Clusters of inflammation in COVID-19: descriptive analysis and prognosis on more than 15,000 patients from the Spanish SEMI-COVID-19 Registry

Rubio‐Rivas, Manuel; Mora-Luján, José María; Formiga, Francesç; González, Miguel Ángel Corrales; Andreu, María del Mar García; Moreno-Torres, Víctor; García, Gema María García; Pedrajas, José Nicolás Alcalá; Boixeda, Ramón; Pérez-Lluna, Leticia; Cortés-Rodríguez, Begoña; Mella-Pérez, Carmen; Alcántara, Maria de la Sierra Navas; Reboiro, Manuel Lorenzo López; Alfaro-Lara, Verónica; Perez-Martin, Santiago; Martín-Oterino, José Ángel; Gutiérrez, Anyuli Gracia; Díez-Canseco, Anabel Martin-Urda; Casanova, Pere Comas; García, Cristina Pérez; Varona, José Felipe; Gómez‐Huelgas, Ricardo; Antón-Santos, Juan-Miguel; Lumbreras-Bermejo, Carlos

doi:10.1007/s11739-021-02924-4

Cited by 5 publications

(6 citation statements)

References 24 publications

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“…The characteristic features of this two-tiered response in COVID-19 can have implications in clinical decisions. Activation of several inflammatory markers has been observed in patients with severe COVID-19 and has been proposed as prognostic markers [ 19 , 60 , 61 ]. Since S100A12 expression displayed a stepwise activation pattern and demonstrated strong association with severe COVID-19, it may serve as a good prognostic marker as well.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, parameters reflecting organ dysfunction have been extensively studied [14][15][16][17]. To assist diagnosis and prognosis, simple models have been constructed based on some of these parameters and demographic information such as age, sex, and number of comorbidities [18][19][20][21][22]. However, these models are far from perfect, reflecting the heterogeneity and complexity of COVID-19.…”

Section: Introductionmentioning

confidence: 99%

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A two-gene marker for the two-tiered innate immune response in COVID-19 patients

Lei

2023

PLoS ONE

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For coronavirus disease 2019 (COVID-19), a pandemic disease characterized by strong immune dysregulation in severe patients, convenient and efficient monitoring of the host immune response is critical. Human hosts respond to viral and bacterial infections in different ways, the former is characterized by the activation of interferon stimulated genes (ISGs) such as IFI27, while the latter is characterized by the activation of anti-bacterial associated genes (ABGs) such as S100A12. This two-tiered innate immune response has not been examined in COVID-19. In this study, the activation patterns of this two-tiered innate immune response represented by IFI27 and S100A12 were explored based on 1421 samples from 17 transcriptome datasets derived from the blood of COVID-19 patients and relevant controls. It was found that IFI27 activation occurred in most of the symptomatic patients and displayed no correlation with disease severity, while S100A12 activation was more restricted to patients under severe and critical conditions with a stepwise activation pattern. In addition, most of the S100A12 activation was accompanied by IFI27 activation. Furthermore, the activation of IFI27 was most pronounced within the first week of symptom onset, but generally waned after 2–3 weeks. On the other hand, the activation of S100A12 displayed no apparent correlation with disease duration and could last for several months in certain patients. These features of the two-tiered innate immune response can further our understanding on the disease mechanism of COVID-19 and may have implications to the clinical triage. Development of a convenient two-gene protocol for the routine serial monitoring of this two-tiered immune response will be a valuable addition to the existing laboratory tests.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A two-gene marker for the two-tiered innate immune response in COVID-19 patients

Lei

2023

PLoS ONE

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“…Mean serum ferritin was markedly elevated in non-survivors (compared to survivors) without psychiatric comorbidity (922.51 ± 1,401.51 vs. 672.68 ± 797.75), but the difference in serum ferritin between non-survivors and survivors among patients with psychiatric comorbidity was much smaller (686.12 ± 748.86 vs. 513.76 ± 950.64). Rich literature document high serum ferritin among COVID-19 non-survivors ( 1 , 25 , 33 – 39 ). Our results show that the marked elevation in serum ferritin typically observed in COVID-19 non-survivors, is not present in patients with psychiatric comorbidity who eventually died from severe illness.…”

Section: Discussionmentioning

confidence: 99%

“…Serum ferritin is a non-specific acute phase protein (12) that is elevated in many different conditions including inflammation (11,(13)(14)(15)(16)(17), malignancy (16,18,19), and certain autoimmune diseases (20)(21)(22). In COVID-19 patients, higher serum ferritin levels are reported in hospitalized (23,24), critically ill patients (25)(26)(27) with more severe illness (23,(28)(29)(30)(31), longer length of hospital stay (32) and in non-survivors (1,25,(33)(34)(35)(36)(37)(38)(39). In addition, one study screened adult COVID-19 survivors (n = 109) for depression and anxiety using Beck Depression and Beck Anxiety Inventories (BDI, BAI) (40,41) on the 15th post-hospitalization day, and reported significant positive correlation between BAI scores and ferritin levels in patients with anxiety (42).…”

