
Covid-19: Do many people have pre-existing immunity? - nradov
https://www.bmj.com/content/370/bmj.m3563
======
WhompingWindows
Epidemiologist here, a few thoughts reading other comments:

-Death data is preferable to new cases in some ways, since it doesn't rely on testing, which ramps up/down from locality to locality and over time.

-To compare deaths from the Spring with deaths recently isn't apples to apples: we know now remdesivir and dexamethasone are helpful treatments, especially the latter, and these may help reduce mortality rate.

-Mortality now may be lower partly due to: if the virus killed off the more vulnerable populations (nursing home) early on, it has less frail individuals to infect now. These communities got ravaged, we had something like 40% of deaths in my area in nursing homes in our 6-week case peak.

-Trying to tease out immunity is very tough as well, early on there were few good tests and their specificity and sensitivity were less well known. At my agency, there were multiple tests we were collating, with different false positive and negative %s, and different reporting times (which all can influence R0, the variable number our behavioral interventions seek to tamp down).

-Comparing different countries is very tricky. Sweden is a favorite example for non-lockdown approach, but there we see it's very tricky to tease out the benefits. On the one hand, they didn't do much better epidemiologically than their neighbors. On the other hand, their economy was surrounded by locked down ones, so that may have tamped down any benefits their non-lockdown would've garnered due to neighbors' activities. Did it pay off? The verdict is still out, IMO.

Things are very complex in infectious diseases epidemiology. It's extremely
hard to know anything for certain with this virus, it's behavioral tangled up
with comorbidity with genetics and demographics and evolving treatment and
viral dosage and strain of virus...it will take a few years of unpacking the
mountains of data before we truly have a grasp of what happened here.

~~~
kybernetikos
Comparing Sweden with its neighbours really highlights how poorly it has done:
[https://ig.ft.com/coronavirus-
chart/?areas=fin&areas=swe&are...](https://ig.ft.com/coronavirus-
chart/?areas=fin&areas=swe&areas=nor&areas=isl&areasRegional=usny&areasRegional=usca&areasRegional=usfl&areasRegional=ustx&byDate=0&cumulative=0&logScale=1&perMillion=0&values=deaths)

Pretty much any way you slice the data, a lot more people died in Sweden than
in its neighbours.

You can see the same pattern in excess all cause mortality too: Denmark 200,
Finland 600, Norway 0, Iceland 0, Sweden 5500.

Now Sweden has a population slightly less than Finland and Norway combined,
and figures can be difficult to compare, but still it's hard to avoid the
conclusion that so far, around 4000 people in Sweden have died because of
differences in policy compared to its neighbours.

~~~
api_or_ipa
The better question that Sweden may help answer is whether shutting down the
economy was worth it. Was the deaths of 5,500 people worth keeping the economy
open, in other words, could you have saved more lives by pursuing other health
priorities and let covid run it's courses as Sweden elected to do?

~~~
EricE
This. The deaths directly attributed to the virus alone aren't the only
relevant deaths. Suicides are up. Domestic violence is up. Child abuse may be
up but schools are all "virtual" so good luck detecting it (as if it wasn't
hard enough when kids were mostly in school).

Talk about throwing out the baby with the bath water...

~~~
kybernetikos
I don't at all doubt that lockdown has had a number of second order problems
(and benefits too), but the the figures I quoted at the end were excess all
cause mortality, so those are all already included. And indeed, many countries
with net 0 excess all cause mortality certainly had corona virus deaths, but
lockdown and related benefits appear to have saved more people than the virus
killed in those countries.

~~~
ynfnehf
I think most people who are worried about secondary effects from lockdowns
don't think that these will be visible immediately during the pandemic. But
rather as a higher baseline of mortality in the coming years. This is just my
guess. I'm not an epidemiologist, so I have no real expertise in how these
effects usually manifest themselves in the statistics.

------
Animats
The ship epidemics give an indication of whether this is the case. The USS
Teddy Roosevelt had an epidemic and everyone onboard was tested. 20% tested
positive for the virus. 60% showed antibodies.

Arctic cruise ship after 21 days: "Of the 217 passengers and crew who remained
on the ship for the entirety of the voyage, 128 tested positive for the
coronavirus, the researchers said. They added that of those who tested
positive, 24 exhibited symptoms and 104, or 81%, did not."[2]

There are many other ship epidemics, but those are ones that had 100% testing.
That puts a ceiling on pre-existing immunity at somewhere around 40%. No floor
from that data.

[1]
[https://www.cnn.com/2020/06/09/health/covid-19-investigation...](https://www.cnn.com/2020/06/09/health/covid-19-investigation-
aircraft-carrier/index.html)

[2] [https://www.cnbc.com/2020/05/27/over-80percent-of-
coronaviru...](https://www.cnbc.com/2020/05/27/over-80percent-of-coronavirus-
patients-on-cruise-ship-had-no-symptoms-study-says.html)

