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Association of self-reported COVID-19 infection and SARS-CoV-2 serology test results with persistent physical symptoms among French adults during the COVID-19 pandemic

Our take —

This nested cross-sectional assessment within an ongoing French population-based cohort study of over 25,000 individuals found that self-reported COVID-19 was positively associated with a number of persistent physical symptoms, while a positive serology test was not associated with many of these same symptoms, except for anosmia. This study highlights the importance of measuring COVID-19 using laboratory methods in studies of long-COVID and the need for further studies to better understand the etiology of persistent symptoms, including a potential psychosomatic cause. While there is the possibility of some selection bias and uncontrolled confounding, this study suggests that we should diligently investigate potential causes of different persistent physical symptoms to improve the management of these symptoms.

Study design

Cross-Sectional

Study population and setting

The goal of the study was to evaluate whether self-reported COVID-19 infection (subjective measure) and/or SARS-CoV-2 serology test results (objective measure) were associated with persistent physical symptoms, or “long COVID.” Overall, 26,823 of the 35,852 individuals invited to participate from an ongoing French, population-based cohort study had complete data and took part in this nested COVID-19 focused study (74.8%). Testing for SARS-CoV-2 antibodies was conducted between May and November 2020 using an enzyme-linked immunosorbent assay (self-sampling dried-blood spot kits mailed to each participant). Both self-reported COVID-19 infection and the presence of persistent physical symptoms were ascertained in a survey conducted between December 2020 and January 2021; participants were asked 1) whether they believed they had experienced COVID-19 infection since March 2020 and 2) whether they had physical symptoms during the previous 4 weeks that had persisted for at least 8 weeks. Participants were asked specifically about the following symptoms: “sleep problems, joint pain, back pain, muscular pain, sore muscles, fatigue, poor attention or concentration, skin problems, sensory symptoms (pins and needles, tingling or burning sensation), hearing impairment, constipation, stomach pain, headache, breathing difficulties, palpitations, dizziness, chest pain, cough, diarrhea, anosmia, and other symptoms.” Multivariable logistic regression models were used to assess associations with each persistent symptom.

Summary of Main Findings

The average age of the participants was 49 years old and just over half were women (51.2%). About 0.5% of participants reported anosmia (loss of smell, n=146) and 10.2% reported sleep problems (n=2,729). In the multivariable regression models, including belief, serology test result, and adjusting for age, sex, education, income, self-rated health, and depressive symptoms, self-reported infection was positively associated with most of the reported persistent physical symptoms, and most strongly associated with breathing difficulties (aOR: 7.75, 95% CI: (5.25-11.43)) and anosmia (aOR: 16.37, 95% CI: (10.21-26.24)). The same models showed no association between positive serology and most of the persistent physical symptoms. Positive serology was only associated with anosmia (aOR: 2.72, 95% CI: (1.66-4.46)).

Study Strengths

A major strength of this study is that they were able to ascertain detailed persistent physical symptom data, asking about a range of physical symptoms and the duration of the symptoms. An additional strength of this study is the availability of serology test results for a large study population.

Limitations

There is the possibility of some selection bias, with about 25% of the initial population recruited to participate not having complete data. A key limitation is that the authors did not adjust for history of SARS-CoV-2 diagnosis in their model, even though it was measured and presented in different models in supplemental tables. Additionally, because the authors specify a model for each persistent symptom, there is a possibility that some of the associations deemed significant exist by chance (though the effect sizes are large). The authors’ hypothesis is that belief in a prior COVID experience alone is associated with symptoms, even after accounting for serological evidence (i.e. antibodies) of infection. While their models explore these associations, the causal interpretations are difficult to parse because it’s unclear whether the symptoms or the belief in a COVID diagnosis came first.

Value added

Some persons who self-report persistent symptoms following COVID-19 may not have truly been infected. True cause of these symptoms deserves further study and could be psychosomatic or due to other conditions and just misattributed to COVID-19. Better attribution of the cause of these persistent physical symptoms could help improve clinical management and therefore long-term patient outcomes.

This review was posted on: 5 January 2022