Kids and the Coronavirus

Several people have asked about this one, specifically with respect to reopening schools or church children's programs.  At this point, everyone knows that kids are much less likely to have severe symptoms, and in most cases, kids have no symptoms at all.  But there is also the specter of this Kawasaki-like inflammatory syndrome that some kids are getting post-covid, and there is also the possibility that kids could pass the virus to their more-susceptible teachers, parents, or grandparents.  

First, the risk from the initial covid-19 disease itself.  According to CDC data, kids under 15 are more likely to die from the flu than from covid.  For older age groups, covid is much, much worse than the flu.  Just for funsies, here is that CDC data put into a graphical form.  We know at this point that the official data is not fantastic, but I think it's okay for a comparison of this kind, to show the age effect.

Because kids have such mild symptoms, they are much less likely than adults to be diagnosed.  There have been a few studies that try to determine whether or not kids are less likely to get the virus if exposed.  The difficulty is that it's hard to know how much someone was exposed.  There are two similar studies, both done in China, that came up with different results. The general idea is to follow secondary contacts of infected people -- mostly people living in the same household.  If one person in the household is diagnosed, who else in the same household gets it?  The first study found that kids were just as likely as adults to get the virus, the second one found that they were less likely to get it.  One explanation may be that early on, we didn't know about the potential for the secondary inflammatory disease in kids, so parents didn't worry about exposing their kids, but later on, they might have changed their behavior to prevent transmission to their kids.

There was also a study in Belgium, right before the lockdown there, in which kids in daycare centers were screened for the virus.  No cases were found, despite lots of the kids having colds.  An antibody screening study in Switzerland found that both kids and older people were less likely to have antibodies.  I think that this suggests that people are protecting groups they see as vulnerable from exposure, but again, it's not definitive.  

So the upshot so far is that while kids are clearly much less likely to have severe cases, I'm not convinced that they are less likely to be infected. It's certainly possible, but not definitive. 

Turning now to Kawasaki Disease / post-covid inflammatory syndrome, various hospitals have noted a sudden increase in the number of kids coming in with symptoms of severe inflammation.  In some kids, it manifests in the heart, others have severe skin rashes, GI symptoms are common.  This paper reports a 13-fold increase in this syndrome at a hospital in Paris. Most of the kids had a positive antibody or PCR test for covid.  

So how common is this syndrome in kids that become infected?  We can try to get a rough estimate based on the Paris report.  The background prevalence of Kawasaki disease in northern France is 9 per 100,000 kids under 5, and typically about 3/4 of the cases are in kids under 5, so overall prevalence is about 11 per 100,000. So we might expect (11 x 13 = 143, minus 11 background is 132 out of 100,000 additional cases in a population that had the same infection rate as the kids in Paris.  This news site reports that about 10% of Paris area kids tested positive for antibodies.  So if all kids were infected, that would be 1320 per 100,000, or 1.3%. If that's real, it would be a solid nope from me, given the severity of symptoms mentioned in the Paris paper.  It describes kids having lumbar punctures and exploratory surgery to try to figure out what was going on with them.  

Just to check another region, here is a study from Bergamo, Italy, in which the incidence of Kawasaki disease increased 30-fold. Background prevalence of KD in Italy is about 22 per 100,000. So 22 x 30 = 660, subtract out the 22 background to get 638 per 100,000. I can't find info on antibodies in kids specifically, but about half the population of Bergamo overall had antibodies.  If that holds for kids, that would be 638 x 2 = 1276 out of 100,000 or 1.3%.  

In both of these cases, the antibodies were measuring the whole outbreak, and the KD increases were measured over just a short period of time, so it's not the best comparison.  So take this as a rough estimate, even though I came up with the same number in two different cities.  

I know people are eager for life to get back to normal, but subjecting kids to a virus that has nasty after-effects in 1 in 100 sounds like a bad idea to me. If anyone has better data on the percent of kids who have the inflammatory syndrome / Kawasaki disease after contracting SARS CoV-2, please do share.  

Don't believe the covid conspiracy theories

I've said this before, but it bears repeating. 

This pandemic is not the kind of thing that could have been engineered. It is possible to make targeted changes to the genome of a virus, but you'd have to know what changes to make.

The reason SARS2 went pandemic, but SARS did not, is that SARS2 has the ability to spread through asymptomatic and pre-symptomatic hosts. We don't know how it does that, even knowing its whole genetic code. Pretty much every virologist on the planet is paying attention to this virus, and no one has come up with an explanation of how the genome of this virus leads to its ability to spread in this way. 

I get the impression that the idea behind these conspiracy theories is that if something bad happens, it can't be due to nature, it must be human agency -- the natural is safe and the artificial is dangerous. But this belief is deeply at odds with the biology. Nature wants to eat you. If you disable the immune system of a human, they will quickly die, because the immune system is constantly fending off microorganisms that are all around us, invisibly licking their chops at the thought of getting access to a nutrient-rich human body. Even the good bacteria that live in your gut are being held in check by your immune system. They are beneficial if you have a functioning immune system, but at the same time, they would eat you if they could. 

