Kiki’s Comments                                                                                                          May 2020

                                                Episode 610: Coronavirus FAQ

            Key Points:

*FDA is approving certain antibody tests for Emergency Use Authorizations (EUAs), but not all antibody tests are equal in sensitivity or specificity—be discerning between tests and with results (Roche’s antibody test is currently of high standard)

*there is no evidence that taking ACE inhibitors or ARBS affect the rate of COVID-19 or severity—continue to take prescribed ACE inhibitors or ARBs

*everyone should wear masks and personal protective equipment, particularly as measures are being relaxed

*Lessons from Taiwan: advanced decisiveness, scientific-thinking, and effective risk communication can help mitigate spread as we lighten lockdown

*increased surveillance and testing is key

*there is zero evidence that CoV-2 came from a lab (that it is man-made) and a lot of evidence that the virus came from nature (zoonotic event)

*coronaviruses do not mutate antigenic properties to develop into strains the way that influenza viruses do

*SARS-CoV-2 does not currently have a known animal reservoir

*the zoonotic origin of the virus is in China, phylogenetic analysis thereafter is useful to show spread

*be careful of journalistic spins on scientific articles—often titles and tag-lines are misleading 

            Coronavirus FAQ:

*antibody tests: FDA has revised their policy. FDA has given 12 EUAs (Emergency Use Authorization) and now has performance and specificity requirements for manufacturing and production of antibody tests.

Roche’s antibody test: EUA-type approval, fewer false positives and fewer false negatives. This type of test is important for a positive predictive value—particularly useful for populations with few infected individuals. 

n.b.i. John Oliver has done an antibody test review on Last Week Tonight for COVID:

n.b.ii. pseudotype is a virus that is modified so that it is using another virus’ surface viral attachment protein—e.g. it will find attach to cells as if it was CoV-2, but it is harmless because the main virus is a harmless adenovirus or other virus

*ARBs and ACE-inhibitors: there is no evidence that taking ACE inhibitors or ARBs affect the rate of COVID-19 or severity

n.b. ACE-inhibitors are often taken for blood pressure and cardiovascular disease

*Institute for Health Metrics and Evaluations—University of Washington Projections: given current conditions, they predict that by August 4, 2020 deaths will have leveled out in the US at 144,000 due to COVID-19. The curves that are modeled do not bottom out as quickly—the pandemic is drawn out longer. The ultimate situation is that at equilibrium, 2-5 years from now, 80% of the population will be seropositive. Best evidence at the moment indicates 250,000 to 1 million deaths in the United States unless a drug or a vaccine is found or created. 


*Kyle: Antibody testing rapid lateral flow came back indicating IgM positive and IgG negative, what does this mean? It is possible that the test result is wrong with both a false IgM positive and a false IgG negative. The test was performed by a lab and test that are not currently approved by the FDA with EUA, but even if it was it is possible that the test result was incorrect. There are many unapproved tests currently being produced and sold, so this should be taken into account. Accuracy can differ widely between tests. It is probable that given the results it is no longer as helpful to self-isolate as it would have been, but follow State protocol and err on the side of caution. 

*Angela: what are your comments on opening Universities and Schools in the Fall? We need to adopt behaviors that allow us to cope with this epidemic in a fashion that leaves the healthcare system capable of giving individuals the best possible care while not completely shutting down society. We will not likely have herd immunity by the Fall, that will likely not happen until the following year, but some sort of social distancing, testing, and social policy may be able to facilitate a Goldilocks paradigm for society. It is important to have universities open, if only to train and produce more medical professionals (nurses, doctors, physicians assistants, registered nurses, etc) to help feed into the system. For K-12, there are likely going to be adjustments to online classes and larger classrooms, while other institutions are shifting to fully online. We have to come back, but we need a plan. The solutions have not yet been found, but they do exist. Testing should be really extensive—as soon as someone is positive, they should be isolated and their contacts traced; it is not too late to implement these policies. 

n.b. blame is not productive—the best thing to do is to learn from different policies and to be more informed and prepared for the future

*Jamie: what is the role of exotic species as pets or held in close contact with humans as reservoirs and should these animals be quarantined? With reservoirs you have an established population of the virus in that species that can then be transferred to another species. Even cats have been shown to be most likely one-off transmissions rather than reservoirs for CoV-2. There is no evidence that CoV-2 can infect camels. It is not crazy that there will be an animal reservoir for CoV-2 when it spills back into animal populations, but right now we do not have evidence for this.

n.b. camels are a reservoir for MERS

*Trish: conflicting information of origin of CoV-2 zoonosis and transmission into humans (particularly referencing transmission in France)—what should we believe? Be careful of journalistic spins on scientific articles. Even looking at the specifically referenced paper, this is a phylogenetic analysis of the virus, but nowhere in the paper does it imply that the virus arose in France. This is #fakenews. The virus originated in China, but the phylogenetic analysis will show the transmission pathway after that zoonotic event. 

