COVID19: Why are we now seeing fewer deaths per infection and how long will the crisis last?

I am not a scientist

I want to preface this by saying I am not a scientist and I do not propose that anyone formulates policy on the basis of what I write.

Like a lot of people, I like to understand the forces that are shaping my life. When these are complex, I like to put my thoughts down on paper. I publish them so that they might help others achieve the level of understanding they require.

The questions

There are many questions that arise from the SARS-Cov-2 virus pandemic, but perhaps the one that troubles people most is the difference in outcomes evident now compared to the first wave of the pandemic in April and May. People want to believe that the virus is less deadly. Is this actually true?

A second question that arises is how long will we have to live like this, and is it more likely that the crisis will end with the availability of a vaccine or through herd immunity.

In this context, herd immunity is the process by which a virus becomes less problematic because a large proportion of the population have developed immunity to it through being infected.

The basics of the virus and how our body deals with it

We need to understand a few important concepts before we can attempt to answer these questions.

Firstly, what happens when the virus enters your body? A virus is a submicroscopic organism capable of causing disease. It can also be referred to as a pathogen.

Basically, the virus attaches to living cells, and uses them to reproduce, compromising the function of those cells. As this process continues, and your body responds, the organs that are under attack become inflamed, inhibiting their function. This is why people die from COVID19. The small sacks in their lungs that exchange oxygen into the body become inflamed and fill with fluid, making it impossible for the patient to breathe.

The degree to which your body is affected is determined by (amongst other things) the presence of antibodies in your bloodstream. Antibodies are proteins that can attach to a virus and prevent it from attaching to living cells. Other cells then destroy the virus. As the virus gradually depletes in your bloodstream, and affected living cells are replaced, you recover (if you recover).

For antibodies to “fight” viruses, they rely on two types of living cell: B-Cells and T-Cells. B-Cells recognise the virus, and T-Cells control the process of disabling and destroying it.

A vaccine is basically a diluted does of a virus. It is strong enough to stimulate a response (the creation of antibodies) but not strong enough to cause medical problems. Getting this balance right is why it takes so long to develop vaccines.

Testing

With this basic knowledge, let’s then consider the different types of test we use in our response to the virus.

PCR Test

This tests for the presence of the actual virus itself. It is very good at finding the virus in small quantities, but it can’t tell at what stage in its life cycle the virus is at: pre-replication (less infectious), replicating (infectious), no longer replicating (less infectious). This is a swab test.

Antibody Test (Seroprevalence)

This test is for the antibodies that the body’s immune system produces to fight the virus. It tests for historical infection. This is a blood test.

Antigen Test

This tests for proteins that are produced when the virus has started replicating. It’s very good at finding people who are infectious, but not good at finding people who have the virus but who haven’t become highly infectious yet. This is a swab test.

Right now in Ireland, we test for infection using PCR tests. This is somewhat controversial, because it is not quantitative (it doesn’t tell us how infectious someone is) but is defended on the basis that it is accurate in finding the virus and is readily available, which is not the case with antibody or antigen tests.

Crucially, a PCR test is capable of returning a positive result even if the patient has the necessary antibodies (i.e. immunity) to repel the threat of the virus very quickly, or has already repelled the virus after a brief period. PCR tests will therefore find lots of “infections’, but may mislead in terms of the impact of this on health services and morbidity.

The “Safe” group and the “Not Safe” group

It is accepted that 4 out of 5 people who return a positive result from a PCR test either do not develop symptoms of the COVID19 disease or develop only very mild symptoms.

The theory (and I emphasise “theory”) behind this is that while nearly everyone has the necessary B-Cells that recognise the threat of a virus like SARS-Cov-2, only 4 from 5 people have the necessary T-Cells that can deal with it. These exist due to previous infections similar to the SARS-Cov-2 viral profile, like certain strains of the common cold. The more of these T-Cells you have, or the closer they match SARS-Cov-2, the lower the impact on you of infection.

Therefore, let’s say that the 4 from 5 people with the magic T-Cells are the “Safe” group, and everyone else is in the “Not Safe” group.

The history of the epidemic and the Infection Fatality Rate

In Ireland, by June 1st, we had recorded approx. 25,000 positive tests, and 1,640 deaths. This equates to an observed Infection Fatality Rate (IFR) of ~6%.

Between June 1st and Oct 14th, we recorded a further ~20,000 positive tests, but only another 195 deaths. In this period, the observed Infection Fatality Rate is 0.9%, a huge decrease.

Some of the decrease in the IFR between the 2 periods is undoubtedly due to the age profile of the people being infected, but this cannot explain all of it. A large part of it has to arise from the underreporting of infections in the initial period, when we were conducting only a fraction of the numbers of tests that we now carry out on a daily basis.

In fact, the scale of infection in the initial period is critical in estimating how long the crisis will continue, and if we will reach the end of it with herd immunity or a vaccine. If lots of people in the “Safe” group were infected in the initial period, we are closer to herd immunity than we think; if not, it’s more likely that a vaccine will arrive before herd immunity.

Investigating the history of the infection rate

In attempting to discover the true rate of infection in the initial period, scientists have carried out seroprevalence blood tests on samples of the population. Remember, these tests look for antibodies that have “fought” the virus. In all of the results, only very low numbers of people were found to have these antibodies, in most cases, less than 10% of the people sampled.

But is there a logic gap here? If only small numbers of people had unknown infections in the initial period, why did so many people die? And if the true IFR is really that high, why are we not seeing similar levels of death in the second period?

The accuracy of the seroprevalence test is therefore crucial.

We know that our bodies produce various types of antibodies to fight the virus, but the seroprevalence test doesn’t look for all of them. What if lots of people had repelled the virus with antibodies that the standard seroprevalence test isn’t looking for?

I am not idly speculating that current antibody tests may be unsuitable for find historical SARS-Cov2-2 infections. This issue has been discussed widely.

https://www.bmj.com/content/370/bmj.m2516

https://www.the-scientist.com/news-opinion/why-the-accuracy-of-sars-cov-2-antibody-tests-varies-so-much-67513

https://www.inquirer.com/health/coronavirus/coronavirus-covid-fda-criticized-antibody-tests-serology-testing-accuracy-20200419.html

Conclusion

If this were true, and be sure that it’s an “if”, it would explain the crucial question of why fewer people are dying in the second wave of the pandemic.

The explanation here is that the IFR in the initial period is many times lower than the one we’ve observed, because there were many, many more infections than we know about or that the seroprevalence tests suggest. Some people refer to this as the “silent epidemic”.

It would also explain to some extent the likely direction of the crisis. We can say that the spread of infection in the “Safe” group in itself isn’t problematic, as these people can deal with the virus without medical assistance. What is problematic is the spread of the infection from the “Safe” group to the “Not Safe” group, as there is a higher probability that these people will need medical assistance.

However, as the number of infections in the “Not Safe” group grows, and eventually reaches a tipping point, the potential for the virus to do harm decreases. If an infection produces immunity in a person in the “Not Safe” group, they are much less likely to become re-infected or transmit the virus to others.

The tipping point if therefore vital. In the theory of herd immunity, an infection rate of 60-80% is needed before a virus becomes manageable. However, manageability increases as the infection rate increases, so a lower rate of infection would probably allow us to return to some level of normality.

We’ll know if there is any truth to this over the coming months. If positive tests continue to exponentially increase in number, but little correlation emerges in terms of the number of deaths, it’s reasonable to say that the virus is beginning to lose its battle with the “Not Safe” group. In that event, we will hopefully not have to wait for a vaccine to return to some level of normality.

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