Viruses are, at least sometimes, a bit gentler than bacteria. They just want to hijack your cells, and turn them into virus factories. Think of them as the Borg of the natural world. You will be assimilated. There are some viruses that manage to lie low and live in what appears at first to be peaceful coexistence, but they too are being held in check by the immune system. Weaken the immune system, and now you've got the virus that gave you chickenpox 50 years ago emerging to cause shingles. 

New viruses have been emerging from the animal world for at least as long as we have been studying them. This is not the first, and it won't be the last. It's the way nature works.

Only a few generations ago, the leading causes of death were infections, attacks from without by nature. We have managed to dramatically reduce those numbers. Part of it was sanitation. We realized that sewage was contaminating the water supplies, and fixed that problem. Part of it was the development of drugs, especially antibiotics. And the biggest part of it was the development of vaccines. They are not perfect, but they are obviously much, much better than the alternative.

Nature can be quite beautiful. Even microorganisms that cause disease are awe-inspiring in their complexity. I'm not anti-nature. But I also approach it with a healthy dose of caution, because even if we have subdued it a great deal, I know that it only appears tame.

Does wearing a mask protect you from coronavirus?

There was some confusion early on in this crisis about masks.  The WHO originally said that "there is currently no evidence that wearing a mask (whether medical or other types) by healthy persons in the wider community setting, including universal community masking, can prevent them from infection with respiratory viruses, including COVID-19.", but has since shifted to a position that a mask alone is not enough.


The US Surgeon General tweeted on Feb 29 "Seriously people- STOP BUYING MASKS! They are NOT effective in preventing general public from catching #Coronavirus, but if healthcare providers can't get them to care for sick patients, it puts them and our communities at risk! https://t.co/UxZRwxxKL9." 

I don't know what that link (which goes to the CDC) originally said, but now it recommends wearing a mask ("Everyone should wear a cloth face cover when they have to go out in public, for example to the grocery store or to pick up other necessities.").  The CDC webpage now even has a video of that same Surgeon General making a mask from an old T-shirt and two rubber bands.

So right now the CDC is encouraging mask use, and the WHO is at least no longer discouraging it.

I've posted a blog post in which I describe how I feel safe going out in public wearing my N95 mask.  I've been posting links on FB along the way, as research came out, FB is not great for finding old posts, so here they are, for those who want them all in one place.


From March 20th
https://www.facebook.com/jennifer.gruenke.5/posts/612546845366

The main study I was looking at was this 2008 study of the filtration capacity of homemade masks.  The best was one made out of a tea towel. In this image, the different colors are different people wearing the mask, the X-axis along the bottom is time, and the Y-axis on the left is a protection factor for the person wearing the mask.  A protection factor of 3, for example, only one-third of the particles make it into the mask.  That's not nearly as good as an N95 mask or a surgical mask, but it's much better than nothing.

I also mentioned this study, which showed that masks protect health care workers from bacterial infections. Not the same as viruses, but still the same general idea.

From March 31https://www.facebook.com/jennifer.gruenke.5/posts/613095540776

This is a study modeling the effect of masks in Wuhan, China.  I'm not crazy about models, but they do cite a meta-analysis, that show a strong reduction in infections in multiple studies of health care workers exposed to various pathogens.

From April 5https://www.facebook.com/jennifer.gruenke.5/posts/613347775296

This is not an official academic source, but it is reporting on filtration by different kinds of fabrics, for those making their own.  The best homemade mask filtered 79% of virus-sized particles.  They said "The best masks were constructed of two layers of heavyweight "quilters cotton" with a thread count of at least 180, and had thicker and tighter weave."

From April 22https://www.facebook.com/jennifer.gruenke.5/posts/614724386556

This was a news report as well, but there is an academic version here.  Researchers put a nylon stocking over a homemade cloth face mask, in order to improve fit to the face, and eliminate air coming in from the edges.  They found that "Use of a nylon stocking overlayer brought the particle filtration efficiency for five of the ten fabric masks above the 3M surgical mask baseline."

From April 23https://www.facebook.com/jennifer.gruenke.5/posts/614884450786

This is a study of outgoing virus, that is, how much you spread to other people with and without a mask. They were using surgical-type masks and found that they blocked coronaviruses (the cold-type; this was before covid came along)

The image below is new, but this math person has made a model for how safe it is to go outside with and without a mask. I'm not generally a big model person, but she at least gives you the spreadsheet so you can download it and change her assumptions as you wish.  And even if it's off by a factor of ten or a hundred, the risk of catching the virus outside your home while wearing a mask and being mindful of hand hygiene is really small.https://medium.com/swlh/so-youre-going-outside-a-physics-based-coronavirus-infection-risk-estimator-for-leaving-the-house-d7dcae2746c0

I definitely remember more studies, for example one in China where the health care workers in the Covid-19 ward were given the N95 masks, and those in other wards had to go without.  Zero health care workers with the masks caught Covid, whereas there were multiple cases among the workers without the masks.  But I can't find the link.

