The Potential of Lung Epithelium Specific Proteins as Biomarkers for COVID-19-Associated Lung Injury

Almuntashiri, Sultan; James, Chelsea; Wang, Xiaoyun; Siddiqui, Budder; Zhang, Duo

doi:10.3390/diagnostics11091643

Cited by 11 publications

(6 citation statements)

References 80 publications

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“…PSPB levels from mild patient samples were not statistically significant relative to HC (adjusted p = 0.53). Consistent with previous reports [ 19 ], we also observed an increase in Surfactant Protein D in the severe relative to the mild infections (adjusted p = 1.39E-05) and HC samples (adjusted p = 3.07E-05). Among the severe infection patients, PSPB levels increased with age ( Fig.…”

Section: Resultssupporting

confidence: 92%

Multi-omics of NET formation and correlations with CNDP1, PSPB, and L-cystine levels in severe and mild COVID-19 infections

Bramer¹,

Hontz²,

Eisfeld³

et al. 2023

Heliyon

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Section: Resultssupporting

confidence: 92%

Multi-omics of NET formation and correlations with CNDP1, PSPB, and L-cystine levels in severe and mild COVID-19 infections

Bramer¹,

Hontz²,

Eisfeld³

et al. 2023

Heliyon

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“…PSPB levels from mild patient samples were not statistically significant relative to HC (adjusted p=0.53). Consistent with previous reports (19), we also observed an increase in Surfactant Protein D in the severe relative to the mild infections (adjusted p=1.39E-05) and HC samples (adjusted p= 3.07E-05). The presence of pulmonary surfactant in the plasma of severe patient populations is consistent with an ARDS presentation with increased pulmonary capillary permeability (20).…”

Section: Resultssupporting

confidence: 92%

Multi-omics Characterization of Neutrophil Extracellular Trap Formation in Severe and Mild COVID-19 Infections

Bramer

Hontz²,

Eisfeld

et al. 2022

Preprint

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SummaryThe detailed mechanisms of COVID-19 infection pathology remain poorly understood. To improve our understanding of SARS-CoV-2 pathology, we performed a multi-omics analysis of an immunologically naïve SARS-CoV-2 clinical cohort from the plasma of uninfected controls, mild, and severe infections. A comparison of healthy controls and patient samples showed activation of neutrophil degranulation pathways and formation of neutrophil extracellular trap (NET) complexes that were activated in a subset of the mild infections and more prevalent in severe infections (containing multiple NET proteins in individual patient samples). As a potential mechanism to suppress NET formation, multiple redox enzymes were elevated in the mild and severe symptom population. Analysis of metabolites from the same cohort showed a 24- and 60-fold elevation in plasma L-cystine, the oxidized form of cysteine, which is a substrate of the powerful antioxidant glutathione, in mild and severe patients, respectively. Unique to patients with mild infections, the carnosine dipeptidase modifying enzyme (CNDP1) was up-regulated. The strong protein and metabolite oxidation signatures suggest multiple compensatory pathways working to suppress oxidation and NET formation in SARS-CoV-2 infections.

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“…ARDS severity can be assessed based on physical exam, chest X-ray, and most importantly the degree of hypoxemia as evaluated by the PaO 2 /FIO 2 ratio [46]. Circulating biomarkers such as inflammation proteins, lung endothelium as well as lung epithelium-specific proteins have been examined so far for lung injury [47,48], but none of them can provide a robust diagnostic or prognostic assessment for ARDS [49]. So far, Krebs von den Lungen-6 (KL-6), primarily secreted by type II alveolar epithelial cells, has been shown an excellent discrimination AUC value among ARDS patients in one cohort [50].…”

Section: Discussionmentioning

confidence: 99%

Plasma TIMP-1 as a sex-specific biomarker for acute lung injury

et al. 2022

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Background Acute respiratory distress syndrome (ARDS) confers high morbidity and mortality, with a death rate reaching 40%. Pre-clinical and clinical studies have cited sex-specific sex hormones as a critical contributor to divergent immunologic responses. Therefore, exploration of sex and sex hormone roles following lung injury and ARDS development is needed. Tissue inhibitor of metalloproteinase-1 (TIMP-1) was the first-discovered natural collagenase inhibitor and is located exclusively on the X chromosome. This study aimed to evaluate the prognostic role of circulating TIMP-1, and if concentration differences between males and females correlate with the mortality of ARDS patients. Methods Human plasma samples from 100 ARDS patients enrolled in Albuterol to Treat Acute Lung Injury (ALTA) trial on the day of randomization were evaluated. The amount of TIMP-1 was measured using an enzyme-linked immunoassay (ELISA). Area under the receiver operating characteristic (AUROC) was computed to assess the predictive power of TIMP-1 for 30 and 90-day mortality. Chi-squared tests and Kaplan–Meier curves were computed to assess different variables and survival. Results AUROC analysis of TIMP-1 and 30-day mortality among females showed that TIMP-1 exhibited an AUC of 0.87 (95% confidence interval [CI] 0.78 to 0.97; P = 0.0014) with an optimal cut-off value of 159.7 ng/mL producing a 100% sensitivity and 74% specificity. For 90-day mortality, AUROC analysis showed an AUC of 0.82 (95% confidence interval [CI] 0.67 to 0.97; P = 0.0016) with a similar cut-off value producing a 90% sensitivity and 76.47% specificity. Stratifying subjects by TIMP-1 concentration as high (≥ 159.7 ng/mL) or low (< 159.7 ng/mL) indicated that high TIMP-1 was associated with increased 30 and 90-day mortality rates (all P < 0.0001). Lastly, high TIMP-1 group was associated with worse other outcomes including ventilator-free days (VFDs) and ICU-free days (all P < 0.05). Conclusion Circulating TIMP-1 appeared to be a promising biomarker for mortality among females with ARDS. The high TIMP-1 group showed worse VFDs and ICU-free days. Circulating TIMP-1 may be a sex-specific biomarker in the setting of ARDS and could improve ARDS phenotyping as well as provide a novel therapeutic target in females.

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The Potential of Lung Epithelium Specific Proteins as Biomarkers for COVID-19-Associated Lung Injury

Cited by 11 publications

References 80 publications

Multi-omics of NET formation and correlations with CNDP1, PSPB, and L-cystine levels in severe and mild COVID-19 infections

Multi-omics of NET formation and correlations with CNDP1, PSPB, and L-cystine levels in severe and mild COVID-19 infections

Multi-omics Characterization of Neutrophil Extracellular Trap Formation in Severe and Mild COVID-19 Infections

Plasma TIMP-1 as a sex-specific biomarker for acute lung injury

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