After lockdown, immune system reacts more strongly to viruses and bacteria Comparison of immune system in people with HIV and a control group

Research from Radboud university medical center shows that the lockdowns during the COVID-19 pandemic had a significant impact on people's immune response to microorganisms. During the lockdown, inflammation level in the body was low, but afterwards, the immune system reacted more intensely to viruses and bacteria. The results are now published in Frontiers in Immunology.

In this study, the researchers examined the effects of various health measures introduced during the pandemic, such as lockdowns and vaccinations. The study was conducted in a large cohort of people living with HIV, as well as in healthy individuals. The researchers found that inflammation biomarkers in the blood were low during the lockdown for people in both groups. However, when they exposed immune cells from the blood to microorganisms like viruses and bacteria in the lab, the immune system reacted much stronger than immune cells of individuals outside the lockdown.

Hygiene Hypothesis

As a possible explanation for this strong immune reaction, Professor Mihai Netea from Radboud university medical center points to the hygiene hypothesis. This hypothesis suggests that regular contact with microorganisms is beneficial because it keeps the immune system both active and tolerant at the same time. A lack of exposure to environmental factors might contribute to an immune system that overreacts, potentially leading to systemic reactions such as those encountered in inflammatory diseases and allergies.

Netea: 'In our daily lives, we are constantly exposed to various micro-organisms. This helps train our immune system, teaching it to recognize which microorganisms are dangerous and which are harmless. During the lockdown, we missed that interaction because everyone stayed home and avoided each other. As a result, during and immediately after the lockdown periods, immune cells exposed to micro-organisms displayed a less well-regulated response, predisposing to hyperinflammation.'

Study Design

This research was made possible through a large study on people with HIV, initiated by Radboudumc and three other HIV treatment centers in the Netherlands. Recruitment for the study took place between October 2019, just before the COVID-19 pandemic, and October 2021. A total of 1,895 people with HIV are participating in this study, which is part of a broader research project on immune system function and the diversity of immune responses.

The study participants were divided into four groups:

• 368 individuals enrolled before the pandemic
• 851 individuals enrolled after the lockdown, but before vaccination or a COVID-19 infection
• 175 individuals who had contracted a COVID-19 infection
• 404 vaccinated individuals

In the lab, the researchers measured the level of inflammation in the participants' blood. They also examined the interaction between isolated blood cells and viruses and bacteria.

Subsequently, the findings were validated in cohort of 30 healthy individuals tested during or after the lockdown period. Professor Andre van der Ven: 'The results of this study primarily reflect people living with HIV, but we also examined a healthy control group. We saw similar results in this group, suggesting the effects may apply to the wider population. However, more research is needed for this group.'

Awareness of Impact

The study also revealed that vaccines and a COVID-19 infection influenced the immune system’s response, but these effects were relatively small and short-lived, Netea explained, and were negligible compared to the impact of the lockdowns on the immune system. Netea: 'Lockdowns were necessary during the pandemic, especially at the beginning. However, it is important that we gain more insight into how social interactions affect and activate our immune system, so we can better manage the consequences. This way, we can apply such drastic social measures effectively and safely in a future pandemic.'

About the publication

This research has been published in Frontiers in Immunology: Impact of COVID-19, Lockdowns and Vaccination on Immune Responses in a HIV cohort in the Netherlands - Twan Otten, Xun Jiang, Manoj Kumar Gupta, Nadira Vadaq, [...], Leo A.B. Joosten, Yang Li, Cheng-Jian Xu, Andre van der Ven, Mihai G. Netea. DOI: 10.3389/fimmu.2024.1459593.