Long COVID: New Review Details Neurological & Psychological Impacts

More than four years after the start of the COVID-19 pandemic, millions worldwide continue to experience long-term health issues following SARS-CoV-2 infection. A comprehensive review article published December 24, 2025, in Nature Reviews Disease Primers details the neurological, psychological, and psychiatric manifestations associated with the condition, often referred to as long COVID or post-COVID-19 condition.

Conservative estimates suggest between 80 million and 400 million people globally have long COVID, a chronic condition linked to over 200 symptoms, including fatigue, shortness of breath, cognitive dysfunction, sleep disorders, and depression. These symptoms significantly impact quality of life and the ability to perform daily tasks and function.

The review, developed by an international panel of 14 experts including Brazilian neurologist Clarissa Yasuda of the State University of Campinas (UNICAMP) and the Brazilian Institute of Neuroscience and Neurotechnology (BRAIN), outlines the current understanding of the disorder’s epidemiology, biological mechanisms, diagnosis, and potential therapeutic approaches. Researchers identified several underlying pathophysiological mechanisms, including persistent viral presence, reactivation of herpesviruses, and chronic immune activation. Other factors include immune system dysregulation, imbalances in gut microbiota, coagulation abnormalities, and damage to the endothelium.

“This disease is new and little understood,” Yasuda told FAPESP Agency. “Many people are studying and trying to understand it, not only because of current cases, but also because humanity is susceptible to other viruses that could cause problems on the scale of that pandemic. We need to learn from it and investigate effectively and quickly. Long COVID greatly disrupts people’s lives, and currently, there’s no specific treatment. The important thing is to get vaccinated and avoid reinfection. That’s another message of the article.”

Currently, diagnosis relies on clinical evaluation, as no definitive biomarkers exist. A recent history of SARS-CoV-2 infection and persistent or recurrent symptoms lasting at least three months are key indicators, with other potential conditions needing to be ruled out through blood tests, imaging, and cardiovascular assessments.

While reported COVID-19 cases in Brazil have decreased in recent years – approximately 432,400 cases were reported in 2025, compared to 984,000 in 2024, and roughly 25,200 cases between January and mid-February 2026 – the impact of long COVID remains substantial. The Brazilian national public health system, the SUS (Unified Health System), has been monitoring post-COVID conditions since 2021, with updated guidance issued in 2023.

An epidemiological bulletin released in 2025 estimated 13.8 million cases of “post-COVID conditions” in Brazil, with women accounting for the majority (8.58 million). The 30-49 age group was the most affected, with 6.2 million cases.

The review also addresses the economic consequences of long COVID. A 2024 study published in Nature Medicine estimated that long COVID resulted in over 803 million lost work hours in Brazil alone, representing a potential economic loss exceeding USD 11 billion – equivalent to approximately 400,000 full-time workers being absent from the labor market for a year. Globally, the study estimated an annual economic impact of around USD 1 trillion, roughly 1% of the global economy.

The authors highlight the stigma associated with long COVID, noting that patients often face barriers to recognition, care, and support, including discrimination and blame. These challenges are particularly acute for individuals from ethnic minorities and can have serious implications for children and adolescents in social and educational settings.

The review recommends a multidisciplinary approach to patient care, involving professionals from various health fields. Future research should prioritize recruiting diverse patient populations and considering the perspectives of those living with long COVID, as well as the influence of social and health determinants.

Yasuda’s research group is currently conducting a longitudinal study to investigate how long COVID alters brain function. She emphasized the importance of continued research, stating that understanding long COVID is crucial for preparing for future viral pandemics.