A recent study published in The Lancet Psychiatry indicates that many individuals who were hospitalized with COVID-19 continue to experience cognitive and psychiatric issues two to three years after their infection. The study sheds light on the long-term effects of COVID-19 on mental health and cognitive function, showing that these issues worsen over time and can negatively impact daily life, including the ability to work.
As COVID-19 spread globally, researchers noticed a concerning trend: many people who had recovered from the initial illness continued to report problems such as anxiety, depression, and cognitive difficulties. For those who were hospitalized, the risk seemed particularly high. However, it was unclear whether these symptoms persisted or worsened over time, or if new issues arose long after the acute phase of the illness.
Previous studies primarily relied on electronic health records, which only offered a snapshot of diagnosis rather than a detailed picture of symptom evolution. Additionally, many of these studies only tracked patients for about 18 months post-infection, leaving a gap in our understanding of what happens beyond this period.
The aim of the new study, called the COVID Fog (C-Fog) study, was to provide a clearer understanding of the trajectory of psychiatric and cognitive symptoms in the two to three years following hospitalization for COVID-19. Researchers also wanted to identify factors that predict long-term symptoms and understand the occupational impact of these cognitive and psychiatric challenges.
“We knew that people who had COVID-19 (especially those hospitalised for COVID-19) were at an increased risk of a range of neurological disorders. However, we did not know whether symptoms improve or persist over time, what predicts them, and how they relate to the ability to work,” said study author Maxime Taquet, a NIHR Clinical Lecturer in Psychiatry at the University of Oxford.
The C-Fog study is part of a broader effort called the Post-hospitalization COVID-19 study (PHOSP-COVID), which followed nearly 8,000 adults discharged from hospitals across the U.K. after COVID-19. For this specific analysis, the researchers focused on a subset of 475 participants who had been hospitalized with COVID-19 and were followed for two to three years after their discharge.
Participants were asked to complete a range of online assessments between late 2022 and mid-2023. These included cognitive tests to measure skills such as memory and reaction speed, and questionnaires that assessed depression, anxiety, and fatigue. The researchers also gathered information about any changes in employment or work capacity, asking participants if they had altered their occupation or working status due to health reasons after their COVID-19 hospitalization.
Importantly, the researchers compared the cognitive and psychiatric symptoms of participants at different time points: six months, 12 months, and two to three years after their initial hospital stay. This allowed them to track how these symptoms evolved over time.
The study’s findings paint a troubling picture of long-term brain symptoms following COVID-19 hospitalization. Cognitive and psychiatric issues, including depression, anxiety, and fatigue, did not diminish over time. Instead, they worsened for many individuals between the one-year and three-year marks.
“We were surprised to see that on average neuropsychiatric symptoms got worse 2 to 3 years after COVID-19 hospitalisation compared to 6 and 12 months post-hospitalization,” Taquet told PsyPost.
Nearly half of the participants reported moderate to severe depression, and about a quarter experienced significant cognitive decline two to three years post-hospitalization. Fatigue was another common problem, affecting 62 percent of participants. Alarmingly, more than one in four people had changed their job or working status due to poor health. The cognitive symptoms, such as difficulty concentrating or remembering things, were strongly linked to these occupational changes.
In addition to tracking symptom severity, the researchers also identified a pattern in how symptoms emerged. Individuals who already experienced symptoms like depression, anxiety, or fatigue at the six-month mark were more likely to develop new or worsening symptoms over the next couple of years. For example, someone with anxiety at six months might later develop depression or experience cognitive decline.
Interestingly, the severity of the initial COVID-19 illness did not appear to predict long-term symptoms. In other words, even people who were less severely ill while in the hospital could still face significant mental health and cognitive challenges years later. Instead, the best predictor of long-term problems was how individuals were faring six months after their hospitalization. Those who had more severe symptoms early on were more likely to continue struggling two to three years later.
“Some people hospitalized for COVID-19 continue to experience symptoms such as cognitive problems, depression, anxiety, and fatigue 2 to 3 years after hospitalization. This is mostly the case among people who already had symptoms 6 months after hospitalization, whereas most of those who were well at 6 months remained well at 2 to 3 years,” Taquet explained.
“People who worked less 2 to 3 years after being hospitalized for COVID-19 were mostly those who had cognitive difficulties, and not necessarily those who had anxiety, depression, or fatigue, suggesting that they stopped working because they could not face the cognitive demands of their job, rather than because they lacked interest or motivation.”
While the C-Fog study provides valuable insights, it is not without limitations. One major limitation is that the study focused only on individuals who were hospitalized with COVID-19, meaning the results may not apply to people who had milder cases of the virus or those who were not hospitalized.
Additionally, only 19 percent of those invited to participate in the follow-up study actually took part. This relatively low response rate raises the possibility that the study may not capture the full range of experiences, as those who were experiencing more severe or long-lasting symptoms might have been more likely to respond.
Looking forward, the researchers highlight several areas for further investigation. One key question is understanding the biological mechanisms behind these persistent symptoms. Early findings suggest that certain blood markers measured during acute COVID-19 infection may be linked to long-term cognitive and psychiatric issues.
For example, elevated levels of a molecule called D-dimer, which is associated with blood clotting, may point to the presence of tiny blood clots in the brain that could be contributing to cognitive decline. However, more research is needed to confirm these findings and identify other potential mechanisms, such as inflammation in the brain.
Additionally, the study’s authors emphasize the need for more research on interventions that could help prevent or treat these long-term symptoms. They suggest that addressing symptoms like anxiety or cognitive difficulties early on, perhaps through therapies targeting these issues, could prevent the development of a more complex and debilitating syndrome over time.
“As a research community, we strive to identify mechanisms and treatments for these symptoms,” Taquet said.
The study, “Cognitive and psychiatric symptom trajectories 2–3 years after hospital admission for COVID-19: a longitudinal, prospective cohort study in the UK,” was authored by Maxime Taquet, Zuzanna Skorniewska, Thomas De Deyn, Adam Hampshire, William R. Trender, Peter J. Hellyer, James D. Chalmers, Ling-Pei Ho, Alex Horsley, Michael Marks, Krisnah Poinasamy, Betty Raman, Olivia C. Leavy, Matthew Richardson, Omer Elneima, Hamish J. C. McAuley, Aarti Shikotra, Amisha Singapuri, Marco Sereno, Ruth M. Saunders, Victoria C. Harris, Natalie Rogers, Linzy Houchen-Wolloff, Neil J. Greening, Parisa Mansoori, Ewen M. Harrison, Annemarie B. Docherty, Nazir I. Lone, Jennifer Quint, Christopher E. Brightling, Louise V. Wain, Rachael A. Evans, John R. Geddes, and Paul J. Harrison on behalf of the PHOSP-COVID Study Collaborative Group.
