You will be hard pressed to find higher quality virological information during this outbreak than you will from guest Dr. Ralph Baric on the latest episode of This Week in Virology.
Ralph Baricis certainly someone to listen to during the COVID-19 pandemic. His experience speaks for itself:
“SARS-like WIV1-CoV poised for human emergence.” — https://www.ncbi.nlm.nih.gov/pubmed/26976607
“A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence.” — https://www.ncbi.nlm.nih.gov/pubmed/26552008
“MERS-CoV and H5N1 influenza virus antagonize antigen presentation by altering the epigenetic landscape.” — https://www.ncbi.nlm.nih.gov/pubmed/29339515
Ralph Baric, PhD — Department of Microbiology and Immunology, UNC
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Link to podcast: http://www.microbe.tv/twiv/twiv-591/
Pease note: I am not a expert in the field. I really wanted to try to put this into terms that made it easier for people to digest the insight throughout & to make it easier to share this podcast with people who might otherwise struggle with some of the technical aspects of what they’re talking about.
For us to have the best outcomes as a society, it is crucial, in my opinion, for people to make informed decisions using the best information possible. I worry about people’s ability to make these decisions amidst the torrential down-pour of fake news & misinformation that has been difficult to avoid in recent weeks.
Please mention any issues you might have with the following to @bigbizze on Twitter, or email me at hpcngmoh@gmail.com & I will update it, if well founded, promptly.
Every blurb of text with a timestamp is a summary of something discussed on the show. I tried to cover all of the content discussed in the ~1 hour interview. The sections with parentheses in italics are me personally interjecting something.
If this kind of thing is in your wheelhouse… seriously… just listen to the podcast, it’s awesome.
This was converted from a reddit post so apologies in advance if there are any issues with it being ported to Medium.
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4:45 —
“There’s no question that there’s community spread & there’s no question that there is asymptomatic spread & there’s no question that we are now in a full blown pandemic. There’s no question that there are undetected networks and transmission chains that exist across the [United States] that are infecting additional people.”
5:56 — Asymptomatic spread is critical because someone not feeling sick does not mean they’re necessarily safe for another person to be around.
7:10 — Fairly certain that only two places a month ago in Africa could do testing. It has improved since but large swathes of the continent still are unable to do tests. It’s difficult to say what we can do about the problem they’re facing, as many countries, including the United States, are having difficulty doing their own testing.
8:10 — Current best estimate for global R0 is somewhere between 2.5 & 3.3, this is quite high. Contemporary flu is much closer to 2 or 1.8 / 1.6; this is explosive spread & rapid transmission. This is made even more so because of super spreaders, some of which can infect 15–20 people just passing through a room.
9:13 — A single meeting at Biogen in Massachusetts resulted in 77 infections ~2 weeks ago.
10:00 — Super-spreaders seem to be a phenomenon more common in emerging coronaviruses than influenza viruses… Is this is also a property of common-cold causing coronaviruses? (remember this point by Dr. Baric as you read / listen)
11:05 — Difficult to estimate # of cases currently because some people can incubate with the virus for 14 days before they start to show symptoms. Most people are in the range of 5–7 days however.
11:25 — The doubling time is dependent on population density, where the virus is replicating, the concentration of the infection & if it is replicating in the upper respiratory tract, exactly where it is doing so. (This is speculative, as Dr. Baric says he does not have a great answer for the question)
12:15 — Seeing 15M+ confirmed cases in the US depends partly on our ability to test for the virus. Determining the degree of infection for this virus should become clear in the not-so-immediate future once we can do sufficient serologic testing. (testing people to see if they have antibodies for SARS-CoV-2).
12:27 — China is not planning on doing serologic testing on their population. (This is second hand information Dr. Baric has been made aware of.) This indicates that there has probably been significantly more infection than what has been reported by China & that they do not want the actual figures to be known.
13:17 — It is fairly likely that the number of undetected cases is significantly higher than detected ones currently & if that ends up being true, the mortality rate will drop accordingly.
15:35 — You can almost certainly expect that there will be some degree of immunity to this virus once someone has been infected and subsequently recovers. However, in MERS, people tend to have a high degree of immunity soon after recovering, which then weakens over the next 1–2 years. This continues until you eventually end up with background-levels of detectable antibodies against the virus. In some cases however, the presence of antibodies could only be detected for 1–2 months.
16:57 — (back to the point I told you to remember) No one knows how coronaviruses maintain themselves in human populations. They don’t rapidly mutate like Influenza where you have 130+ common types of it endemic in humans (there are ~4 coronaviruses endemic to humans)… There is a hypothesis that coronaviruses can cause acute infection when they first make the zoonotic jump to humans, which they leverage to become endemic with humans by causing only mild disease from then on.
