A Covid-19 update from Dr. Nicholas A. Christakis, Sterling Professor of Social and Natural Science at Yale
People are asking whether patients with Covid-19 who don?t have symptoms, e.g. cough or even just fever, can transmit the disease to others. The answer seems to be yes. Alas, this is not good news, but we can still take rational steps. Let?s talk about this ?quarantine loophole.?
Should you avoid getting near symptomatic relatives? Yes, alas. What about college students or travelers returning home who aren?t showing symptoms? That?s harder. If they could have been exposed, you should practice physical distancing for a while, even if they?re asymptomatic.
If people are asymptomatic but have credibly been exposed to Covid-19, they should be in home quarantine for 14 days, to be safe. But for how long can someone be asymptomatic and still transmit? It appears that this is on the order of two to four days.
Let?s do some epidemiology.
The period between exposure and showing signs or symptoms of the infection is called the ?incubation period.? The period between exposure and becoming infectious (able to spread the disease to others) is called the ?latent period.? (The image below modified from Marcel Salath?).
Let?s call difference between the latent period and the incubation period the ?mismatch period? (latent minus incubation), which can be negative (e.g., in HIV, where asymptomatic carriers can be infectious) or positive (e.g., in smallpox, where patients are usually symptomatic before they are infectious).
This difference (the ?mismatch period?) between the incubation and latent periods has also been called the ?omega? period in some veterinary studies, or it can be called the ?period of subclinical infectiousness.?
From point of view of a pathogen, it might be good to evolve to be transmissible without incapacitating the host or (in a fiendish alternative) to evolve to elicit caring behavior by other humans, so as to infect them (a subject for another day, discussed in my book ?Blueprint?.)
The latent period is partly related to disease dynamics (including social network interactions and even diurnal rhythms, since they determine the time point from which the pathogen can be transmitted from infected to healthy hosts). Diurnal rhythms are highly relevant to disease transmission.
In contrast, the incubation period of a pathogen is primarily related to the biology of the interactions between hosts and pathogens (for instance how quickly the host mounts an immune response to clear the pathogen).
When the latent period is shorter than the incubation period (as shown in the big red arrow in the figure below), this can present a challenge to epidemic management since asymptomatic patients can spread the disease.
If most transmission occurs before disease is apparent (e.g., HIV), reactive control measures will be ineffective. Conversely, successful disease eradication (e.g., smallpox and SARS in 2002) is facilitated by low transmission by asymptomatic people.
That is, for diseases with an incubation period shorter than the latent period, detection and thus quarantine of symptomatic hosts is possible before they become a source of pathogen, leading to better disease control.
The success of reactive disease control strategies has been shown to depend on the timing of the onset of infectiousness relative to the onset of detectable clinical symptoms. How long is the mismatch?
This is why testing asymptomatic or minimally symptomatic people is so important, and why the lag in implementing widespread testing for Covid-19 in the USA (compared to Korea, say) is so unfortunate.
Now, what do we know about the Covid-19 incubation and latency periods? Like everything else related to Covid-19, which has scientists worldwide scrambling to understand it from genetic, clinical, epidemiological, and sociological points of view, we cannot yet be 100% sure. However, a careful study of 468 infector-infected pairs found that 12% involved transmission before the infector was symptomatic.
Examination of 124 Wuhan cases with a clear contact history showed an incubation period of 5 days (range: 1?11 days). It found that 73% of secondary cases were infected before the onset of symptoms in first case. It estimated the mismatch period to be three days.
A fine analysis of cases from China (N=135) & Singapore (N=93) found that the incubation period was about 7?9 days. And there was pre-symptomatic transmission, with infection occurring on average 2.9 days (China) and 2.6 days (Singapore) before symptom onset in the infector.
Another analysis looking at 28 pairs of individuals suggests that ?a substantial proportion of secondary transmission may occur prior to illness onset.?
Here is a note from February 18 in The New England Journal of Medicine regarding two cases in Germany suggestive of possible asymptomatic spread of COVID19.
A study of 52 Chinese patients found the incubation period to average 5 days, with a typical range of 2?14 days. Such analyses yield the widespread recommendation of a 14-day quarantine period (so as to be sure a person is not infected, whether symptomatic or not).
A further wrinkle is that these numbers are averages. Even if the latent period were not shorter than the incubation period, on average, it could still be so for some patients. Indeed, this may be one of the factors that can make some individuals super-spreaders.
And here is work, as of March 16 in Science, using a modeling approach, to show that ?undocumented infections? (which are numerically more common than documented infections) were the original source of 79% of documented Covid-19 cases.
Lastly, here is more evidence of pre-symptomatic transmission of COVID19, which I think we must now regard as the reality we are facing. This paper estimates that 44% of transmission could occur 2?3 days before first symptoms.
The likely existence of asymptomatic transmission of SARS-CoV-2 causing Covid-19 does not mean we should not bother to test patients (e.g., to see if they are febrile) and ask them to self-isolate. Isolating carriers and patients is still essential!
It is wise to detect and sequester patients, as is widely done (in China, Korea, Singapore, and so on) by offering widespread free testing using real-time (rRT-PCR) detection of the SARS-CoV-2 virus (detecting viral RNA) and by conducting fever checks (which is much easier for screening).
Incidentally the CDC released new guidelines for RNA testing on March 9.
And here is good advice about how to prepare your household for COVID19 from the CDC.
In sum, on average, Covid-19 patients take about 7 days from exposure to SARS-CoV-2 to show symptoms (typical range 2?14 days), and a meaningful percentage of carriers can spread the disease for 2?4 days before they are symptomatic. We have our work cut out for us in confronting this pandemic.
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