I was reading this talk by Amesh Adalja back in 2018. Amesh was certainly correct that the most likely candidate of a GCBR  pathogen would be a airbourne RNA-virus. But I saw this question and now I'm wondering if there are elaborate answers for this in the wider community.

"Question: How about things that may be dormant for a long time or asymptomatic for a long time, how does that kind of change the analysis of this stuff?"

 It seems to me that Amesh recognised that a patheogen like HIV would be able to spread through the population and create a very different problem from the typical GCBR scenario, but he didn't get to elaborate on the possible responses to this (and I'm not quite sure why it matters that this doesn't fall into the GCBR definition nicely). 

I wonder if there are other folks working on biosecurity and pandemics who have talked about this particular scenario, how it would likely work out, the relative risk, and what should be done to detect/control such an event, since it's definitely within the realm of possibility (HIV is one that has already given us plenty of trouble, and Amesh mentioned HLTV-1, which seems to be a possible candidate too).

 

This also brings me another question: are we in the clear about covid-19 yet? 

There is no question that, with vaccination programs and previous infections, the majority of people now experience covid-19 as a relatively mild illness and make a full recovery with no noticeable issues. And if this is the whole picture, we should be able to handle covid-19 from now on like "just another illness" that doesn't threaten us with societal collapse anymore. 

However, some people do develop serious health issues after the acute illness, and seemingly the virus is capable of staying in our body after recovery. So, what if covid-19 is capable of causing a more serious illness, months or years after a person recovered from the acute infection? 

It is definitely not unheard of: HIV is a classical example, and even more "mundane" pathogens like measles, EBV, or herpes are fully capable of creating serious or even fatal illnesses after the acute infection in a (small) fraction of patients who made full recoveries from the acute illness.

If covid-19 is somehow capable of causing serious illness in a larger fraction of the population in the future, we could indeed face a challenge that could cause societal collapse (and mass casualties). 

Do we currently know enough about covid-19 to rule out this possibility, or assign it a low enough "likelihood", that it would be more effective to put biosecurity resources on newer, emerging diseases, than to continue investing in covid-19 response? My main concern is that, we don't have any data about "how are people doing, 10 years after catching covid-19". And I'm not sure if there are any good "substitute" methodologies to gain information about this.

And maybe, this is something that should be watched out for whenever we encounter a novel pathogen? 

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  1. The infectious period and the symptomatic period, and how they interact, is generally more important than how long a pathogen can lay "dormant". However, HIV is an example of when a case can be infectious even during the dormant period- that is very concerning, it's like asymptomatic transmission for COVID-19 but on a much larger scale. People are certainly concerned about a pathogen that has an infectious period that starts before the symptomatic period- it's even bolded on the slidedeck from the presentation you linked to: 
    "I have bolded this because in multiple modeling studies, and in experience...if a disease is contagious during the incubation period, when you're not sick, then it's very, very hard to control".
  2. There will certainly be some patients who die in the next few decades from some damage the SARS-CoV-2 infection did to an organ system or from immune system dysregulation from a SARS-CoV-2 infection. Novel pathogens that infect large swathes of the population often have longer term effects. Following the 1889 "Russian flu" pandemic there was even a noticeable increase in suicides among flu victims (https://macsphere.mcmaster.ca/handle/11375/14366; it was likely not a flu but in fact a novel coronavirus!). However, the magnitude is nowhere near the level needed to bring SARS-CoV-2 into GCBR status. While it is true that people can die of measles, EBV, or herpes after recovering from an acute infection, this is by no means likely. HIV is the outlier here, but it has meaningful differences from SARS-CoV-2: it has a much, much higher mutation rate, it uses reverse transcriptase to integrate its genome into the host cell's genome, and it preferentially attacks immune cells (measles also attacks the immune system in a different way, by attacking memory cells). So yes, in my opinion, we are out of the woods with COVID-19 with regards to GCBRs. 
  3.  The main countermeasure to pathogens that take a while to cause symptoms is good epidemiologic surveillance systems. This "starts the clock" faster on countermeasures. Ideally, you would want a pathogen agnostic system, like what is being worked on at the Nucleic Acid Observatory. There's a game called Plague Inc that models this one aspect well- the sooner humanity realizes something is spreading, the sooner they slow the spread and create cures.

The main countermeasure to pathogens that take a while to cause symptoms is good epidemiologic surveillance systems. This "starts the clock" faster on countermeasures.

Could you expand on this a little please? Obviously this would allow you to identify the infectious agent, but you wouldn't have any way to calibrate your response appropriately. Ie, your likely conclusion would be that something is spreading but causes no ill effects (like the majority of microbes in our body).

4James Montavon4d
Yeah, you bring up a really good point: most of the "bugs" circulating aren't harmful, so if we have a surveillance system that's completely pathogen agnostic we'll be chasing beneficial gut bacteria or harmless phage. In my previous job in a wastewater testing lab, one of the positive controls we used was a virus that infects peppers- we'd find tons of it. With regards to viruses, the virus needs to be able to enter human cells, take over the cellular machinery to replicate, and evade the human immune response. We know broadly what kinds of virus families can do this and what kinds can't, so if we see a virus in a family that can infect humans that is increasing exponentially in our surveillance system, we know there is an outbreak/epidemic. We can then do some bench science to figure out what human cells it's infecting, how it's evading the immune system, etc. The viruses that we coexist with relatively well, such as human cytomegalovirus, have coevolved with humans over millennia. A novel virus that was increasing rapidly in a human population would be cause for concern even if there is no symptoms yet. Also, many times there are symptoms, but they are not connected to the novel pathogen because they look so much like other diseases- flu and COVID-19, for example. With regards to bacteria, I'll admit I'm not as knowledgeable there, but I'm also not as worried in the near term about GCBRs from bacteria. You write: The second part of your statement makes sense to me- the vast majority of microbes in our body cause no ill effects in people with a healthy immune system. However, I'm not so sure about the first statement: if it's spreading, that means it's either taking over human cells and turning them into virus factories, or it's colonizing more and more human tissue. That means the balance between the immune system and this microbe is out of whack. "Harmless" bacteria or viruses that start spreading out of control kill immunocompromised people all the time- a

I would agree with 1., yeah. Generally a disease that doesn't transmit during the "dormat" period would not be much different from a disease that is very acute. 

I think "mild acute illness that lays dormat and comes back later" can blur the lines a bit. Say, if we have a disease similar to HIV that causes flu-like illness in the acute phase and was highly infectious at point of time (but doesn't show up to be a serious illness until much later and wasn't transmissive during the dormat period) would probably make the non-transmissive dormat period rele... (read more)

1James Montavon7d
Glad to find another Plague Inc fan. I think in the vast majority of cases, that winning strategy only works in the game, because symptoms are directly related to viral replication and the immune system's response to viral replication. You're right that when we're talking about engineered pandemics this is something to keep an eye out for, but luckily our immune systems are very good at keeping their eyes out
2Kinoshita Yoshikazu (pseudonym)4d
I do think what Plague Inc is doing..is far from a simulation of an infectious disease... The pathogen in PI receives "updates" from a handler, and cannot be cleared from a host without intervention (nobody in PI recovers from the pathogen unless a cure is distributed). This reminds me more about computer malware than any biological agent...