This chart below is the final nail on the covid panic (and yet, this is a serious disease – I don’t mean to downplay its seriousness – see my text below).
This chart was created by someone who used Neil Ferguson’s model, applied it to Sweden, and then plotted actual deaths (see tweet).
And btw, my research (a couple of hours of googling) confirms that for the world as a whole, there’s been virtually no virus that has ever infected more than 25% per cent of the population. Spanish flu infected only 25% or so (see my tweet thread) – that that was without any vaccination; H1N1 (2009) infected 24%, As a general rule, pandemic influenzas only infect a quarter of the people (see New York government’s website).
This confirms the validity of Anne Marie Knott’s analysis. Not more than 20-30% persons in the average country are likely to get this coronavirus, no matter how hard they try. This proportion is also called the attack rate by some epidemiologsts (e.g. Encyclopedia Britannica), but other epidemiologists use a different meaning for attack rate (the number of persons one infected person can infect), so let’s just call this the infection rate.
What explains this huge gap – why don’t the other 70-80% of the people get infected? The innate immunity issue is very significant here (and it varies for each virus), and the viral load factor. Viral loads are low in most adult interactions and probably highest in pre-school centres, but children seem to have innate immunity for this virus (something for future researchers to explain). In elders innate immunity decays rapidly – therefore two-thirds of Kirkland Life Care Center nursing home’s residents caught the infection. The 25% infection rate is only an average.
Now coming to Sunetra Gupta’s analysis that there will be no second wave in some places.
From the Spanish flu example (for which there was no vaccine), we see that herd immunity for such viruses is generally around 25%. The estimate of 60% bandied about by “experts” is absurd, to say the least. For COVID, HI levels should be in the same range, i.e. 20-30%.
Antibody figures in parts of UK and Sweden are close to 20% (or slightly more). And we know that the actual extent is likely to be higher since not everyone produces measurable antibodies. This confirms that the further spread of this virus in these countries is going to be extremely slow – close to non-existent. Therefore Sunetra Gupta is correct.
The basic point is that the initial modelling was absolutely off the charts. Neil Ferguson (copied into this email) might wish to publish a public statement withdrawing his extreme estimates.
I’ll do so some further work and write about it in next TOI blog post over the next few days. Happy to have any thoughts/ inputs to this analysis, so that I don’t make fundamental mistakes!
After reviewing comments here, I’ve tentatively concluded:
There are two reasons to explain the resistance: (a) social distancing leading to low viral load, so the virus doesn’t reach transmissible levels, and (b) innate immunity.
The key point, as Vernon Smith has pointed out, is that “the claim is that the 80% “resistance” accounts for discrepancies across different data“.
I read two other examples cited above in the comments which suggest that innate immunity is unlikely to be much greater than the 10-15% I had earlier estimated.
But even if innate immunity (and cross-reactivity) is in that range, it can have a dramatic impact. Stockholm’s case suggests it is already reaching herd immunity.
And if one adds the natural distancing that is part of life in many rural communities (with reduced viral loads in human interactions), it would drop further – which is probably why Sweden’s rural areas have also seen a rapid drop-off in cases.
The cases which oppose the studies that Knott has cited are:
At least 44 of 70 UT-Austin students who chartered a plane to Mexico for spring break tested positive (they flew back separately), as did 52 of 61 who attended a choir practice in Washington. [a comment in the FB post linked above]
This strongly suggests that viral load is a key variable. However, it also suggests that in communities where people don’t get cooped up together, the virus will never spread to the same extent. I’m assuming something on the lines of an inverse square relationship to distance applies: i.e. viral load is proportional to (1/distance^2).
Therefore there are two main sub-groups of the resistant population:
a) those who are innately immune (around 10-15% perhaps),
b) those who rarely, if ever, come into close proximity with others for an extended duration of time. Depending on the nation, the community, and occupation, this could be anywhere from 10-25% of the people. E.g. farmers and tradies are unlikely to come into close contact with virtually anyone outside their own household for an extended duration.
I want to note that Knott’s flu analysis is flawed. At least I couldn’t confirm it from here or here.
I’ve also studied this chart by Michael Levitt (which was linked by Knott here):
While virus transmission for an individual is random, it is a constant for society, a sum of constants for each segment (occupational, rural/urban, cultural).
