Natural immunity

Conditional on Infection, the Vaccine May Not Protect Against Death in Over 60s

In a recent article, I noted that vaccine effectiveness against death may have been overestimated due to the ‘healthy vaccinee’ effect – the tendency for people who get vaccinated to be healthier and more risk-averse than those who don’t.

Likewise, Will Jones recently reported on a large Swedish study, which observed declining effectiveness against severe outcomes, particularly after six months. Discouragingly, the decline in effectiveness was most pronounced among older, frail individuals ­– the group most at risk from Covid.

Now a new study (which hasn’t yet been peer-reviewed) has made a similar finding. Maxime Taquet and colleagues analysed data from a large database of electronic health records in the U.S.

Their sample comprised ~19,000 individuals who’d had a confirmed SARS-CoV-2 infection between January 1st and August 31st 2021. There were two groups: those who had been vaccinated at least 14 days prior to infection, and those who had not been vaccinated prior to infection.

The two groups were matched not only on basic demographic characteristics, but also on a large number of medical risk factors. In addition, the unvaccinated individuals were selected from among those who’d ever received a flu vaccine. Overall, substantial efforts were made to ensure the two groups were comparable.

Taquet and colleagues’ main finding is shown in the figure below. The lines on each chart show the cumulative probability of death for vaccinated and unvaccinated people, respectively. (Note: they also looked at other severe outcomes; see Fig. 3.)

The chart on the left indicates that, on average, vaccinated people had a lower risk of death than unvaccinated people. However, as the other two charts indicate, this difference was seen primarily in those under 60. Among those over 60, it was small and not statistically significant. The authors note:

Receiving 2 vaccine doses was associated with lower risks for most outcomes. Associations between prior vaccination and outcomes of SARS-CoV-2 infection were marked in those < 60 years-old, whereas no robust associations were observed in those ≥ 60 years-old.

Why would vaccination have a stronger effect among those under 60? The researchers speculate that:

In younger patients, effective B-cell response to vaccination might be followed by infection with variants against which antibodies have less neutralising activity … In older patients, the B-cell response to vaccination might itself be ineffective

It’s important to keep in mind that their finding concerns the risk of death conditional on SARS-CoV-2 infection. To the extent to that the vaccine protects against infection, it will protect against serious illness and death too.

However, it’s still noteworthy that effectiveness against death in over 60s was minimal among those who had been infected. Of course, this is just one study, so it shouldn’t be given too much credence. But the researchers did make substantial efforts to ensure the two groups were comparable and thereby obviate the ‘healthy vaccinee’ effect.

If their finding is true, it would suggest that previous observational studies have overestimated vaccine effectiveness against severe outcomes in older age-groups. It would also suggest that most of the protective effect for these age-groups comes from immunity against infection, which we know wanes rapidly in the absence of boosters.

The evidence from Taquet and colleagues’ paper could therefore be taken as supporting voluntary boosters for high-risk groups, as well as the continued build-up of natural immunity in the rest of the population.

Neil Ferguson Makes the Case for Focused Protection

Neil Ferguson, a.k.a. ‘Professor Lockdown’, isn’t the first person you’d expect to be making the case for focused protection. But that’s more or less what he did in a BBC interview last week.

Britain, the professor noted, is in a “quite different position” from countries like the Netherlands and Germany – both of which recently posted their highest infection rates since the pandemic began (despite the presence of mask mandates and vaccine passports).

“We’ve had very high case numbers,” Ferguson continued, “between 30,000 and 50,000 a day – really for the last four months.” And this has “paradoxically” had the effect of “boosting” population immunity.

I’m no expert in epidemiology, but I don’t really see the “paradox” here. If you have large numbers of infections, and they’re heavily concentrated in low-risk groups, then – yes – population immunity will be boosted.

(I suppose we shouldn’t be too surprised. As Martin Kulldorff and Jay Bhattacharya note, many scientists who should know better have downplayed or even denied the existence of natural immunity to Covid.)

Anyway, back to Neil Ferguson. Whether he realised it or not (and I’m leaning towards not), he was making the case for focused protection.

The whole point of that strategy is to protect high-risk groups, while allowing immunity to build in the rest of the population. “As immunity builds,” to quote the Great Barrington Declaration, “the risk of infection to all – including the vulnerable – falls.”

Given that the vaccines don’t provide lasting protection against infection, they’re best seen as a way to protect the most vulnerable. And even before the vaccines arrived, building population immunity in low-risk groups made sense, as a way to minimise the time that high-risk groups would have to spend shielding.

