In a recent study published in The Lancet, researchers analyzed the nature, incidence, and severity of 23 coronavirus disease 2019 (COVID-19)-related persistent symptoms among the people of the Netherlands.
The researchers accounted for the same symptoms before severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection to compare the symptom dynamics in the control population presenting without COVID-19.
Previous studies assessing the post-COVID-19 prevalence and symptoms did not include a control group or made adjustments for the occurrence of somatic symptoms in the population without COVID-19. Additionally, these studies could not assess whether somatic symptoms reported after a COVID-19 diagnosis was present before SARS-CoV-2 infection. Furthermore, since these were clinical studies, they disregarded post-COVID-19 conditions in the general population.
As long-COVID could be the next public health catastrophe in the making, there is an urgent need for empirical data informing on the scale of the long-term consequences of COVID-19 to help develop an adequate healthcare response.
In the present study, researchers used data from Lifelines, an observational population-level cohort study with all COVID-19-related information of the people residing in the north of the Netherlands. They matched test subjects with controls 1:2 by gender, age, and time of completing questionnaires that indicated a COVID-19 diagnosis to assess symptom severity before and after COVID-19.
The researchers invited all the adult participants of Lifelines to complete a digital COVID-19 questionnaire. Initially, they collected responses weekly and then every two weeks from June 2020 onwards, but later this became every month.
The team used the collected data to measure the longitudinal dynamics of 23 somatic symptoms among COVID-19 cases diagnosed using 24 consecutive measurements between March 31, 2020, and August 2, 2021. They evaluated all 23 symptoms using a five-point Likert scale, where one indicated that the participants were least bothered by the respective symptom and five marked extreme discomforts. Only when a symptom had a score of three (moderate score) did the researchers consider it to be present persistently. In this way, the researchers computed a mean pre-COVID-19 score per symptom for each participant.
The researchers presented population characteristics as absolute numbers or as means with standard deviation (SD), if appropriate. Further, they examined study data for normality using Q-Q plots and histograms. Finally, the researchers presented a moving average symptom report for each COVID-19-positive participant stratified further by gender and symptom.
The response rate to digital COVID-19 questionnaires varied between 28% and 49% during the study duration. In total, 76,422 study participants, with an average age of 53.7 years, completed 883973 questionnaires. Over 60% of these participants were female; of these, the authors matched 4231 COVID-19 diagnosed cases with 8462 controls.
In 90 to 150 days following COVID-19 diagnosis, these individuals experienced several symptoms, including chest pain, painful breathing, breathing problems, muscle pain, anosmia, lumps in the throat, hot and cold sensations (alternately), tingling extremities, heavy arms or legs, and fatigue. Interestingly, these symptoms could be attributed to COVID-19 in only 12.7% of patients, as even COVID-19-negative controls experienced a substantial increase (moderate severity, i.e, score of ≥3) in at least one of these symptoms at a matched timepoint.
It is noteworthy that merely 39% of the experts considered tingling extremities as an important post-COVID-19 symptom, while 56% considered a headache to be important for the case definition. However, the current analysis indicated that while tingling extremities was a core symptom, the headache was not related to COVID-19. These differences highlighted the need for longitudinal cohort studies in the general population with pre-infection data and controls to define the scale and scope of the post-COVID-19 condition.
Overall, the study findings indicated that post-COVID-19 symptoms might occur in one of eight SARS-CoV-2-infected individuals in the general population. According to the authors, this is the first study to document and characterize symptom prevalence and severity in COVID-19 patients at the population level. They were reliably corrected for each symptom present before SARS-CoV-2 infection and for the symptom dynamics reported by sex- and age-matched controls with no infection in the same period.
Additionally, the study examined the changes in these long COVID conditions due to public health measures taken during the pandemic and seasonality. Most importantly, the study highlighted that the most prevalent symptoms were not the most distinctive symptoms for the post-COVID-19 condition. Future studies should further investigate the nature of core symptoms identified in the current review to inform the health-care response to long COVID.