The current general attitude of one nerd node of trust towards the coronavirus

I’ve been searching daily for interesting articles in the primary literature and posting them on FB with short summaries, but I haven’t really given much of my personal sense of the current gravity of the situation.  When I started grad school, we were all put in a room and taught how to read a scientific paper.  You should focus on the methods (what the researchers did) and the results (what they saw happen), but come up with your own conclusions before reading the discussion section, where the authors give their conclusions and interpretation of the data.  In fact, you might even consider skipping the discussion section altogether.  So my instinct is to show people data and let them draw their own conclusions.  But sometimes discussion sections can be really helpful.  The authors have more experience with their system, and may well have thought of something I haven’t. So while I still like the data-focused approach, I can see the value of a periodic “discussion section” to my blog / FB wall to give people a sense of what I think the data mean.

I first became aware that there was a coronavirus outbreak in China shortly after Christmas.  The CDC website had a page on it, and I was looking at their viral surveillance section to try to figure out what the crud that was going around was caused by (that disease was clearly not covid.  It didn’t kill enough people).  At that point, I was thinking of this new coronavirus as another SARS or MERS -- sad in that it was killing people far away, but unlikely to spread through the whole world. But by early March it was clearly starting to spread, and by March 11, it was declared a pandemic, which means that it was spreading quickly through many different countries.  The thing that apparently makes this virus more prone to becoming a pandemic than SARS or MERS is that it can be spread by people with no symptoms at all.  With SARS, you could take someone’s temperature before they got on a plane and have a pretty good idea whether or not they were shedding virus.  But this new virus is being spread by people in the 5-day incubation period, and by some people who never have symptoms. I took that as a sign that this could be "the big one," which I always assumed would be flu, but life is full of surprises. 

By March 15^th, I was wearing a mask when I went out in public.  I was the only one. I was sanitizing my hands with alcohol, and wiping down all the packages that I brought into my house.  I was avoiding going out as much as possible.  I’m not a paranoid person, and definitely not a germophobe.  I knew that as a healthy middle-aged person, I was very unlikely to die of the virus, and because I work alone at home, I’m unlikely to pass it to anyone else if I did catch it.  But I don’t really have health insurance.  I have a health sharing plan with a very high deductible.  And I know our broken health care system could result in medical bills that might not be covered and could ruin me financially. People who land in the hospital with covid stay there for 1-3 weeks.  That is not a small medical expense.  I had planned to move to France in December of this year, and France has an excellent and inexpensive health care system.  My plan was to not get sick or injured before then.  I’m still not entirely sure what my chances of being hospitalized would be if I caught the virus.  But I don’t think the CDC estimates of 20% are crazy.  Beyond the cost, there are also many people who survive but have a long road to recovery.  People are having strokes and heart attacks because of the virus.  Being on a respirator for weeks can permanently damage your lungs.  So I am highly motivated to avoid catching this virus.

I’ve known since the beginning that the quarantine by itself was not going to prevent infections and save lives.  What the quarantine gives us is time to study the situation and figure out some way to deal with it.  It doesn’t look like we’ve come up with a wonder drug, and we still don’t know why some areas are harder hit than others.  But there has been a lot of progress toward a vaccine, and one group in the UK has announced that they expect to have their first million doses available by the fall, and they will know for sure if they’re on the right track by June.  At this point, I’m confident that there will be a vaccine that works well enough to stop the virus, and once we’ve gotten it and waited the six weeks (ish) it takes for it to activate the immune system, we can get back to normal.

In the meantime, we have also learned that masks work really well in preventing infections.  Back in mid-March, I was wearing my N95 mask, but I wasn’t entirely confident that it would protect me, and now I am.  They’re not comfortable, but they work. If masks were 100% effective, we would need about 60% of people to wear them to prevent exponential growth of the virus. I would link to all the studies here, but I think masks need their own post, so I'll link to it once I'm done. Update: link here.

Another happy discovery is that sunlight kills the virus within minutes.  So in the time it takes me to roll my cart full of groceries to my car, unload them into the car, and put the cart where it belongs, I’m exposed to enough sunlight that I’m not worried about virus clinging to my clothes or hair and coming home with me.  I still alcohol my hands, because I can imagine that my palms don’t get enough sun to kill the virus, and hands are a major source of transmission of viruses in general.  But I’m not worried that I’ve contaminated myself by going to the grocery store. 

If you look at various studies that track R0, you see a pattern happening over and over again.  The R0 is high at first, for example this study estimates 4.5, then it comes down to the 2-3 range.  This suggests to me that a big part of transmission is the sort of thing that was easy to change.  People were shaking hands with someone who probably didn’t wash their hands after using the bathroom, and then rubbing their eyes.  Once the first wave of sick people showed up, everyone started being more careful, even as they went about their normal lives of school and work. This helped a lot. By March 15th, which is the point where I was aware that I needed to be careful, the R0 for most of the US was already down to 1.5 or so. Then we went into quarantine, and the R0 went down even more.  You can see graphs of R0 over time for US states here. The large majority of states are currently in negative growth of the virus. (Side note: this website uses the term Rt instead of R0.  There seems to be disagreement between epidemiologists about whether R0 should be reserved for the "background" level of spread without taking measures like we are now.  The thing is, it's almost impossible to define what behavior counts as background, so I just use R0 to mean whatever the reproduction rate of the virus is at a given point.)  