More than a month ago, I asked whether we should encourage young people to get the virus, so as to build up more immunity before the winter? If the latest data are anything to go by, it seems the answer to my question was “yes”.

Why Are We Still Talking About Infection Rates?

Covid’s now been with us for almost two full years. Here in the UK, we’ve had three separate lockdowns. And as of Monday, two thirds of the entire population has been fully vaccinated.

Yet people are still fretting over infection rates. Last week, the New York Times published an absurd article titled ‘Needless Suffering: Britain offers a warning of what happens when a country ignores Covid.’

If three separate lockdowns and a mass vaccination program qualifies as “ignoring” Covid, I’d hate to see what “addressing” it looks like. Spending 90% of GDP on suppression and renaming the Health Secretary ‘Minister for Covid’, perhaps?

“Cases have surged this fall,” the authors write, “more so than in the rest of Europe, the U.S. or many other countries.” So? Covid’s rapidly becoming an endemic disease, and infections will creep up from time to time. But there’s no evidence that lots of people are getting seriously ill or dying.

What’s more, infections have actually been falling for the past three weeks. Indeed, they’d already started falling when the Times article was published – a reminder that, in the era of Covid, life comes at you fast.

Given that natural immunity confers stronger protection against infection than the vaccines, case numbers are likely to remain elevated until enough people have had the virus at least once. I’m not sure what fraction of people are currently in this category, but it might be about a third.

That means we’ve got a few months to go before the disease becomes truly endemic. And as vaccine-induced immunity wanes, there are going to be more infections. Why not just get them out of the way now?

Rather than being concerned about Britain’s moderately high infection rate, maybe we should be happy about it. The more people who get infected now, the less who’ll get infected a few months hence – when the NHS comes under greater pressure.

We’ve already offered the vaccine to all over 50s – three times over in some cases. Why should it matter if another ten thousand 20 year olds catch the virus? Aside from remaining vigilant in hospitals and care homes, there’s really nothing left to do.

I’ve made an alternative headline for the New York Times: ‘Needless Panic: Britain offers an illustration of what happens as Covid becomes endemic’.

People are Still Pushing ‘Zero Covid’

If there was ever a time that ‘Zero Covid’ – the goal of eliminating Covid altogether – made sense, it was when the virus first appeared in Wuhan. Had the Chinese authorities raised the alarm sooner, and scrambled to contain the virus, perhaps there never would have been a pandemic.

But there was one. Covid has now been with us for two full years (perhaps longer). Hundreds of millions have been infected, and even greater numbers have received the vaccine. At this point, you might say, ‘Zero Covid’ is a non-starter.

Yet people are still pushing the idea. A recent article in the Daily Kos – a left-wing news site in the U.S. – argues that “COVID-19 must be eliminated, not become endemic, if America is to survive”.

Is this just a case where the headline is much more radical than the article itself? No – the one thing of which the author can’t be accused is attempting to downplay his position. “We cannot live with endemic COVID-19,” he writes, “Hang on, let me say that again: We. Cannot. Live. With. Endemic. COVID-19.”

Let’s consider his arguments, one by one. The author begins by comparing Covid to the flu, noting that the former is much more contagious. Whereas seasonal influenza has a basic reproduction number of 1.4, he notes, “COVID-19 has a R0 that is over five. Maybe as high as 10.”

I don’t know where he got the figure of ‘10’ from, but even if you take the higher estimates of Covid’s R0 at face value, they correspond to circumstances in which the population was immunologically naïve.

Once enough people have caught the virus at least once, the number still susceptible to infection will be substantially reduced. Not to zero, of course, as even natural immunity wanes – but enough to forestall the kind of transmission levels we saw in the spring of 2020.

Note: this is evident not just from the protective effect of natural immunity, but also from the declining transmission advantage of new variants. As immunity to each new variant rises (particularly among the subset of individuals who’re most likely to infect others), the effective reproductive number correspondingly declines.

The author then claims that a world with endemic Covid will be one where health care is much more expensive, due to demands placed on the system by constant surges of new Covid patients. Here again, however, he ignores the impact of natural and vaccine-induced immunity.

“Endemic COVID-19,” he writes, “would behave exactly the same as epidemic COVID-19: in surges, waves, or spikes.” Would it? What seems far more likely is that endemic Covid would not behave in this way. At the very least, any “surges, waves, or spikes” will be smaller and less deadly than those observed during the epidemic phase of the disease.

The author’s next argument is that, even once Covid becomes endemic, we’ll still see a lot of deaths. But as before, he fails to take account of immunity. “If the level of COVID-19 fatalities could be dropped to just 0.5%,” he writes, “then the rate of deaths would be “just” 160,000 people a year.”