~~~
whiddershins
Pre existing immunity may not preclude testing positive?

Not an expert here but could preexisting immunity just mean the virus has
trouble really taking hold and wreaking havoc before it is shut down, as
opposed to never being infected at all?

I guess what I’m asking is whether immunity is truly binary.

~~~
dtech
It does. To test positive viral load needs to be at a certain level, that can
only happens if cells are infected and producing virus particles. If that's
happening you're not immune.

~~~
timr
Current US PCR tests are set to be so sensitive that they can detect a _single
copy_ of viral RNA. This has been an under-reported fact that should be more
widely known:

[https://www.nytimes.com/2020/08/29/health/coronavirus-
testin...](https://www.nytimes.com/2020/08/29/health/coronavirus-testing.html)

------
zaroth
This is another really great reason why the herd immunity threshold is lower
than it has naively been claimed. If the effect is as large as TFA says then
the threshold is actually _much_ lower than the ~60% level.

This has a big impact on the estimated death rate for achieving herd immunity.
The other factor in that estimate is the CFR which is also plummeting over the
summer, although there’s reason to believe CFR could go back up somewhat in
the winter depending on how much the gain was environment versus how much is
due to better treatment protocols and therapeutics.

For example, if the immunity threshold goes from 60% -> 20% and the CFR goes
from 5% -> 1% the estimate death toll is reduced to 1/15th (6.6%) of the
original estimates.

~~~
lukeschlather
> This is another really great reason why the herd immunity threshold is lower
> than it has naively been claimed.

It sounds like you're starting from the happy assumption - herd immunity is
much easier to achieve than we believe - and working backward to find data
which justify your hope. To get good predictions, we have to be dispassionate
and not assume the happy case.

A realistic assessment would probably assign some sort of a probability range
to different thresholds - a model might suggest there's a 60% chance the
threshold is 60%, a 5% chance it is 40%, a 20% chance it is 80%, a 10% chance
it is 90%.

And any model has to take into account that any piece of data might be wrong,
including this data about T-cell immunity.

~~~
modeless
In my area, as in Sweden, cases have been declining for many weeks now.
Lockdown didn't become stricter. People didn't become more compliant; rather
the opposite. Why aren't cases skyrocketing the way they were a couple of
months ago? What explanation is there other than the herd immunity thresholds
being wrong?

~~~
meddlepal
Mask compliance is reducing spread?

~~~
jtbayly
Sweden has recommended _against_ wearing masks. So mask "compliance" would
mean not wearing one, which should have led to an explosion of cases, no?

~~~
alkonaut
I’d say there has just not been a recommendation or mandate to wear them.
There hasn’t been a recommendation _against_ them. It could still happen they
say, at least regionally e.g in public transport in one region for example.

------
gnusty_gnurc
Michael Levitt has been saying this since the Diamond Princess event.

Scratch that - he hasn't been maintaining there's pre-existing immunity,
rather asking the question to anyone who'd listen...he doesn't have a
background in biology, but that's one of the few conclusions he could surmise
from studying the data.

~~~
apcragg
[https://www.latimes.com/science/story/2020-03-22/coronavirus...](https://www.latimes.com/science/story/2020-03-22/coronavirus-
outbreak-nobel-laureate) He seems to be a perfect example of the axiom that
deep knowledge in one field doesn't necessarily give you expertise in others.
Seems like he should leave Epidemiology to the epidemiologists.

~~~
aeternum
Since when is that an axiom? He carefully analyzed the data and presented a
falsifiable prediction along with his methodology. If he was wrong we should
look at why and learn from it. (Did he fail to account for the virus mutating,
could different regions have different co-morbidities or immunities?)

We should _not_ rely on appeals to authority, those expert epidemiologists
didn't do much better.

