An important new study in the New England Journal of Medicine had a primary objective of determining the nature of durability of antibody responses to SARS-CoV-2.
In other words, the primary questions these researchers were asking were: do people show clear evidence of immunity after a COVID19 infection, and does that immunity last for months?
The answers to those questions were yes, and yes. Clear evidence of immunity- in the form of carefully confirmed IgG antibodies- did develop in the majority of those known to have been sick with COVID and recovered, and those antibody levels remained robust four months later.
That might be the whole story, and if it were- the study would be important, the research a success, and the news- excellent.
But there is much more to this paper out of Iceland, and even more to the timely importance of this tale when it is placed in the context of other recent COVID-related discoveries and disclosures.
Based on extensive testing among different population groups, the investigators from various universities and government offices in Iceland showed that over 90% of those who had been sick with COVID months prior had stable levels of IgG antibodies against it. The antibody levels peaked at about 2 months, and then plateaued- meaning they had not declined at 4 months. That’s good news.
But let’s read between the lines a bit. These findings also suggest that even among those who get infected, and sick with COVID, some 10% who recover do not have measurable IgG. Since these people did have the infection, and did recover from it, they likely have some level of immunity, even though the assays used in this study did not find it.
This makes sense when we add context. Consider that even during a pandemic, when the mechanics of peer review are much accelerated, it still takes time to gather and analyze data, write up a paper, have it reviewed, and see it grace the pages of arguably the world’s most prestigious medical journal. During that time, we have seen many other studies and reports telling us that most bouts of COVID are asymptomatic, and that in those with mild and asymptomatic infections, IgG antibodies do not tend to develop. There is apparent immunity even so, however, in the form of memory T cells and IgA. The new study did not test for these “lesser” forms of immunity.
We also know now- and did not when these authors submitted their paper- that a very mild bout of COVID could allow for reinfection with a different strain months later- with the second bout even milder than the first, again suggesting partial immunity achieved and maintained.
Lastly, and probably most important at the population level- we now also know that many of us seemingly had partial immunity to COVID before ever the pandemic began, because of prior exposure to common cold coronaviruses (CCCs).
In other words, by using meticulous methods limited to IgG antibodies, the Iceland researchers almost certainly underestimated the extent of COVID infection, and subsequent immunity, in the population, by an enormous margin. This is not a criticism- their study is powerful, timely, and important. It is just context none of us had when they began their effort.
Based on the numbers they did gather, the researchers suggest that about 1% of the population of Iceland has been infected with SARS-CoV-2 to date. Given what we now know about asymptomatic infection, native resistance, and the failure to make detectable IgG after a mild bout, this number is almost certainly too low by many multiples. A great many more Icelanders have probably had or been exposed to COVID than this paper indicates.
That notwithstanding, the numbers in the paper tell an extremely encouraging tale about the prospects for herd immunity. Assuming that 1% of the Icelandic population has had COVID, their infection fatality rate is 0.3%. In other words, 99.7% of those infected recovered, and 0.3% died.* This fatality rate is roughly 3 times that of seasonal flu. But that’s not the whole story.
The COVID fatality in Iceland, as elsewhere around the world, was very concentrated. The fatality rate in those under age 70 was 0.1%, roughly commensurate with seasonal flu. The fatality risk in those over age 70 was 4.4%. These are the numbers that issue directly from the data in the study. If, however, ten times more Icelanders had experienced mild SARS-CoV-2 infection than testing revealed – these numbers would be correspondingly lower by that order of magnitude. As reported, these estimates thus represent the high end of the range of realistic values for fatality.
To summarize, then, this study shows that immunity reliably develops after symptomatic COVID infection, and persists at robust and stable levels for at least months. It reaffirms that the risk of death from COVID is massively concentrated among the elderly, and that the overall fatality risk at the population level is a fraction of a percent. For those under age 70, the risk of dying from COVID is one tenth of one percent, apparently at most. Data from other sources suggest it is even much lower than that.
This is all excellent news.
Oddly, though, when the popular press got a hold of it, they focused on one implication only: that it lends support to vaccine development. This, however, was not among the authors’ own conclusions. In fact, I searched the full text of the article for the word “vaccine;” it does not appear- not once. The investigators chose to focus on the low national infection rate of 1%, and warned that Iceland thus remained vulnerable to a second wave.
So, in accord with prevailing and gloomy perspective, failure was wrested from the jaws of apparent success, and the media took this story in a direction the researchers themselves did not propose.
Because of all we have learned over recent weeks about the “immunological dark matter” of COVID- apparent exposure, infection, and immunity without IgG- I very much doubt the 1% figure in Iceland. But even if that low exposure rate were valid, the implications of this paper in context seem very encouraging to me, and rather different than what the media, or even the authors, have chosen to emphasize.
If the COVID related risks are as comparable to flu as they appear to be in this study, we could, and should, be talking about naturally achieved herd immunity. In particular, with risk so clearly concentrated among those over age 70- with additional concentration among those with well-known risk factors- we should be talking about doing so while carefully protecting those who should not be exposed. We should be doing so all the more as the evidence of the many harms of extended lockdown, to adults and in particular to children, mount.