Yet ‘0.5%’ is an implausibly high estimate of the IFR for a world where Covid is endemic. In a recent Twitter thread, Professor Francois Balloux used the figure of 0.1%, adding that even this was “probably far too pessimistic”.

The author then invokes the spectre of long Covid, noting that persistent symptoms “are not rare”. However, if he’d referred to the latest estimates from the ONS, he’d know that only 2–3% of patients still report symptoms after 12 weeks, and this is before you factor in widespread immunity.

Even if ‘Zero Covid’ were achievable, which it almost certainly is not, the costs of getting there would be enormous. We’d not only need a massive annual re-vaccination program, but also constant vigilance at the border, as well as large-scale testing in perpetuity.

“Whatever the price of defeating COVID-19 may be,” the Daily Kos article concludes, “it must be paid.” And that more or less sums up the case for, and against, ‘Zero Covid’. For you can’t take a proposal seriously if there’s no estimate of costs.

The Flaw in the New ZOE Study Showing Vaccine Protection Better Than Natural Immunity

The ZOE Covid Study App (which recently changed its estimates again, which doesn’t exactly instil confidence) released a study earlier in the month (or rather a press release with no link to an actual study) which claimed natural immunity following infection “only gave 65% protection against catching it again”. This compared to 71% protection from the AstraZeneca vaccine (rising to 90% for those who had tested positive for Covid before) and 87% protection from the Pfizer vaccine (rising to 95% for the previously test-positive). The researchers say the results came from during the U.K. Delta wave.

This is a surprisingly low estimate for the protection given by natural immunity. Other estimates have tended to be more like 80% against testing positive and 90% against symptomatic infection. A recent study from Israel (not yet peer-reviewed) found natural immunity was 13 times better than Pfizer vaccination at preventing PCR positives during the Delta surge and 27 times better at preventing symptomatic infection.

The ZOE result is similar, however, to a recent (very flawed) study based on the ONS infection survey, which claimed to find just 55% protection from natural infection. A similarly flawed study from Oxford University, also based on the ONS survey, found natural infection just 66% effective.

The main problem with the ZOE study is that it only looks at infections from May and June 2021. This was mostly a time of very low prevalence, though with the beginnings of the Delta surge occurring in the latter half.

Immunity to Covid Is Still Present 12 Months After Infection

Back in October of 2020, the John Snow Memorandum was published as a letter in the Lancet. Originally co-signed by 31 scientists, hundreds of others have since added their names.

Although it does not explicitly name the Great Barrington Declaration, the Memorandum is widely understood as a response to that document. It refers to “a so-called herd immunity approach”, which proponents claim “would lead to the development of infection-acquired population immunity in the low-risk population”.

However, the Memorandum states: “This is a dangerous fallacy unsupported by scientific evidence.” And it goes on to claim “there is no evidence for lasting protective immunity to SARS-CoV-2 following natural infection”.

According to the organisers’ website, more than 6,900 scientists, researchers and healthcare professionals have signed the Memorandum to date (including names from Oxford and Harvard). So almost 7,000 people with supposed expertise deemed it plausible that natural immunity would not provide any lasting protection against reinfection.

Incidentally, the language used in the Memorandum may be partly responsible for the Great Barrington Declaration being mischaracterised as a ‘herd immunity strategy’. As the authors have been at pains to point out, this is like describing a pilot’s plan to land a plane as a ‘gravity strategy’. (Their approach is more properly described as ‘focused protection’.)

It’s now one year on from the John Snow Memorandum. Is there any evidence for “lasting protective immunity to SARS-CoV-2 following natural infection”? Yes, in fact, there is.

A recent systematic review (which has not yet been peer-reviewed) found that natural immunity confers a high degree of protection against reinfection. The researchers analysed 10 studies, and calculated a weight-average risk reduction of 90%.

But is this protection lasting? According to a new study published in Clinical Infectious Diseases, immunity persists for at least 12 months in the vast majority of convalescents (those who’ve previously been infected).

Chinese researchers carried out a “systematic antigen-specific immune evaluation” on 74 individuals, 12 months after their original infection. They found that “humoral immunity is present within ~95% of convalescents and T-cell memory against at least one viral antigen is measurable among ~90% of subjects at 12m post-infection”.

Note: ‘humoral immunity’ refers to the type of immune response mediated by antibodies, whereas ‘cellular immunity’ refers to the type mediated by T-cells (as well as phagocytes and cytokines).

Although the researchers also had data from 28 healthy controls (individuals who’d never been infected), their sample was not large enough to estimate the protective effect of natural immunity on reinfection. Though it’s worth noting that not a single participant reported reinfection.