17:28— In other words, it seems likely that novel coronaviruses lead to strong initial immunity that quickly goes away, followed by mild infections and that this is how they maintain themselves. There have been a number of cases in China now where people were confirmed positive, recovered, RT-PCR tested negative, went home & then became reinfected a month later or so.
19:55 — Allowing everyone to get infected for quick herd immunity, even if it is a valid way for the acute pandemic to end, is a brutal way to handle a new emerging infection. Reducing the transmission chains of the virus is a better approach. Long-term, we will need ~70% herd immunity for this virus to go extinct, it’s preferable that we do this via vaccination.
25:40 — We do not know what the intermediate animal between bats & humans was for SARS-CoV-2. As a result of this outbreak, there is potential for new animals (that are not humans) to contract this virus & become reservoirs for it. This poses the risk of it, or a recombination of it, resurfacing again from these other animals at some point in the future, even if it were eradicated in humans in the next decade.
27:15 — The intermediate vector is without a doubt, definitely not pangolins. They do carry viruses similar to SARS-CoV-2 however.
29:23 — Summer will likely decrease transmission of the virus & will reduce explosive transmission, but will not drive it to extinction by itself. The decrease expected is due to heat, humidity & UV radiation all degenerating the reproductive viability of viruses on surfaces. This decrease could thankfully make it more vulnerable to public health measures that are pursued in the summer.
32:15 — It’s worth noting that influenza is not only seasonal in temperate areas but also in tropical ones too & we have no idea what drives that phenomenon. This is despite it being hot & humid in the tropics during winter.
32:35 — Degree of contact vs. droplet spread of SARS-CoV-2019 is unknown, however Dr. Baric feels that both make contributions & that the cruise ships are clear evidence of droplet transmission. Fecal transmission is also likely possible. During SARS in 2003, aerosolized fecal matter plumed out of one condominium & the droplets from it were able to infect people in a different condominium building.
33:55 — Airplane bathrooms have potential to create aerosols of fecal matter (due to flushing mechanism).
36:43 — Large droplets are the main cause of spread and non-aerosolized airborne transmission does not seem likely from what Dr. Baric has heard in his circles. Aircraft re-circulation of air is not likely to be a huge risk. With SARS in 2003, passengers were infectious to a 6–8 foot radius around them when on an airplane in the few cases recorded of airplane transmission then. He emphasizes that this is a new virus however.
38:35 — Super-spreaders are a very serious problem with SARS-CoV-2
Dr. Baric — “In Canada, there was one example of a super-spreader who simply walked through an emergency room that was packed, fairly packed with individuals, & infected 19 people in the less than 15 seconds they were in the emergency room as they walked through it”
Dr. Rich Condit — “Wow, that’s like Measles”
Dr. Baric— “That’s like Measles”
40:15 — Vast majority of people do not require hospitalization. 18% of people require some sort of respiratory support. People who develop acute respiratory distress syndrome (ARDS) are at high risk for death. There have only been two pathology reports but Dr. Baric speculates that the most likely prognosis is that the virus destroys cells in the alveoli that line the parts of the lungs that diffuse oxygen into your bloodstream. When they die, it exposes your lungs to bodily fluids that can then diffuse into the lungs.
“The little balloons that transmit oxygen to your blood stream become water balloons so you drown in your own fluids.”
The other primary way people die is due to your body layering cells to repair the damaged alveoli cells, but the thickness ends up being too great to diffuse oxygen afterwards so you suffocate. This is exactly the same type of disease that SARS, MERS, H5N1 & H7N9 cause. The NIH has spent hundreds of millions on trying to improve our ability to treat this disease & their work has decreased the mortality rate of ARDS from ~50% to ~30% over the last few decades.
43:44 — Cytokine storms (where one’s immune system’s overzealous response to an infection can inflict significant self-harm to the person) play a role in the whole process of acute lung injury.
44:00 — We do not know why children under 9 do not have issues with the virus. They have very high concentrations of virus & there’s no obvious reason they should not transmit efficiently to those around them. Not enough work has been done to determine if children can be super-spreaders nor what their burden of spread is. X-rays of children’s lungs show that they are clearly diseased & clearly infected, but they don’t show any symptoms.
47:08 — Not only is this not likely to be caused by physiological (size, diameter, throughput etc.) differences between children & adult lungs, if it were a physiological difference, there is reason to believe that we should be seeing this disease affecting children more aggressively than adults.
47:36 (back to the point I told you to remember) Children might very well get infected with the common-cold causing coronaviruses in the first 3–4 years of their life & become immune. This immunity to the age-dictated severity of effects from first-infection could be what is preventing these otherwise seemingly benign viruses from presenting disease similar to that of emerging coronaviruses such as COVID-19 if they were able to more frequently infect adults (and not children), that have never been exposed to it before.