So the question now is, how much can we open up while still keeping the spread rate negative?  We are clearly being more cautious now in TN than before the quarantine began.  I see about three-quarters of people wearing masks in the grocery store, and before the quarantine, it was none.

We don’t really know at this point whether or not eating in a restaurant with six feet of space between tables will lead mass outbreaks, but apparently we Tennesseans (and several other states) are going to do that experiment.  There was one instance of spread in a restaurant in China, apparently due to air flow over much longer distances.  I most definitely will not be eating out in the near future.  I’m hoping that the people who do are young and have good health insurance. 

I was encouraged by this study, which found that voting in Wisconsin apparently did not lead to a big spike in cases.  We don’t know how many of the voters were wearing masks, but probably at least some.  So this isn’t an indication of what will happen with restaurants. But it is probably more exposure to other people than one would experience going to a store, given that people were waiting in line to vote for hours.

So my prediction for Tennessee is that there will be an increase in spread now that restaurants are allowed to open, but I don’t think it will be the high rate of spread seen in New York at the very beginning, or even what we had at the beginning of the outbreak here, because most public spaces are conducive to mask-wearing, and it appears that most people are now wearing masks in them. I just don’t know if it will be higher than R0 = 1, which would give increasing numbers of new cases over time.   Again, I’m hoping that the older and at-risk people stay home until we see the results of the not-very-scientific experiment.  

If you are someone who is highly motivated not to catch the virus, you can protect yourself by wearing a mask, by sanitizing your hands and things you bring into your house, and by not touching your face until you get back home.  If you want to go the extra mile, you can change clothes as soon as you come home.  It will be an annoyance, but your risk of catching the virus will be dramatically reduced.  

Sweden, the US, and Covid-19

Sweden has been somewhat slower than other countries to implement social distancing, although looking into it for this post has revealed to me that the difference between Sweden and the US are not as great as is generally believed.

General recommendations and awareness to do social distancing appear to have been happening at more or less the same time in both countries, although that is hard to pin down exactly, because the US is huge and recommendations varied across the states.

In the US, the US federal government officially recommended closing schools and avoiding gatherings of more than 10 people on March 16th. On the same day, the Swedish government recommended that people over 70 should stay home, and that employers should consider letting their employees work from home. At this point, Sweden shut down universities and schools for older kids. But schools for young children remain open, even now. The argument there is that healthcare workers need somewhere for their young kids to go while they are working. Older kids can be home alone and do school online. So there is one real difference. In the US, elementary-aged kids have been out of school since about 3/16, whereas in Sweden they are still in school.

On 3/24, Sweden placed restrictions on restaurants, in which eating at crowded bars was prohibited, but take-out and socially-distanced eat-in tables were allowed. In the US, we shut down all eat-in tables around 3/16. So that's another real difference.

Sweden eventually banned (as opposed to just a recommendation) all gatherings over 50 people (on 3/27). The March 16th recommendation by the White House recommended limiting gatherings to 10. That's another difference.

So far, those are only differences in recommendations and laws, which are not the same as people actually socially distancing. If we look at Google’s cellphone tracking data, the US has a 38% decrease (as of 4/26) in tracking people to workplaces.  In Sweden it’s a 36% decrease, probably not a statistically significant difference. The US has a 14% increase in residential locations, whereas in Sweden it’s 11%. The only major difference in location data for the two countries is for parks (which includes public spaces like beaches).  People in these spaces has decreased 16% in the US, but *increased* 56% in Sweden.  I don’t know enough about public spaces in Sweden (or much of the US, for that matter) to say how difficult it would be to maintain distance there.  The other difference is that retail movement in the US went down 45% and stayed there.  In Sweden it has bounced around a bit, and is now at an 18% decrease.  This gives the impression that people are genuinely spending more time in public spaces in Sweden than in the US. 

Now, if we look at the results (via Worldometer) in terms of Covid-19, the US has 166 deaths per million, whereas Sweden has 217 deaths/million.  We also need to consider testing.  Countries that test more will have more official Covid-19 deaths.  The US is at about 16k tests per million, and Sweden is at 9.3k per million. This suggests that Sweden might be missing more of their Covid deaths than is the US, which would make the difference even greater. 

If you look at the graphs of deaths per day on Worldometer, Sweden appears to be processing tests on a weekly cycle, which makes trends hard to identify.  But to my eye, it looks like the US is leveling out more than is Sweden.

It's at least possible that Sweden's strategy will have an unintended beneficial effect.  There is some evidence that you can re-awaken immunological memory to other coronaviruses to help fight this one.  The idea is that through low-level exposure over time, you will wake up the memory T-cells from prior infections.  But you could get this same benefit without the risk of people actually getting sick by giving everyone low levels of inactivated virus, perhaps by putting it into the water supply.

It's pretty clear that both the people on the left claiming that Sweden is seeing a huge spike, and those on the right claiming that Sweden has managed to avoid the negative consequences without shutting down are both wrong. Sweden is partially shut down, probably not quite as much as the US, and is seeing a moderate increase in deaths relative to the US.

