Performance of serum apolipoprotein-A1 as a sentinel of Covid-19

  1. Thierry Poynard
  2. Olivier Deckmyn
  3. Marika Rudler
  4. Valentina Peta
  5. Yen Ngo
  6. Mathieu Vautier
  7. Sepideh Akhavan
  8. Vincent Calvez
  9. Clemence Franc
  10. Jean Marie Castille
  11. Fabienne Drane
  12. Mehdi Sakka
  13. Dominique Bonnefont-Rousselot
  14. Jean Marc Lacorte
  15. David Saadoun
  16. Yves Allenbach
  17. Olivier Benveniste
  18. Frederique Gandjbakhch
  19. Julien Mayaux
  20. Olivier Lucidarme
  21. Bruno Fautrel
  22. Vlad Ratziu
  23. Chantal Housset
  24. Dominique Thabut
  25. Patrice Cacoub

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Abstract

Since 1920, a decrease in serum cholesterol has been identified as a marker of severe pneumonia. We have assessed the performance of serum apolipoprotein-A1, the main transporter of HDL-cholesterol, to identify the early spread of coronavirus disease 2019 (Covid-19) in the general population and its diagnostic performance for the Covid-19.

Methods

We compared the daily mean serum apolipoprotein-A1 during the first 34 weeks of 2020 in a population that is routinely followed for a risk of liver fibrosis risk in the USA (212,297 serum) and in France (20,652 serum) in relation to a local increase in confirmed cases, and in comparison to the same period in 2019 (266,976 and 28,452 serum, respectively). We prospectively assessed the sensitivity of this marker in an observational study of 136 consecutive hospitalized cases and retrospectively evaluated its specificity in 7,481 controls representing the general population.

Results

The mean serum apolipoprotein-A1 levels in the survey populations began decreasing in January 2020, compared to the same period in 2019. This decrease was highly correlated with the daily increase in confirmed Covid-19 cases in the following 34 weeks, both in France and USA, including the June and mid-July recovery periods in France. Apolipoprotein-A1 at the 1.25 g/L cutoff had a sensitivity of 90.6% (95%CI84.2–95.1) and a specificity of 96.1% (95.7–96.6%) for the diagnosis of Covid-19. The area under the characteristics curve was 0.978 (0.957–0.988), and outperformed haptoglobin and liver function tests. The adjusted risk ratio of apolipoprotein-A1 for survival without transfer to intensive care unit was 5.61 (95%CI 1.02–31.0; P = 0.04).

Conclusion

Apolipoprotein-A1 could be a sentinel of the pandemic in existing routine surveillance of the general population. NCT01927133, CER-2020-14.

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  1. ScreenIT

    SciScore for 10.1101/2020.09.01.20186213: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: Ethics: The prospective observational study in Covid-19 patients was approved by CER-Sorbonne University IRB,CER-2020-14, with a signed informed consent.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot 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:
    These results have certain strengths and limitations. Decrease of apolipoprotein-A1 in 2020: The originality of these results was not the decrease in apolipoprotein-A1 during the peak of the pandemic in April, as very low levels of HDL-cholesterol in sera collected in Covid-19 were known in severe pneumonia since 1920 (supplementaryTable1).2 More intriguing was the very early decrease observed since January 2020 in the USA when the number of Covid-19 cases was unknown. The first known Covid-19 patient was detected on 27/12/2019 and 19/01/2020 in France and the USA, respectively(supplementaryFile3). The larger sample size of the US surveillance population, compared to the French, allowed detection of a significant 1% increase in the proportion of subjects possibly infected using the 1.25 g/L cutoff in January (fig1C), without any inflammatory signal using haptoglobin. We hypothesized that the SARS-CoV2 virus influenced the liver or intestinal synthesis of apolipoprotein-A1, in asymptomatic patients or in those with unusual mild symptoms. Confounding factors: The decrease of apolipoprotein-A1 in 2020 vs. previous years, as well as the time-related association of apolipoprotein-A1 in 2020 and Covid-19 might be due to numerous confounding factors. In the context of the pandemic we used cohorts of subjects requiring surveillance of liver fibrosis biomarkers which represent at least 30% of the general adult population in the USA and in France. In these cohorts 70% of the subjects h...

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

    IdentifierStatusTitle
    NCT01927133Unknown statusLIVER FIBROSIS PREVALENCE IN FRANCE

    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.
    • Thank you for including a protocol registration statement.

    About SciScore

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  2. Version published to 10.1371/journal.pone.0242306
  3. Version published to 10.1101/2020.09.01.20186213v1 on medRxiv