In other words, these many months into the pandemic, and based on this new paper along with all we have learned over recent weeks about asymptomatic infection; about memory T-cells and immunologic dark matter; about IgG and IgA; about common cold coronaviruses and native resistance; about reinfection- I emphatically maintain that a policy of total harm minimization by means of vertical (risk-stratified) interdiction efforts was right at the start, is right now, and would be right- if only we could manage it.
But I don’t see it happening. We cannot even talk about naturally achieved herd immunity, even when the evidence so glaringly supports it, without disdain and intimations of sociopathy. We need to ask: why?
There are, I believe, two answers.
The first is generic, in other words, not COVID specific: we are calamitously polarized. Total harm minimization by means of vertical interdiction is nuanced; it is a middle path that runs across what should be common ground. It is neither “lock it all down,” nor “liberate my state.” It is the antithesis of either extreme view.
In better times, such temperate places might tempt us to come together in common cause. But in these times, they garner vitriol from both poles of opinion. The nuanced middle is the place where epithets and projectiles arrive from both directions.
Then, there is the COVID-specific reason. In the United States, we have thus far failed horrifically at every aspect of pandemic management. We are, as I have noted before, a daily master class in what not to do and how not to do it. The current administration is a broken clock. Even, then, if they happen to be right about herd immunity- because broken clocks are famously right once (digital) or twice (analog) a day- we know we can’t trust them to stay current, keep time, or tell the truth.
We tested too few, too late, and too shoddily. We locked down too late, and opened up too early and too indiscriminately. We did not even manage to secure our nursing homes and protect our loved ones there.
With only such failure on display, and 190,000 lost lives - how could anyone trust the prospect of herd immunity? If we extrapolate from our experience to date, it certainly looks as if a strategy of naturally achieved herd immunity would mean a terrible toll of avoidable deaths. No wonder any mention of it smacks of heresy, evoking sanctimonious derision.
I oppose paying for herd immunity with lives as emphatically as my most ardent and self-righteous detractors from the extreme left of our political spectrum. I just oppose the sanctimony and disdain, too.
Were we not so utterly inept in our national response, herd immunity could be achieved without casualties above the background levels of risk. Note that is not zero risk; there is no such thing as zero risk. Before the pandemic, some 8000 people died every day in the United States of miscellaneous causes. Before the pandemic, nearly 3 million of us died yearly for one reason above all: we are mortal. We die.
So, no degree of pandemic mastery would prevent every last death. But the understanding available to us now from global ascertainment suggests that well conducted pandemic management could, indeed, get us to herd immunity with casualties that fall into the prevailing background levels of epidemiology-as-usual, and with no undue demands on our medical system.
But that would be in a parallel universe where expertise was valued, and where decent, compassionate, thoughtful people were in charge of the country. Here, and now, I quite understand why talk of herd immunity sounds like heresy.
We are talking about complex, subtle public health policy - in a veritable house of cards. Every floor we have constructed to date is ill conceived, flimsy, and apt to fall out from under us. Whatever floor we build on top of all that- however well-constructed the floor- is apt to crash out from under us, too, because it rests on a foundation of failure.
So it is that herd immunity is heresy not so much because the implications of COVID infection make it so. Rather, the implications of our colossal ineptitude make it so. The case is all the more tragic accordingly, since the combined losses of lives and livelihoods need not be, and the enemy is us.
The new paper in the New England Journal of Medicine provides very good news. The infection fatality rate is a fraction of a percent at worst; immunity develops reliably, and it persists. In the context of all we have learned during the weeks this paper ran the gauntlet to publication, the news is better still.
But in a public health house of cards, herd immunity is heresy. Where federal pandemic response policy has been an amalgam of bravado, denial, dithering, derision, and delusion- hope succumbs to distrust, and understandably so.
The news in the New England Journal is very good, but so what? As Gertrude Stein famously said, “a difference, to be a difference, must make a difference.” Until or unless we get out of our own way and pull together; until or unless hope prevails over experience and distrust alike – we seem destined for more of the same.
*An infection fatality rate of 0.3% implies that the United States has experienced not 6 million COVID infections, but at least 63 million COVID infections to date, or roughly one out of every five of us.
If half of those infected fight the virus without symptoms or development of antibodies as studies suggest, that number could be twice as great- nearly 130 million- or one out of every two to three of us.
David L. Katz, MD, MPH, FACPM, FACP, FACLM, is the Founding Director (1998) of Yale University’s Yale-Griffin Prevention Research Center, and former President of the American College of Lifestyle Medicine. He has published roughly 200 scientific articles and textbook chapters, and 15 books to date, including multiple editions of leading textbooks in both preventive medicine, and nutrition. He has made important contributions in the areas of lifestyle interventions for health promotion; nutrient profiling; behavior modification; holistic care; and evidence-based medicine. David earned his BA degree from Dartmouth College (1984); his MD from the Albert Einstein College of Medicine (1988); and his MPH from the Yale University School of Public Health (1993). He completed sequential residency training in Internal Medicine, and Preventive Medicine/Public Health. He is a two-time diplomate of the American Board of Internal Medicine, and a board-certified specialist in Preventive Medicine/Public Health. He has received two Honorary Doctorates.