Acute and postacute sequelae associated with SARS-CoV-2 reinfection

Acute and postacute sequelae associated with SARS-CoV-2 reinfection | Nature Medicine

Is it possible to get damage from repeated infections?

Yes, with every infection that is possible. So, prevention is always better. But, in the long run this is often not possible and practical to completely prevent. What the article here shows is that having a re-infection is worse than not having a re-infection. Nothing more! Yet, it is frequently claimed that it does show other things. So, worth a closer look.

This study predates Omicron (the study ended April 6, 2022, after 6 months follow up), which bypasses more antibodies, and reinfections are tilted towards more vulnerable. A Delta breakthrough does not imply the same consequences or selection bias as an Omicron breakthrough: but it is a good start to understand what a reinfection does.

What would be expected? After a first infection, your immune system has stored memory cells. These are T and B cells selected for their capacity to recognise SARS-CoV-2. They are much quicker than naive T and B cells that first have to be selected in the draining lymph nodes, activated and expanded. In addition, the B cells have gone through affinity maturation and improved the affinity of the antibodies they make to bind to SARS-CoV-2. A extremely large body of work tells us that this means that, on average, secondary and subsequent infections are much milder.

Watch out: that does not mean a subsequent infection is asymptomatic! Symptoms are the result of your immune system fighting the virus (e.g. pain, swelling, fever, mucus production) and the activity of the virus. It is perfectly possible to have strong symptoms, even sometimes a bit stronger than the first infection, but you will clear the virus robustly and quickly; preventing damage and other consequences from the virus itself. It will not have the opportunity to spread far from its original infection site.

​The cohort used in this study is a bit particular. Nothing wrong per se, but important to keep in mind and not to extrapolate data from this to the whole population. The average age is older (60 years old), 90% is male, there is very low vaccination status, and also includes many vulnerable (more immunocompromised: although there is some correction). Re-infections hit vulnerable people worse, so they are worse off than people who have not been re-infected.

The hospital setting also raises some concerns: If you have more C19 infections and all are diagnosed with a PCR test or antigen on your record, then you have more symptoms than someone going through the reinfection at home; anyway; PCR in hospital = more chance to be/be included in hospital. In addition, the authors equate hospitalisation with COVID-19 infection. But that is not so clear. In the setting used, the infection could be the result of the hospitalisation (where members of this more vulnerable group end up more frequently) thereby overstating the infection effect. IHR ~10%! Or it could be this specific cohort.

Independent of what people interpret, and not included in the preprint, the authors make it very clear that their study should not and cannot be used to compare the risk of reinfection with that of a first infection. This is what they write;

"The aim of our analyses was to examine the health risks associated with those individuals who had reinfection (compared to no reinfection). Our analyses should not be interpreted as an assessment of severity of a second infection versus that of a first infection, nor should they be interpreted as an examination of the risks of adverse health outcomes after a second infection compared to risks incurred after a first infection. Our analyses do not provide a comparative assessment of the risks of reinfection with different variants or subvariants."

This limitation you can see in supplemental figure 2, which is applicable to figures 1-4. Situation 1 - infected on day 1 symptoms assessed days 90-180 Compared to situation 2 - infected on day 1, re-infected in days 90-180 and symptoms assessed.

The comparison done:
1 - days 90-180 after primary infection
2 - days +1 to 90 after reinfection

In graphics, it looks like this
(Source and discussion: https://twitter.com/MichaelSFuhrer/status/1615142268796821510?s=20&t=j4jYcyCmsdyb6U28arruAA)

​There have been many studies that do compare 2nd infections, a recent meta-analysis shows a -80% reduction in disease: Protective effectiveness of previous SARS-CoV-2 infection and hybrid immunity against the omicron variant and severe disease: a systematic review and meta-regression - The Lancet Infectious Diseases

What this article shows is that the health risks arising from reinfections are not zero. That is important information, but it does not show that a second or third SARS-COV-2 infection is worse than the previous one. That data is not in this paper and such a conclusion is not supported by the data shown. 
The risk is highest shortly after infection. Which makes sense: yet there is an increase risk of complications for a time after infection: especially in cohorts like used here. It emphasis that infections, as we know, are better avoided.

But, the risks associated with reinfection seem more likely to be in the acute phase, compared to first infection. This can also be seen in the supplementary tables. The excess burden from reinfection starts out higher than the no-reinfection burden, but then drops.

All this seems at odds with the interpretation that multiple infections cause one to be more vulnerable (a first infection can, and during the acute phase this is certainly possible, for all infections, not only SARS-CoV-2). It is in agreement with the many studies as in the metaanalysis and later.
As with most infections; - the acute risk of disease is lower for reinfection than 1st infection. - those infected, after the acute phase, seem less in need of hospitalisation over time compared with 1st infection.

This is how it generally works: we have a very sophisticated immune system, that remembers previous encounters and makes sure we deal with subsequent encounters much quicker and better, thereby limiting any damage caused by the pathogen.