~~~
gnusty_gnurc
He's been talking about this a lot - the (lack of) communication and debate in
the science community.

People interested in _truth_ invite criticism: "Please give me contrary
evidence! Show me I'm wrong!"

~~~
ineedasername
"Show me I'm wrong" is not the starting point in the scientific method.

~~~
GavinB
It kind of is. Hypothesis rejection is the primary means of advancing
knowledge.

"We tried to prove this hypothesis wrong and could not" is the main thing you
want a study to do. Having everyone try to prove your hypothesis wrong, and
failing, is the main way that science advances.

~~~
gamblor956
No, science proceeds on the basis of trying to prove a hypothesis is
_correct._ As in, I hypothesize A should B, evidence XYZ supports this.

You accomplish very little trying to prove a hypothesis wrong, because most
are.

~~~
disgruntledphd2
While you are correct conceptually, most scientific research using statistics
does in fact attempt to provide evidence against no-effect (the null
hypothesis).

The p-value of a scientific study is the probability that the given data would
have been observed, given that there is no effect. Hence why small p-values
can be associated with the success of the alternative hypothesis (i.e. what a
scientist actually thinks will happen).

------
gibolt
From a medical perspective, 'immunity' means triggering any immune system
response, not that someone will not get or have symptoms of a disease.

This is an important nuance that has muddled research for lay people during
the pandemic.

Edit: Definition of Immunity - [https://medical-
dictionary.thefreedictionary.com/immunity](https://medical-
dictionary.thefreedictionary.com/immunity)

~~~
burtonator
No it doesn't. It means to _resist_ harmful infection.

If you catch a serious disease, like HIV, malaria, etc, and you die, you have
an immune system response - it just failed.

Even people that die of COVID had an immune system response. It just couldn't
cope with it.

The somewhat frightening thing is that our immune system, literally right now,
is fighting the good fight and saving your life.

One of the confusing aspects of AIDS is that you don't die from AIDS - you die
from the opportunistic infections that happen from not having an immune
system.

~~~
throwaway894345
My understanding was that the immune response was responsible for a lot of the
harmful effects of covid in the first place. I thought the virus itself wasn't
actually causing mass cell death?

~~~
coding123
I'm not a doctor or anything, but there's also reports that a "vitamin D
hammer" has dropped death rate from 86% intubated patients to 36%, and vitamin
D triggers a huge immune response. So my guess is that it's either NOT an
immune response, or a bad one, until you add the Vit. D.

------
choeger
Right now, this seems to be the best explanation for a lot of the unexpected
observations we made so far:

* few children seem to be sick from that virus * geographical disparity in Europe (compare northern Germany vs. northern Italy), even considering population density * the high number of reportedly asymptomatic cases * uneven distribution of infectiousness ("superspreaders")

My pet theory so far is that one or more very similar viruses have been in
circulation for a while and that "asymptomatic" carriers of COVID-19 are in
fact at least partially immune due to exposure to these similar viruses.

Note that this _also_ means that COVID-19 is much scarier than it looks.
Because if you are not among those with prior immunity, you are much more
likely to suffer from the bad effects of that virus.

~~~
gnusty_gnurc
My pet theory is that chronic disease like obesity, combined with pre-existing
immunity, and possibly some correlation to vitamin-d deficiency explains most
of how this has played out.

Factor in a glut of people who're living into advanced age, due to the
progress of medical technology, so naturally in a precarious place against
_any_ infection. And of course, mismanagement of those people in nursing homes
means guaranteed disaster.

