The idea of SARS-CoV-2 as ‘textbook’ has been promoted to help calm fears that the novel virus that emerged in 2019 might be responsible for high rates of sickness and excess death being seen around the world. But the term should not comfort, because the textbooks actually tell us SARS-CoV-2 is likely to have a detrimental impact on human health and life expectancy if it continues to reinfect the population.

Some members of the medical and scientific community, and a significant proportion of the public believe exposure to pathogens through infection toughens us and is a net benefit to our health. This belief is based on a fundamental misunderstanding of the so called ‘hygiene hypothesis’, which was formulated several decades ago to explain the apparent rise of immune system dysregulation conditions (allergies, auto-immune disorders, and others) against a backdrop of advanced industrialization and improved living standards.

The hygiene hypothesis is the idea that the immune system needs to be ‘trained’ during childhood to properly develop immune tolerance to microbe, but it specifically refers to bacteria, protozoans and helminths, most of which are normally beneficial, neutral or not significantly harmful to humans. It does not advocate repeated exposure to viruses, especially highly pathogenic ones. This false reading of the ‘hygiene hypothesis’ over the last three years has led to a high degree of complacency in the face of a serious and ongoing threat to public health.

What do the textbooks tell us about coronaviruses?

Prior to 2020, there were four endemic human coronaviruses – OC43, NL-63, 229E, and HKU1 – which were known to cause 10% to 15% of common colds – the common cold coronaviruses (CCCs). Since at least the 1970s, we’ve known infection with these coronaviruses does not lead to lasting protection from reinfection - this has been textbook knowledge for decades.

Many people assume that the CCCs would cause severe symptoms if they were to be introduced into a naive population of adults, and it is only the ‘novelty’ of SARS-CoV-2 that has resulted in the deaths of millions. According to this assumption, if everyone had been infected by SARS-CoV-2 many times as children, then all subsequent reinfections would be “mild”.

The available data does not support this conclusion.

CCCs are not just colds – they can cause severe pneumonias and exhibit a risk profile very similar to SARS-CoV-2 with age. If reinfection strengthened immunity against CCCs, older people would be least affected because they have been infected with diverse variants of these viruses many times in the past. But SARS-CoV-2 is not a CCC. It has a wide array of accessory proteins that silence and disrupt our normal immune responses.

There is no evidence to support the widespread belief that endemic SARS-CoV-2 will become a ‘common cold’ simply through repeated exposure. Other viruses, such as smallpox and measles, have not lost their virulence despite centuries of circulation in humans. Our ability to exist with these pathogens depends on infection acquired immunity, which comes at great cost, or vaccination, which in the case of measles and smallpox generally protects against infection and lasts decades if not a lifetime.

What do the textbooks tell us about our immune systems?

As we get older, our immune systems start to lose their effectiveness and we become more susceptible to disease. This process is called immunosenescence and research suggests it is caused by environmental and lifestyle factors.

Exposure to viral infections is well understood to accelerate the aging of the immune system, which in turn increases people’s susceptibility to ill-health, autoimmunity and disease.

SARS-CoV-2 is a particularly nasty virus, triggering the hyperactivation of our own immune systems to cause severe disease. Repeated exposure to a virus such as SARS-CoV-2 will fast-track more people into immunosenescence at ever earlier ages, with potentially serious repercussions for their health and longevity.

And then there is the risk of autoimmunity, which is when the immune system mistakes part of our body for a pathogen and creates autoantibodies to attack the threat. Infection by SARS-CoV-2 has been shown to lead to an increase in autoantibodies and autoimmune disease. Approximately 25% of people who develop an autoimmune disease will experience multiple autoimmune syndrome, risking a cascade of autoimmune conditions.

This is why vaccines, not infection, are the best way to give the immune system the protective information it requires. This is true in both adults and children. Not only are vaccines less dangerous, they also generate a higher quality immune response due to higher avidity, a measure of the strength with which antibodies bind.   

What do the textbooks tell us about systemic viruses?

People are being encouraged to believe that endemic SARS-CoV-2 is a good thing: once the virus is no longer novel, it will cause only “mild” disease because our immune systems will have been “trained” to prevent worst-case scenarios. This hypothesis relies on framing SARS-CoV-2 as a textbook respiratory virus where it joins the ranks of the CCCs, RSV, rhinovirus and so on. 

However, SARS-CoV-2, like SARS-CoV-1, is both a respiratory and a systemic virus, with an extremely broad cell type and tissue tropism covering nearly the whole body. Its ability to infect and do damage to lungs, hearts, kidneys, cardiovascular systems and brains is particularly well documented.

What does that mean for the future? Under the most optimistic ‘mild endemicity’ model, whoever has survived the first infection, without death or severe complications, is set for life and doesn’t have to worry about future infections. Under the less optimistic ‘mild endemicity’ model, it will take a few reinfections to get to that point. 

The most optimistic scenario has already been completely debunked by evidence – reinfections are common, people suffer organ damage and some die as a result of reinfection, and even though the risk of Long Covid reduces by about a third, it does not go to zero.

If each subsequent infection results in additional internal organ and immune system damage, then at some point the damage accumulated, together with the accelerated immune system aging and normal aging processes, can reasonably be expected to outweigh the protective benefits of immunity developed from previous infections. The baseline risks for any given age will thus shift higher. This is what we see with the CCS and influenza. We should not expect SARS-CoV-2 to behave any differently to these textbook viruses, but we must keep in mind that SARS-CoV-2 reinfects more frequently than influenza, infects a wider range of organs, does more damage and seems capable of persisting in a range of organs.

So, if SARS-CoV-2 behaves like a textbook virus, but does more damage and does it more quickly, at what point does the body reach this tipping point?

This is something the textbooks cannot tell us because never in modern history have we lived alongside a widely circulating, re-infecting and system-damaging virus such as SARS-CoV-2.

We can, however, sensibly hypothesize that the excess deaths being witnessed around the world are a signal of what’s to come. In the UK, which now includes two pandemic years in its five-year average, excess deaths are 7% above expectations and in Holland, excess mortality is rising in all age groups, but most quickly in the younger age groups.

We believe the evidence is already accumulating to suggest this population-scale experiment of mass infection by SARS-CoV-2 will force a rethink of the ‘mild endemicity’ hypothesis, but by then it will be too late.

If you’d like to read about SARS-CoV-2 and textbook immunity in detail and explore the evidence for yourself, please click here.

If you’d like advice on how to reduce your risk of infection, please click here.