Pre-Existing Immunity

Some Healthcare Workers Have Pre-existing Immunity to Covid, Study Finds

The question of whether some people have pre-existing immunity to Covid has been with us since the early days of the pandemic. Many scientists initially assumed there would be little or no pre-existing immunity. After all, SARS-CoV-2 was novel, highly infectious virus that appeared well adapted for human transmission.

However, in the spring of 2020, scientists began to report cross-reactive T-cell activity in people who hadn’t been infected with the virus, and – in some cases – in those who hadn’t even been exposed. However, it remained unclear whether such T-cell activity played any role in immunity.

Were individuals with cross-reactive T-cells less likely to become infected? Were they less likely to get seriously ill, conditional upon being infected? We simply didn’t know. Some even speculated that T-cell activity might predispose to more severe disease…

Evidence is now emerging that T-cell activity does play a role in immunity. In a recent study, Chinese scientists studied Covid patients and their close contacts who did not become infected. They observed “significant levels of SARS-CoV-2-specific memory T-cell immunity” in the uninfected contacts, hinting at a role for T-cells in staving off infection.

In a separate study, the same group of scientists studied Covid patients who experienced varying degrees of disease severity. They found that activation of two types of T-cell was “strongly and inversely correlated” with the severity of disease. One caveat is that their sample comprised only 12 people.

The most convincing evidence to date comes from a recent study published in the Nature by a team of British scientists. Leo Swadling and colleagues followed 700 healthcare workers in London for 16 weeks during and after the first wave of the pandemic.

They identified a subset of participants who had never tested positive for Covid and were seronegative at week 16. They then matched these individuals by age, sex and ethnicity to participants who had been infected by week 16. They also matched them to healthy adults who’d been sampled before Covid began circulating.

What did the researchers find? The seronegative participants had SARS-CoV-2-specific T-cells that were “comparable in breadth” to those of participants who had been infected. What’s more, participants’ T-cells were higher in “magnitude and breadth” than those of the healthy adults sampled before the pandemic.

These findings strongly suggest (but do not prove) that some healthcare workers were protected against infection by pre-existing T-cell immunity.

One of the study’s authors, Francious Balloux, noted that the “ability to control infections through pre-existing T-cell immunity likely stemmed from constant pre-pandemic low-level exposure of HCWs to endemic coronaviruses”. If he’s right, than pre-existing T-cell immunity might be much less common in the general public.

Professor Balloux also cautioned that “X-reactive T-cell immunity may not be sufficient to control infections by the more aggressive α/δ strains”. (Recall that the study was based on data from the first wave, before Alpha, Delta or indeed Omicron had emerged.)

While more research is clearly needed, evidence suggests that pre-existing immunity to Covid has been underestimated. This is consistent with what scientists like Sunetra Gupta (co-author of the Great Barrington Declaration) have been arguing since last year.

Imperial Finally Acknowledges Pre-Existing Immunity to COVID-19. What Took It So Long?

T-cells from common cold coronaviruses can provide protection against COVID-19, an Imperial College London study has found. Reuters reports on the findings, which were published in Nature.

The study, which began in September 2020, looked at levels of cross-reactive T-cells generated by previous common colds in 52 household contacts of positive COVID-19 cases shortly after exposure, to see if they went on to develop infection.

It found that the 26 who did not develop infection had significantly higher levels of those T-cells than people who did get infected. Imperial did not say how long protection from the T-cells would last.

“We found that high levels of pre-existing T cells, created by the body when infected with other human coronaviruses like the common cold, can protect against COVID-19 infection,” study author Dr Rhia Kundu said.

The researchers suggest vaccines based on imitating the internal virus proteins that T-cells target may be more resilient to mutations and new variants as those proteins, unlike the spike protein targeted by the current vaccines, “mutate much less”.

