Anthony writes:
Hi Vincent & crew, absolutely love the podcast, I’m a new listener (since the beginning of the pandemic) and I find the show so fascinating that I’ll be a listener for long after the pandemic too. Dr. Griffin’s updates are a wonderful insight into the heroic work being done by physicians and front-line professionals like him, and the rest of the episodes and guests are a fascinating insight into the equally heroic work being done our scientists who are working tirelessly on understanding viruses, and ultimately protecting us all.
My question is for Dr. Griffin – early in the pandemic the advice for those with suspected or confirmed Covid-19 was to take it easy at home, have a pulse-ox handy and head to the hospital if they have enough trouble breathing. I’m wondering what lessons have been learned over the past 8 months with respect to the best practices for self-care at home, and the best time to seek more advanced care, either at a hospital or outpatient setting. As case numbers spike, I hope that folks knowing how best to take care of themselves will reduce the burden we’re starting to see on hospitals. Equally if people understand when to seek help, this will hopefully reduce the numbers arriving at the hospital when it’s too late or they require more significant care.
Keep doing everything you’re doing, you’re all true heroes.
Dave writes:
Hi Twivers,
I’d like to address this question to Dr Daniel Griffin. Despite my best efforts to mask in public and physical distance, I found out today that I have tested positive by a 15minute Rapid Antigen Test (SOFIA, I think?) I decided to get tested because I started developing symptoms of cough, chest congestion, and a fever of 99.4 today (under the tongue). I’m hoping (and fairly optimistic) that my symptoms stay mild. But it really got me wondering if there was any data on the likelihood of someone being a “long hauler” and if the severity of the disease can predict whether they are more likely to have chronic symptoms or not.
For what it’s worth, I work as a pharmacist for a major retail chain, and am therefore considered an “essential worker” and have been working the entire time throughout the pandemic. I told family and colleagues “its a matter of *when* I catch it, not *if*” and so I guess my time has finally come. I wish I could share a picture of the pathetic lack of physical barrier my company has provided to protect its pharmacy employees (in an already dangerously open layout) but alas, I do not. So I’m pretty sure I either caught it from a patient unawares or from a coworker on the front end of the store that tested positive 2 days after the last shift we worked together, despite me trying to keep my distance, wear a mask, and limit communication with him.
Thanks for the wonderful podcast and and all the great information y’all provide
Dave Hale, pharmD
Salt Lake City, UT
50 degrees F
46% humidity
Jaki writes:
Hello, I am a listener from the Metro Vancouver area in Canada. I am not in the medical field. In fact, I am a youth pastor. I have grown slightly in my understanding of things from listening to you guys since March and I find myself hungry for information.
I so appreciate that you guys give the facts and present them clearly as they are currently known!
I love that it is always, “this is what we know right now” and that you guys communicate clearly what you don’t know as well. There is so much terrible information out there, and you guys have been a breath of fresh air. I am thankful.
I have a question for you.
My dad was diagnosed in September 2019 with Pulmonary Fibrosis. He was given two to two and a half years to live. Since COVID-19 safety measures came into effect in BC, we have not hung out with my dad indoors — We have been socially distancing outside and when my kiddos are talking loud/singing around him, they are wearing masks.
(Just FYI as of November 2nd, Canada as a whole was at 2.2% Positive. Canadians are fairly good at following directives, wearing masks and social distancing… although obviously, we have seen numbers rise in schools and in our 20-35s as well. Schools have been open with modifications since September and I have 2 six year olds.)
My predicament is that we want to do Christmas with my parents (I am aware that this might be my daddy’s last Christmas… hopefully not, but maybe.) SO, we had planned to quarantine for 14 days starting on the 11th of December. And then, be able to give my mom and dad hugs and kisses for Christmas.
HOWEVER… my bubble was burst when Daniel Griffin was speaking about the NHL and how they had to test again because if people brought it in, then people could be pre-symptomatically or asymptomatically spreading and then we have the next incubation time to wait out… and so one or more of us could be contagious on Christmas day while none of us have symptoms. (There are five of us in our household).
