Reassessment of persistent symptoms, self-reported COVID-19 infection and SARS-CoV-2 serology in the SAPRIS-SERO cohort: identifying possible sub-syndromes of Long Covid

  1. Nicola Spiers

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Abstract

Background

Long Covid remains a relatively new phenomenon with emerging understanding. Estimated UK prevalence of Long Covid with three or more symptoms lasting for 12 weeks or more was 2.2% at the end of 2021. The population-based French SAPRIS-SERO cohort has novel information about the pattern of symptoms of Long Covid that has been obscured by controversy around the original paper.

Methods

Secondary analysis was used to describe and re-interpret the frequencies of persistent symptoms by IgG seropositivity and self-reported Long Covid in the published report of the SAPRIS-SERO survey. Participants in the cross-sectional analysis were 26 823 individuals from the French population-based CONSTANCES cohort, included between 2012 and 2019, who took part in the nested SAPRIS and SAPRIS-SERO surveys. Between May and November 2020, the Euroimmun enzyme-linked immunosorbent assay was used to detect anti-SARS-CoV-2 antibodies. Surveyed online between December 2020 and January 2021, participants self-reported previous COVID-19 infection and physical symptoms during the previous four weeks that were new since March 2020, and had persisted for at least eight weeks.

Results

There was similarity of prevalence over the majority of symptoms in those self-reporting COVID-19 infection, regardless of blood test result. Persistent symptoms significantly associated with self-reported COVID-19 infection and common in both groups include respiratory tract symptoms and a group of symptoms that might be related to chronic fatigue, malaise or postural issues. Seropositivity for IgG antibodies did not predict symptoms independently of self-reported Long Covid, except for anosmia.

Conclusions

There may be three common sub-syndromes of Long Covid, one with persistent anosmia, another with other respiratory tract symptoms and a third, currently under researched, with symptoms relatable to chronic fatigue. Antibody tests are insufficient for case detection while Long Covid remains poorly understood.

Key Messages

  • IgG seropositivity is insufficient to identify potential cases of Long Covid

  • Persistent anosmia is very strongly associated with IgG seropositivity and may define a subsyndrome of Long Covid

  • Other potential subsyndromes are those with persistent respiratory symptoms and those with persistent symptoms relatable to fatigue, malaise or postural issues

  • The Long Covid research effort should be rebalanced towards understanding the fatigue/tiredness subsyndrome.

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  1. ScreenIT

    SciScore for 10.1101/2022.02.25.22271499: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Participants responding to an annual questionnaire from the CONSTANCES population5 were invited to complete the Euroimmun assay for SARS-CoV-2 IgG antibodies between May and November 2020 and an internet questionnaire between December 2020 and January 2021.
    SARS-CoV-2 IgG
    suggested: None

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    As well as false positives and false negatives on the assay, already discussed, limitations of the SAPRIS-SERO cohort include ageing of the sample and selective attrition by education, income and self-rated health. The list of symptoms reported is also limited. With REACT, SAPRIS-SERO is one of only two large-scale population-based studies, including those non-infected, of persistent symptoms after COVID-19. These provide an essential complement to non-probability surveys, positive test cohorts and numerous smaller-scale studies of Long Covid, often in hospitalised patients7, especially as Long Covid is often reported after mild initial disease8. Although clustering of symptoms was not analysed, the SAPRIS-SERO findings are suggestive of three clusters: one with anosmia, a second with other respiratory tract symptoms: chest pain, breathing difficulties and cough, and a third with symptoms that might be related to chronic fatigue, malaise or postural issues. These findings are consistent with those reported in a preprint from REACT2. Symptoms persisting for 12 weeks identified by REACT fell into two clusters, a “tiredness cluster” experiencing high prevalence of tiredness, co-occurring with muscle aches, difficulty sleeping and shortness of breath, and a “respiratory cluster” experiencing high prevalence of respiratory symptoms including shortness of breath, tight chest and chest pain. Similar associations of persistent symptoms with test positivity were also reported in a con...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

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  2. Version published to 10.1101/2022.02.25.22271499 on medRxiv