Covid-19: four fifths of cases are asymptomatic, China figures indicate
BMJ 2020; 369 doi: https://doi.org/10.1136/bmj.m1375 (Published 02 April 2020) Cite this as: BMJ 2020;369:m1375Read our latest coverage of the coronavirus outbreak
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Dear Editor,
Michael Day [1] claims there are 78% asymptomatic cases in China based on the daily report of China National Health Commission on COVID-19 cases. The report is based on an incorrect reading of Chinese reports [2], and both its scientific and other inferences are incorrect. Given the importance of these inferences, the article should be retracted immediately.
In particular, the article incorrectly assumes the report from China about 36 symptomatic and 130 asymptomatic are both from the same population. It also assumes that the asymptomatic cases are not pre-symptomatic, i.e. they may develop symptoms later, typically within a few days. Both these assumptions are incorrect and lead to an incorrect understanding and conclusions.
For clarity, we report below the details of the Chinese report for March 31 through April 2. The newly reported results by China require careful interpretation as we learn what each category represents.
For background, there are 3 distinct populations that the Chinese reports refer to, A: International arrivals, B: Quarantined close contacts, C: The general public. Understanding that there are more than one populations is essential to understanding the Chinese reports.
CHINESE REPORTS
March 31 (reported one day later on April 1, this is the report Day[1] cites):
• 36 new symptomatic, 35 from A
• 130 new asymptomatic from A, B, and C
Comment: If these were from the same population, then the percentage of asymptomatic would be 130/(130+36)=78%. However this is not the case, as most of the symptomatic individuals are from population A and most of the asymptomatic are from population B and C (see subsequent days).
April 1:
• 35 new symptomatic, all from A
• 55 new asymptomatic, 17 from A
• 9 asymptomatic cases convert on April 1 to symptomatic, all from A
• 226 cumulative asymptomatic from A
Comment: We see that within population A, there are 35 new symptomatic and 17 new asymptomatic for this day. However, the statement that there are conversions shows they may be pre-symptomatic rather than asymptomatic cases
April 2:
• 31 new symptomatic, 29 from A
• 60 new asymptomatic, 7 from A
• 7 asymptomatic cases convert on April 2 to symptomatic,
all from A
• 221 cumulative asymptomatic from A
Comment: As a result, within A, 29 are new symptomatic, 7 are new asymptomatic
Comment: To understand the number of cumulative asymptomatic cases from A on April 2 requires additional information from the Chinese report. The report states that 101 asymptomatic cases, 5 of which from A, are released from medical observation on the day of the report, after a 2-week quarantine and consecutive negative test results. On April 2, asymptomatic cases from A start at 226, there are added 7 new imported asymptomatic cases, subtracted 7 converted to symptomatic, and subtracted 5 released, leading to the 221 cumulative asymptomatic from A.
We note that the asymptomatic number from B and C is much larger than that from A (849:226 as of April 1), but the 16 conversions are all from A. This suggests that many of the current reported asymptomatic cases from international arrival are pre-symptomatic. The high ratio between asymptomatic cases from B and C compared to A makes sense due to the presence of long term asymptomatic cases, that continue to test positively, remaining as a residual from the large number of cases in China.
[1] BMJ 2020;369:m1375
[2] http://www.nhc.gov.cn/xcs/yqtb/202004/28668f987f3a4e58b1a2a75db60d8cf2.s...
http://www.nhc.gov.cn/xcs/yqtb/202004/be27dc3c4a9544b081e2233537e762c3.s... http://www.nhc.gov.cn/xcs/yqtb/202004/4786774c1fd84e16b29d872f95241561.s...
Competing interests: No competing interests
Dear Editor
I thought this 4/5th figure was previous acknowledged in modelling work from the original spread in Wuhan.
Certainly a point prevalence of 4/5th being asymptomatic does not suggest they will remain so. The figures from the "Diamond Princess" told us that of the 3,000 odd who were tested 634 were positive and most of those were asymptomatic. However (and I guess they knew they had tested positive), just 20% went on to report no symptoms on follow up.