48:18 — Humans have only defined these common-cold causing coronaviruses as ones causing mild disease in recent history. In reality they all originated in other animals at some point. Because of that, we do not know how severe the disease caused by them was when they first infected humans.
“We have no idea how severe they were in adult & naive-adult populations. Most likely they weren’t mild. They were probably brutal disease just like SARS, MERS & SARS-2 are to adult individuals as they get older.
If that hypothesis is true, then the prediction would be that as SARS-2 goes around the globe and infects the adult population, we will become immune, & the virus will now preserve itself in the population by infecting young children who don’t get serious disease. As they grow up, they are pre-immune so they never get serious disease and SARS-2 will now be relegated to the role of being a benign common contemporary coronavirus who somehow lost its pathogenic potential. When the real reason it lost its pathogenic potential is all of the adults are immune.
If that’s the case then we have a 1 to 3 year pandemic that we will be facing until sufficient herd immunity occurs to drive the virus into this type of persistence mechanism.
50:15 — Due to what we know about common contemporary coronaviruses, it is unlikely that immunity or resistance to one coronavirus will protect you from a different one.
51:25 — Dr. Baric & his colleague’s research has shown that there are plenty of SARS-like coronaviruses in bats that are different than SARS-CoV-2 by up to 30% genetic variation that are poised to use human receptors & make a zoonotic jump (the papers I linked at the top are relevant to this). A few of these are more closely related to MERS & there is no way of telling if their transmissibility is more likely to be similar to SARS-CoV-2, something in between or not easily transmissible. In all likelihood a virus fitting each of these bills of properties probably exists out there somewhere & it’s just a question of time until a human contracts another one.
52:50 — It is just as plausible that a person living in rural China, came into contact with a bat in a bat cave collecting guano and spread the outbreak to Wuhan as something involving a wet-market.
53:30 — Most of the data we have so far indicates that this virus primarily infects the digestive system of bats. This has not been well studied, however Dr. Baric knows for a fact that similar coronaviruses are found in guano because it is something they often bring back to the lab in search of them.
54:45 — There are two distinct vaccines prototypes that are moving rapidly towards phase 1 trials. One is an RNA-based vaccine (they found another molecule of RNA to act as the structure for the vaccine), & the other is a recombinant protein-based vaccine (two or more protein molecules that have been combined, either naturally or engineered, to act as the structure for the vaccine). The RNA vaccines are known to elicit a strong response from human immune systems, meaning they potentially can lead to our immune system building up strong resistance to the deactivated virus attached to the RNA structure. This is a good thing.
(To speculate, the genetic language of many of these viruses, such as SARS-CoV-2, are RNA themselves, so if you were to take the spike protein, or the spikes on the outside of the virus that the virus uses to infect target cells, and attach that on some other benign molecule of RNA, the human immune system would have good reason to treat it like an active pathogen and because of that may elicit an immune response leading to the correct antibodies being developed & the desired effect of immunity from the virus being achieved).
55:10— (This is to the best of my understanding, this part is definitely way more advanced than anything I’ve learned since I first became interested in this ~2 months ago, if anyone more knowledgeable wants to give me a better explanation for this, please feel free) Dr. Baric is speculating on what the potentially dangerous overreactions from your immune system due to a vaccine might be (white blood cells, cytokine proteins etc.). These are the things that scientists need to ensure don’t happen for a vaccine that could potentially be used on everyone in the world.
55:55 — The RNA-based vaccine Dr. Baric mentioned is, like I described above, the spike protein of SARS-CoV-2, attached to some messenger RNA, surrounded in a non-polar lipid layer so that it can both emulate a virus, but also not disintegrate on contact with, for example, saliva . (This is similar to what happens when you pour oil on a plate of water, the fatty layer prevents water from dissolving it when immersed in the almost entirely water-based bodily fluids of a person. If it didn’t have this layer, it would react more like pouring salt or alcohol in water instead & disintegrate).
57:25 — A vaccine being developed in under 18 months would be a record for speed of vaccine development. However, there is reason to be optimistic that this is feasible, as the plug-and-play nature of using messenger RNA as a vaccine development platform like this is exactly the type of system that could see us break our record.
57:50 — In order to have safe & effective vaccines at record-breaking speed, we likely need to be doing phase-1 human trials at the same time as some of the animal testing & we need to be in a position to do phase-2 testing in human populations in September & October to ensure that it precedes the next round of infections when COVID-19 starts picking up again next Fall.
Alright guys, back to Rust, hopefully this proves useful for some!