Serology (antibody) studies to determine the extent of covid-19 spread

Antibodies are proteins that can recognize specific pathogens that you've been exposed to in the past.  They are produced by plasma cells, which develop from B-cells.  The first time you're exposed to a new pathogen, your immune system will sort through all its B-cells until it finds the ones that produce antibodies that will stick, at least somewhat, to some part of the pathogen.  Those B-cells then go through a process of dividing, while at the same time tailoring their antibodies to stick to the pathogen really well.  Once that process is done, some of the B-cells mature into plasma cells, which are little antibody factories, and some form memory B-cells, which can reawaken if you're exposed to the same pathogen again.  Some antibodies are found in the blood, others in various secretions, like mucus and breast milk. For SARS Cov-2, the antibodies in the mucus layer lining your respiratory and digestive tracts are probably the most relevant to preventing infection. In high enough numbers, they will physically prevent the virus from ever reaching your cells.

What this means is that there is a period of some months, sometimes over a year, after exposure to a pathogen when you can take a blood sample and find those specific antibodies.  Lack of antibodies is not really a good indication that the person doesn't have immunity, because they might have memory B-cells in reserve, and there are also memory T-cells, which are totally different ways to fight a virus.  And it's possible to have antibodies without having full protection against the pathogen.  But in general, antibodies in the blood are a good indication that sometime recently that person has been exposed to the pathogen and had an immune response to it. 

We are now getting to the point where we can screen populations in an attempt to determine how many of them have antibodies to the virus.  This doesn't necessarily mean that they had an infection.  They might have had memory B-cells to previous cold-type coronaviruses, and their immune system recognized the similar pathogen and woke up those B-cells to start making antibodies.  This is the most prominent theory of why flu viruses go away in the summer.  The idea is that during the winter, people are exposed to low levels of the flu virus, and awaken their immunological memory, even without an infection, to the point where the population gets herd immunity to the flu going around that winter. 

In order to get herd immunity to covid-19, we need personal immunity in roughly 60-80% of the population. None of the populations studied so far have gotten close to that, but it's worth paying attention to these numbers.  Aside from monitoring how close we are to herd immunity, the other consequence of knowing how many people in a population have antibodies is that it *might* allow us to get a better handle on the case fatality rate, or at least on the general "danger level" of the virus in the future.  If we assume that everyone who has antibodies was actually infected, we can assume that the total cases are equal to the survivors with antibodies plus the fatalities.  Divide the fatalities into the total cases, and you'd have the case fatality rate.  But as I described above, I don't think that it's safe to assume that everyone who has antibodies was infected.  We can't even assume that they are now totally immune, although they probably have at least partial immunity.  But it does give us a reading on the overall immunological situation.

So with that introduction, here are the serology studies I know about to date:

Santa Clara County, California: 

https://www.medrxiv.org/content/10.1101/2020.04.14.20062463v1

This is a serology study done in northern CA in early April, about 2 months after the first official case in this location. They advertised for volunteers on FB and screened blood samples for antibodies to the virus. Out of about 3300, 50 were positive. That's 1.5%, which is much higher than suggested by the official cases at the time. The authors noted that minority groups were underrepresented in their sample, and so corrected upwards.

My concern with this study is that they might have gotten a self-selected bias. That is, people who suspected that they had been infected might be more likely to answer the ad and go to the trouble of getting tested. While they did ask people whether or not they had been symptomatic, they didn't report anything about those answers. I suspect that the reviewers are going to call them on that. Their estimate of cases is high enough that it leads to the conclusion of a very low case fatality rate. That suggests that either the fatalities are dramatically under-counted, or their sample is over-representing cases.

So while it seems likely that the true number of cases is under-reported everywhere, due to the shortage of tests, I don't think that they are under-reported as much as these authors suggest.

Scotland

https://www.medrxiv.org/content/10.1101/2020.04.13.20060467v1

In this study they are screening blood donors, which excludes symptomatic people. In mid-March, there were zero blood donations with anti-SARS2 antibodies. But in late March, there were 5 out of 500 that had neutralizing antibodies, that is, antibodies able to prevent infection, and a sixth was positive for antibodies, but not necessarily neutralizing antibodies. That's 6/500 or 1.2% of the blood-donating population.

Assuming that there is a 7-day delay in testing, the number of people who had tested positive at this time was 1600. Divide that into 5.3 million, and you get 0.03%. So far more antibodies in the population than suggested by the official tests.

I think this study is better than the one in Santa Clara, CA, because they are probably avoiding self-selection by people who really want a test.  There are rumors circulating that you can get a free covid test by donating blood, but my guess is most people are not going to assume that that's the case.  It's also better to test for neutralizing antibodies, rather than just any antibodies, given that we care whether or not the antibodies present will actually prevent infection.

The really interesting thing here is that the blood was all negative on March 17th, but 1.2% positive for the samples collected between March 21-23.  It takes at least a few weeks to get a new antibody response going in a mild case, (see for example this paper) and two weeks prior to March 21-23, there were only a few official cases in Scotland.  This suggests to me that they're getting re-activation of memory B-cells from colds, which happens more quickly, not totally new immune responses from silent infections. But we don't know that for sure.

