Prolonged effect of Long COVID on the immune system

For two years, we have followed a large group of patients who experienced a COVID-19 infection. This concerns 350 patients who experienced a mild to severe infection and were already followed in the RECoVERED study from the start of the COVID-19 pandemic onwards. About half of them, 175 patients, were found to develop symptoms matching those of Long COVID. In the ongoing study, we have examined the immune system of all study participants: how did their immune system respond to the disease? Did inflammations occur? And what effect did the COVID-19 vaccination have on the Long COVID symptoms? We also collected blood samples over time to measure the inflammatory parameters and the participants completed questionnaires.

The research question was whether the symptoms of Long COVID appeared after a COVID-19 vaccination. The idea was that COVID-19 vaccination could reset the immune response. The participants receive 2 vaccinations during the course of the study. Half of them also had Long COVID symptoms at the moment of vaccination. Unfortunately, the vaccination had no favourable effect on the symptoms. We already published these results at the end of last year.

Although Long COVID symptoms can differ considerably, a common picture arises from blood tests. It was striking that 24 weeks after experiencing the infection, people with Long COVID symptoms had demonstrable inflammations in the circulatory system. This suggests that several months after experiencing a COVID-19 infection, the immune system still appears to be disrupted. We presented these initial results at a large international conference this spring.

It is not yet clear exactly why the immune system is disrupted after experiencing a COVID-19 infection. However, we think that we first of all need to know more about the clinical picture of Long COVID, which consists of a diverse range of symptoms, indicating that not all Long COVID patients are the same. We should look at the subgroups and try to determine whether the symptoms can be traced back to abnormalities in different organ systems. For example, some patients are mainly tired, whereas others have muscle complaints. It might be the case that different inflammatory processes occur in these different subgroups. Only when we have a good idea about that can we also say more about the clinical picture of Long COVID and why the immune system becomes so confused.

We have never previously been able to set up a prospective cohort study so fast. The trajectories were completed quickly, such as satisfying the privacy regulations and obtaining approval from the medical ethics committee. We encountered few problems during the process.

We need to join forces with other current cohorts to accurately answer the research question. It is not that easy to discover why these prolonged inflammations arise. Does the coronavirus do something to the body as a result of which the immune response persists? Or is it a normal immune system response to a viral infection, which can also occur for other viral infections such as flu, for example? In addition, we are also interested in other clinical pictures, such as symptoms after experiencing other viral infections. We want to examine whether those clinical pictures demonstrate the same type of response from the immune system.

It was good to see new research questions arising in the wake of the COVID-19 pandemic. The techniques we used to investigate the immune system were mainly inspired by research experiences with other virus infections, especially research that we do into the HIV virus. This greatly helped us to conduct our research quickly. Overarching collaborations with other research groups also strongly facilitated this research, and we are really pleased about that. We hope that these collaborations can enhance the general knowledge about virus infections and immune system responses.

• The effect of SARS-CoV-2 vaccination on post-acute sequelae of COVID-19 (PASC): A prospective cohort study