surveill 2020;25. doi:10.2807/1560-7917.ES.2020.25.10.2000180
- Zhou X, Li Y, Li T, et al. Follow-up of the asymptomatic patients with SARS-CoV-2 infection. Clin Microbiol Infect Published Online First: 28 March 2020. doi:10.1016/j.cmi.2020.03.024
- Nishiura H, Kobayashi T, Suzuki A, et al. Estimation of the asymptomatic ratio of novel coronavirus infections (COVID-19). Int J Infect Dis Published Online First: 13 March 2020. doi:10.1016/j.ijid.2020.03.020
- Otmani M. COVID-19: First results of the voluntary screening in Iceland – Nordic Life Science – the leading Nordic life science news service. Nordic Life Science – the leading Nordic life science news service. 2020. https://nordiclifescience.org/covid-19-first-results-of-the-voluntary-screening-in-iceland/ Acessed 26th April 2020
- https://www.usatoday.com/story/news/world/2020/04/10/coronavirus-covid-19-small-nations-iceland-big-data/2959797001/. Accessed 26th April 2020.
- Sutton D, Fuchs K, D’Alton M, Goffman D. Universal Screening for SARS-CoV-2 in Women Admitted for Delivery. New Engl J Med April 13, 2020. doi:10.1056/NEJMc2009316