Post-covid medical complaints after SARS-CoV-2 Omicron vs Delta variants - a prospective cohort study

  1. Karin Magnusson
  2. Doris Tove Kristoffersen
  3. Andrea Dell’Isola
  4. Ali Kiadaliri
  5. Aleksandra Turkiewicz
  6. Jos Runhaar
  7. Sita Bierma-Zeinstra
  8. Martin Englund
  9. Per Minor Magnus
  10. Jonas Minet Kinge

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Abstract

To examine whether persons infected with the SARS-CoV-2 omicron variant have an altered risk of post-covid complaints and healthcare use when compared to 1) persons testing negative, and 2) persons with delta.

Design

Prospective cohort study with 126 days follow-up and a time-to-event approach.

Setting

A registry-based study including Norwegian residents.

Participants

All persons aged 18-70 years living in Norway and who had a negative polymerase chain reaction (PCR) test for SARS-CoV-2 (N=105 196, mean (SD) age 42 (14), 50% women)) or positive test with confirmed omicron variant (N=13 028, mean (SD) age 37 (13), 50% women) or delta variant (N=23 368, mean (SD) age 40 (12), 50% women) in December 2021. Individuals with hospital contacts or non-screened PCR test were excluded.

Main outcome measures

Symptoms/complaints and diagnosis of musculoskeletal pain, fatigue, cough, heart palpitations, shortness of breath, anxiety/depression and brain fog at the general practitioner or emergency ward as recorded in national registries and as observed for the whole follow-up period as well as in periods 14-30 days, 30-90 days and 90 days or more.

Results

Persons with omicron or delta had similarly increased risk of post-covid fatigue compared to persons testing negative, with a hazard ratio (HR)=1.21 (CI:1.10-1.33) for omicron and HR=1.26 (CI: 1.17-1.35) for delta, for up to 126 days after the test date. They also had an increased risk of shortness of breath (HR=1.43, CI, 1.14-1.80 and HR=1.70, CI, 1.46-1.98 for omicron and delta, respectively, relative to negative). Omicron was related with a similar, and no increased risk of musculoskeletal pain, cough, heart palpitations, anxiety/depression when compared to delta and when compared to test negative. The risk of complaints was similar for omicron and delta and decreased over time for the post-covid periods 14-30 days, 30-90 days and 90 days or more.

Conclusions

SARS-CoV-2 omicron and delta infection are associated with similarly increased risks of post-covid complaints when compared to non-infected. The omicron variant will likely lead to a temporarily increased burden on healthcare services.

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  1. ScreenIT

    SciScore for 10.1101/2022.05.23.22275445: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Institutional board review was conducted, and The Ethics Committee of South-East Norway confirmed (June 4th 2020, #153204) that external ethical board review was not required.
    Sex as a biological variablenot detected.
    RandomizationFinally, because persons testing negative may be more prone to get tested and subsequently visit primary care due to (persistent) symptoms from similar bodily systems as those affected by SARS-CoV-2, we repeated the time-differentiated analyses using a comparison group consisting of untested persons (aged 18-70 years, non-hospitalized, never tested for SARS-CoV-2 and assigned a random, hypothetical test date during our study period) in a sensitivity analysis.
    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: Strengths of our study include the use of sequenced data allowing comparison of omicron vs delta during the same calendar period when the two variants had the largest overlap, combined with health care register data with no attrition. Further, equal access to SARS-CoV-2 testing at no cost for the individuals as well as a universal tax-funded health care system, improve generalizability of findings to other countries. A limitation of our study is that we could not include antigen or home tests as they were not registered. Polymerase chain reaction testing was however mandatory for everyone with a positive antigen test during our study period. Moreover, all parcitipants in our study had a PCR test in a period characterized by great uncertainty regarding the severity of the new SARS-CoV-2 omicron variant. It is possible that our population consisted of particularly health-conscious persons who were highly prone to get tested and who were more prone to seek medical care after knowing they had been ill. We believe our methodological approach ensuring comparison of persons who were tested in the same calendar week limits this potential bias arising due to anxiety. Further, we have previously reported that register-based studies comparing persons with positive test with persons with negative test likely will lead to an underestimation of post-covid outcomes’ prevalence, as persons testing themselves may represent a particularly health-conscious sample of t...

    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 10.1101/2022.05.23.22275445v1 on medRxiv