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. 2021 Feb 1;49(2):228-239.
doi: 10.1097/CCM.0000000000004724.

Inflammatory Response and Phenotyping in Severe Acute Respiratory Infection From the Middle East Respiratory Syndrome Coronavirus and Other Etiologies

Yaseen M Arabi  1   2   3   4 , Dunia Jawdat  2   3   4   5 , Ali H Hajeer  3   4   6 , Musharaf Sadat  1   2   3   4 , Jesna Jose  2   7 , Ramesh K Vishwakarma  2   3   4   8 , Walid Almashaqbeh  2   3   4   5 , Abdulaziz Al-Dawood  1   2   3   4
Affiliations

Inflammatory Response and Phenotyping in Severe Acute Respiratory Infection From the Middle East Respiratory Syndrome Coronavirus and Other Etiologies

Yaseen M Arabi et al. Crit Care Med. .

Abstract

Objectives: In this study, we evaluated the inflammatory response in patients with severe acute respiratory infection due to the Middle East respiratory syndrome and non-Middle East respiratory syndrome and assessed the presence of distinct inflammatory subphenotypes using latent class analysis.

Design: Prospective cohort study.

Setting: A tertiary care ICU in Riyadh, Saudi Arabia.

Patients: Consecutive critically ill patients with laboratory-confirmed Middle East respiratory syndrome severe acute respiratory infection and non-Middle East respiratory syndrome severe acute respiratory infection.

Intervention: None.

Measurements and main results: We measured cytokines on days 1, 3, 7, and 14 of ICU stay. We included 116 patients (40 with Middle East respiratory syndrome severe acute respiratory infection and 76 with non-Middle East respiratory syndrome severe acute respiratory infection). On ICU day 1, both patients with Middle East respiratory syndrome severe acute respiratory infection and non-Middle East respiratory syndrome severe acute respiratory infection had higher levels of interleukin-3, interleukin-4, interleukin-6, interleukin-8, interleukin-17A, eotaxin, and epidermal growth factor compared with healthy controls. There were no differences in cytokines over time between patients with Middle East respiratory syndrome severe acute respiratory infection and non-Middle East respiratory syndrome severe acute respiratory infection. Using day 1 cytokine levels, latent class analysis categorized patients into two subphenotypes: subphenotype 1 (n = 74 [64%]) and subphenotype 2 (n = 42 [36%]); the latter had significantly higher levels of interleukin-1β, interleukin-1ra, interleukin-2, interleukin-6, interleukin-7, interleukin-8, interleukin-10, interleukin-12p70, interleukin-15, interleukin-17A, inducible protein-10, monocyte chemoattractant protein-1, macrophage inflammatory protein-1α, macrophage inflammatory protein-1β, tumor necrosis factor-α, granulocyte-macrophage colony-stimulating factor, granulocyte-colony stimulating factor, interferon-α, and interferon-γ. Although baseline characteristics were not different between the two subphenotypes, patients in the subphenotype 2 had higher ICU mortality compared with the subphenotype 1 (18/42 [43%] vs 17/74 [23%]; p = 0.03).

Conclusions: One third of critically ill patients with Middle East respiratory syndrome severe acute respiratory infection and non-Middle East respiratory syndrome severe acute respiratory infection demonstrated a subphenotype characterized by increased proinflammatory cytokines, consistent with cytokine storm. Further research is needed to examine whether immunomodulators have differential effects based on inflammatory subphenotypes.

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Conflict of interest statement

Dr. Arabi is the principal investigator on a clinical trial for lopinavir/ritonavir and interferon in Middle East respiratory syndrome; he is an investigator on A Randomised, Embedded, Multi-factorial, Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) and Board Members of the International Severe Acute Respiratory and Emerging Infection Consortium. The remaining authors have disclosed that they do not have any potential conflicts of interest.

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