In a recent study published in the journal Nature Medicine, researchers conducted an interdisciplinary review to examine the current scientific evidence on long coronavirus disease (long COVID) and its impact on individuals, health systems, and national and global economies. They also synthesized a roadmap for future research and policies on long COVID.
Review: Long COVID science, research and policy. Image Credit: p.ill.i / Shutterstock
Background
One of the long-term impacts of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections is the complex assortment of post-acute sequelae commonly known as long COVID. The symptoms of long COVID are associated with various organ systems apart from the pulmonary system, including the cardiovascular, endocrine, immune, nervous, gastrointestinal, and renal systems.
Common manifestations of long COVID are fatigue, brain fog or cognitive impairments, and post-exertional malaise. Studies have also found that long COVID impacts individuals of all ages, across sexes, races, ethnicities, and health status at baseline. Some variants of SARS-CoV-2, such as Delta, have a higher risk of long COVID than others, such as the Omicron variants. Furthermore, while coronavirus disease 2019 (COVID-19) vaccinations can lower the risk of long COVID, SARS-CoV-2 reinfections can also trigger long COVID.
In the present review, the researchers examined the current research on the mechanisms and treatment options for long COVID and its impact on health systems, individual health, and the economy.
Long COVID research
The high degree of variation in the manifestations of long COVID symptoms across individuals and the heterogeneity of the studies investigating long COVID have presented challenges in estimating the burden of long COVID. Furthermore, the type of COVID-19 vaccines, their effects, and the impact of reinfection further complicate the process of deciphering the long COVID burden.
Studies have found that complex mechanisms and numerous pathological pathways contribute to the complex symptoms of long COVID. Mitochondrial dysfunction, dysregulation of immune mechanisms, viral persistence in tissues, and dysbiosis of various microbiomes have been explored and implicated as potential mechanisms driving long COVID.
The persistence of SARS-CoV-2 fragments in various tissues is thought to trigger an immune cascade of inflammation and tissue damage, leading to the persistent symptoms that constitute long COVID. Other potential mechanisms include neuroinflammation, vascular dysfunction, and metabolic dysregulations.
COVID-19 vaccines and other non-pharmaceutical disease prevention methods have been found to lower the risk of long COVID. Vaccines were reported to lower long COVID risk by 40% in adults. Furthermore, research indicated that the use of antivirals to treat acute SARS-CoV-2 infections could lower the risk of long COVID in individuals with various comorbidities. While the research on gut microbiome modulations and their role in improving long COVID symptoms are ongoing, there have been no conclusive results.
The dearth of appropriate diagnostic tools, standardized care pathways, and adequate awareness among healthcare professionals have been limiting factors in the development of long COVID care protocols. Existing research suggests that long COVID is an evolving complex syndrome that will require a tailored management and care approach.
Long COVID impacts
The post-COVID sequelae have had long-reaching effects, from impacts on the daily lives of individuals to affecting global economies and the goals for sustainable development. The persistent symptoms of long COVID lower the individual's ability to perform daily life functions, resulting in reduced quality of life.
Close to 75% of the individuals who have experienced long COVID symptoms report a decrease in their ability to work, socialize, and perform social activities, which also affects their families and communities. Furthermore, the social exclusion experienced by some individuals due to long COVID symptoms also impacts their mental health, cumulatively impacting their sense of self and worth.
The prolonged healthcare requirements due to long COVID also add to the concerns of most countries' already overburdened healthcare systems. The strain on healthcare systems due to long COVID has resulted in longer wait times for consultations and medical care and higher costs. The lack of standardized diagnosis and treatment protocols also hampers healthcare providers.
The significant healthcare burden and the decrease in labor participation due to the impact of long COVID on individuals' ability to work have also impacted the economies of many countries. Many countries have experienced decreased productivity and labor shortages after the COVID-19 pandemic. Statistics from 2022 indicated that the United States experienced a loss of $3.7 trillion due to long COVID, a figure equated to the global recession of 2008.
Additionally, the exacerbation of already existing social inequalities, as well as lower labor participation and economic productivity, have also widely affected several sustainable development goals related to social well-being and health.
Roadmaps for long COVID research and policies
The review also presented a comprehensive roadmap for future long COVID research and policy development focused on the long-term care and management of long COVID patients and prevention initiatives.
The researchers believe that a coordinated and equitable patient-centered approach is essential to understand the biological mechanisms of long COVID, identify biomarkers, develop improved diagnostic tools, and assess the therapeutic and clinical outcomes.
Policy roadmaps include measures to prevent SARS-CoV-2 infections, improved and equitable access to healthcare, and support for long-term COVID patients. The researchers believe that the establishment of global collaborations and professional support groups and societies is needed to achieve effective responses.
Journal reference:
- Al-Aly, Z., Davis, H., McCorkell, L., Soares, L., Wulf-Hanson, S., Iwasaki, A., & Topol, E. J. (2024). Long COVID science, research and policy. Nature Medicine. DOI:10.1038/s41591024031736, https://www.nature.com/articles/s41591-024-03173-6
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