Los Angeles

http://publichealth.lacounty.gov/phcommon/public/media/mediapubhpdetail.cfm?prid=2328

This is a press release, not an academic paper.  The meat of it is found in this quote:

"Based on results of the first round of testing, the research team estimates that approximately 4.1% of the county's adult population has antibody to the virus. Adjusting this estimate for statistical margin of error implies about 2.8% to 5.6% of the county's adult population has antibody to the virus- which translates to approximately 221,000 to 442,000 adults in the county who have had the infection. That estimate is 28 to 55 times higher than the 7,994 confirmed cases of COVID-19 reported to the county by the time of the study in early April. The number of COVID-related deaths in the county has now surpassed 600."

Unlike the study in Santa Clara county, they are attempting to get a random sample of the population: "Participants were recruited via a proprietary database that is representative of the county population. The database is maintained by LRW Group, a market research firm."

It's hard to say too much with so little to go on, but this at least looks encouraging.  It's tempting to speculate that the reason CA has not been hit as hard as NY is that Californians passed around a cold-type coronavirus in the past few years and are now awakening their immunological memory.

Swiss military recruits

https://militaryhealth.bmj.com/content/jramc/early/2020/04/16/bmjmilitary-2020-001482.full.pdf

One recruit out of 140 in the whole company went on vacation, and four days later became symptomatic.  That initial case tested positive via RT-PCR, and was isolated.  55 recruits who had been in contact (direct or indirect) with that first patient were put into quarantine.  In one quarantine room, seven out of nine recruits developed symptoms.  Only one of those tested positive via RT-PCR, which brings our official positives to two.  The interesting thing here is that the second case was never in direct contact with the first case, only indirectly through a third person who never tested positive. The other interesting thing here is that only the two official positive cases developed antibodies.  None of the others, including the six who had mild symptoms, and the person who was presumed to have carried the virus from patient 1 to patient 2, developed antibodies.  It's possible that the tests (both PCR and antibodies were not sensitive enough to pick up low levels.  Or it's also possible that the transmission from patient 1 to patient 2 via the third person was just through carrying the virus on his hands.  But what we're not seeing here is young healthy people developing a robust immune response to the virus.  It appears that they're just not very susceptible to catching it, compared to the general population.

The effect of quarantine on the spread of coronavirus

The R0 of a virus is the number of people each person infects, assuming the whole population is susceptible (i.e. no herd immunity).  It's not a fixed number for each virus, as it depends not only on how inherently contagious the virus is, but also on the behavior of the population in question.  You will therefore see ranges rather than fixed numbers for R0.  Social distancing is an attempt to bring down the R0, so is the wearing of masks.  If you can get the R0 down below 1, the virus will die out, as there are not enough new cases to replace the old ones. 

Highly infectious viruses with high R0 values include measles (12-18) and chickenpox (5-10).  Flu is much lower, in the range 1-2.5. 

R0 estimates for the new coronavirus vary widely, with the most commonly reported range 2-3.  But in the case of the Diamond Princess cruise ship, we have a worst-case scenario of crowding.  Interestingly, the R0 value increases over time from the 2-3 range to as high as 11.  The latter high number appears to have happened after the implementation of quarantine of passengers to their individual rooms.  Couples and families were then stuck together in a small space, giving it to each other.  But once everyone who was going to get it had gotten it, the rate of spread dropped.

In this graph, the vertical dashed line is the beginning of the quarantine to individual rooms.  The horizontal dashed line is the reproduction number of 1, the point where spread will die out.

Source here

Note that five days after the ship's version of social distancing was implemented, transmission had dropped dramatically.  And by 10 days after, transmission had dropped below 1.

If we look instead at the graph of daily new cases, a number we're getting from various countries in quarantine now, we see an initial increase over a few days, followed by a slow decline. 

Italy, by comparison, looks like this, with the vertical line placed on 3/18, the point where my one FB friend in Italy tells me that they really started tightening down movement in public.

The good news is that Italy has had two consecutive days of decline.  Yes, I know the data aren't perfect; it could be under-testing.  But it could also be the beginning of the end, paralleling the decline on the Diamond Princess.  The bad news is that the decline in new cases was pretty slow on the ship. 

France has technically been on lockdown since 3/17, a week ago.  But the French are not exactly rule-followers, and there were initially several days where the police were first giving out a small fine, then a larger one. But people are even now still reporting that they are seeing some groups of people still gathering on the street, against the rules.  Every day the rules get tightened a little more.  I'm going with 3/19 as the point where people started to take it seriously, although there is some wiggle room there.

I will definitely be watching France over the next few days.

Is it bad to take ibuprofen if you have coronavirus? What about elderberry (sambucus) syrup?

There have been articles circulating on FB about both of these, and I've been asked about them.

Ibuprofen

Ibuprofen is an NSAID, or non-steroidal anti-inflammatory drug.  It is known to reduce levels of IL-6, the inflammatory cytokine that is elevated in severe cases of covid-19 (more here). So you'd think it would actually help prevent severe symptoms, as the anti-IL6 drug Actemra does.  This is also theoretically the mechanism of action of chloroquine and derivatives.  It reduces IL-6 levels and therefore the severe inflammation that threatens to kill the patient.