Here is the kicker: In BC right now, we are ONLY allowed testing if we have symptoms. It is a NAT/PCR test and we typically wait 1-3 days for results.
Do you think that with the lower instance of covid here, it would be okay to do the 14 days? Or, should we try to acquire a test 4 days before Christmas and wait for the results (still leaving the 3 days of variable in between?)
I would love your thoughts.
Thanks heaps!!
Jaki
Anonymous writes:
I am attaching the official statement from the relevant Danish authority
https://en.wikipedia.org/wiki/Statens_Serum_Institut
(kind of sort of the Danish CDC equivalent) posted on the official Danish government corona web site. Maybe a translation program will do a reasonable job.
The notice sent to WHO may also be available and provide information. As I understand it they first identified a number of mutations by sequencing a large number of regular human samples, ones from mink and ones from contacts. In doing so they found a distinct variant (cluster 5) with 4 mutations in the spike.
They then grew a standard variant and the new variant, tried to neutralize both with antibodies from convalescent patients and saw that they did not neutralize the new variant as well as the old one.
My understanding is that these people are very competent and the lab is very good, but it is very far from my area of research.
Will let you know if I see anything else of interest and will look
forward to your next episodes. I really enjoy them!
Sincerely,
Anonymous
PS. 7C/45F and sunny.
Here is a google translate of the Danish document: (highlight vr) – original in Danish here https://nyeborgerlige.dk/wp-content/uploads/Risikovurdering-af-human-sundhed-ved-fortsat-minkavl_03112020.pdf
As of 2 November 2020, SARS-CoV-2 infection has been found on 191 mink farms. This development has taken place despite intensive efforts on the part of the authorities with regard to to limit infection. At the same time, infection is seen with new types of SARS-CoV-2 virus that adapts to mink (mink variants) in the local population, and there is a strong geographical and temporal connection between the number of positive mink farms and the incidence of infection among humans. Mink with SARS-CoV-2 constitutes a large reservoir of viruses, which is a major business risk associated with mink breeding in infected areas, and it has not been possible to limit further spread to the surrounding community. Due to the changes that occur in the spike protein in several of the mink variants of the virus, there is a risk that vaccines that target the spike protein will not provide optimal protection against the new viruses that occur in the mink and the immunity from over COVID-19 infection may provide less protection against the new virus variants.
If mink production continues in Denmark, so that a large population of mink is re-established in 2021, it is considered highly probable that this population will be susceptible to infection. In addition, SARS-CoV-2 is still expected to be circulating in humans and no significant immunity in the population until the majority of the population has been vaccinated. Thus, there is a significant risk of recurrence of the spread of infection among mink and humans, which has been seen in Western Denmark in 2020. This is considered to involve a great risk to public health, both by causing a greater disease burden among humans, and by a large virus reservoir in mink increases the risk of recurrence of new virus mutations against which vaccines do not provide optimal protection. Overall, the herd immunity obtained through vaccination or over-the-counter infection may be at risk of being weakened or absent. At the same time, it must be expected to mean a significant deterioration of our opportunities to maintain epidemic control in Denmark, which may mean that further restrictions and limitations on society, etc. must be introduced.
Conclusion: Continued mink breeding during an ongoing COVID-19 epidemic involves a significant risk to public health, including the potential for vaccine prevention of COVID-19.
Background
Since the beginning of June 2020, a total of 191 mink farms have been infected with SARS-CoV-2. These are primarily located in the North Jutland Region and in Central and Western Jutland. Knowledge about the introduction of infection as well as consequences for infection between mink and human is primarily based on data from North Jutland. In summary, it is probable that the introduction of infection with SARS-CoV-2 to the first mink farm has taken place in connection with human-to-mink infection in the weeks leading up to the outbreak.
Subsequently, in June 2020, there was a pronounced spread of infection to local communities in connection with outbreaks in a nursing home, caused by a variant of SARS-CoV-2 developed among mink (hereinafter referred to as SARS-CoV-2 mink variant). Since the beginning of August 2020, 168 mink farms in the North Jutland Region have been infected – all with the SARS-CoV-2 mink variant. In parallel, an increasing incidence of SARS-CoV-2 has been found among citizens in the North Jutland Region, where now approx. half is due to the SARS-CoV-2 mink variant (for details see Appendix 1).
