Apparent medical misinformation from an unlikely source: Asymptomatic, Presymptomatic, and Minimally Symptomatic.

On Monday, during a World Health Organization virtual press briefing, Dr Maria Van Kerkhove issued a statement that seemingly shook our entire understanding of the COVID-19 pandemic. Dr. Van Kerkhove is an Epidemiologist specializing in emerging infectious diseases and has been the technical lead for the WHO COVID-19 response team. The statement, which was immediately picked up by multiple news outlets, was this one:

It still appears to be rare that an asymptomatic individual actually transmits onward.

Dr Maria Van Kerkhove, World Health Organization

Needless to say, the response was immediate, and massive. For months we have been treating every person we interact with, including and especially ourselves, as though we were potential sources of COVID-19, in order to flatten the curve and prevent both a surge of cases and the possibility of our healthcare systems being overwhelmed. We were told, early and often, and with increasing levels of scientific certainty, that it was not enough to simply stay home if you were coughing or had a fever; that we could spread the virus even before we had developed symptoms, or if our symptoms were only very mild, and that the person we spread it to might not be so fortunate. Suddenly, the WHO seemed to be making an about-face.

For those that are exhausted of the caution made necessary by the pandemic, and the associated anxiety (read: all of us) it was welcome, if somewhat annoying, news. For those who have consistently proclaimed the pandemic to be something between an overblown flu being used for political purposes to an actual hoax or planned conspiracy, it was a triumph; even the WHO was saying it wasn’t anything to worry about. But for many of us who have been following emerging evidence, testing methods, contact tracing techniques, and COVID-19 data from around the world since March, it sounded too good to be true.


What we all wanted it to mean.

The idea of asymptomatic transmission, the virus actually being transmitted from a person who does not feel ill, who may not even know they have been exposed, is pretty terrifying. It means that you could, without ever knowing it, be the agent of delivering a deadly pathogen to a loved one; and that you may not ever know you were the one that gave it to them even after the fact. The idea of someone who has never had the virus losing a family member to it, and then finding out months later that they are antibody positive and have thus been a carrier at some point, is heart breaking. For me, it conjures epidemiology computer simulations of faceless grey figures gradually turning red, as the world slowly but surely is overcome.

This is the stuff of nightmares.

If Dr. Van Kerkhove’s statement meant that only those with symptoms could possibly pass along the virus, it would make all the difference in the world. For one thing, it would drastically change our isolation and transmission control strategies, shifting our focus from social (physical) distancing and treating all contacts as possible COVID-19 contacts, to simply monitoring very well for cough and fever and other viral symptoms, like we already do for influenza and other respiratory illnesses. Although it wouldn’t mean the virus was less dangerous, it would mean that exposure to it was somewhat predictable; if we were careful, our biggest risk would be those few bad actors who had symptoms but denied them, and persisted in exposing others.

And yes, it would also mean that many of the experts, epidemiologists, and physicians (including myself) (that’s an oxford comma folks, and I’m definitely only including myself in that last group) had been wrong about both the degree and the nature of risk to our society. But here’s the thing; we would be fine with that. It would be a big hit to the ego, for sure, and I’d of course have to delete this blog before I applied for my next job, but overall eating crow is an incredibly small price to pay for the assurance of safety for my family and my patients, and for the assurance of a sound strategic path forward in defeating this virus once and for all. As we’ve said all along; every doctor who sounds like an alarmist about COVID-19 also hopes they are wrong. We are the exact people who would be the happiest if it somehow turned out it wasn’t that big of a deal.

It would also mean that somebody had a lot of work to do to figure out how COVID-19 had overwhelmed so many healthcare systems and decimated entire cities and nations. We would need to account for those 404,000 deaths worldwide, a quarter of which have occurred in the United States. If those people were all exposed by individuals with definite and likely identifiable symptoms, we would need to figure out why we had failed so badly at fighting such a straightforward viral disease.


Always go to the source.

When I first read the headlines and articles, I was cautiously optimistic; but very cautiously. This defied what we had believed all along, and it defied most of what we know about the way that respiratory viruses spread. It didn’t make sense with the transmission patterns we have seen and the reported K value of the virus for it to only spread through fully symptomatic patients. It also conflicted with two recent studies from China and Singapore that seemed to indicate that transmission does in fact occur, and at a high rate, from patients without any respiratory or viral symptoms. These studies reached similar conclusions despite very different methodologies, which is always more convincing than reaching the same conclusion with the same method or data set. The Singapore study concluded,

“The evidence of presymptomatic transmission in Singapore, in combination with evidence from other studies, supports the likelihood that viral shedding can occur in the absence of symptoms and before symptom onset. “

https://www.cdc.gov/mmwr/volumes/69/wr/mm6914e1.htm

Still, I was hopeful. When I reviewed those studies there had been some assumptions and a few minor (and one major) methodological issues I wasn’t exactly comfortable with, and at any rate those studies were published back in April and we have learned an awful lot about SARS-CoV-2 since that time. I assumed that Dr. Van Kerkhove and the WHO were working from the most up-to-date data, so I did what I always advise people to do when evaluating emerging medical information; I went directly to the source. It’s a bit long but it’s worth reading Dr. Van Kerkhove’s entire answer and not just the excerpts that have been used in the various articles above.

Now, I know what you are asking; if these statements were confusing, why didn’t I ask her to clarify? Well, actually… that was a different TJ altogether.


Asymptomatic vs. Presymptomatic vs. Minimally Symptomatic.