But one doctor in France observed four young covid-19 patients whose symptoms worsened after taking ibuprofen, and raised an alarm.  It is entirely possible that they would have worsened without ibuprofen.  At this point, we have no controlled trials of any kind on this question.  We just don't know.

On one hand, it doesn't make a lot of sense that an anti-inflammatory would worsen a disease that appears to cause an over-reaction of the immune system.  On the other hand, there have been rare but real cases of bad reactions in children given aspirin (another NSAID) for fevers.

At this point, the French Minister of Health is recommending against NSAIDs for fevers, but the European Medicines Agency has put out a press release stating "There is currently no scientific evidence establishing a link between ibuprofen and worsening of COVID‑19. EMA is monitoring the situation closely and will review any new information that becomes available on this issue in the context of the pandemic."

So the short answer is that we don't know.

Elderberry

Elderberry / Sambucus syrup has been sold as an alternative treatment for the flu for many years.  I first became aware of it when I as in grad school and researching flu.  Someone gave me a bottle and asked me to test it to see if it interfered with flu's ability to infect cells.  I did and it didn't.  But the claim of at least some proponents of taking sambucus for flu is not so much that it blocks infection directly, but raises the immune response, which then fights off the flu.

This is at least plausible, but by no means certain. There is at least one report that human immune cells produce increased levels of IL-6 and other pro-inflammatory cytokines when they are removed from the body and exposed to sambucus syrup.

Given that severe cases of covid-19 have elevated IL-6, it makes sense to avoid sambucus/elderberry if you think that you might have the virus.  However, there have been no reports of adverse reactions to elderberry in actual covid-19 patients.

How is the covid-19 pandemic different from the H1N1 pandemic in 2009?

An infectious disease is classified as a pandemic when it is widespread across multiple countries.  There is also usually a requirement that it have a certain degree of severity.  There are many cold viruses that are worldwide, but are not normally considered pandemic because their symptoms are mild.

The H1N1 flu, or "swine flu" because it came from pigs, was declared a pandemic in early 2009, and it lasted for about a year and a half.  At the time, epidemiologists were worried about this particular flu because the last time a flu virus classified as H1N1 spread worldwide was 1918.  Here is a graph of life expectancy in the US.  Note that neither WWI or WWII killed enough Americans to make a noticeable blip in the graph.  But because that H1N1 strain killed large numbers of young adults who would normally live many more years, it is really obvious in the graph.

US Life Expectancy

So when a new variety of H1N1 started to spread rapidly, more rapidly than normal seasonal flu, epidemiologists took notice. The virus also disproportionately affected young people, just like in 1918.  Because it was a flu, though, we already had structures in place to put a vaccine into production quickly.  The US has huge flocks of chickens in undisclosed locations that lay eggs that we can grow the virus in to make flu vaccine. So the flu vaccine machine swung into action, and there were lots of news reports telling people to be sure to get their flu shot that year.  I remember getting mine.

There were some localized quarantines and school closures, especially early on, but it eventually became apparent that even though the virus was spreading rapidly, it was not like the 1918 version in terms of disease severity.  It was actually less fatal than the regular seasonal flu.  In the end, the case fatality rate was 0.03%, compared to about 2% for the 1918 flu.  Those most at risk of death from the 2009 flu were young children and pregnant women (pregnancy suppresses the immune system). So even though it infected somewhere in the neighborhood of 15% of the world's population, deaths were probably less than half a million worldwide.  By comparison, the 1918 flu infected about a quarter of the world's population, and killed somewhere between 1 and 6 percent of all people alive at the time.

The vaccine probably helped.  We know that it's not hugely effective, but it's better than nothing.  Even if your immune system didn't get activated enough to create full immunity, it might be enough to reduce disease severity.  

Now if we look at the current pandemic, we have a coronavirus instead of a flu virus.  We have never successfully created a human coronavirus vaccine, so we don't know if it's even possible to do so.  We know that there are four human coronaviruses that cause mild symptoms, and two human coronaviruses (SARS and MERS) that are horrible.  SARS has a 10% fatality rate, and MERS has a 34% fatality rate.  So right from the beginning, the CDC and WHO were watching what was going on in China with this new virus.

The new coronavirus is officially called SARS 2, which I think is rather confusing, so I'm going with "new coronavirus" or "this virus," or "covid-19 virus."  Covid-19 is the name of the disease, rather like AIDS is a disease caused by HIV. 

The fatality rate of the this new coronavirus is not as bad as SARS or MERS (thank goodness!).  It's fatality is far worse than the H1N1 flu virus, though. It may be in the neighborhood of the 1918 flu that everyone was afraid of in 2009. I have another post about trying to understand the case fatality rate here, and I concluded that it might be in the neighborhood of 2%, which is roughly what it was for the 1918 flu.

The insidious thing about this virus, compared to SARS and MERS, is that about half of the people, even older people, who get it have no symptoms.  So they spread it without even knowing.  With SARS, we were taking temperatures at airports, and if you had a fever, you couldn't get on the plane.  MERS made people so sick that they couldn't spread it if they wanted to. So those diseases were relatively easy to control. 

