Antibodies

The Imperial Graph that Shows Infections Declined Before Lockdown and Increased Under It

The above graph is the COVID-19 epidemic curve for England, reconstructed by Imperial College’s REACT antibody survey by asking those who tested positive in an antibody test when their symptoms began. I’ve added the start dates for lockdowns in red and the end dates in blue.

It’s a very useful graph because it does not involve any PCR tests at all, only lateral flow immunoassay tests, self-administered at home. This means it does not suffer from the problem of detecting non-infectious virus as it is not detecting virus at all but antibodies. (Its specificity is reported as 98.6%, giving it a 1.4% background false positive rate, which the researchers adjust for.) This means, for example, that the epidemic decline is much faster than in the familiar “case” curves, and the curves are more symmetrical.

What does it show? Here’s what I take from it. You might see more.

Firstly, it provides further evidence that SARS-CoV-2 was circulating at low levels in England throughout December 2019 and to some degree also in November. This fits with widespread anecdotal evidence of people falling ill with Covid symptoms in December. It doesn’t fit with the original official timeline of an outbreak beginning in Wuhan in December.

Secondly, despite circulating widely during the winter of 2019-20, SARS-CoV-2 did not undergo fast spread in England until the end of February. Indeed, the winter of 2019-20 was the least deadly on record in terms of age-adjusted mortality, despite SARS-CoV-2 being around and infecting people.

Then, around February 25th 2020, it suddenly launches into a three-week long spike of extraordinary exponential growth. This abruptly comes to an end around March 17th, and after a short plateau till around March 21st it enters just as extreme a decline. This is all ahead of the first lockdown on March 23rd of course.

The mystery is: what happened on February 25th (or thereabouts – we don’t know whether Imperial’s assumptions about the incubation period are exactly right) to cause a virus that had been circulating for at least three months at a low level suddenly to go bang and spread like wildfire? It wasn’t panic – no one was panicking at the end of February. Mobility levels were still normal until around March 12th. There was nothing unusual about the weather. Suggestions on this welcome in the comments below.

Almost 70% Of English Adults Have Covid Antibodies

New data from the Office for National Statistics (ONS) shows that across the U.K. more than half of adults are likely to have Covid antibodies. The figure is highest in England, where 68.3% are likely to have antibodies based on the ONS’s testing, which suggests that almost 70% of the population has had the infection or been vaccinated. Sky News has the story.

Almost 70% of the adult population in England now have Covid antibodies, the latest figures suggest.

An estimated seven in 10 adults (68.3%) in private households were likely to have tested positive for coronavirus antibodies in the week to April 11th, according to the ONS.

The latest estimate is up from one in two, or 53.1%, two weeks earlier.

The presence of Covid antibodies suggests someone has had the infection or has been vaccinated – and the inoculation rollout has now reached more than 33 million people across the U.K..

In Wales, some six in 10 adults (61%) in private households tested positive for antibodies in the week to April 11th, according to the same new figures.

This is also up from around one in two adults, or 48.2%, two weeks before.

The ONS said that the rise in antibody levels in older age groups is likely a reflection of the fact that over 12 million people (largely in this group) have had a second dose of a Covid vaccine.

The Mail also highlighted that the number of adults with Covid antibodies now is likely higher than the ONS is currently reporting.

Antibody levels are likely to be even higher now because millions more have been jabbed since the blood tests were conducted more than a fortnight ago, and it takes about two weeks for immunity to kick in… 

Official data [also] shows nearly 40 million people in England live in practically “Covid-free” areas, where two or fewer cases were recorded during the latest week. 

The Sky News report is worth reading in full.

You Can Catch Covid Twice – But it’s Very Rare and Very Mild

Can you catch Covid twice? The challenge trials at Oxford University have now turned their attention to this question, deliberately exposing people who have had the disease before to the virus again to see how their immune systems respond.

Other studies have already looked into this question, though without the controversial deliberate exposure aspect. The most recent, published in the Lancet last week, tested around 3,000 U.S. Marine recruits aged 18-20 for Covid antibodies and then followed them over six weeks while they completed basic training together to see how many became infected. The living in close quarters would likely have ensured that all were exposed to the virus.

The study found that around 10% of seropositive (with-antibodies) participants (19 out of 189) tested PCR positive for the virus versus around 50% of seronegative participants (1,079 out of 2,247). This means that having antibodies from a previous infection gives about 80% protection from testing positive for the virus again. This finding closely matches that of a large Danish study published last month, that found those who had tested positive for the virus in the spring were about 80% less likely to test positive again in the autumn. And also a UK study of NHS workers from January that found being PCR positive for the virus at one point made workers around 80% less likely to test positive again at a later date.

The new study was being used last week to promote the idea of vaccinating young people who had previously been infected, on the grounds that protection via infection was not enough. Thus Sky News reported: “Young people who have already tested positive for coronavirus are not fully protected against reinfection.”

The study itself supported this use, stating its results suggest “COVID-19 vaccination might be necessary for control of the pandemic in previously infected young adults”. Professor Stuart Sealfon of Icahn School of Medicine at Mount Sinai, New York, and senior author of the study, said:

As vaccine rollouts continue to gain momentum it is important to remember that, despite a prior COVID-19 infection, young people can catch the virus again and may still transmit it to others. Immunity is not guaranteed by past infection, and vaccinations that provide additional protection are still needed for those who have had COVID-19.

What such claims appear not to allow for is that questions are being asked about how the balance of risks stacks up for young people to be vaccinated even when they have not had Covid, let alone when they have and have 80% protection already. To this balance must be added that severe side-effects are considerably more common in those who have previously had Covid.

The 80% protection figure is also not the full story on immunity following infection. Noteworthy is that symptomatic infection was much less common among those who had antibodies. In fact, only three out of 19 (16%) seropositive PCR positives were symptomatic, versus 347 out of 1,079 (32%) seronegative PCR positives. The large proportion of PCR positive infections that are asymptomatic even among those without antibodies (68%) may be an indication of the high degree of pre-existing immunity among the young.

The infections among those with antibodies were also much less likely to be infectious, with average Ct of 27-28 versus around 24 for the seronegative infections (Ct or cycle threshold corresponds inversely to viral load, which corresponds to infectiousness). This translates to a viral load about ten times lower, which is considerably less infectious.

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.