Why the prejudice against tests for Covid-19 immunity?

Simon Thornley

27/5/2020

Words: 1090

A curious phenomenon has developed in the race to beat Covid-19. Advisors to the government have recently become anti anti-bodies. Before I explain what that means, let me provide some context. While we’ve weathered the initial Covid-19 storm, we now have a more challenging set of questions ahead of us as we decide how far and fast to ease social restrictions and open our borders back up to the world.

One of the most critical is: just how widespread is this virus? If, as the Government’s advisors believe, it’s a case of ‘what you see is what you get’, then our options are limited. But if, as we are seeing around the world, the virus has spread through far more of our population than we are aware, then that changes everything. All of a sudden, we need to radically re-think whether our control measures make sense. The genetic test that we are relying on can tell us if the virus is active in the here and now. That is the focus of the daily case counts. These tests are accurate, and the best for diagnosing cases, but they don’t give us a complete picture.

In almost all infectious diseases, antibody tests play a crucial role in determining who is protected from the germ and who is not. They tell us that a virus or germ has been and gone. They are the fingerprints that the virus leaves behind, and allow us to be better prepared for the next encounter. For Covid-19, we may not otherwise know we have met and dispatched the virus, since not all of us develop symptoms. In Iceland, of the few areas of the world a survey was carried out, rather than only testing sick people, 1% of the population tested positive, but half all these positives were perfectly well. It is now clear that just because we don’t have a fever, runny nose or cough, it doesn’t mean we haven’t seen the virus. For this reason, we simply cannot rely on genetic tests from people with symptoms to tell us how far the virus has spread. To really get a handle on how many of us have seen a virus, we need to not only count active cases, but start measuring people who have seen the virus before with antibodies.

New Zealand is now at a cross-roads. We have two explanations for our results. Professor Michael Baker, one of the main experts advising the government, has expressed that antibody tests “would be a waste of time and resources” since a “vanishingly small” proportion of the population have been exposed. Through Baker’s eyes, the lockdown was astonishingly effective, quashing the virus, while leaving all except the one and a half thousand or so cases sitting ducks waiting for infection to strike. We had better live in fear and shut down the borders hard. This narrative goes with the elimination story. So much for our travel and tourist industry. Sorry Rotorua and Queenstown, we have laid you on the altar as a casualty on the path to vanquishing the virus.

Another explanation for the rise and fall of cases in New Zealand is from growing immunity, rather than from the lockdown. The cases of infection rise as the virus encounters more susceptible people. This is great for the virus until it encounters people who have seen the virus before. Their bodies have wised up, thanks to our miracle antibody factories, and the virus sees the door is shut. Some may not even need antibodies. The innate and cellular immune system, like a razor wire fence, may keep the virus out before the soldier-like antibodies need to be enlisted.

Immunity from other viruses is also likely to play a part. A recent study estimated that half of people who haven’t seen the novel virus before, have T cells that react against it which are primarily directed against ‘common cold’ coronaviruses. The virus looks elsewhere, but the door is shut with the next person, and the next, and it soon has nowhere to go. This has been the way we have defeated almost every other lung virus of equivalent severity to Covid-19 in the past.

Now critics will say there are holes in this immunity theory. If that had really happened, we should have seen chocka intensive care units like in Italy. Well, we may have, or we may not. It is clear that New Zealand is not Milan, London and New York, as we would like to believe. We are simply nowhere near as population-dense as these metropolises.

Surely we would have noticed excess deaths? Or excess people coming to hospital with influenza-like symptoms? Since the deaths from Covid-19 are about the same average age as our life expectancy, we may not have noticed. If we hadn’t tested for it, we would have probably not batted an eyelid. We would have put the death down to the growing list of diseases that were likely to have afflicted the deceased. And it is not as if Covid-19 gives a unique clinical presentation. As a former hospital doctor, I know only too well that patients who present with flu-like illness are extremely common. A recent positive test in a French patient well before the ‘official’ epidemic occurred support this theory of widespread infection.

Teasing out which of these two beliefs to follow is now critical. History may help. In recent memory, a story played out according to the widespread immunity theory. We strongly believed that H1N1 was a killer virus, rapidly spreading out of Mexico. The death rate was astonishingly high initially. The clamour to ‘stamp out’ the virus in New Zealand was long and loud. It was, at least, until needles were put in veins, and antibodies were present in 47% percent of some age groups. These tests established that many New Zealanders had seen the virus and the chorus to defeat the virus lost its stuffing.