What I do not follow is Tom Jefferson's response that this invalidates the reasons for our semi-lock-down. If, at any point in time, those who test positive are more likely to be asymptomatic, is that not a good reason to try and break the chain of infection?
Competing interests: No competing interests
Dear Editor
The Diamond Princess data (1) shows that, in an environment where one might have expected 100% of the population to have been exposed, about 20% had a positive test, of whom 17.9% were estimated to have been asymptomatic. This Chinese data looks only at the sample who were tested positive and found a large proportion who were asymptomatic (asymptomatic negatives are not included in the sample).
This new data supports the lockdown since it implies that, for every person with symptoms (community cases of COVID-19 are diagnosed clinically), there are about 4 who have the disease and don’t know it. That is “why the hell we are locking down”. Perhaps the lockdown should be a multiple of the incubation period of COVID-19 so that those at risk can be protected from those asymptomatic carriers (including healthcare staff) who might keep patients safer by wearing masks.
1. Mizumoto Kenji, Kagaya Katsushi, Zarebski Alexander, Chowell Gerardo. 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(10):pii=2000180. https://doi.org/10.2807/1560-7917.ES.2020.25.10.2000180
Competing interests: No competing interests
Dear Editor
This is an interesting and extremely topical article given the current worries about the potential of asymptomatic spread of COVID-19. The article however fails to make an extremely important division of the people who tested positive but were asymptomatic. We have known since the start of this outbreak that it takes in most people 3-5 days from infection before symptoms become apparent. Hence, virtually all infected individuals go through an asymptomatic phase. The key question that remains unanswered by the article is how many of the 130 individuals who tested positive, but were asymptomatic, were actually recently infected individuals, who will go on to develop symptoms at a later date. That is typical carriers of the disease, tested at the early asymptomatic stage. Second, a certain number of these single tests will be false positives. There is a suggestion that up to 10% of tests with some kits may provide false positive values. And finally, the number we really need to know, how many of them are real asymptomatic carriers who will continue to be infectious but not ever manifest symptoms. Yesterday the WHO stated that individuals of this third type, who are asymptomatic and do not ever develop symptoms, are extremely rare. Although the headline of this article challenges this statement, the actual data as presented do not.
Sincerely,
John R, Speakman FRS - in quarantine in Beijing.
Competing interests: No competing interests
Dear Editor
“Four fifths of cases” of coronavirus disease 2019 (Covid-19) are not asymptomatic. The fraction of people testing positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is not the same as the fraction with Covid-19. Also, the numbers cited do not show that “the large majority of coronavirus infections do not result in symptoms.” It is not possible to extrapolate a proportion of people without symptoms at a single time point, to a general statement about the natural history of an infection. Michael Day’s News item (https://www.bmj.com/content/bmj/369/bmj.m1375.full.pdf) is inaccurate and misleading.
The data cited are not “new evidence”. They are routine reports of “166 new infections… identified in the 24 hours to the afternoon of Wednesday 1 April” in China. The people tested are a mixture of people with symptoms that they report, people with mild or non-specific symptoms that they don’t report, people who are pre-symptomatic but will develop symptoms later, and people who are and will remain asymptomatic. If the aim of testing is case-finding, it makes sense to test people who might not yet know they are infected and to isolate the cases to break transmission chains. This is the point of contact tracing.
An asymptomatic SARS-CoV-2 infection can only be established by follow-up of people who test positive. Those who continue without symptoms until at least the end of the incubation period, generally accepted as 14 days from the date of infection,1 have had an asymptomatic infection. This group is thought to comprise a small proportion of all those who have been infected with SARS-CoV-2.1 It is not known how transmissible a truly asymptomatic infection is. SARS-CoV-2-infected people who are asymptomatic when tested, but who go on to develop symptoms of coronavirus disease 2019 (Covid-19) are pre-symptomatic.2 These people might be infectious 1 to 3 days before they develop symptoms.2
The difference between asymptomatic and pre-symptomatic is not just semantic. Stating that there is a large fraction of “asymptomatic cases” is misinterpreted as an indication that “large swathes of the population” have been infected, infected others and become immune. This hyperbole implies a level of herd protection which is at odds with modelling suggesting that, as of 28 March 2.7% (95% credibility estimate 1.2%-5.4%) of the United Kingdom population had been infected.3
We need better empirical evidence about the proportions of people who remain asymptomatic during the course of SARS-CoV-2 infection and of those who are pre-symptomatic. Through a living systematic review (https://osf.io/9ewys/), we will publish and update the evidence as it emerges. Accurate communication about the findings of this review should improve public understanding about the definitions, frequency and implications of asymptomatic and pre-symptomatic SARS-CoV-2 infection.