A study published last year analysed data on ten healthy males over a period of three decades, to see how often reinfections with seasonal coronaviruses occurred. They found that the median reinfection occurred after 30 months, suggesting that protective immunity lasts for years, not decades.

If SARS-CoV-2 is anything like the four other coronaviruses, we can expect immunity against reinfection to wane on a similar timescale. However, this seems more than sufficient to achieve focused protection, in the sense of shielding the vulnerable through the initial epidemic, and allowing time for treatments and vaccines to be developed.  

Lockdown proponents might respond that lockdown need only have lasted as long as it took to develop the vaccines. But this argument completely ignores the costs side of the ledger. Focused protection could have worked, if only we’d bothered to try it.

Stop Press: The Brownstone Institute has compiled a list of 29 studies showing that natural immunity to SARS-CoV-2 is “robust, long-lasting, and broadly effective”.

More Evidence that Natural Immunity Beats Vaccine-Induced Immunity

I previously wrote about the Israeli study which found that natural immunity provides much better protection against infection than the Pfizer vaccine.

Sivan Gazit and colleagues tracked two groups of people over time: fully vaccinated people who’d never tested positive; and unvaccinated people who had tested positive. Of the 257 cases that were detected at follow-up, 93% occurred in the vaccinated group, and only 7% occurred in the previously infected group.

And indeed, a recent systematic review (which has not yet been peer-reviewed) confirms that natural immunity confers a very high degree of protection against infection. The researchers analysed 10 studies, and found that the “weighted average risk reduction against reinfection was 90.4%”.

Compare this to studies of the vaccines’ efficacy against infection. In July, the Israeli Ministry of Health reported that the Pfizer vaccine’s effectiveness had dropped to just 39%. And a pre-print study by Qatari researchers found that it fell to zero after six months. (Though the vaccines’ efficacy against severe diseases appears to hold up well.)

Adding to the evidence outlined above, there are now studies comparing natural and vaccine-induced immunity at the cellular level.

I should mention that I am not qualified to evaluate the methods used by these studies, so I will have to assume the authors have done things properly. With that qualification in mind, it’s worth briefly discussing what they found.

In a recent paper published in Cell Reports, researchers from Minneapolis compared the memory B cells generated after natural infection versus mRNA vaccination. Memory B cells (MBCs) are part of the adaptive immune system; they are responsible for recognising antigens, and triggering a secondary immune response.

The researchers found that “infection-induced primary MBCs have better antigen-binding capacity and generate more plasmablasts and secondary MBCs of the classical and atypical subsets than vaccine-induced primary MBCs”. As a result, infection-induced MBCs “produce more robust secondary responses”.

In a second study, published as a preprint, researchers from Boston compared the durability and breadth of antibodies after natural infection versus mRNA vaccination. They found that infection-induced antibodies “exhibited superior stability and cross-variant neutralisation breadth than antibodies induced by a two-dose mRNA regimen”.

In other words, individuals who’d already been infected had better immunity against the then-novel Delta variant, as compared to ‘naïve’ individuals who’d received an mRNA vaccine.

Taken together, the statistical and immunological evidence suggests that natural immunity provides better protection against infection than the mRNA vaccines. This does not mean that nobody stands to benefit from vaccination. The vaccines are still an important way of achieving focused protection for high-risk groups.

But it does undermine the case for vaccine passports, and for vaccinating 12-15 year-olds. As Jay Bhattacharya wrote back in July: “Any infection-blocking effects are probably short-term unless the vaccine does very much better than natural immunity, which is rare in medicine.”

Vaccinating Young People Is Unethical; Those Vaccines Should Go to Poor Countries

On September 3rd, the Joint Committee on Vaccination and Immunisation (JCVI) – an independent panel of experts – advised against offering COVID-19 vaccines to healthy children aged 12-15.

The panel concluded that, although “the health benefits from vaccination are marginally greater than the potential known harms”, the margin of benefit is “too small to support universal vaccination”. However, it did recommend expanding the list of underlying health conditions that would qualify someone in the relevant age-group for vaccination.

The panel’s recommendation apparently came “as a blow to the Government”, which for some reason really wants to vaccinate healthy children.

Immediately after the announcement, Health Secretary Sajid Javid wrote to the U.K.’s Chief Medical Officers asking them to “consider the matter from a broader perspective” (which reads like bureaucratese for “ignore the recommendation of the JCVI, and find a new justification for the policy”).

And it’s worth asking: if the Government does decide to ignore the JCVI’s recommendation, and offer the vaccine to healthy children anyway, will it adopt the slogan: “Don’t necessarily follow the science.”