Several mutations have occurred on an ongoing basis in the SARS-CoV-2 mink variant, where 5 clusters have been found so far. In addition, two new SARS-CoV-2 types have been introduced in the municipalities of Esbjerg and Vejle, respectively, which are not related to the mink variant.
Mutation in viruses
Virus mutations are small changes in virus genetic material that occur continuously in connection with the virus copying itself. The more viruses that are copied, the greater the likelihood of mutations occurring. A virus’s genetic material, and thus any mutations, can be detected by whole genome sequencing (WGS). Among the mink variants of SARS-CoV-2, several examples of changes in the spike protein have been seen. The spike protein is essential, as humans after a natural infection form antibodies to the spike protein, and the potential COVID-19 vaccine candidates are also based on this protein. There is therefore a risk that the effect of spike-based anti-COVID19 vaccines may be affected when changes occur in this part of the genetic material.
The presence of an extensive reservoir of viruses in mink poses a serious threat to public health, as viruses spread from animals to humans. The risk of mutations makes this risk particularly serious. Mutations in the spike protein also occur in viruses among humans (worldwide) unrelated to mink farms, but not or extremely rarely the same mutations that occur in mink. However, it has been shown that the current vaccine candidates will be able to cover the variations of virus that have emerged among humans over the spring.
Concerns about changes in the spike protein in mink variants of SARS-CoV-2 were raised by the State Serum Institut when the first mutations were detected. Among the mink variants, seven different mutations have been seen in the Spike protein and examples of up to 4 different changes in the Spike protein in the same virus. A specific virus with 4 changes in the genes for spike protein has been detected in five North Jutland mink farms and in 12 patient samples, of which 4 with direct connection to three of these farms (cluster 5). Preliminary studies suggest that this virus exhibits decreased susceptibility to neutralizing antibodies from multiple individuals with a history of infection. This has been demonstrated in a laboratory experiment, where it is seen that the particular mink virus is not inhibited to the same extent in the growth of antibodies from humans who have been infected with a non-mink-related variant of SARS-CoV- 2. Ongoing studies will further uncover the problem . Additional variants have been identified by sequencing but have not been investigated for neutralization yet. This is worrying as it could potentially have an impact on the future COVID-19 vaccine’s efficacy against infection with new mink variants, and pose a risk of impaired immunity to these following COVID-19 infection, which is important for the individual and for herd immunity in society.
Significance for human health if mink production continues as normal
If the mink production continues as normal, after fur there will be a number of live mink left which will be used as breeding animals for next year’s production. The number corresponds to approx. 20% of the annual stock of approx. 17 million mink. In light of the current situation, this number will consist of 1) mink that are not infected with SARS-CoV-2, 2) some mink that have probably formed antibodies against SARS-CoV-2, and 3) presumably some mink that are unknown infected with SARS-CoV-2. The distribution of these groups is unknown. This means that in the coming months after fur, outbreaks and the occurrence of SARS-CoV-2 infection among mink can still be expected. Therefore, there will also continue to be a risk of infection from mink to humans.
In connection with the start of next year’s breeding season, there will continue to be a risk of SARS-CoV-2 infection among mink. Among mink that have not been exposed to SARS-CoV-2, all mink will be at risk of becoming infected. Among mink that have previously been infected with SARS-CoV-2, it is expected that some will have developed antibodies to SARS-CoV-2. It is not known to what extent, -or how long-, these antibodies protect against new infection with SARS-CoV-2, nor is it known to what extent these antibodies will be passed on to mink puppies. However, it is estimated that at the beginning of the newborn mink’s life there will be protection from maternal antibodies. However, this protection is expected to decrease, so that after a few months there will again be a large population of mink without antibody protection against SARS-CoV-2.