This new virus has an unusually wide spread of responses from different people infected.  Half have no symptoms, but roughly 20% get very ill and need medical attention, and 1-2% die. There is a lot of concern that if 20% of the world's population gets it, and 20% of those need medical attention, that means 4% of all humans are going to need the attention of the medical system.  Because it's spreading so quickly, all those people are going to need medical help at about the same time.  That's going to overwhelm the medical system.  The medical professionals are gearing up for things to get much worse, but there's only so much they can do. 

The covid-19 virus is spreading rapidly, probably more rapidly than the 1918 flu.   Numbers have come down in China and South Korea, but all of Europe and the US are still on the rise, both in terms of cases and of deaths. 

We don't know yet how much it will spread.  That depends on so many factors, like social distancing and whether or not we can come up with a vaccine.  It will probably not be as bad as the 1918 flu, but it's already worse than the 2009 flu. 

 It isn't the end of the world.  The human race has survived far worse bouts of infectious disease.  But it is a reminder that we are more vulnerable than we think we are. 

 

About me

I will transfer this to a real about page the next time I go back to the house with internet access, but for now:

I am a semi-retired academic biologist with a background in virology and immunology.  I'm not a medical professional of any kind. When the coronavirus started gaining steam, I posted a few thoughts on Facebook about the science of it, and found that there was a sudden intense interest in all things related to viruses and the immune system. So I kept posting, making my posts public.  But FB is not well-suited to organizing information,  and I've started to get a lot of friend requests from people I don't know. So on 3/22/20, I copied all my previous FB posts into this blog. I will continue to cross-post to this blog and my FB, so if you are my FB friend,  you can ignore this blog and see everything I post there. And if you were sent here by one of my FB friends (most of which are my former students) you can follow just the blog. 

Stay safe and isolate on!

Diabetes and Covid-19

We've know for awhile that people with various pre-existing conditions are at higher risk of death from coronavirus.  In the original report from the Chinese CDC, people with diabetes had a 3x higher case fatality rate than the general population.  But people with diabetes tend to be older, so it might just be correlation with age. A recently posted preprint matched diabetic covid-19 patients with controls that were similar in age and other health problems. The result was that the diabetics fared worse. They had roughly double the risk of acute respiratory distress, heart damage, kidney damage, and secondary infection. The mortality of diabetic patients was 35%, compared to 20% for matched controls. Median age was 66. 

This makes a lot of sense,  because diabetes comes with increased inflammation,  including increased IL-6, which appears to be a major driver of severe covid-19 disease. 

The prevalence of diabetes is about the same in China and the US, although it's not evenly distributed here.

Stay safe and isolate on!

https://papers.ssrn.com/sol3/JELJOUR_Results.cfm?form_name=journalBrowse&journal_id=3526432&Network=no&lim=false

Coronavirus spread through the air vs on surfaces

I went looking for research on methods of spread of coronavirus, and came up with this interesting study comparing actual spread of SARS in hospital wards with models of airborne only, surfaces only, or some combination. Covid-19 is similar but not identical. They concluded that spread was about 60% through the air / 40% through touch (either surfaces or being touched by medical personnel).

This image shows actual spread in a standard hospital ward, with the bed labeled "1" as the index case.  The other beds are labeled with the probability that its occupant contracted the virus. 

Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5519164/

Will covid-19 decrease in the summer?

(Original FB post March 12)

For those looking for a bit of good news regarding covid-19, this is a figure from a paper that has been submitted, but not yet reviewed. It makes the case that the virus spreads most easily in a narrow range of climate conditions (5-11C (41-52F) average temp). I think their case makes a lot of sense. Aside from the correlation between the largest outbreaks and a narrow temperature band, many viruses, including other coronaviruses, are strongly seasonal. The virus was expected to be severe in nearby areas to the south of China, like Bangkok, which had the first case outside of China. But as of today, there has been only one death in Bangkok, compared to 30 in Washington state. Bangkok has had highs of about 90F for the month of Feb.

I'm a bit surprised that the virus appears not to be spreading rapidly in colder climates. We know that heat kills the virus, but not cold.

Update 3/22/20:

Examples that fit this theory:

• The hottest US states (Arizona, New Mexico) still do not meet the requirement of  >6 deaths to get a circle on the map, although many more states in the yellow zone now do.
• Mexico (only 2 official deaths, but I'm not sure how much testing is being done there)

Counter-examples to the theory (i.e. hot climates with more than 6 deaths):

• Indonesia has 48 deaths
• Brazil has 25 deaths
• The Philippines have 25
• Ecuador has 14
• Malaysia has 10
• Australia has 7

Ambiguous cases: 

• Spain has had 1756 deaths, and it is in the light orange area. 
• Algeria has 17, mostly clustered in the cooler part of the country, which is orange on the map

Given that the numbers in the counter-examples are low compared with cooler countries, I think this theory is still reasonable.  But only time will tell.

See also this post: https://coronavirusandcovid19.blogspot.com/2020/03/the-mostly-non-fatal-coronaviruses.html