Cross-immunity to SARS-CoV-2 from other coronaviruses has been proposed since early on in the pandemic as an important element in reaching herd immunity and endemicity (for example, it was mentioned in this Scientist article from March 2020), and became a particular focus of interest in the autumn of 2020 as evidence of it accumulated (see here, here and here). It’s good to have further confirmation of this from Imperial (and also recently from UCL), but it has to be said it’s pretty late to the party, and it’s not clear why a study which began in September 2020 during a public health emergency has taken 16 months to report, particularly when vaccines were brought to market in 10 months. The emphasis of the researchers is on the potential usefulness of the findings for developing new and more resilient vaccines, which contains a tacit admission that the existing vaccines are failing, but also leaves one wondering whether the research has only been published now that it is useful for making new pharmaceutical products. It might be added that the studies on the efficacy of generic off-label medicines against Covid are taking an awfully long time to report.

As Dr. Mike Yeadon explained in his October 2020 piece for the Daily Sceptic, “What SAGE Has Got Wrong“, the assumption of a lack of pre-existing immunity and hence universal susceptibility was one of the great errors made by Government advisers throughout the pandemic and which led to an over-reaction that continues to this day. Now that Imperial researchers have acknowledged the existence of prior immunity, will Neil Ferguson’s modelling team update its assumptions?

What SAGE Gets Wrong: The Evidence that Almost Everyone is Exposed During a Surge and Most Are Immune

During a Covid surge, what proportion of the population is exposed to an infective dose of the virus, which they either fight off with no or minimal symptoms or are infected by? This is one of the most important questions scientists need to answer.

It’s closely related to the question of whether lockdowns work. If lockdowns work then, as per SAGE and Imperial orthodoxy, the restrictions successfully prevent the virus from reaching most people, who remain unexposed and susceptible – and hence in need of vaccination to protect them when the protective restrictions are lifted. If lockdowns don’t work, however, then they don’t prevent the virus spreading, and thus the majority of people will be exposed to it as it spreads around unimpeded by ineffectual restrictions.

Another related question is: What proportion of exposed people are infected? Using ONS data we can estimate that around 10-15% of the country tested positive for SARS-CoV-2 over the autumn and winter. How many were exposed to the virus to produce this number of infections? Was it, say, 10-20%, with half to all of them catching the virus? Or was it more like 80-90%, with around 10% being infected? It’s a question that makes all the difference in our understanding of the virus and how to respond to it.

If almost all are exposed during a surge, and relatively few of them are infected, then a number of things follow. First, most people have enough immunity to fight off the virus when exposed to it, and only a small minority become infected. Second, the surge ends when enough of that small minority who are particularly susceptible to this virus or variant acquire immunity through infection, i.e., when herd immunity is reached. Third, there won’t be another surge or wave until there is a new virus or variant which evades enough of the existing population immunity to require herd immunity to be topped up via a further spread of infections.

If, on the other hand, very few are exposed during a surge, and most of them are infected, none of these things is true. It means: Most people have little immunity and are highly susceptible. A surge which infects 10-20% of the population has exposed not much more than that. The surge does not end because of herd immunity but because of restrictions. And there will be another surge as soon as restrictions are eased or behaviour changes and the unexposed begin to be exposed again. SAGE orthodoxy, in other words.

The evidence, however, is strongly supportive of the first position – ubiquitous exposure – not the second, limited exposure.

New Study: Exposure to COVID-19 Confers Immunity Even When Not Infected

The mainstream preoccupation with antibodies as a signal of protection from COVID-19, coupled with worries about their declining levels, often fails to acknowledge the crucial role played by T-cells in conferring longer lasting immunity.

A new study in Nature shows that not only do people infected with SARS-CoV-2 develop lasting T-cell immunity, but so too do their close contacts who never experience a detectable infection and have no detectable antibodies.

The authors write:

Close contacts, who are SARS-CoV-2-exposed, are often both NAT [PCR] negative and antibody negative, indicating that SARS-CoV-2 failed to establish a successful infection within these individuals, presumably due to their exposure to limited numbers of viral particles or a short time of exposure. However, our analysis of the samples from 69 of these close contacts showed the presence of SARS-CoV-2 specific memory T-cell immunity.

For those infected, the study found the level of T-cell immunity was similar regardless of whether the infection was severe, moderate or asymptomatic. It also found T-cell levels stabilised and did not diminish over the course of three months, implying lasting protection.

