Comprehensive Research Sheds Light on Long COVID

In-depth analysis of around 10,000 American COVID-19 cases provides further knowledge on long COVID, a condition characterized by persistent symptoms such as fatigue and cognitive impairment (or “brain fog”) which can last for months, or even years, after the initial infection. The condition seems more severe in patients infected prior to the emergence of the 2021 Omicron variant. The study led to the development of a symptom-based scoring system for identifying long COVID, the identification of four distinct symptom clusters, and highlighted the importance of understanding the biological underpinnings of long COVID for creating effective treatments.

Pennington Biomedical is part of the RECOVER Consortium, funded by the NIH. The consortium has successfully recognized common symptoms, established potential subgroups, and developed an initial symptom-based scoring system.

The research project, which involved a substantial number of Americans, many of whom had contracted COVID-19, brought forth valuable insights into long COVID. This term encapsulates a range of post-infection conditions that can potentially affect nearly every tissue and organ within the human body. Clinical symptoms including fatigue, cognitive impairment, and dizziness can linger for a prolonged period following recovery from the initial infection.

The investigation, financed by the National Institutes of Health, discovered that long COVID tended to occur more frequently and with greater severity in participants who were infected prior to the Omicron variant’s appearance in 2021.

The research, published in JAMA, was carried out under the NIH’s Researching COVID to Enhance Recovery (RECOVER) initiative. This nationwide project focuses on understanding why some individuals experience persistent symptoms post-COVID-19 infection and, crucially, how to diagnose, treat, and prevent long COVID. Researchers anticipate that this study will pave the way for potential long COVID treatments, which could have a profound impact on the health of millions of Americans.

The study evaluated data from 9,764 adults, 8,646 of whom had contracted COVID-19 and 1,118 who had not. Over 30 symptoms were assessed across multiple bodily areas and organs. Statistical analyses pinpointed 12 symptoms that clearly differentiated those with and without long COVID, including post-exertional malaise, fatigue, cognitive impairment, and dizziness, among others.

Based on these symptoms, the researchers developed a scoring system. Each of the 12 symptoms were assigned a certain number of points, which determined each patient’s score based on symptom combinations. Using these scores, the team established a threshold for identifying participants with long COVID. They also discerned that certain symptoms tended to occur together, defining four subgroups or “clusters” with varying impacts on health.

Long COVID was observed in about 10% of a subset of 2,231 patients who first contracted COVID-19 after Dec. 1, 2021, during the circulation of the Omicron variant. These preliminary results are based on a survey of a diverse group of patients and are not conclusive. Further validation will be performed by comparing the survey results with a variety of lab tests and imaging.

To date, over 100 million Americans have been infected with SARS-CoV-2, the virus causing COVID-19. As of April, the Household Pulse survey conducted by the federal government estimates that about 6% of those infected with the virus continue to experience symptoms associated with long COVID, a condition that researchers and patients have linked to over 200 symptoms.

The study is seen as a significant step toward defining long COVID beyond individual symptoms. This approach is expected to provide a solid foundation for further scientific discoveries and treatment designs. Understanding the underlying biological mechanisms of long COVID is seen as a crucial component of developing informed interventions and identifying effective treatment strategies.

The study also found that those who were unvaccinated or had contracted COVID-19 prior to the Omicron variant’s emergence in 2021 were more likely to suffer from long COVID and experience more severe cases. Additionally, reinfections were associated with a higher frequency and severity of long COVID compared to those who only had COVID-19 once.

While the scoring system developed in this study is a valuable research tool and an initial step toward diagnosing and monitoring patients with long COVID, the study’s authors acknowledge its limitations. As treatments are developed, it will be crucial to consider the complete symptom profile.

The findings from the ongoing RECOVER research are planned to be the groundwork for forthcoming clinical trials, with interventions targeting many of the symptoms identified in this study. Clinical trials under the RECOVER initiative are projected to begin patient enrollment in 2023.

This study was funded by NIH agreements OT2HL161841, OT2HL161847, and OT2HL156812. It also received additional support from grant R01 HL162373.

The research paper, titled “Development of a Definition of Postacute Sequelae of SARS-CoV-2 Infection,” was published in JAMA on May 25, 2023.

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More about Long COVID research

• National Institutes of Health
• RECOVER Initiative
• Pennington Biomedical
• JAMA Study: “Development of a Definition of Postacute Sequelae of SARS-CoV-2 Infection”
• Household Pulse Survey