Section: Introductionmentioning

confidence: 99%

Attenuated initial serum ferritin concentration in critically ill coronavirus disease 2019 geriatric patients with comorbid psychiatric conditions

Abulseoud

Yehia²,

Egol³

et al. 2022

Front. Psychiatry

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We examined the effects of psychiatric comorbidity, sex, and ICU admission on serum ferritin concentration in 628 elderly patients (79.7 ± 8.5 years) with positive SARS-CoV-2 PCR test. Hospitalization was required in 96% of patients and 17% required ICU admission. Patients with COVID-19 and psychiatric comorbidities (n = 212) compared to patients without psychiatric comorbidities (n = 416) had significantly lower ferritin concentration (570.4 ± 900.1 vs. 744.1 ± 965, P = 0.029), a greater incidence of delirium (22.6 vs. 14.4%, P = 0.013) and higher mortality (35.3 vs. 27.6%, P = 0.015). Furthermore, we found significant effects for sex (P = 0.002) and ICU admission (P = 0.007). Among patients without comorbid psychiatric conditions, males had significantly higher ferritin compared to females (1,098.3 ± 78.4 vs. 651.5 ± 94.4, P < 0.001). ICU patients without comorbid psychiatric conditions had significantly higher serum ferritin compared to ICU patients with comorbid psychiatric conditions: (1,126.6 ± 110.7 vs. 668.6 ± 156.5, P < 0.001). Our results suggest that the presence of comorbid psychiatric conditions in elderly patients with COVID-19 is associated with higher rates of delirium and mortality and lower ferritin levels during severe illness. Whether high serum ferritin is protective during severe infection requires further investigation.

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“…Despite the great effort in the innovative development of vaccines and drugs [ 1 , 2 ], too many lives have been lost in this pandemic. For a disease dominated with problems in immune dysregulation [ 3 ], we may have to dig deeper in our understanding of the cascade of host immune response to respiratory viral infection.…”

Section: Introductionmentioning

confidence: 99%

Hypoxia and Activation of Neutrophil Degranulation-Related Genes in the Peripheral Blood of COVID-19 Patients

Lei

2024

Viruses

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Severe COVID-19 is characterized by systematic hyper-inflammation and subsequent damage to various organs. Therefore, it is critical to trace this cascade of hyper-inflammation. Blood transcriptome has been routinely utilized in the interrogation of host immune response in COVID-19 and other infectious conditions. In this study, consensus gene dysregulation in the blood was obtained from 13 independent transcriptome studies on COVID-19. Among the up-regulated genes, the most prominent functional categories were neutrophil degranulation and cell cycle, which is clearly different from the classical activation of interferon signaling pathway in seasonal flu. As for the potential upstream causal factors of the atypical gene dysregulation, systemic hypoxia was further examined because it is much more widely reported in COVID-19 than that in seasonal flu. It was found that both physiological and pathological hypoxia can induce activation of neutrophil degranulation-related genes in the blood. Furthermore, COVID-19 patients with different requirement for oxygen intervention showed distinctive levels of gene expression related to neutrophil degranulation in the whole blood, which was validated in isolated neutrophils. Thus, activation of neutrophil degranulation-related genes in the blood of COVID-19 could be partially attributed to hypoxia. Interestingly, similar pattern was also observed in H1N1 infection (the cause of Spanish flu) and several other severe respiratory viral infections. As for the molecular mechanism, both HIF-dependent and HIF-independent pathways have been examined. Since the activation of neutrophil degranulation-related genes is highly correlated with disease severity in COVID-19, early detection of hypoxia and active intervention may prevent further activation of neutrophil degranulation-related genes and other harmful downstream hyper-inflammation. This common mechanism is applicable to current and future pandemic as well as the severe form of common respiratory infection.

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Clusters of inflammation in COVID-19: descriptive analysis and prognosis on more than 15,000 patients from the Spanish SEMI-COVID-19 Registry

Cited by 5 publications

References 24 publications

A two-gene marker for the two-tiered innate immune response in COVID-19 patients

A two-gene marker for the two-tiered innate immune response in COVID-19 patients

Attenuated initial serum ferritin concentration in critically ill coronavirus disease 2019 geriatric patients with comorbid psychiatric conditions

Hypoxia and Activation of Neutrophil Degranulation-Related Genes in the Peripheral Blood of COVID-19 Patients

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