Trajectory of long covid symptoms after covid-19 vaccination: community based cohort study

  1. Daniel Ayoubkhani
  2. Charlotte Bermingham
  3. Koen B Pouwels
  4. Myer Glickman
  5. Vahé Nafilyan
  6. Francesco Zaccardi
  7. Kamlesh Khunti
  8. Nisreen A Alwan
  9. A Sarah Walker

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Abstract

Objective

To estimate associations between covid-19 vaccination and long covid symptoms in adults with SARS-CoV-2 infection before vaccination.

Design

Observational cohort study.

Setting

Community dwelling population, UK.

Participants

28 356 participants in the Office for National Statistics COVID-19 Infection Survey aged 18-69 years who received at least one dose of an adenovirus vector or mRNA covid-19 vaccine after testing positive for SARS-CoV-2 infection.

Main outcome measure

Presence of long covid symptoms at least 12 weeks after infection over the follow-up period 3 February to 5 September 2021.

Results

Mean age of participants was 46 years, 55.6% (n=15 760) were women, and 88.7% (n=25 141) were of white ethnicity. Median follow-up was 141 days from first vaccination (among all participants) and 67 days from second vaccination (83.8% of participants). 6729 participants (23.7%) reported long covid symptoms of any severity at least once during follow-up. A first vaccine dose was associated with an initial 12.8% decrease (95% confidence interval −18.6% to −6.6%, P<0.001) in the odds of long covid, with subsequent data compatible with both increases and decreases in the trajectory (0.3% per week, 95% confidence interval −0.6% to 1.2% per week, P=0.51). A second dose was associated with an initial 8.8% decrease (95% confidence interval −14.1% to −3.1%, P=0.003) in the odds of long covid, with a subsequent decrease by 0.8% per week (−1.2% to −0.4% per week, P<0.001). Heterogeneity was not found in associations between vaccination and long covid by sociodemographic characteristics, health status, hospital admission with acute covid-19, vaccine type (adenovirus vector or mRNA), or duration from SARS-CoV-2 infection to vaccination.

Conclusions

The likelihood of long covid symptoms was observed to decrease after covid-19 vaccination and evidence suggested sustained improvement after a second dose, at least over the median follow-up of 67 days. Vaccination may contribute to a reduction in the population health burden of long covid, although longer follow-up is needed.

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  1. Version published to 10.1136/bmj-2021-069676
  2. ScreenIT

    SciScore for 10.1101/2021.12.09.21267516: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Study data: Data were obtained from the CIS (ISRCTN21086382, www.ndm.ox.ac.uk/covid-19/covid-19-infection-survey/protocol-and-information-sheets) [20], a longitudinal survey of individuals aged 2 years or over in randomly sampled UK households (excluding communal establishments such as hospitals, care homes, halls of residence, and prisons), with ethical approval from the South Central Berkshire B Research Ethics Committee (20/SC/0195).
    Consent: After verbal agreement to participate, each selected household was visited by a study worker to provide written confirmed consent (from parents/carers for those aged 2 to 15 years; those aged 10 to 15 years also provided written assent).
    Sex as a biological variablenot detected.
    RandomizationStudy data: Data were obtained from the CIS (ISRCTN21086382, www.ndm.ox.ac.uk/covid-19/covid-19-infection-survey/protocol-and-information-sheets) [20], a longitudinal survey of individuals aged 2 years or over in randomly sampled UK households (excluding communal establishments such as hospitals, care homes, halls of residence, and prisons), with ethical approval from the South Central Berkshire B Research Ethics Committee (20/SC/0195).
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    No key resources detected.

    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:
    Strengths and limitations: With 28,356 adults in our sample, this is the largest study to date internationally on Long Covid and COVID-19 vaccination, and the first to investigate post-vaccine symptom trajectories. The main strength of the study is its use of the CIS, a large survey of approximately half a million people from the community population of the UK with longitudinal follow-up. Random sampling from address lists mitigates against selection bias, while the prospective design means that survey responses are not subject to outcome recall bias (such as participants overestimating the duration of previously experienced symptoms). All CIS participants are swabbed for SARS-CoV-2 at every follow-up visit, irrespective of symptoms, so our study includes asymptomatic as well symptomatic infections. The study also has limitations. Its observational nature means that causality cannot be inferred, and placebo and side effects of vaccination may have contributed to our findings; however, estimates were robust to excluding follow-up visits within the first week of each vaccination, suggesting that the impact of these effects is likely to be small. Although we adjusted for a wide range of potential confounders, unmeasured factors, such as those related to take-up of a second vaccination, may remain. The observed changes after vaccination could be related to the relapsing-remitting nature of symptoms experienced by many people living with Long Covid [3–5] rather than a causal effec...

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    ISRCTN21086382NANA

    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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  3. Version published to 10.1101/2021.12.09.21267516v1 on medRxiv