Researchers Propose List of Core Symptoms to Better Define Long COVID

Researchers proposed a list of core symptoms that could offer a better working definition of long COVID, based on an observational cohort study from the Netherlands.

Among over 1,700 COVID patients, 21.4% had at least one core symptom — including chest pain, breathing difficulties, painful muscles, ageusia or anosmia, tingling or heavy extremities, lump in throat, feeling alternately hot and cold, dizziness, headache, nausea, and general fatigue — that worsened 90 to 150 days after diagnosis compared with 8.7% (361 of 4,130) of controls without COVID at a matched time point, reported Judith Rosmalen, PhD, of University Medical Center Groningen, and colleagues.

This suggests that 12.7% of these patients experienced persistent somatic symptoms as a result of their infection, they noted in The Lancet.

“After recovery from acute COVID-19, a substantial proportion of patients continue to experience symptoms of a physical, psychological, or cognitive nature,” Rosmalen and team wrote. “These long-term sequelae of COVID-19 have been described as the next public health disaster in the making, and there is an urgent need for empirical data informing on the scale and scope of the problem to support the development of an adequate health-care response.”

Of note, for certain symptoms, the researchers noted differences between men and women, with women showing longer persistence of increased symptom severity after COVID-19 than men.

In addition, “research shows that COVID-19 might also affect brain functioning and mental health. Therefore, future research should not overlook mental health symptoms (e.g., depression and anxiety symptoms), nor additional post-infectious symptoms that were not assessed in this study (e.g., brain fog, insomnia, and postexertional malaise),” Rosmalen and team concluded. “Additionally, future intersectional research should assess how ethnicity, gender, age, socioeconomic status, other social identities, and the presence of underlying chronic diseases are associated with symptom dynamics surrounding COVID-19 and risk of post-COVID-19 condition.”

In an accompanying comment, Christopher Brightling, PhD, and Rachael Evans, MBChB, PhD, of the NIHR Biomedical Research Centre at the University of Leicester in England, noted that this study “does not provide new mechanistic insights, which are key to uncovering new therapeutic targets. In other studies, clustering of patient-reported outcomes has identified different severity groups of long COVID and identified increased systemic inflammation in people with very severe long COVID. How patient-centered outcomes, together with biomarkers, can further refine long COVID diagnosis and inform precision medicine approaches warrants further consideration.”

For this study, data were taken from the Lifelines COVID-19 and Dutch Lifelines cohort studies, which examine the health and health-related behaviors of people living in the north of the Netherlands. All participants (mean age 53.7 years, 60.8% women) were sent digital questionnaires regarding their symptoms, which were assessed using 24 repeated measurements from March 31, 2020 to Aug. 2, 2021.

Rosmalen and colleagues matched participants with COVID-19 (a positive test or a physician’s diagnosis) by age, sex, and time to COVID-negative controls, and recorded symptom severity before and after infections in participants with COVID and compared that with matched controls.

The authors noted that serological assays were used to detect SARS-CoV-2 infection, but patients with long COVID might have lower antibody responses, which was a study limitation. In addition, the cross-sectional nature of the study may have led to recall bias. Furthermore, nearly all participants were white, which may affect the generalizability of these results.