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. 2020 Aug 14:17:22.
doi: 10.1186/s12979-020-00194-w. eCollection 2020.

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

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

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

Aurora Jurado et al. Immun Ageing. .

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.

Keywords: ACE2; C-reactive protein; COVID-19; Immunity; Immunosenescence; Interleukin-6; Lymphocytes; Renin-angiotensin system; Severe acute respiratory syndrome coronavirus 2; Spain.

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Conflict of interest statement

Competing interestsThe authors stated no conflicts of interest.

Figures

Fig. 1
Fig. 1
Severity factors and comorbidities interactions. Pearson’s Chi Squared p-values
Fig. 2
Fig. 2
Age related changes of laboratory parameters. Significant associations to severity. Oneway ANOVA (normal n < 30 parameters) and Kruskal Wallis (n < 30 or significant Kolmogorov Smirnov test for normal distribution parameters) p-values Abbreviations: CRP, C-reactive protein; LDH, lactate dehydrogenase, NK, Natural Killers. IgG, immunoglobulin G; IgA, immunoglobulin A; IgM, immunoglobulin M
Fig. 3
Fig. 3
Gender related changes of laboratory parameters. Significant associations to severity. Oneway ANOVA (normal n < 30 parameters) and Kruskal Wallis (n < 30 or significant Kolmogorov Smirnov test for normal distribution parameters) p-values Abbreviations: CRP, C-reactive protein; LDH, lactate dehydrogenase, NK, Natural Killers. IgG, immunoglobulin G; IgA, immunoglobulin A; IgM, immunoglobulin M
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References

    1. Du Toit A. Outbreak of a novel coronavirus. Nat Rev Microbiol. 2020;18(3):123. doi: 10.1038/s41579-020-0332-0. - DOI - PMC - PubMed
    1. COVID-19 Dashboard by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University (JHU). Available at: https://coronavirus.jhu.edu/map.html. Accessed 11 July 2020.
    1. Kenji Mizumoto K, Gerardo CG. Estimating Risk for Death From 2019 Novel Coronavirus Disease, China, January–February 2020. Emerg Infect Dis. 2020;26(6). 10.3201/eid2606.200233. - PMC - PubMed
    1. Oksanen A, Kaakinen M, Latikka R, Savolainen I, Savela N, Koivula A. Regulation and trust: 3-month follow-up study on COVID-19 mortality in 25 european countries. JMIR Public Health Surveill. 2020;6(2):e19218. doi: 10.2196/19218. - DOI - PMC - PubMed
    1. Cui J, Li F, Shi ZL. Origin and evolution of pathogenic coronaviruses. Nat Rev Microbiol. 2019;17(3):181–192. doi: 10.1038/s41579-018-0118-9. - DOI - PMC - PubMed