Unraveling Post-COVID

In the Netherlands, hundreds of thousands of patients struggle with long-term symptoms following a SARS-CoV-2 infection, commonly referred to as post-COVID. Through nine dedicated research projects and the post-COVID Center of Expertise, Amsterdam UMC aims to develop new insights and treatment options.

Five years after the outbreak of the COVID-19 pandemic, much remains unknown about the lingering symptoms following acute COVID-19. For large parts, the virus’s ability to cause a wide range of symptoms remains a mystery. Additionally, there is no standardized treatment for patients with long-term post-COVID complaints, which include shortness of breath, fatigue, concentration problems, and in some cases, lasting damage to the heart, lungs, and brain.

‘Post-COVID presents as a complex condition with many faces,’ says Joppe Hovius, professor of internal medicine and co-director of the Amsterdam Institute for Immunology and Infectious diseases (AI&I). ‘Its symptoms and underlying mechanisms vary widely. There is evidence suggesting that mitochondrial dysfunction plays a role: a disruption in cellular energy production, leading to energy supply issues. This might explain extreme fatigue and the inability to recover after physical exertion. Neuroinflammation, or inflammation of the central nervous system, may cause memory issues and concentration problems, commonly referred to as brain fog. Additionally, the immune system might continue attacking the body’s cells after COVID-19, worsening and prolonging symptoms. Psychological and behavioral factors may also play a role in the development and persistence of these symptoms.”

Focus on research

At the end of 2024, three post-COVID expertise centers opened in the Netherlands, including one at Amsterdam UMC. This center, led by internist-infectiologist and professor Michèle van Vugt, will investigate whether existing medications can relieve patients’ most common symptoms. These centers will also function as platforms for sharing data and knowledge to develop new treatments.

In parallel, 21 post-COVID research projects across the Netherlands have been funded by ZonMw, with Amsterdam UMC receiving €6.5 million for nine studies. These studies aim to uncover the causes of lingering symptoms, particularly the potential role of an exaggerated and persistent immune response.

Researchers are developing lab models with human cells to pinpoint what goes wrong in post-COVID patients. Imaging techniques, such as PET scans, will be used to identify microclots that may be characteristic of post-COVID and investigate their formation. Diagnostic markers are also studied to enable faster identification of post-COVID, especially in children, allowing earlier intervention. In addition, clinical trials will explore the effectiveness of existing drugs and therapies in relieving symptoms such as fatigue, cognitive issues, and blood pressure fluctuations. These advancements could significantly enhance patients’ daily lives.

“Post-COVID is a complex condition with many
faces”

Joppe Hovius

Professor of internal medicine and co-director of the Amsterdam Institute for Immunology and Infectious diseases (AI&I)

PAIS

The nine post-COVID studies are executed by AI&I researchers and are part of AI&I’s broader research focus on post-acute infection syndromes (PAIS). Prof. Hovius explains, “PAIS refers to conditions where patients experience persistent symptoms after an infection has cleared. Alongside post-COVID, this group includes post-treatment Lyme disease syndrome, Q fever fatigue syndrome, and post-sepsis syndrome. PAIS often has a significant impact on patients' lives, limiting their quality of live and ability to participate in social activities. Some patients are so severely affected leaving them partially or completely unable to work due to their symptoms.”

Research into PAIS is a focus area for AI&I. Prof. Hovius believes that the collective existing knowledge within AI&I will enhance post-COVID studies, while insights from post-COVID research could improve the diagnosis and treatment of other PAIS conditions. “Collaborations between expertise centers, such as the Post-COVID Center of Expertise and the Lyme Disease Expertise Center, provide opportunities for innovation. These efforts for example include improving long-term care and offering occupational health support. This momentum positions AI&I as a leading institute addressing long-term infection-related conditions.”

Multidisciplinary collaboration

Amsterdam UMC’s leading role in COVID research has drawn international attention. “Our studies on mitochondrial dysfunction and autoimmunity as potential causes of post-COVID have been major contributions to the field,” says Prof. Hovius. He emphasizes that a multidisciplinary approach has been essential in this progress: “AI&I unites over 1,000 researchers, clinicians, and scientists in tackling infectious diseases and immunology. By combining this expertise with neurobiological and clinical insights, we can identify patterns faster and develop innovative diagnostic and treatment methods. Prof. Hovius: “This dynamic collaboration speeds up the transition from fundamental to clinical research, creating unique opportunities to unravel complex post-acute infection syndromes like post-COVID. These efforts establish a strong foundation for understanding infection-related conditions and improving care for all PAIS patients.”

This article is a revised version of one originally published in Dutch in Janus: The Popular Science Magazine of Amsterdam UMC, written by Caroline Wellink.