There is one major component of Dr. Van Kerkhove’s answer that has been lost from most of the majors news stories and social media posts. Medicine and public health are subtle and detail heavy sciences, and it is unfortunate but perhaps unsurprising that the nuances of the above statement were lost, and that major news outlets reported “WHO says no asymptomatic spread,” when the real answer is much more restrained.

Dr. Van Kerkhove spends a considerable part of her answer specifically delineating between asymptomatic, presymptomatic, and minimally symptomatic cases, and it’s hard to put too fine a point on this distinction.

  • Asymptomatic cases are people who have been exposed to the virus, and it has reproduced itself within their bodies at a high enough rate that it becomes detectable by our testing methods; either it is present in their blood stream at a detectable rate at some point in time (they have a positive PCR test) or they have developed an immune response that can be detected after the fact (they have a positive antibody test). They have had the virus. However, they have never at any point had any symptoms they can identify; no day of fever, no fatigue, no cough, no ‘I thought I caught something but it got better’; they are fully non-symptomatic.
  • Presymptomatic cases are people who meet all of the above criteria at a certain point in time, but will eventually develop symptoms from the virus. Unless they are followed very closely, it is impossible to distinguish them from asymptomatic cases.
  • Minimally Symptomatic cases are people who have the virus but develop only very mild symptoms, or symptoms not as commonly associated with the COVID-19 syndrome. This is very, very challenging from both a diagnostic and an epidemiological standpoint. Many people have chronic cough, allergy symptoms, or shortness of breath related to chronic medical issues. Figuring out whether these symptoms worsened at a certain time that coincides with their SARS-CoV-2 infection, and that the infection was actually the cause, is nearly impossible, yet the way these cases are treated has huge implications in the way we understand data on asymptomatic transmission.

If you are reading this and thinking that these distinctions seem a little murky and difficult to unravel, you aren’t wrong. I don’t do contact tracing directly, but the idea of clearly delineating, over the phone and after the fact, between these three situations seems like a nightmare. Yet our understanding of the spread of this virus, and thus our risk to one another, hinges strongly on public health workers involved in contact tracing categorizing people into these groups with a high degree of fidelity. It is sound epidemiological work and is necessary and important, but realizing how much subtlety and difficulty is involved should make us wary of any overly optimistic (and yes, overly pessimistic as well) statements about risk based on such data. This is why it is so important that this data is compared to research on modes of transmission, viral shedding, and viral load in asymptomatic patients, and that all of those types of evidence be weighed together very carefully.


When misspeaking and misunderstanding becomes medical misinformation.

So the substance of Dr. Van Kerkhove’s answer is that unpublished data from an unknown number of countries, relying on methodology that is hardly foolproof (but may be the best we have available), seems to show that transmission of SARS-CoV-2, from the subset of people who will never develop even very mild symptoms, is rare. It is good news, but it is an incredibly measured response when properly understood, and the phrasing left it alarmingly ripe for misunderstanding. As soon as media outlets picked up this story it was clear that the original intent had not been understood, and that widespread confusion, vexation, and misinformation would result. On Tuesday, Dr. Van Kerkhove and the WHO attempted to clarify the statement.

“The majority of transmission that we know about is that people who have symptoms transmit the virus to other people through infectious droplets. But there are a subset of people who don’t develop symptoms, and to truly understand how many people don’t have symptoms, we don’t actually have that answer yet.”

Dr. Maria Van Kerkhove

But as you might have suspected, the damage was done. One of the most alarming things about misinformation in general, and medical misinformation in particular, is how those who share it are seemingly impervious to correction. They will choose to continue to believe information that has been demonstrated to be impossible, videos that have been proven to be a hoax, and now even statements that have been immediately retracted and clarified by those who uttered them. When confronted with the retraction, I have seen people essentially say, “well I believe it anyway.” Even today we are seeing people spread the original articles and double-down on the claim that asymptomatic spread (meaning, in their vernacular, ‘anyone without cough and fever’) is not possible, and that the WHO has finally confessed their complicity in this global conspiracy.


So… Is asymptomatic transmission still a thing?

I had hoped that we would be presented with the data Dr. Van Kerkhove had reviewed indicating the rarity of asymptomatic transmission. We have not seen that information yet, but other studies have reviewed available contact tracing data and arrived at a very different conclusion. Two recent studies were published on asymptomatic and minimally symptomatic spread within the last two weeks, one on May 28th in the journal of the Infectious Disease Society of America, and one on June 3rd in Annals of Internal Medicine. They offered similar conclusions:

“This review summarizes evidence that SARS-CoV-2 transmission is not only possible but likely highest during pre-symptomatic and asymptomatic phases.”

https://doi.org/10.1093/cid/ciaa654

“The early data that we have assembled on the prevalence of asymptomatic SARS-CoV-2 infection suggest that this is a significant factor in the rapid progression of the COVID-19 pandemic. Medical practice and public health measures should be modified to address this challenge.”

https://www.acpjournals.org/doi/10.7326/M20-3012

Both studies supported the high viral load and infectivity of presymptomatic individuals who would later go on to develop symptoms, which had been found in the China and Singapore studies in April. Both established, firmly, that transmission from asymptomatic individuals who would not go on to develop symptoms does in fact occur. They both analyzed the limitations of their methodologies and data sets, and explored the difficulties in distinguishing between asymptomatic, presymptomatic, and minimally symptomatic patients. Hence they both appropriately shied away from assigning any firm degree of risk or responsibility for transmission to asymptomatic spread of the virus. Unfortunately, we do not have reliable numbers for how many people are getting the virus from someone who will never know they have it. More studies are needed, but it seems clear that asymptomatic transmission is here to stay, at least as long as COVID-19 is.

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