The sum of this constant + innate immunity will inform herd immunity.
This virus likely won’t infect 60-65% of the world’s population because of insufficient viral load. Another 10-15% will beat it off with their innate immunity.
Only 20-30% will likely get the disease, of which only a very few will die.
This also means that in cities and countries that have seen significant deaths, the pandemic has effectively passed (some precautions can still help).
In other places, people can revert to normal with a few extra extra precautions.
THE ORIGINAL POST
This is the most pathbreaking piece of research I’ve come across so far on COVID-19, by Anne Marie Knott – Washington University’s Olin’s Robert and Barbara Frick Professor of Business.
This research was shared by the best (in my view) economist alive today – Vernon Smith (Nobelist, of course) on his FB page. He doesn’t share such stuff mindlessly.
This research suggests 80% innate immunity. If so, the IFR might well be high but the total effect is rather low. Herd immunity could be as low as 15%.
This analysis is very persuasive and we need to take it very seriously. This is very strongly supportive of Sunetra Gupta’s claims. I wish she had provided me with serious data and evidence – since the whole world needs evidence and logic – not just claims.
I’m going to share this widely – so everyone with some capacity can analyse this to identify any loopholes/ gaps. I will write about this on my TOI blog after I’ve had a chance to think about it, and read any critiques.
This is preparatory material for a TOI blog post I plan to write to address Tim Colbourn’s question.
The idea here is to understand the concept of innate immunity further and to work out whether Sunetra Gupta is right.
My last tweet first:
This article suggests innate immunity can work excessively (cytokine storm) – which can be dampened with high levels of Vitamin D. The elderly often have very low Vitamin D.
We might be facing a Vitamin D deficiency issue here, not a deadly virus per se.https://t.co/ZutObT8L4v
— Sanjeev Sabhlok, Pope @Church of Reason & Liberty (@sabhlok) May 23, 2020
Where is the evidence for innate immunity to SARS-Cov-2?
This is a new deadly disease and surely given the number of deaths in many places the precautionary principle should hold? More people died in London of Covid19 in April than during the Blitz in WW2!
Following entry into the respiratory tract and infection of predominantly epithelial cells, viruses trigger the innate immune responses including the inflammatory response.
Neutrophils enter the lung parenchyma within hours of infection, followed by monocytes/ macrophages, natural killer (NK) cells and then T cells within a few days of infection. The T cell infiltration peaks at 7 days post-infection, correlating with viral clearance from the lung. Neutralizing anti-bodies are also present around 7 days post-infection, and are maintained in the host as a first line of defence against re-infection.
The innate immune cells elicit an early anti-viral response following recognition of the pathogen by pattern recognition receptors including Toll-like receptors (TLRs) and RIG-like receptors. The engagement of these receptors induces signalling cascades that generate type I interferon (IFN) and pro-inflammatory cytokines. These molecules control the infection by mechanisms of viral cleavage and inhibition of viral fusion, replication and translation, by activating cytolytic cells and stimulating humoral factors including acute phase proteins, defensins, collectins and complement proteins. However, as these responses can lead to immunopathology in the lung mediating the morbidity and mortality of respiratory viral infections, they require immune regulation. [source]
FURTHER
Innate immunity comprises a suite of individual defenses against pathogens that is genetically predetermined and that ensures immediate protection without requiring prior stimulation and subsequent reactive response (Rumyantsev, 1983; Soosaar, 2005). Innate immunity is a general biological principle that provides relevant antimicrobial defense to all types of living beings, including humans (Fig. 3). This type of resistance is of primary importance not only in its phylogenetic origins, but also for its contemporary significance (Rumyantsev, 1983, 1998; Kaufmann et al. 2002). Innate protection factors develop during ontogeny without interaction with any particular parasite or parasitic product. They are inherent and present in the body before attack by disease-causing agents. The manifestations of innate immunity can be observed in species, populations and individuals, as well as in cells and subcellular structures. [Source]
The nature of such innate insusceptibility remains undiscovered and the true number of susceptible individuals among humankind elusive. The mainstream of immunology has not been involved in this kind of immunity. Therefore, nobody can predict today which kind of influenza virus could induce the next pandemic among humans, or where and when such a pandemic might occur. [Source]
Species and individual diversity in genetic immunity to many infections is already a widely known fact. For a long time, however, this phenomenon was neglected by both immunologists and epidemiologists, although regarded as essential (Boyd, 1966; Kaufmann, 2002). Near the end of the last century, that situation began to change (Rumyantsev, 1983, 1998; Bieniasz, 2004; Kimman, 2001; O’Brien & Dean, 1997). It was discovered that this kind of immunity is determined by genetically programmed and very specific constitutional features of the individuals, populations and species. [Source]
====NOTES===
Innate immunity is a pattern recognition mechanism – act on a wide range of viruses: a non-specific system.
