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. 2022 Feb:150:155790.
doi: 10.1016/j.cyto.2021.155790. Epub 2021 Dec 25.

Role of immune mediators in predicting hospitalization of SARS-CoV-2 positive patients

S Ashrafzadeh-Kian  1 , M R Campbell  1 , J C Jara Aguirre  2 , J Walsh  3 , A Kumanovics  1 , G Jenkinson  3 , P Rinaldo  1 , M R Snyder  1 , A Algeciras-Schimnich  4
Affiliations

Role of immune mediators in predicting hospitalization of SARS-CoV-2 positive patients

S Ashrafzadeh-Kian et al. Cytokine. 2022 Feb.

Abstract

Background: Several immune mediators (IM) including cytokines, chemokines, and their receptors have been suggested to play a role in COVID-19 pathophysiology and severity.

Aim: To determine if early IM profiles are predictive of clinical outcome and which of the IMs tested possess the most clinical utility.

Methods: A custom bead-based multiplex assay was used to measure IM concentrations in a cohort of SARS-CoV-2 PCR positive patients (n = 326) with varying disease severities as determined by hospitalization status, length of hospital stay, and survival. Patient groups were compared, and clinical utility was assessed. Correlation plots were constructed to determine if significant relationships exist between the IMs in the setting of COVID-19.

Results: In PCR positive SARS-CoV-2 patients, IL-6 was the best predictor of the need for hospitalization and length of stay. Additionally, MCP-1 and sIL-2Rα were moderate predictors of the need for hospitalization. Hospitalized PCR positive SARS-CoV-2 patients displayed a notable correlation between sIL-2Rα and IL-18 (Spearman's ρ = 0.48, P=<0.0001).

Conclusions: IM profiles between non-hospitalized and hospitalized patients were distinct. IL-6 was the best predictor of COVID-19 severity among all the IMs tested.

Keywords: COVID-19; Hospitalization; IL-6; Immune mediator; Multiplex assay; SARS-CoV-2.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
CLIR plot by multiple conditions of 14 immune mediators’ concentrations in SARS-CoV-2 positive patients plotted as multiples of the reference median. Upper whisker end: 97.5th percentile; top of the box: 90th percentile; line in the box: median; bottom of the box: 10th percentile; lower whisker end: 2.5th percentile. Severity groups shown are non-hospitalized (NH), hospitalized < 10 days (<10 d), hospitalized > 10 days (10 + d), and deceased (DEC). If the group median line exceeded the top of the green shaded range (>97.5th percentile of reference population), the analyte differences were considered clinically informative.
Fig. 2
Fig. 2
Initial IL-6 concentrations (pg/mL) for all patients versus symptom day. Deceased patients (DEC), hospitalized non-deceased patients (H), non-hospitalized patients (NH), and healthy controls (HC) are shown. The maximum for HCs is denoted by the line. The two non-hospitalized patients reclassified from non-hospitalized to hospitalized (NH to H) are color-coded separately. Spearman’s ρ for all hospitalized patients was 0.20 (P = 0.0047), showing a weak positive correlation.
Fig. 3
Fig. 3
ROC curve for seven IMs to discriminate between the non-hospitalized (NH) group and the combined non-deceased hospitalized groups (<10 d + 10 + d).
Fig. 4
Fig. 4
Association between IMs. Correlation matrices were constructed for each analyte for hospitalized, non-hospitalized, and combined cohorts. Spearman’s rho (ρ) is shown for each pair and statistically significant pairs are highlighted red (P=<0.05).
Supplementary figure 1
Supplementary figure 1
Scatter plots and histograms for each possible pair of candidate IMs (pg/mL). Deceased (DEC), Hospitalized (H) and Non-Hospitalized (NH) SARS-CoV-2 positive patients are displayed.
See this image and copyright information in PMC

References

    1. Kong A.-N., Lau A.T.Y., Brunetti L. Hot Topic Commentary on COVID-19. Current Pharmacology Reports. 2020;6(3):53–55. - PMC - PubMed
    1. Zhang H., Penninger J.M., Li Y., Zhong N., Slutsky A.S. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med. 2020;46(4):586–590. - PMC - PubMed
    1. Huang C., Wang Y., Li X., Ren L., Zhao J., Hu Y.i., Zhang L.i., Fan G., Xu J., Gu X., Cheng Z., Yu T., Xia J., Wei Y., Wu W., Xie X., Yin W., Li H., Liu M., Xiao Y., Gao H., Guo L.i., Xie J., Wang G., Jiang R., Gao Z., Jin Q.i., Wang J., Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan. China. Lancet. 2020;395(10223):497–506. - PMC - PubMed
    1. Laing A.G., Lorenc A., del Molino del Barrio I., Das A., Fish M., Monin L., Muñoz-Ruiz M., McKenzie D.R., Hayday T.S., Francos-Quijorna I., Kamdar S., Joseph M., Davies D., Davis R., Jennings A., Zlatareva I., Vantourout P., Wu Y., Sofra V., Cano F., Greco M., Theodoridis E., Freedman J.D., Gee S., Chan J.N.E., Ryan S., Bugallo-Blanco E., Peterson P., Kisand K., Haljasmägi L., Chadli L., Moingeon P., Martinez L., Merrick B., Bisnauthsing K., Brooks K., Ibrahim M.A.A., Mason J., Lopez Gomez F., Babalola K., Abdul-Jawad S., Cason J., Mant C., Seow J., Graham C., Doores K.J., Di Rosa F., Edgeworth J., Shankar-Hari M., Hayday A.C. A dynamic COVID-19 immune signature includes associations with poor prognosis. Nat Med. 2020;26(10):1623–1635. - PubMed
    1. Thwaites R.S., et al. Inflammatory profiles across the spectrum of disease reveal a distinct role for GM-CSF in severe COVID-19. Sci Immunol. 2021;6(57) - PMC - PubMed

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