I can understand why children with an underlying health condition would be worried about getting COVID-19, and it seems right that they’re being offered a vaccine. However, for the overwhelming majority of healthy children, the disease poses virtually no serious risk.

The main justification for vaccinating young people is to protect older people. But given evidence that natural immunity provides better protection against infection than the Pfizer vaccine (the only vaccine approved for those aged 12-15), this justification looks increasingly weak.

It’s now abundantly clear that vaccinated people can transmit the virus. Hence the only true safeguard – for a child visiting a vulnerable grandparent, say – is a negative COVID-19 test beforehand.

However, even if the vaccines had no side effects and offered the same level of protection as natural immunity, it would be unethical to vaccinate children at the present time. And that’s because it’s a waste of vaccines that could go to people who actually need them.

Rather than offering vaccines to children and young people, rich countries like the U.K. – which have so far been hogging all the vaccines – should donate them to elderly people in poor countries.

Even though a government must always look to the interests of its own citizens first, the benefit/cost ratio of donating vaccines to poor countries is so vast that this principle is hardly relevant. People forget that the risk of death from COVID-19 is not just higher, but orders of magnitude higher, for elderly people.

I said that Britain should donate its remaining vaccines to poor countries in an article back in July. The same argument has been made by several other commentators, including – mostly recently – two scientists writing in the journal Nature.

Zain Chagla and Madhukar Pai argue against vaccine ‘booster’ programs on the grounds that far more lives could be saved by administering vaccines in poor countries. The global vaccine supply is limited, they note, so “this is a zero-sum game”. Every vaccine given to a healthy British 12 year-old is one that can’t go to a 70 year-old in Africa or Latin America.

Even discounting side effects, it’s unethical to vaccinate 12–15 year-olds in Britain when a such small share of the population in poor countries has been offered a vaccine. COVID-19 is a disease that disproportionately targets older people, while posing almost no risk to children. Our vaccination policy should reflect that.

Israeli Study Finds that Natural Immunity Protects Much Better Against Infection than Pfizer Vaccine

Since the start of the global vaccine roll-out, it’s become increasingly clear that – although the vaccines provide strong protection against severe disease – they provide only limited protection against infection.

Israel and Iceland, two of the most vaccinated countries in the world, have recently seen major outbreaks of COVID-19. Both countries had fully vaccinated 60% of the population by July 1st. Yet by early August, Iceland had posted its largest daily total for the number of new infections since the pandemic began, and case numbers in Israel were soaring.

However, the question of whether vaccines are superior to natural immunity in terms of protection against infection has remained open. According to a Guardian article titled “Common myths about Covid – debunked”, which was written by a member of Independent SAGE, natural immunity is “not as good as the protection you get from being vaccinated”.

Yet a new paper suggests the reverse may be true: natural immunity is stronger and longer-lasting than vaccine-induced immunity.

Sivan Gazit and colleagues analysed a large sample of anonymised patient records from Israel. Their sample included two key groups: fully vaccinated people who’d never tested positive; and unvaccinated people who had tested positive.

In addition to matching these two groups for size, and average demographic characteristics, they controlled for ‘immune activation time’. This was done by limiting the sample to people who’d been vaccinated or infected between January 1st and February 28th, 2021.

Patients’ Covid outcomes (subsequent infection, hospitalisation or death) were measured during a follow-up period between June 1st and August 14th.

What did the researchers find? Of the 257 cases that were detected in the follow-up period, 93% occurred in the vaccinated group, and only 7% occurred in the previously infected group. And of nine hospitalisations, eight occurred in the vaccinated group, compared to just one in the previously infected group.

These results indicate that natural immunity confers substantially more protection against infection than vaccine-induced immunity. They also suggest that natural immunity confers more protection against hospitalisation, although one should be cautious here, as there were only nine hospitalisations in total.

The researchers point out that their results may only apply to the Delta variant, and to the Pfizer vaccine, and that they couldn’t control for all relevant differences between the two groups. Nonetheless, their paper provides the strongest evidence to date that natural immunity beats vaccine-induced immunity when it comes to infection.

Francious Balloux of UCL, a self-described “militant corona-centrist”, said the paper “is a bit of a bombshell”. Though he added that “essentially every adult who hasn’t been infected yet greatly benefits from being vaccinated”.

Gazit and colleagues’ findings still need to be replicated. But if they prove to be robust, then government priorities may shift substantially going forward. The case for vaccinating healthy young people will be even weaker. And the case for donating surplus vaccines to poor countries will be that much stronger.