Elevated IFNA1 and suppressed IL12p40 associated with persistent hyperinflammation in COVID-19 pneumonia

Abstract

IntroductionDespite of massive endeavors to characterize inflammation in COVID-19 patients, the core network of inflammatory mediators responsible for severe pneumonia stillremain remains elusive. MethodsHere, we performed quantitative and kinetic analysis of 191 inflammatory factors in 955 plasma samples from 80 normal controls (sample n = 80) and 347 confirmed COVID-19 pneumonia patients (sample n = 875), including 8 deceased patients. ResultsDifferential expression analysis showed that 76% of plasmaproteins (145 factors) were upregulated in severe COVID-19 patients comparedwith moderate patients, confirming overt inflammatory responses in severe COVID-19 pneumonia patients. Global correlation analysis of the plasma factorsrevealed two core inflammatory modules, core I and II, comprising mainly myeloid cell and lymphoid cell compartments, respectively, with enhanced impact in a severity-dependent manner. We observed elevated IFNA1 and suppressed IL12p40, presenting a robust inverse correlation in severe patients, which was strongly associated with persistent hyperinflammation in 8.3% of moderate pneumonia patients and 59.4% of severe patients. DiscussionAberrant persistence of pulmonary and systemic inflammation might be associated with long COVID-19 sequelae. Our comprehensive analysis of inflammatory mediators in plasmarevealed the complexity of pneumonic inflammation in COVID-19 patients anddefined critical modules responsible for severe pneumonic progression.

Changes in Serum IL-12 Levels following the Administration of H1-Antihistamines in Patients with Chronic Spontaneous Urticaria

“…Cytokines play a central role in monitoring and regulating immune and inflammatory responses in allergic processes [ 2 , 4 , 7 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ]. The meticulous quantification of cytokines provides valuable information about pathophysiological processes, therapy adjustment, diagnosis, and the stage and prognosis of various human conditions [ 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ]. Investigating the involvement of the IL-12 cytokine family in CSU management is a challenge.…”

“…Investigating the involvement of the IL-12 cytokine family in CSU management is a challenge. The IL-12 family consists of five natural members, namely IL-12, IL-23, IL-27, IL-35, and IL-39, and two synthetic members, IL-X and IL-Y [ 25 , 26 , 27 , 30 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 ]. The members of the IL-12 family, including their structure, specific receptor nature, signalling pathways, target cells, and biological activities, have been extensively studied ( Table 1 ) [ 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 ].…”