T cells

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?

Do Your Genes Determine How Sick You Get From COVID-19?

We’re publishing today a piece by John Collis, a recently retired nurse practitioner, in which he uses the work of Professor Daniel M. Davis to explore the role of genes in the immune system and asks whether genetic diversity between individuals and groups might explain why some people are worse affected by Covid than others. Here’s the introduction:

Why are different people affected differently by a SARS-CoV-2 infection? Through this article, based on The Compatibility Gene by Professor Daniel M. Davis, I hope to be able to provide some insight. While this is a very complex subject, with the understanding of the different components and their interactions having developed over the past 60 years or so, I will set it out as clearly as I can. To simplify matters I do not discuss here the role of cytokines or other chemical signalling between cells.

The immune system is built around the body’s ability to distinguish between components that belong there (self) and those that don’t (non-self). Pathogens such as bacteria, protozoa and parasites have very different DNA and are relatively easy to identify as non-self. Viruses are different: how does the immune system distinguish between a healthy ‘self’ cell and an infected ‘self’ cell?

The part of the immune system that is responsible for this are T-cells. T-cell production is controlled by the Thymus gland located in the chest, between the lungs. Significantly, this gland is large in children, starts to shrink post puberty and is very small in older adults. Could this explain why children are less susceptible to the effects of SARS-CoV-2 infection? Could the changes in the thymus gland explain the effects being seen in teenagers and young adults? Are some of these adverse events immune system mediated?  

Worth reading in full.

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.