For close contacts who were not infected, there were some differences in the quality of their T-cell immunity compared to those infected. The authors write:

The size and quality of the memory T-cell pool of COVID-19 patients are larger and better than those of close contacts. … The results show that 57.97% and 14.49% of close contacts contained virus-specific memory CD4+ and CD8+ T-cells, respectively.

Disappointingly, the study found that in those never exposed to SARS-CoV-2 (because the samples came from before September 2019) there was no evidence of T-cell cross-immunity from other coronaviruses.

In order to investigate whether the observed expanded T-cells may have originated from pre-existing cross-reactive T-cells specific for common cold coronaviruses from previous infections, we tested blood samples of 63 healthy donors collected before September of 2019. Following a 10-day in vitro peptide expansion only 3.17% of the healthy donors contained detectable levels of virus-specific memory CD4+ and CD8+ T-cells, respectively, suggesting that cross-reactive T-cells derived from exposure to other human coronaviruses do exist but are at a significantly lower frequency than those observed in close contacts.

They acknowledged that this was contrary to other recent studies and suggested the issue needed further study.

In agreement with recent reports,17,25 our data also demonstrated the presence of cross-reactive memory CD4+ and CD8+ T-cells, which target various surface proteins of SARS-CoV-2, in unexposed healthy donors. However, the failure of these cross-reactive memory CD4+ and CD8+ to expand in vitro suggests they have limited potential to function as part of a protective immune response against SARS-CoV-2. It is noteworthy that the SARS-CoV-2-reactive T-cells detected in the unexposed healthy donors in our study were lower than those detected by Grifoni et al.17 and Braun et al.26, but were consistent with those reported by Peng et al.27 and Zhou et al.28 Assumably, due to the use of different methodologies in assessing SARS-CoV-2-specific T-cell responses, it is difficult to directly reconcile the cell-number data between different studies. Thus, a thorough investigation is needed to determine whether the cross-reactive T memory can provide any protective immunity and exert an influence on the outcomes of COVID-19 disease.

The fact that exposure to SARS-CoV-2 can result in the development of more robust immunity (perhaps because of an immune system part-primed from earlier viral infections), rather than infection, is a salutary reminder of how the circulation of viruses helps us to develop and maintain healthy immune systems capable of fighting off a variety of diseases. Trying to avoid infection by staying away from people, insofar as that is possible, can be counterproductive as it can weaken our immune system by leaving us unexposed to a whole variety of pathogens.

It’s also a reminder that antibody testing is a very limited way of determining who has been exposed to and developed immunity to COVID-19. If millions of people exposed to the virus are developing immunity without ever being infected or developing antibodies, what does that mean for reaching herd immunity? It must be closer than we think.

The Diamond Princess Told Us About Pre-Existing Immunity, Asymptomatic Infection and the Infection Fatality Rate. Why Were Those Lessons Ignored?

A reader who’s just completed a PhD in biology has got in touch to point out just how prescient the data from the Diamond Princess cruise ship was. Why was that data ignored by public health panjandrums?

I thought to bring your attention to a paper published in MedRxiv by Russell et al from the London School of Hygiene and Tropical Medicine on the 9th March 2020. They were looking at data from the Diamond Princess to try and establish case fatality rates. They got it wrong, but they did give the original data they used.

3,711 passengers and crew were on the Diamond Princess. Median age 58.

The virus had circulated undetected for 2 weeks, so given that masked-up health officials had caught COVID on board (The Maritime Executive 12.2.2020), it’s probably safe to assume everyone on the ship (or possibly only almost everyone) had been exposed.

Everyone on board had a PCR test (eventually)

619 out of 3,711 tested positive (17%)

Of which:

Symptomatic: 301
Asymptomatic: 318

Observed deaths:
(70 – 79 age bracket): 6
(80 – 89 age bracket: 1

So, it’s not unreasonable to suggest that 83% of passengers and crew may have had prior immunity.

Of positive tests, half were asymptomatic.

Of those who tested positive, ~1% died. No one died under the age of 70.

In the light of all the data collected in the last year as this pandemic has ranged across the world, it’s startling to think that the broad outline of what we could expect was already known, just no-one wanted to see.