tetano
Editor, Senior Moderator
Crit Care Med
. 2020 Nov 12.
doi: 10.1097/CCM.0000000000004724. Online ahead of print.
Inflammatory Response and Phenotyping in Severe Acute Respiratory Infection From the Middle East Respiratory Syndrome Coronavirus and Other Etiologies
Yaseen M Arabi[SUP] 1 2 3 4 [/SUP], Dunia Jawdat[SUP] 2 3 4 5 [/SUP], Ali H Hajeer[SUP] 3 4 6 [/SUP], Musharaf Sadat[SUP] 1 2 3 4 [/SUP], Jesna Jose[SUP] 2 7 [/SUP], Ramesh K Vishwakarma[SUP] 2 3 4 8 [/SUP], Walid Almashaqbeh[SUP] 2 3 4 5 [/SUP], Abdulaziz Al-Dawood[SUP] 1 2 3 4 [/SUP]
Affiliations
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.
. 2020 Nov 12.
doi: 10.1097/CCM.0000000000004724. Online ahead of print.
Inflammatory Response and Phenotyping in Severe Acute Respiratory Infection From the Middle East Respiratory Syndrome Coronavirus and Other Etiologies
Yaseen M Arabi[SUP] 1 2 3 4 [/SUP], Dunia Jawdat[SUP] 2 3 4 5 [/SUP], Ali H Hajeer[SUP] 3 4 6 [/SUP], Musharaf Sadat[SUP] 1 2 3 4 [/SUP], Jesna Jose[SUP] 2 7 [/SUP], Ramesh K Vishwakarma[SUP] 2 3 4 8 [/SUP], Walid Almashaqbeh[SUP] 2 3 4 5 [/SUP], Abdulaziz Al-Dawood[SUP] 1 2 3 4 [/SUP]
Affiliations
- PMID: 33181590
- DOI: 10.1097/CCM.0000000000004724
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.