So really, I think it's much less dangerous than we've let on, but deadly to
certain demographics, that happen to be larger in the West (obese, diabetic,
etc.).

~~~
acqq
No. "Obesity" and "vitamin-d deficiency" can't explain what happened in Italy
(a lot of sun), and also can't explain what happened in the Nordic countries
(much less sun), including Germany and Sweden (the later having order of
magnitude more deaths than the former, measured as the percentage of the
population). Sweden is particularly bad, having the deaths per capita even
worse than the U.S. the last time I've checked.

What we see is that countries that were lucky enough to do strong enough
prevention actions early enough had order of magnitude less deaths than those
who didn't do them (and Sweden is in the latter camp, even if they did have
more response than most admit -- they did close all universities, for
example). The scale of deaths seen in New York would have never happened, had
the use of masks been common early enough.

Eidt: Regarding "vulnerable populations" Italy and Germany have similar number
of "vulnerable" and it seems Sweden would be better than Germany then:

[https://commons.wikimedia.org/wiki/File:Population_pyramid_o...](https://commons.wikimedia.org/wiki/File:Population_pyramid_of_Italy_2016.png)

[https://commons.wikimedia.org/wiki/File:Population_pyramid_o...](https://commons.wikimedia.org/wiki/File:Population_pyramid_of_Germany_2016.png)

[https://commons.wikimedia.org/wiki/File:Sweden_population_py...](https://commons.wikimedia.org/wiki/File:Sweden_population_pyramid_\(2018\).jpg)

~~~
samsa
It is worth noting that living in a sunny country does not guarantee the
larger population receiving adequate Vitamin D through sun exposure, as many
such populations somewhat paradoxically avoid sun exposure, as there are
legitimate health reasons for doing so (extreme heat, concerns about skin
cancer, etc.).

~~~
acqq
To support that you'd have to show that Italians have order of magnitudes
higher deficiency than most of Nordic countries, and I don't think it is
possible.

Another country with equivalent sun exposure to Italy is Greece, again orders
of magnitude less deaths (like Germany). They also had strong lockdowns and
early enough.

It's the measures. Analyzing what happened in Europe (and still happens) can't
be explained with anything else.

Compare it with fires. Small fires are easy to extinguish. Pretending "it will
go away" will simply result in a big fires. Eventually there won't be anything
to burn. With people, eventually everybody who can and "feels the heat" will
try to protect themselves.

A lot of older people in Sweden stay in their homes and take care not to be
infected. Masks are common in the supermarkets, etc.

~~~
username90
> To support that you'd have to show that Italians have order of magnitudes
> higher deficiency than most of Nordic countries, and I don't think it is
> possible.

Sweden adds vitamin D to food items so I wouldn't be surprised if Sweden has
less vitamin D deficiency than many southern countries.

[https://www.nutraingredients.com/Article/2015/05/28/Sweden-t...](https://www.nutraingredients.com/Article/2015/05/28/Sweden-
to-expand-mandatory-vitamin-D-fortification)

~~~
gnusty_gnurc
Can we find order of magnitude difference among darker skinned people? We've
all heard about the disparity there.

------
chasil
Let me post an informational link, with some explanation of potential
increased resistance:

"[HCoV-NL63] is an enveloped, positive-sense, single-stranded RNA virus which
enters its host cell by binding to ACE2... Further analysis of HCoV-NL63
pathogenicity seems warranted, in particular because of recent evidence that
this virus uses the same cellular receptor as SARS-CoV (ACE2)."

[https://en.wikipedia.org/wiki/Human_coronavirus_NL63](https://en.wikipedia.org/wiki/Human_coronavirus_NL63)

------
santa_boy
Looking at situation in India which is extremely crowded in many cities, the
number of cases and deaths is relatively is very low.

Many share the opinion that there is some sort of immunity among the
population here.

Not sure about the scientific validity, but I'm inclined to believe that the
lack of such immunity would have made the situation extremely dire by now.

~~~
nradov
A recent study in Mumbai found that 57% of slums residents were seropositive
for SARS-CoV-2 antibodies, which indicated an infection fatality rate (IFR) of
0.05 - 0.10%. That's much lower than most other places and it's not clear what
accounts for the discrepancy.

[https://www.cnbctv18.com/healthcare/57-sero-prevalence-in-
sl...](https://www.cnbctv18.com/healthcare/57-sero-prevalence-in-slums-16-in-
non-slums-in-mumbai-says-survey-of-3-wards-6475141.htm)

~~~
lukeschlather
Any antibody testing done this year is pretty suspect. We simply don't know
which tests have a high false-positive rate. Studies like that one should be
testing the test but instead are trying to draw conclusions about the virus
spread based on a test with unknown efficacy.