Evidence from other countries supports the idea of widespread immunity. The very small secondary overseas outbreaks, such as in China and the Australian state of Victoria are further evidence that widespread immunity is growing. If, instead, immunity were sparse, we should expect many further large outbreaks. Other commentators have condemned the low accuracy of Covid-19 tests, however, Roche now has produced a test that has sensitivity and specificity values approaching perfection (100%) that has now got widespread acceptance in Europe. Not even many of our established antibody tests have achieved this.

The philosopher George Santayana reasoned, “those who cannot remember the past are condemned to repeat it.” At this crucial juncture, history indicates that the value of antibody tests and the idea of growing immunity cannot be so easily dismissed. If the virus is more widespread than the genetic tests indicate, we need to urgently reconsider whether or not border closures and social restrictions are really worthwhile.

 

What should we do when we get another wave of Covid-19 cases?

Simon Thornley

15/5/2020

New Zealand has now progressively opened up, and we are now at level two. The next item to consider is what happens if we have another cluster of cases? What if the number of cases rises steeply? The government has stated that it has achieved ‘elimination’ of the virus, although there are dribs and drabs of new cases, mostly related to known sources. Recently, outbreaks occurred in Hokkaido, Japan, after lockdown was relaxed. The Northern Japanese island locked down for a second time in response to this second wave. Should we follow suit?

Our response depends on the answer to a number of questions. These include:

  • How effective are lockdowns?
  • How do similar viruses behave?
  • How widespread is immunity?
  • What are the risks to our health?

On the questions of the efficacy of lockdowns, there is likely to be ongoing squabbles, which will inevitably spill a lot of academic ink. We now have some compelling evidence that lockdowns in Europe were not especially effective. The trajectory of the epidemic was already declining in many countries when lockdowns were implemented, and the author of the article concluded that lockdowns were unlikely to have saved lives. Other evidence, such as a comparison of US States, that are either under lockdown or not reinforces this view. This analysis has now been subject to major revisions and re-analysis, but the conclusion remains the same – per capita cases and deaths from Covid-19 in each State are not materially different under either policy. The main factor linked to cases and deaths was testing rates. The more tests that were carried out by State, the more cases were found. Closer to home, our New Zealand – Australia comparison, in which New Zealand locked down harder and tighter than our cousins over the Tasman did not support the “hard lockdown” theory.

It is hard to believe with the Covid-19 blinkers on, but there are a number of other coronaviruses that have been circulating for many years that we pay little attention to. As well as the deadly SARS that has been eliminated, there are other coronaviruses that we have been living with for many years that have escaped our gaze. These latter examples are more similar to Covid-19 than SARS and MERS. These coronaviruses, including HCoV-229E, HCoV-HKU1 and HCoV-OC43 have a history of causing fatalities in resthome populations, like our new virus on the block. These viruses have now become endemic with winter seasonal peaks. With these similarities, it is likely that we will have to learn to live with future Covid-19 cases, particularly with winter around the corner.

The risk of future waves is likely to be related to the extent of our exposure to the virus. Tests of immunity in hard hit countries are returning immunity levels of about 5%, such as in Spain. Other tests of cell mediated immunity suggest higher real levels of immunity than those obtained from antibody tests alone. In Germany, 34% of antibody negative healthy donors showed markers of cellular immunity. In New Zealand, we don’t yet know our immune status, since we haven’t tested for it. With the comparative evidence that indicates that lockdowns are not especially effective, the fall in case numbers in New Zealand strongly indicates that widespread immunity is rising. The rise, fall and now low number of cases in China, with only smaller contained outbreaks after the initial peak, suggest that immunity is sustained, at least in the medium term.

We also need to consider how much of a threat the virus poses. In even hard hit countries, for the majority of working age people, the risk of death from the virus is about the same as a daily thirty kilometer trip by car. For those under the age of forty, the mortality risk is extremely low. We now know that hospitals in Australasia were never stretched, even at the epidemic’s peak. It simply makes little sense to squirrel children and working age people away, when the economic effects of lockdowns are ruinous.