1. World Health Organization. Report of the WHO-China Joint Mission on Coronavirus Disease 2019 (COVID-19). Available at https://www.who.int/docs/default-source/coronaviruse/who-china-joint-mis... (Accessed 03.04.2020)
2. We WE, Li Z, Chiew CJ, et al. Presymptomatic Transmission of SARS-CoV-2 — Singapore, January 23–March 16, 2020. MMWR Morb Mortal Wkly Rep. ePub: 1 April Estimating the number of infections and the impact of non-pharmaceutical interventions on COVID-19 in 11 European countries2020. DOI: http://dx.doi.org/10.15585/mmwr.mm6914e1 (Accessed 03.04.2020)
3. Flaxman S, Mishra S, Gandy A, et al. Report 13 – Estimating the number of infections and the impact of non-pharmaceutical interventions on COVID-19 in 11 European countries. Available at https://www.imperial.ac.uk/media/imperial-college/medicine/mrc-gida/2020... (Accessed 03.04.2020)
Competing interests: No competing interests
Dear Editor,
Unlike a very powerful tornado or a cyclone that destroys everything in its path, here is this COVID 19 that has unfortunately been found to destroy and shatter the lives of about 2 % of all those infected by it. Remaining 98% or more scrape through and are almost fine in about a week or two. What more, it is only symptomatic in one out of five patients who are infected by this virus [1]. It is a given that this new corona virus is quite contagious, much more than whatever we might have come across so far, but it is not so virulent as Ebola is. Ever since COVID 19 made its first appearance in December 2019, in a short duration of time we already have millions who are already infected by this virus. However, this doesn't mean that all those who are infected are going to die.
It is almost a common knowledge that up until now we have witnessed increased mortality only amongst the weak, frail, and in those individuals who are suffering from multi-morbidities, malignancy, are bed ridden for prolonged period, have undergone transplantations, are recovering from major surgery, and also those who have precariously low immunity levels, for whatever reason. So far, this is the trend. This virus has luckily, for all of us, not undergone any mutation. We are sorry to be blunt, but COVID 19 is selectively seeking out its prey, and we already know who they might be. It is certainly not that every elderly person would die, or that only the elderly would die. The chances are that those elderly who are weak and frail, and have other serious diseases and conditions alongside, will have to be more careful now on. People at risk of bad prognosis must take additional precautions, including wearing masks, avoiding fomites, keeping social distance, isolating themselves from the normal crowd, etc, so that they can escape getting this contagion. They should try and weather it out as best as they can. Governments should be fully supportive for that. Weathering it out from within the confines of comfort zone needs to be explored rather than packing everyone off to an Alcatraz type establishment for safety.
Instead of trying to protect and isolate the individuals at risk of facing a bad prognosis, trying to isolate everyone by total lockdown of towns and cities may be overreaching and not be attainable. Instead, what can be achieved using the present resources must be given a try first, and the net may be cast wider once we succeed in our initial steps. As of now this virus seems to be too clever for mankind, and has been getting under the skin of even some of the high and mighty. Across the world, for all we know, many individuals, far more than the current statistics and figures, might have already been infected by COVID 19. It may also be possible that many amongst them would have barely realized it, as the sickness is usually quite mild in all those hale and hearty. The news is already out that in China, more than four fifths of cases of COVID 19 were asymptomatic [1].
