COVID-19: age, Interleukin-6, C-reactive protein, and lymphocytes as key clues from a multicentre retrospective study

  1. Aurora Jurado
  2. María C. Martín
  3. Cristina Abad-Molina
  4. Antonio Orduña
  5. Alba Martínez
  6. Esther Ocaña
  7. Oscar Yarce
  8. Ana M. Navas
  9. Antonio Trujillo
  10. Luis Fernández
  11. Esther Vergara
  12. Beatriz Rodríguez
  13. Bibiana Quirant
  14. Eva Martínez-Cáceres
  15. Manuel Hernández
  16. Janire Perurena-Prieto
  17. Juana Gil
  18. Sergi Cantenys
  19. Gema González-Martínez
  20. María T. Martínez-Saavedra
  21. Ricardo Rojo
  22. Francisco M. Marco
  23. Sergio Mora
  24. Jesús Ontañón
  25. Marcos López-Hoyos
  26. Gonzalo Ocejo-Vinyals
  27. Josefa Melero
  28. Marta Aguilar
  29. Delia Almeida
  30. Silvia Medina
  31. María C. Vegas
  32. Yesenia Jiménez
  33. Álvaro Prada
  34. David Monzón
  35. Francisco Boix
  36. Vanesa Cunill
  37. Juan Molina

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Abstract

Background

The SARS-CoV-2 infection has widely spread to become the greatest public health challenge to date, the COVID-19 pandemic. Different fatality rates among countries are probably due to non-standardized records being carried out by local health authorities. The Spanish case-fatality rate is 11.22%, far higher than those reported in Asia or by other European countries. A multicentre retrospective study of demographic, clinical, laboratory and immunological features of 584 Spanish COVID-19 hospitalized patients and their outcomes was performed. The use of renin-angiotensin system blockers was also analysed as a risk factor.

Results

In this study, 27.4% of cases presented a mild course, 42.1% a moderate one and for 30.5% of cases, the course was severe. Ages ranged from 18 to 98 (average 63). Almost 60 % (59.8%) of patients were male. Interleukin 6 was higher as severity increased. On the other hand, CD8 lymphocyte count was significantly lower as severity grew and subpopulations CD4, CD8, CD19, and NK showed concordant lowering trends. Severity-related natural killer percent descents were evidenced just within aged cases. A significant severity-related decrease of CD4 lymphocytes was found in males. The use of angiotensin-converting enzyme inhibitors was associated with a better prognosis. The angiotensin II receptor blocker use was associated with a more severe course.

Conclusions

Age and age-related comorbidities, such as dyslipidaemia, hypertension or diabetes, determined more frequent severe forms of the disease in this study than in previous literature cohorts. Our cases are older than those so far reported and the clinical course of the disease is found to be impaired by age. Immunosenescence might be therefore a suitable explanation for the hampering of immune system effectors. The adaptive immunity would become exhausted and a strong but ineffective and almost deleterious innate response would account for COVID-19 severity. Angiotensin-converting enzyme inhibitors used by hypertensive patients have a protective effect in regards to COVID-19 severity in our series. Conversely, patients on angiotensin II receptor blockers showed a severer disease.

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  1. Version published to 10.1186/s12979-020-00194-w
  2. ScreenIT

    SciScore for 10.1101/2020.05.13.20101345: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    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:
    The present study has two major limitations. The firs one is derived from its retrospective design. As we are reporting on the very first cases of the disease in Spain, several immunological parameters of interest were not systematically tested. The other constraint is the short follow-up period of patients, which limits the possibility to have a full track of those who were still in hospital by data collection deadline. Consequently, the relationship among other variables such as treatment or other outcomes such as death, have not been here analysed.

    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.

    About SciScore

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  3. Version published to 10.1101/2020.05.13.20101345v2 on medRxiv
  4. Version published to 10.1101/2020.05.13.20101345v1 on medRxiv