The evidence that I see simply does not add up to an endorsement of further lockdowns. The elderly, particularly those who live in rest homes, deserve the greatest protection we can afford. For the rest of us, we can safely get on with our lives and progressively open up the country, even in the face of further cases.

How to respond to a spike in COVID-19

Media Statement

17 May 2020

Epidemiologist Simon Thornley says is likely that there will be a rise in COVID-19 cases in New Zealand, so while there is no need to return to national lockdown, protection of vulnerable people is necessary.

“Internationally lockdowns have not prevented subsequent spikes in the number of cases, such as in Hokkaido, Japan. Lockdowns just slow or delay the inevitable resurgence of COVID-19.

“While the evidence does not endorse further lockdowns, even in the face of further cases, the elderly deserve protection. The rest of us can safely get on with our lives.

“I expect COVID-19 to join other coronaviruses such as HCoV-229E, HCoV-HKU1 and HCoV-OC43 as endemic with winter seasonal peaks – when they cause fatalities in rest homes. So, we need to take particular care toward older people and those with co-morbidities.

Thornley says that to justify a renewed lockdown the Government would need to argue health services were at risk, public immunity was low, and the risk to people’s health was major.

“The nation may lack immunity due to lockdown – but we have no information because the Government hasn’t done serology tests. But we do appear to have enough health service capacity, and for most of us the virus poses very little danger.”

There is now compelling evidence that lockdowns in Europe were not especially effective, and that there was no difference in per capital cases and deaths in a comparison of US States. The main factor linked to cases and deaths has been found to be testing rates; the more tests that were carried out by State, the more cases were found.

The risk of future waves is related to our exposure to the virus. Tests of immunity in hard hit countries are returning immunity levels of about 5%, such as in Spain. Other tests of cell mediated immunity suggest higher real levels of immunity than those obtained from antibody tests alone. In Germany, 34% of antibody negative healthy donors showed markers of cellular immunity. The rise, fall and now low number of cases in China, with smaller contained outbreaks after the initial peak, suggest that immunity is sustained, at least in the medium term.

In even hard hit countries the risk of death from the virus for the majority of working age people, especially those under the age of forty, the mortality risk is very low.

Contact: Simon Thornley, 021 299 1752

Video: epidemiologist’s take on Covid-19

Dr. Simon Thornley

  • Deaths due to coronavirus have been exaggerated
  • Mean age of death – 80 years old

Did lockdowns save anyone?

Sweden’s former top state epidemiologist has claimed unless a vaccine is found soon, lockdowns like New Zealand’s won’t prevent any deaths at all – just push them into the future.

Johan Giesecke’s call, published by journal The Lancet, comes the same week a new paper claims lockdowns in hard-hit western Europe haven’t saved a single life at all, which has split opinion among experts.

Sweden has taken a different approach to handling the COVID-19 pandemic than most other countries, deciding against a lockdown of any kind, instead relying on people following social distancing guidelines. As of Monday, it had 26,300 confirmed cases and 3225 deaths – far more than its Scandinavian neighbours, but only a fraction of those seen in Spain, Italy and the UK, which have all implemented lockdowns of various kinds.

https://www.newshub.co.nz/home/world/2020/05/coronavirus-did-europe-s-lockdowns-save-anyone-at-all.html

10 Reasons to end lockdown

Dr John Lee, Retired Professor of Pathology, writing in The Spectator:

Even if one could understand why lockdown was imposed, it very rapidly became apparent that it had not been thought through. Not in terms of the wider effects on society (which have yet to be counted) and not even in terms of the ways that the virus itself might behave.

 

…at the start, there was hardly any evidence. Everyone was guessing. Now we have a world of evidence, from around the globe, and the case for starting to reverse lockdown is compelling.

 

…Covid is not, in fact, an extraordinarily lethal pathogen, just a nasty one, similar to many others.

 

…our new normal should look very much like our old, perhaps with the addition of some social responsibility in the face of respiratory illness. It is the only way for us to live in the world.

https://www.spectator.co.uk/article/ten-reasons-to-end-the-lockdown-now

 

What you need to know about Covid19 serology

By Simon Thornley

19 May 2020

Why does New Zealand need a serosurvey?