*Anonymous: are there mutant coronavirus of CoV-2? The viruses in the paper are alpha coronaviruses, rather than beta coronaviruses (CoV-2 is a beta coronavirus). We do not yet have evidence of mutant CoV-2 coronaviruses.

*Sean: could the novel coronavirus have been brought into the US via the jet stream from China? Probably not—viruses do circulate in the atmosphere, but it is much more likely and traceable in some cases that this has to do with human-mediated travel (airlines, etc).

*Tom: (Oregon) there is a state-wide surveillance for volunteers to be monitored and tested daily for a year—what is your opinion? This would be great for as many people as possible. This should be done by the government, for example the CDC, as this would be very helpful for implementing policies, such as whether to open schools. This is a great thing to do.

*Daniel: (Taiwan) In Taiwan, we have done test-trace-isolates (isolation of individuals in contact with someone positive) and closed boarders early. We have also done a mass production for protective supplies. This has meant that much of life has been able to continue, though in a socially-distant fashion. Lessons from Taiwan: Advanced decisiveness, scientific-thinking, effective risk communication. Thoughts? This is excellent. There are a lot of simple things that can be done to limit the spread (masks, hand sanitizer, common sense measures). It is possible to limit spread, but these have to be adhered to. We can learn lessons from Taiwan that can be utilized in the United States and other countries with the capacity. 

n.b. MASKS ARE RECOMMENDED FOR EVERYONE—the CDC did not recommend them for everyone at first, but this has changed with evidence and now masks are universally recommended

*Zach: why is CoV-2 considered SARS-like or MERS-like? SARS-like is the genome, they just happen to use similar receptors. The genome dictates everything—it is where they fall on that evolutionary tree depending on their genome that determines the scale of MERS-to-SARS. 

*Anonymous: if you got the common cold coronavirus, would that be protective for COVID-19 caused by CoV-2 similar to how the Oral Polio Vaccine (OPV) worked? The innate immunity phenomenon is based on trained immunity. We don’t know enough about this yet with CoV-2. It is possible. Certain pathogens induce this immunity particularly well, but common cold coronaviruses have common reinfection, which would point to lower likelihood of protectiveness—possibly this could be protective for a couple of months. 

*Margaret: what are your thoughts on the Wuhan bioterrorism theory—intelligent people apparently are going into conspiracy theories? Quote from Ed Young in the Atlantic (quoting someone else) “Journalists still think of their job as producing new content, but if your goal is public understanding for COVID-19, one piece of new content after another doesn’t get you there, it requires a lot of background knowledge to understand the updates and the news system is terrible at providing that knowledge. Instead the staccato pulse of reports merely amplifies the wobbliness of the scientific process, turns incremental bits of evidence into game changers, and intensifies the already palpable sense of uncertainty that drives people towards misinformation.” Plain English explanations:

  1. how do you know SARS-CoV-2 is not man-made, man altered, or genetically engineered? Evidence points to CoV-2 originating in nature NOT in a lab. First you would need a virus to start with that we can then engineer—from all the papers and genomes that are accessible in the databases, there was no virus that we had accessed that was close enough to CoV-2 that could have been human modified to the current form, except a bat virus from 2013 that is still genetically very different. Nobody took a virus that did not infect people and modified it so that it could: first, because scientists currently do not know how to do that, second, because there is nothing genetically close enough to be a precursor. Again scientists wouldn’t know what to do—the viruses being made have all had research into infecting animal vectors like mice, so there is a large gap in knowledge. While it is possible to chemically synthesize this virus from scratch, it is very unlikely that scientists would know what to make. There are differences from the 2013 bat virus in the receptor binding domain (RBD) and the furin cleavage site that make sense for increased infection capability and to make the virus pathogenic to people, but there are also a lot of accrued mutations (eg mistakes and changes in the RNA) that don’t appear to have any particular effect. It is hard to imagine how all of those random changes would have been picked up if this was being made in a lab—seeing all of the random mutations or genetic drift that would be seen if the virus was evolving in nature but not what you would see if the virus was evolving in the lab is the biggest indicator that this is not man-made. There are too many natural-looking mutations to be likely created. The furin site as an intention insertion is off-base as it is not necessary to infect humans. There are bits and pieces that people would not have thought to combine into a successful virus. Also, some of the changes to the RBD are novel and had a very unexpected impact on viral transmission, so this would be incredibly unlikely to have been found and used with no prior research. Bottom line: there is zero evidence that CoV-2 came from a lab and a ton of evidence that the virus came from nature

How do you know SARS-CoV-2 is not mutating into different strains like the flu virus? We know because with our history of studying corona viruses, they do not mutate the way that influenza viruses do. Coronaviruses are all antigenically stable, unlike influenza. This is shown in the genome. We can test this in cells to show they have the same properties. In other words, RNA viruses mutate—influenza is an RNA virus and it mutates, coronavirus is an RNA virus and it, too, mutates, but the mutation that happens in the influenza virus is changing its antigenic properties so that we have different influenza viruses each year that we need new vaccines to, while the coronaviruses are not changing the surface proteins the antibodies are reacting to. It is mutating, but not in the way of influenza.