~~~
nradov
Nope. They used the Abbott IgG antibody test which was validated to have
99.63% specificity and 100% sensitivity. There is no need for field
researchers to test the test. Unless there was widespread contamination of
specimens or something the study results are solid.

[https://www.medrxiv.org/content/10.1101/2020.08.27.20182741v...](https://www.medrxiv.org/content/10.1101/2020.08.27.20182741v1)

[https://www.abbott.com/antibody-testing/top-
COVID-19-antibod...](https://www.abbott.com/antibody-testing/top-
COVID-19-antibody-test-questions.html)

------
djsumdog
Immunity is complex. Our immune systems are very complex. We've measured
immunity based on antibodies for decades, but what if that's not the entire
picture?

Our immune systems have Memory T-cells, a Complement Protein system, and
several other components to both our adaptive and inane immune systems. The
sheer complexity of it is due to millions of years of bizarre evolutionary
warfare. Just look at this video that simplifies the Complement system:
[https://www.youtube.com/watch?v=BSypUV6QUNw](https://www.youtube.com/watch?v=BSypUV6QUNw)
.. it's still insanely complex even when simplified.

The majority of vaccines we have today are not byproducts of careful genetic
manipulation or breeding. They're other viruses that are similar to the one we
want to protect against, but less harmful in humans, or they're inactivity
through heat or chemical treatment. The first vaccine was based on
horse/cowpox 185 years ago by Jenner, and was tested on random people because
thousands were going blind or dying and we didn't have the ethical standards
on human testing we do today.

They produce antibodies, yes, but there could be hundreds of other
interactions there that help different parts of our immune systems build
memory. Our immune system is like looking at millions of years of bad software
engineering; microservices that were randomly put together by monkeys on
typewriters that randomly got things right here and there along the way.

SARS1 and MERS vaccines resulted in some subjects developing Immunopathic
responses or Immune Enhancement syndrome. These new vaccines that are being
produced seem focused on just generating antibodies using synthetic proteins,
which might be missing a bigger and more complex set of interactions that we
don't realize is happening with inactivated viruses as vaccines.

~~~
greatquux
This is why I wish we'd done more basic research on the immune system long
ago. Maybe if we'd invested more time and money into a vaccine for HIV/AIDS, a
disease which attacks the immune system directly, we'd realize we need to do
this basic research on how our immune system works in order to even begin to
understand a pandemic and our response to it. But at least I have hope we're
getting it now so when something worse comes along we'll be more ready for it.

------
thewhitetulip
According to sero survey done in India 40% population had Corona anti bodies
in May.

By that logic, herd immunity must be kicking in right?

The rules of nature mean that many people will be immune to corona or would
have little to no symptoms.

Those with co morbidities will face issues unless a vaccine or a medicine
comes out.

The only major issue is that cities are running out of beds. In my town
hospitals have a 15day waiting and people are literally at home despite having
symptoms

~~~
just-juan-post
> The only major issue is that cities are running out of beds. In my town
> hospitals have a 15day waiting and people are literally at home despite
> having symptoms

Hello could you post some articles about this?

I have yet to see an article about people being turned away from hospitals and
dying anywhere in the world.

~~~
thewhitetulip
[https://www.deccanherald.com/city/top-bengaluru-
stories/no-b...](https://www.deccanherald.com/city/top-bengaluru-stories/no-
beds-bengaluru-hospitals-turn-away-covid-19-patients-856371.html)

------
ricksunny
If there were components of commonly consumed foods that turned about to be
inhibitory to the virus' action (infecticity or replication), and these foods
were unevenly consumed across the population, would this read out to an
epidemiologist looking from a birds-eye view similarly to "immunity"?

------
SomeoneFromCA
The thing is that Rn depends on the people behavior very strongly, and what
are precise behavioral characteristics increasing the spread are still
unknown. The level necessary to achieve her immunity may be like 60% for one
nation, but be 25% for some other. Small mutations may also matter.

------
TMWNN
This is consistent with what Karl Friston said in May
([https://www.theguardian.com/world/2020/may/31/covid-19-exper...](https://www.theguardian.com/world/2020/may/31/covid-19-expert-
karl-friston-germany-may-have-more-immunological-dark-matter)):

>For example, it looks as if the low German fatality rate is not due to their
superior testing capacity, but rather to the fact that the average German is
less likely to get infected and die than the average Brit. Why? There are
various possible explanations, but one that looks increasingly likely is that
Germany has more immunological “dark matter” — people who are impervious to
infection, perhaps because they are geographically isolated or have some kind
of natural resistance. This is like dark matter in the universe: We can’t see
it, but we know it must be there to account for what we can see.

