Nearly three years after the SARS-CoV-2 pandemic was declared over, conservative estimates suggest that between 80 million and 400 million people worldwide have long COVID. This chronic condition associated with the infection is linked to more than 200 symptoms, including fatigue and shortness of breath, as well as neuropsychiatric issues ranging from cognitive dysfunction and sleep disorders to depression and memory loss. These issues impact quality of life and hinder the performance of daily tasks and work.
Underlying pathophysiological mechanisms (processes that occur in the body and help explain certain symptoms and changes) include viral persistence of SARS-CoV-2, reactivation of herpesviruses (when immune stress allows latent viruses of the Herpesviridae family to become active), and chronic immune activation. Other mechanisms include immune system dysregulation, an imbalance in the function of microorganisms in the gut (microbiota dysbiosis), coagulation abnormalities, and endothelial damage. Regarding the brain, there are structural changes and abnormal functional connectivity.
However, significant progress in understanding long COVID requires further scientific studies to standardize definitions and nomenclature for the disorder, as well as more clinical trials with potential therapies.
The first review article published by the journal Nature Reviews Disease Primers provides an overview of this topic and is dedicated to the neurological, psychological, and psychiatric manifestations associated with COVID-19. The paper provides a comprehensive analysis of its epidemiology, biological mechanisms, diagnosis, therapeutic approaches, impact on quality of life, and the challenges facing science.
An international panel of 14 experts developed the article, which includes a single Brazilian author: professor and neurologist Clarissa Yasuda , from the Faculty of Medical Sciences at the State University of Campinas (UNICAMP) in the state of São Paulo. Yasuda is also a researcher at the Brazilian Institute of Neuroscience and Neurotechnology ( BRAINN ), a FAPESP Research, Innovation, and Dissemination Center ( RIDC ). Since 2020, she has coordinated a series of studies on long COVID (read more at agencia.fapesp.br/41738 ).
"This disease is new and little understood. 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," Yasuda tells Agência FAPESP.
In the study, the researchers emphasize that avoiding SARS-CoV-2 infection is the only way to prevent long COVID so far. They note that diagnosis is based on clinical evaluation. Since there are no available biomarkers, a recent history of infection with the virus is required, as well as persistent or recurrent symptoms for at least three months. Other conditions must be ruled out, which may require blood and imaging tests, electrocardiography, and echocardiography.
In Brazil, the number of reported cases of COVID-19 has been falling year after year but remains high. In 2025, the Ministry of Health reported approximately 432,400 cases, compared to 984,000 the previous year. Between January and the second week of February of this year, approximately 25,200 cases were reported.
Quality of life
In the section on quality of life, the article discusses the effects of long COVID on the labor market and the stigmas associated with the disease, in addition to its health impacts.
The authors point out that individuals may experience job and income loss, as well as difficulty returning to work due to a lack of support from social welfare systems. They also mention that affected individuals may experience periods of "ups and downs," "breakdowns," "depression," and "lows," which can leave them feeling unable to maintain the same level of activity.
In 2024, scientists from U.S. institutions published an article in Nature Medicine estimating that long COVID resulted in over 803 million lost work hours in Brazil alone that year, with a potential cost of more than USD 11 billion. This equates to approximately 400,000 full-time workers being out of the labor market for a year. The same study estimated that long COVID could have an annual global economic impact of approximately USD 1 trillion – about 1% of the global economy.
Professor Yasuda herself experienced difficulties resuming her activities after having long COVID. She contracted the virus in August 2020 and experienced mild symptoms without a fever. However, about a month later, she realized that cognitive dysfunction was hindering her academic work.
In the article "I Want My Brain Back," published in the Scielo Brasil digital library in June 2022, she recounted her experience. "At the time, I described my recovery efforts and the strategies I used to cope with the persistent limitations in cognitive performance. After a lot of effort and discipline, I improved," she says.
Long COVID, also known as "post-COVID-19 condition," has been monitored by Brazil's national public health system, the SUS (Sistema Único de Saúde), since 2021, with an update in 2023 via Technical Note No. 57 . An epidemiological bulletin on the topic released in 2025 estimated that there were 13.8 million cases of "post-COVID conditions" in the country, the majority of whom were female (8.58 million). The most affected age group was 30 to 49 (6.2 million Brazilians).
Stigma
Regarding stigma, the scientists note that patients face multiple barriers when trying to have their condition recognized and gain access to care and support. These experiences can range from discrimination and inadequate treatment to blame. Individuals from ethnic minorities experience particularly high levels of stigma.
They also note that there can be serious implications for social and educational interactions for children and adolescents.
Therefore, they recommend multidisciplinary teams, including professionals from various health fields, provide patient care.
For future studies, they recommend recruiting a diverse and representative patient population and taking the perspectives of people with long COVID and the role of social and health determinants into account.
In this context, Yasuda's group is conducting a longitudinal study to understand how the disease changes the brain. "Being invited to participate in this review was very important and an international recognition of the work we're developing at the BRAINN RIDC," says Yasuda, who also receives support from the National Council for Scientific and Technological Development (CNPq), a funding agency linked to the Ministry of Science, Technology, and Innovation.
About São Paulo Research Foundation (FAPESP)
The São Paulo Research Foundation (FAPESP) is a public institution with the mission of supporting scientific research in all fields of knowledge by awarding scholarships, fellowships and grants to investigators linked with higher education and research institutions in the State of São Paulo, Brazil. FAPESP is aware that the very best research can only be done by working with the best researchers internationally. Therefore, it has established partnerships with funding agencies, higher education, private companies, and research organizations in other countries known for the quality of their research and has been encouraging scientists funded by its grants to further develop their international collaboration. You can learn more about FAPESP at www.fapesp.br/en and visit FAPESP news agency at www.agencia.fapesp.br/en to keep updated with the latest scientific breakthroughs FAPESP helps achieve through its many programs, awards and research centers. You may also subscribe to FAPESP news agency at http://agencia.fapesp.br/subscribe.