There are currently no signs that the infection in mink farms is decreasing over time. A continued presence of SARS-CoV-2 in mink production, and the fact that the infection is typically detected late in the process in the individual farms, will entail a risk of spreading in relation to trade in breeding animals. In addition, the risk will depend on the prevalence of SARS-CoV-2 found in humans at the time. Both the start of the first and second phase of the outbreak occurred at times with relatively low incidence in the population, and it must be expected that further increase in the population incidence will increase the risk of introducing new virus types to mink from humans, most recently in Esbjerg and Vejle municipalities .
If mink production continues in Denmark, so that a large population of mink is re-established in 2021, it is considered highly probable that this population will be susceptible to infection. In addition, SARS-CoV-2 is still expected to be circulating in humans and no significant immunity in the population until the majority of the population has been vaccinated. Thus, there is a significant risk of recurrence of the spread of infection among mink and humans, which has been seen in Western Denmark in 2020. This is considered to involve a large risk to public health, both by causing a greater disease burden among humans, and by a large virus reservoir increasing the risk for the re-emergence of new virus mutations against which vaccines do not provide optimal protection. Overall, the herd immunity obtained through vaccination or over-the-counter infection may be at risk of being weakened or absent. At the same time, it must be expected to mean a significant deterioration of our opportunities to maintain epidemic control in Denmark, which may mean that further restrictions and limitations on society, etc. must be introduced.
I wrote Anders Fomsgaard of the State Serum Institute:
There are three issues that worried us:
1) A parallel epidemic in mink was developing where the numbers of mink farm (each with 10-00-20-00 minks) are exponentially increasing with 2-3 new farms every other day from now 217, AND spreading geographically in Denmark. This fast spread will not stop until all 1,200 farms have been infected! Our control-measures (restriction on visits, masks, clothes shift, wash etc etc) don’t work at all!?
2) These increasing giant reservoirs of virus are infecting the danes in the community (parallel increasing curves in infected farms and infected humans). More than 50% of the infections in people in North Jutland are with different mink variants! We are sequencing a lot of virus routinely from humans and minks – and would never have discovered this if not! Sequence – sequence – sequence!
3) ON TOP OF THIS (and for some reason this aspect is the only one people have heard?) we have tested two mink variants after culturing (sequencing before, during and after culture of course) for sensitivity to antisera from 10 convalescent patients, and one of the variants (with 4 mink unique mutations in the spike) was less sensitive to neutralization by these sera as compared to virus without the same combination of mutations.
WHICH demonstrate the possibility of these mutating virus from the animal species to become less sensitive to antibodies e.g. after a spike based vaccine PERHAPS.
We will not take the risk from point 1-2-3
Now we are pcr screening people for infection by mink variants suspected to influence neutralization to intensify contact tracing and interrupt any chains of transmission. I think the variants will disappear then (it is an acute virus not a chronic one)
Sequences will be put on GISAID and more information posted and published and told to all that like to know as fast as we can
Yours Anders
Anders Fomsgaard, professor overlæge dr. Med.
Leder af Visur Forskning & Udvikling
Statens Serum Institut
Anonymous writes:
The Danish prime minister, minister of health, science head of SSI (Kåre Mølbak) and various others just held a press conference. Some interesting points:
1. A technical description of SSI’s analysis will be made available as soon as they can (days?). Will point you to it if/when I see it.
2. There was a discussion about mutation rates in RNA viruses, host adaptation and antibody escape mutations. Interesting with such technical details in a prime time televised government press conference. Would seem relevant to consider based on the high infection rate in the mink and the millions of animals.
3. Everybody in the affected region (about 280000 people) are strongly urged to be tested over the next days, some more than once. Majority probably will. Clearly a logistical challenge. I think that it represents the entire PCR test capacity of the (quite small) country for something like 3 days. And overall capacity in Denmark is around 10% of the populations per week, a lot more than most places.
4. All positive samples will be sequenced.
5. They have not seen the variant for over a month. The combination of mutations has not been seen in sequences in the rest of the world. Statistical significance of those observations is unclear.
6. Significant further tightening of restrictions in the region.