New Zealand urgently needs to test for antibodies to Covid-19. The standard test for Covid-19 at present is a genetic test that only detects whether or not the virus is currently in the body. Serology is a test of a person’s immune response to the virus and persists long after the virus has disappeared. This test gives important information about who in the community has recovered from infection and is thus unlikely to get the infection and pass it on to others. The overwhelming picture from this information is that the virus is much more widespread than is shown from genetic test positive cases.

In the response to swine flu in 2009, a serosurvey provided crucial information to dial back the clamour to stamp out the virus, since that survey showed that the virus was much more widespread than initially thought. As a consequence, it also followed that the virus was much less deadly than initially believed.

We can now count a total of 18 regions or countries that have conducted serological surveys and reported results in English to determine the extent of population exposure to the virus (Table). The proportion of the population who were found to have positive Covid-19 antibodies ranged from between 0.5%  in Colorado to 25.9% in Northern France. In some studies, the rate of positivity increased substantially as the study progressed. Even in the low prevalence regions, these findings strongly indicate that the virus is widespread and unlikely to be amenable to an elimination strategy.

Table 1. Prevalence of positive antibody tests to Covid-19 in surveys from around the world.

Region, Country Sample size Prevalence (%)
Northern France 171 25.9%
Guilan, Iran 552 22.0%
Gangelt, Germany NA 14.0%
New York State, USA 15000 12.3%
Barcelona, Spain 578 11.2%
Wuhan, China 1402 10.0%
Aspen Colorado, USA 198 9.9%
Miami-Dade, USA 1400 6.0%
Switzerland, Geneva 760 5.5%
Los Angeles County, USA NA 4.1%
Finland 147 3.4%
Kobe, Japan 1000 3.3%
Moscow, Russia 1000 3.0%
Santa Clara, USA 3324 2.8%
Netherlands 7361 2.7%
Denmark 9496 1.7%
Colorado, USA 5455 0.5%

NA: not available.

What are antibodies?

Antibodies are like keys in a lock that the body makes in response to viruses and other bacteria. Antibodies only fit a specific virus or bacteria. The shape of the antibody locks on to the microbe so that the body’s immune system can more easily eliminate the virus. Once a high proportion of the community have antibodies to the virus, it becomes very difficult for the virus to spread throughout the community, since it is hard for the virus to find new susceptible people to spread to.

Antibody tests are generally not used to diagnose the infection, since there may be a delay of one to three weeks from the time of infectiousness with the virus to the time that antibodies are generated by the body. Genetic tests, such as PCR, are usually used for making the diagnosis as they are positive earlier in the course of the illness.

What sort of antibody tests are available for Covid-19?

An antibody test generally involves the collection of venous blood or a finger prick to collect capillary blood. A number of test kits have been authorised by the US Food and Drug Administration for use for Covid-19. The Center for Disease Control has developed a test which is reliable for detecting SARS-CoV-2. The test is claimed by the organisation to be 99% sensitive (low false-negative rate) and 96% specific (low false-positive rate).

At present, tests of immunity are mainly recommended for assessing the extent of infection, and what proportion of the population has had mild disease from the virus. Until more information comes to light, researchers are not certain that test-positive individuals are unable to be re-infected, although this is likely to be true.

Are there other types of immunity to Covid-19 apart from antibodies?

As well as using antibodies which come from “B” white blood cells, our immune system also has “T” cells that recognise the virus directly, without the need for antibodies. A recent study from Germany has demonstrated that 83% of genetic test positive Covid-19 cases tested positive for T cells that react to the virus. Also, 34% of healthy blood donors, who were test-negative for antibodies, had evidence of reactive T cells, but at lower levels than cases. It is likely that these T cells confer some immunity to the virus, but it is unclear to what extent such people are protected.

What is the NZ government experience of antibody tests?

A wide range are available, but none have been rigorously tested in New Zealand yet. In order to be confident that these tests are useful, media interviews suggest that the government requires local evidence of testing their accuracy, despite overseas studies showing excellent accuracy with some tests. A number of tests are now endorsed by regulatory agencies in the United States.

If someone tests positive for antibodies, does that prove immunity?

The long term immunity associated with Covid-19 antibodies is not known. It is likely that they confer partial immunity, as seen with other antibodies for coronaviruses. This depends on the dose and route of administration. For example, in an animal study, mice administered coronavirus in the nose maintained immunity for at least 12 months, however, those that had exposure to the virus by mouth had high levels of immunity at one months, but lower levels at 6 and 12 months.