We must not forget the importance of "herd immunity". So far there was no herd immunity for COVID 19, and this allowed COVID 19 to spread so swiftly all across the globe. Now we have millions who are infected by this virus, and many who had been tested positive have recovered fully. Howsoever best we may try to deal with this pandemic, we may not be able to test everyone. As the numbers of all those infected by this virus is expected to increase exponentially, it will be getting more difficult to trace and test all their primary, secondary and tertiary contacts. Even if this exercise is taken up with top most sincerity, it will turn out to be such a colossal exercise and possibly even those countries with the best of resources and limited population, may find it difficult to complete this whole exercise of getting their figures right.
But is it the figures of all those who are infected that we are interested in? So far these figures have created a panic of sorts and therefore those who are actually sick should be released to the media. Likewise, exposure of the general public to the data obtained from mathematical models and statistical work ups, should be delivered with caution, so as to avoid undue panic. There is as yet no real protection in the form of a vaccine or a specific cure, hence we may as well consider this wild card denoting "herd immunity", which will ultimately help rescue us from this pandemic. So, in a way, since this disease is usually mild in healthy individuals, the sooner this herd immunity gets to reach a certain threshold level because of them, the better it will be. While at it, it will be best and perhaps cost effective as well, if we dig into the immunoglobulin levels, wherein the knowledge of IgM levels as well as the IgG levels would be helpful in management.
From the present trend, in the coming days we may expect a steep rise in the number of new infections all across the globe, barring the People's Republic of China, Italian Republic, Kingdom of Spain, etc, where COVID 19 has already had a free run. However in the South Asian countries, where the elderly population is not as high as in developed countries, mortality rates will be much lower as compared to regions and countries where the percentage of elderly patients with multiple co-morbidities is high. Moreover we already know for sure that only one out of five persons who get infected by this new corona virus become symptomatic [1], and the overall mortality is below 2%. This percentage could be lower still on account of the sunny days ahead. Furthermore, existing bond in the families and the society will help ease the management of COVID 19 pandemic in this region. Much has already been said earlier [2-5].
If not soon anytime now, certainly the posterity will be reflecting upon the measures that were taken against COVID 19, and at what personal costs and financial outgo. They would surely be exploring whether we could have done any better than what we did, without the lockdowns, or isolation in Alcatraz type fashion for the whole population, pushing the economy so far back, and in bringing the whole world to a near halt for COVID 19. Given the information [1], where was that need for overreaction and overshoot, they might consider. Perhaps they will also be considering measures to stop undue panic, stress and anxiety that had nearly reached the Moon, back then.
Best regards.
1. Dr (Lieutenant Colonel) Rajesh Chauhan
MBBS (AFMC), Master in Medicine (CMC Vellore), PGDGM (Geriatric Medicine), PGDDM (Disaster Management), AFIH (Industrial Health), DFM (Family Medicine), FISCD, ADHA (Hospital Administration) & LLB
2. Dr. V.T.K. Titus.
MBBS (AFMC), MS (Ortho), Diploma National Board (Ortho), Diploma Orthopedics
Professor & Head, Department of Orthopedics,
CMC Vellore, Tamil Nadu. INDIA.
References:
1. Day Michael. Covid-19: four fifths of cases are asymptomatic, China figures indicate BMJ 2020; 369 :m1375
2. Chauhan Rajesh. COVID 19 : Fresh approach, initiative, and opportunity. BMJ 24 March 2020. Available at : https://www.bmj.com/content/368/bmj.m1141/rr-4 Accessed on 03 April 2020
3. Chauhan R, Singh AK, Chauhan S.. Covid-19 : Catch the tiger by its tail.
BMJ 28 March 2020. Available at : https://www.bmj.com/content/368/bmj.m1190/rr-1 Accessed on 03 April 2020
4. Chauhan R, Singh AK, Chauhan S.. COVID 19: The last straw that broke a weak camel's back. BMJ 01 April 2020. https://www.bmj.com/content/368/bmj.m1199/rr-11 Accessed on 03 April 2020
5. Bhutta Zulfiqar A, Basnyat Buddha, Saha Samir, Laxminarayan Ramanan. Covid-19 risks and response in South Asia BMJ 2020; 368 :m119
Competing interests: No competing interests
Dear Editor,
The question "What the hell are we locking down for?" has a very obvious answer: To prevent the collapse of our health systems and the additional suffering and loss of life that would be caused by it.