There are three types of cells in the innate immune system. 1. Sentinel cells in tissues: dendritic cells, macrophages and mast cells 2. Circulating phagocytles and granulocytes: neutrophils, monocytes and eosinophils 3. Lymhpocytes – mainly the NK or natural killer cells.
A word about the lymphocytes: There are two other types – the T lymphocytes and B lymphocytes, which are part mainly of the adaptive immune system.
Mammalian cells have evolved conserved pattern recognition receptors (PRRs) that sense pathogen associated molecular patterns (PAMPs) derived from viruses, bacteria and parasites (31–33). Following virus infection, infected cells initiate signaling events that induce the expression of antiviral and pro-inflammatory cytokines (33–35). Antiviral cytokines, such as interferons (IFNs), activate the expression of IFN-stimulated genes (ISGs) that inhibit virus replication through different mechanisms [Source]
Emerging bat-borne viruses, such as coronaviruses that cause SARS and MERS inhibit innate antiviral responses in the infected host while inducing a strong pro-inflammatory cytokine response that is associated with immunopathology and significant morbidity and mortality [Source]
SIGNALLING NK CELLS
Interferons (Type I, being alpha and beta) are a cytokyne produced when a virus infects a cell. They percolate outside the infected cell and latch on to neighbouring cells, leading them into an anti-viral state. These interferons also signal NK cells to kill the infected cells.
NATURAL KILLER CELLS PLAY A KEY ROLE IN FIGHTING SARS-COV-2
INNATE IMMUNITY IS NOT JUST REACTIVE, IT IS ADAPTIVE AS WELL
It is crucial to note that “there is a growing appreciation that the adaptive and innate immune systems may have many similar characteristics.” [Clinical Immunology Principles and Practice, 4e by Robert R. Rich et al]
This suggests that those with prior exposure to coronaviruses (in common cold) are likely to have had stronger innate immunity. This is also the reason why “trained immunity” occurs, and virtually any live vaccine can trigger a wider innate immune response.
CORONAVIRUSES ARE GOOD AT EVADING INNATE IMMUNITY
The current coronavirus is pretty good at evading the innate immune system, unfortunately, [Source]
INNATE IMMUNITY AND CORONAVIRUSES
For many coronaviruses, there is no known mechanism of how they evade the host innate immune system. It is hypothesized that it is by either (1) actively producing IFN antagonist proteins, (2) using their own replicase proteins to modify host proteins or by (3) the formation of double membrane vesicles and compartmentalizing replication and perhaps other coronavirus RNAs. The use of double membrane vesicles could hide the RNAs produced by protecting them from the RNA sensing machinery. There may also be a role for N in shielding the viral RNAs from the dsRNA and ssRNA sensing pathways. Many of these possibilities are being actively investigated. [Source]
coronaviruses are RNA viruses that replicate in the host cytoplasm and evade innate immune sensing in most cell types, either passively by hiding their viral signatures and limiting exposure to sensors or actively, by encoding viral antagonists to counteract the effects of interferons. [SOURCE]
Innate immunity is considered as the first line of defense against invading pathogens. The cells engaged in the innate response include phagocytic cells (monocytes, macrophages, and neutrophils), natural killer (NK) cells, and other cells releasing inflammatory mediators (basophils, eosinophils, or mast cells). During the development of an innate immune response, neutrophils and macrophages play an essential role in the elimination of microbes using various mechanisms, including the production of reactive oxygen species (ROS). In addition, this frontline protection is supported by NK cells guarding against infections and tumors (Delves and Roitt 2000). [Source: Immunomodulatory Role of Vitamin D: A Review – Agnieszka Skrobot et. al]
