Community Spread of nCoV2019: Is Endemicity Possible?

Lately, one of the questions I’ve been asked is how I see the novel coronavirus outbreak ending. It is a complicated question that is hard to answer. One outcome that I think is worth exploring, as a thought experiment, is that the novel coronavirus outbreak ends with the virus become one of the coronaviruses we deal with perennially (i.e. it becomes endemic as a human viral respiratory virus). The trajectory of the virus has demonstrated its capacity for sustained human-to-human spread at a rate higher than SARS. As such, I believe this virus is spreading akin to a community-acquired coronavirus such as OC43, 229E, HKU1, or NL63. With those coronaviruses, a winter/spring seasonality is present. Thus, I wonder if this virus — absent control efforts currently underway that may dampen the seasonality or smooth it— would exhibit this type of seasonality. It has clearly no need, currently, for whatever animal reservoir(s) it jumped to humans from.

It is hard to completely understand severity yet as very limited data is available but it is evident from observing case counts and death counts that this virus has at maximum an intermediate coronavirus fatality rate. That is, it lies between the community acquired coronaviruses and below SARS. I have seen some estimate it’s fatality rate to be 1/50th of that of MERS. It does appear, from early case studies, that deaths cluster in older adults with comorbidities.

The WHO today stated that they believe control measures are still thought capable of halting transmission and perhaps these efforts will be aided by the natural coronavirus seasonality. However, if transmission isn’t entirely stamped out and low-level transmission continues it could be the case that next winter the novel coronavirus appears again as part of the viral respiratory virus cast. If that happens could it be we will just have another sometimes severe respiratory virus to contend with (of course containment should be the goal so long as it is possible). We have examples of these potentially perilous infections in adenovirus 14, adenovirus 7, the AFM-induced EV-D68, and several others. These viruses are hazards to be dealt with seasonally and are challenging with high burdens of illness in some individuals. Another important example is that of the 2009 H1N1 influenza A strain that emerged in the spring of 2009 and displaced the prior H1N1 strain to transition from a novel pandemic strain to an endemic seasonal strain.

I don’t know how the emergency phase of this outbreak will end or how quickly events will either support or reject this idea I proposed but I think there is more than a zero probability that a 5th community-acquired coronavirus has appeared.

A Hypothesis about nCoV2019: Thinking about Patient 1 and Patient 0

As the novel coronavirus outbreak evolves, I have been contemplating and developing various hypotheses. One I think I want to explore in a little more depth involves the timestamp of this outbreak: When did first cases occur? When did this virus end up in humans?

I am asking this because as I look at the trajectory of this outbreak I am beginning to think that maybe this case count reflects large community-based transmission that has been ongoing for some time. I have thought that maybe the cluster at the seafood market was a “red herring” (pun intended) and came to light because of the epidemiologic linkage of patients and I am beginning to increasingly think that it may be the case. The Lancet paper on the 41 seafood market cluster tellingly reveals that patient number 1 had no contact with the market and became ill December 1 — weeks before this outbreak came to light. This suggests that this outbreak had been ongoing since at least November unbeknownst to clinicians. Remember, viral upper respiratory infections and even pneumonias largely go undiagnosed to a specific microbiologic level (to wit, I rounded this weekend and had multiple such cases that defied microbiologic diagnosis even in a nationally renowned quaternary care medical center).

In light of the above, the logical question is: if Patient 1 wasn’t linked to the market, where was the virus acquired? Who is Patient 0? We need serological anitbody-based surveys to see how prevalent exposure to this virus was pre-outbreak detection.

Phylogenetic analysis of the virus suggests a single introduction to humans but little variation in the limited human isolates available so far — they all share a common ancestor. However, does that suggest when the jump to humans occur? There are known rates of coronavirus mutations in humans and that can give some clue to how much divergence has occurred in humans and it appears that it has not diverged much at all. I wonder if this virus, like other coronaviruses, was circulating in the midst of a relatively forceful flu season and not diagnosed or noticed because many of the cases mimic influenza and other respiratory viruses. The data, based on assumed mutation rates, suggests this jumped no earlier than October 29, 2019 which would give the virus an almost 2 month head start to spread comingled in the flu season.The Makona variant of Ebola Zaire, which was the result of a single viral spillover from bats, circulated for 3 months before notice in Guinea.

If this is so, I expect case counts to rise as the virus circulates and deaths to rise as well (though at a much lower rate). Maybe this virus will become another established seasonal coronavirus with severity that is intermediate between the community acquired coronaviruses (OCV43, 220E, NL63, HKU1) and MERS and SARS? (Note that HKU1 can cause severe disease and may be an intermediate coronavirus as well)

I also believe if there is widespread community prevalence of this virus there is likely a significant severity bias in case reporting as well as in conceptualization of this viral syndrome. Imagine if you didn’t know anything about influenza and RSV and scoured adult ICUs and hospital floors. You would get a totally different picture of these diseases than if you were out in urgent care centers and PCP offices?

None of the above is meant to minimize this outbreak but my attempt to make sense of it.

If DA were here, I would ask him and know he would have an answer in a minute. It is at times like these that his giant, reasoned, prescient voice is what the world needs.