We have observed exponential growth of both case numbers and deaths in multiple countries, and we have seen health systems become overwhelmed in China and Italy (as well as Spain, France, New York). We now also have evidence of lockdowns slowing the spread of Covid-19 and thus alleviating the burden on the health system. There is absolutely no reason to believe that the growth rate of daily hospitalisations will suddenly drop in countries that are close to overwhelming their health system, even if the results presented in this article turn out to be representative.
Why Mr. Jefferson thinks this is a valid question to ask in response to these findings is beyond me. In the context of widespread misinformation and "Covid-19 denial" hindering lockdown efforts in strongly affected areas, the publicisation of his comments in this journal is quite regrettable.
What the findings do give hope for, though, is that the lockdowns might be required for much less time than we currently anticipate. Further research to substantiate (or refute) the results is therefore very useful. But decisions on lifting or reinstating lockdowns will hopefully still be made based on the dynamics of the number of new cases, hospitalisations, and deaths. Or in other words: evidence-based.
Best regards,
Christian Thiemann
Competing interests: No competing interests
Dear Editor
While 80% of recent cases in this report from China are currently asymptomatic, the virus has been circulating there for several months. Calls to consider ending lock-downs may be both premature and dangerous in areas with more recent spread of pandemic coronavirus. Such decisions must be informed by local seroprevalence data.
My concern is that uncritical acceptance of this data may do both public health and economic harm. Indeed evidence from the 1918 pandemic, published by authors from the New York Federal Reserve and MIT, suggests that aggressive social distancing efforts "not only lower mortality; they also mitigate the adverse economic consequences of a pandemic".
Andrew M Davis, MD, MPH
Correia, Sergio; Luck, Stephan; and Verner, Emil. Pandemics Depress the Economy, Public Health Interventions Do Not: Evidence from the 1918 Flu (March 30, 2020). Available at SSRN: https://ssrn.com/abstract=3561560 or http://dx.doi.org/10.2139/ssrn.3561560
Competing interests: No competing interests
Dear Editor
Jefferson and Heneghan contend: "Lockdown is going to bankrupt all of us and our descendants and is unlikely at this point to slow or halt viral circulation as the genie is out of the bottle". Have they consulted with physicians in Italy, France, Spain or New York City? Clearly there is an association of social distancing with reduction in the surge of disease. Jefferson and Heneghan may be forgetting that this virus is entirely novel to the human race. Even if 75% of cases are asymptomatic (something most educated people on the subject have been speculating for some time already) empiric evidence clearly suggests that significant morbidity and mortality ensues by unchecked transmission.
The authors would be much more realistic to not dispute what is evident, but instead consider proposals for a way forward: Clearly, what these data suggest, if correct, is that broad serological testing is paramount to an orderly reopening of the economy. Such point-of-care testing already exists. If applied (e.g. at physicians' offices), it would allow individuals who have demonstrated seroconversion to re-enter the economy, while sero-negative individuals would have to exercise more caution and would be subject to isolation if they develop symptoms. This proposal assumes that seroconversion confers immunity, something that is not yet proven. However, it is based on more than wishful thinking, since convalescent sera are being used in the treatment of severe COVID19 cases (thus suggesting some effect) and would permit for a thoughtful and testable way to avoid prolonged economical shutdowns.
Competing interests: No competing interests
Re: Covid-19: four fifths of cases are asymptomatic, China figures indicate
Please help as I am trying to understand this data.
If 4/5th of those who tested +ve [in a random population sample] but had no COVID symptoms might it be that a proportion who tested +ve, and then died, had no symptoms either ?
Its just that there seems to be no data about how many of those that die +ve in fact die of pneumonia
Can you help?
Competing interests: No competing interests