~~~
lowdose
Physics is especially a poor domain to pick an analogy from at the moment. But
if we can borrow from that whole religious domain I think the following is
more apt.

Maybe the people of Germany have an invisible halo protecting them from bad
woo woo from Wuhan.

~~~
tonyedgecombe
>Maybe the people of Germany have an invisible halo protecting them from bad
woo woo

Yes, it's called Angela Merkel. The numbers are difficult ro read but it looks
like countries with female leaders have faired better than the rest.

------
techbio
Why is this article so filled with question-marks? The opinions and anecdotes
attributed to various names from around the world do not seem to form a
coherent thesis nor address the headline.

I'm not even clear whether Betteridge's Law applies. The answer seems to be
"maybe?".

[https://en.wikipedia.org/wiki/Betteridge%27s_law_of_headline...](https://en.wikipedia.org/wiki/Betteridge%27s_law_of_headlines)

------
forgot_user1234
annecdata: My family physician in small town in India has treated 70 covid
patient. 55 were totally asymptomatic.

~~~
iso1631
> 55 were totally asymptomatic

What treatment were they given?

------
lymeeducator
Thanks for posting. It lends credence to collecting more data from everyone to
better determine T-cell reactivity to a number of pathogens (virus, bacteria,
etc) and then let the patients own their data with the freedom/incentive to
share that data for research and education. I prefer trying to gather data to
identify levels of pre-existing immunities and who is higher risk. The higher
risk people could opt for an immune hammer (vaccine).

~~~
jeanvaljean2463
Agree with your position on this, your take sounds very sensible. I wondered
at the start of this if some of the larger DNA databases would be mapped and
analysed to look for markers for this exact sort of thing. ( 23andme, DOD,
ancestry )

------
known
Vaccine/Treatment should activate Tcells + Bcells + IgM + IgG in Immune system
to kill the Virus

[https://en.wikipedia.org/wiki/Antibody#/media/File:Antibody_...](https://en.wikipedia.org/wiki/Antibody#/media/File:Antibody_Opsonization.svg)

------
dmtroyer
Can someone give an educated tl:dr; of all the comments, please? :-)

~~~
salmon30salmon
tl;dr

People are overinvested in the opinions they held in March, and will find
evidence to support what they believed then.

On one side, we have the cohort of people who see this as literally the worst
thing ever and we will all die. And you hate children and humanity if you want
to eat at a restaurant.

On the other side, you have the crowd who sees this as a moderate case of the
sniffles and society is overreacting due to the fact that the news media hyped
this so aggressively

There is a very, very small minority of people who see it as squarely in the
middle, a scary disease that we should protect people from, but with a more
nuanced approach than lockdowns.

~~~
tarruda
Perfect :)

------
diminish
> Could pre-existing immunity be more protective than future vaccines? Without
> studying the question, we won’t know.

TLDR!

~~~
tboyd47
> At least six studies have reported T cell reactivity against SARS-CoV-2 in
> 20% to 50% of people with no known exposure to the virus.5678910

I suppose if the vaccine trial studies going on now return with anything more
than half the infections of the control group (however they want to measure
it), we'll have our answer.

------
moultano
Betteridge's law of headlines seems to apply. It's a mistake to assume that
public policies, such as lockdowns, are the primary thing that changes human
behavior, when mobility data has shown similar patterns in different places
regardless of public policy. Natural social distancing, due to fear, by itself
will change the replication number, especially since covid spread seems to be
driven primarily by superspreading events among the most risky activities.

I'm glad people are researching all the possibilities, but spreading minor
hypotheses like this around social media brings out the worst of armchair
epidemiology.