Conclusion

New Zealand urgently needs to test for antibodies to determine community exposure to the virus. If antibody levels are high, then this suggests that the virus is widespread. This also means that the virus is much less deadly than we feared.

 

 

 

Covid immunity passports: yeah, nah

COVID-19 immunity passports and vaccination certificates: scientific, equitable, and legal challenges

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31034-5/fulltext

The Lancet: The invisible pandemic

It has become clear that a hard lockdown does not protect old and frail people living in care homes—a population the lockdown was designed to protect.

Neither does it decrease mortality from COVID-19, which is evident when comparing the UK’s experience with that of other European countries.

 

PCR testing and some straightforward assumptions indicate that, as of April 29, 2020, more than half a million people in Stockholm county, Sweden, which is about 20–25% of the population, have been infected (Hansson D, Swedish Public Health Agency, personal communication). 98–99% of these people are probably unaware or uncertain of having had the infection; they either had symptoms that were severe, but not severe enough for them to go to a hospital and get tested, or no symptoms at all. Serology testing is now supporting these assumptions.

Everyone will be exposed to severe acute respiratory syndrome coronavirus 2, and most people will become infected. COVID-19 is spreading like wildfire in all countries, but we do not see it—it almost always spreads from younger people with no or weak symptoms to other people who will also have mild symptoms. This is the real pandemic, but it goes on beneath the surface, and is probably at its peak now in many European countries. There is very little we can do to prevent this spread: a lockdown might delay severe cases for a while, but once restrictions are eased, cases will reappear. I expect that when we count the number of deaths from COVID-19 in each country in 1 year from now, the figures will be similar, regardless of measures taken.

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31035-7/fulltext

Mean age of Covid-19 death equal to average life expectancy

5 April 2020

Simon Thornley

To understand the risks of ending lockdown, it is useful to think of a worst-case scenario. What would happen if ending lockdown led to a fate like Spain, Italy and New York.

A well-known epidemiologist has calculated the answer. For individuals aged less than 65 years, even in ‘pandemic hotbeds’, the risk of dying during the outbreak in hard hit European countries, is about the same as that associated with driving a car between 15 and 100 kilometres per day, throughout the pandemic. For people aged forty or younger, the risk is almost zero. Females have a risk two to three times lower than for males. For people aged younger than 65 years, with no medical conditions, the risk of death is extremely low, with this group contributing only 1/100 of all Covid-19 deaths.

Underscoring the low risk of death, the authors of the study noted that the mean age of death is approximately equal to the average life expectancy at each center. The exact ages of cases are not given for New Zealand cases, but if these are fixed at their midpoint for those for whom only a decade is given, the mean age of death is 81.6 years. This very closely approximates New Zealand’s life expectancy of 82 years. Since the numbers are so close, it is very difficult to argue that the virus is causing early death. In fact, such a pattern is replicated in almost all countries heavily affected by Covid-19. The risk of death in people aged less than 65 years was at least 92% lower compared to their older counterparts in eleven hard hit Covid-19 regions.

This analysis must force us to ask difficult questions, such as if our population of working age are at so low risk, why are we locking down our entire population? If the risks posed by the virus are so low, what are the downsides of locking down? Why are we closing our borders, and devastating our economy due to such a threat? On the basis of such a threat, why are we so obsessed with eliminating the virus?

There are really two choices that continue to be open to us to contain the virus, in the case of increased spread. These two combinations are ongoing lockdowns, or opening up the majority of society, returning us to work and school and protecting the vulnerable. The question of the closure of our borders continues to loom, as we consider whether we can remain cut off from the rest of the world or we work toward a sort of Australasian bubble.

The lockdown affects people of all ages, taking children away from school and workers away from their jobs. In contrast, protecting the vulnerable largely means that people over working age, past their 65th birthday are vulnerable.

The toll is starting to mount. In Queenstown, 30% of the population faces unemployment. Now, more than 100,000 kiwis are looking for mortgage relief. The true magnitude of the effect of the lockdown will take some time to be realised.

At the same time that we are dialing back the real risks posed by the virus, the downsides of putting the country in handcuffs are becoming more apparent. We urgently need to get back to work and school and do our utmost to protect the vulnerable.