Clinical and immunological factors that distinguish COVID-19 from pandemic influenza A(H1N1)

Choreño-Parra, José Alberto; Jiménez-Álvarez, Luis Armando; Cruz‐Lagunas, Alfredo; Rodríguez‐Reyna, Tatiana Sofía; Ramírez-Martínez, Gustavo; Sandoval-Vega, Montserrat; Hernández-García, Diana Lizzeth; Choreño-Parra, Eduardo M.; Balderas-Martínez, Yalbi I.; Martinez-Sanchez, Mariana Esther; Márquez-García, Eduardo; Shiutto, Edda; Moreno-Rodríguez, José; Barreto-Rodríguez, José Omar; Vázquez-Rojas, Hazel; Centeno-Sáenz, Gustavo Iván; Alvarado-Peña, Néstor; Salinas-Lara, Citlaltépetl; Sánchez-Garibay, Carlos; Hernández, Gabriela; Mendoza-Milla, Criselda; Domínguez, Andrea; Granados, Julio; Mena-Hernández, Lula; Buenfil, Luis Angel Pérez; Domínguez-Cheritt, Guillermo; Cabello-Gutiérrez, Carlos; Luna, César Alejandro Fernández de; Salas-Hernández, Jorge; Santillán-Doherty, Patricio; Regalado, Justino; Hernández-Martínez, Angélica; Orozco, Lorena; Garcı́a-Latorre, Ethel; Hernández-Cárdenas, Carmen Margarita; Khader, Shabaana A.; Zlotnik, Albert; Zúñiga, Joaquı́n

doi:10.1101/2020.08.10.20170761

Cited by 7 publications

(8 citation statements)

References 63 publications

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“…During such a predicted scenario, the differentiation of influenza and COVID-19 by clinical characteristics may be complicated. Indeed, our results and previous studies show that only a few non-specific symptoms and routine laboratory tests are useful for this diagnostic dilemma (20)(21)(22). However, the discrimination of the causative pathogen has direct therapeutic implications, including the selection of the adequate anti-viral drug.…”

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confidence: 60%

CXCL17 Is a Specific Diagnostic Biomarker for Severe Pandemic Influenza A(H1N1) That Predicts Poor Clinical Outcome

et al. 2021

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The C-X-C motif chemokine ligand 17 (CXCL17) is chemotactic for myeloid cells, exhibits bactericidal activity, and exerts anti-viral functions. This chemokine is constitutively expressed in the respiratory tract, suggesting a role in lung defenses. However, little is known about the participation of CXCL17 against relevant respiratory pathogens in humans. Here, we evaluated the serum levels and lung tissue expression pattern of CXCL17 in a cohort of patients with severe pandemic influenza A(H1N1) from Mexico City. Peripheral blood samples obtained on admission and seven days after hospitalization were processed for determinations of serum CXCL17 levels by enzyme-linked immunosorbent assay (ELISA). The expression of CXCL17 was assessed by immunohistochemistry (IHQ) in lung autopsy specimens from patients that succumbed to the disease. Serum CXCL17 levels were also analyzed in two additional comparative cohorts of coronavirus disease 2019 (COVID-19) and pulmonary tuberculosis (TB) patients. Additionally, the expression of CXCL17 was tested in lung autopsy specimens from COVID-19 patients. A total of 122 patients were enrolled in the study, from which 68 had pandemic influenza A(H1N1), 24 had COVID-19, and 30 with PTB. CXCL17 was detected in post-mortem lung specimens from patients that died of pandemic influenza A(H1N1) and COVID-19. Interestingly, serum levels of CXCL17 were increased only in patients with pandemic influenza A(H1N1), but not COVID-19 and PTB. CXCL17 not only differentiated pandemic influenza A(H1N1) from other respiratory infections but showed prognostic value for influenza-associated mortality and renal failure in machine-learning algorithms and regression analyses. Using cell culture assays, we also identified that human alveolar A549 cells and peripheral blood monocyte-derived macrophages increase their CXCL17 production capacity after influenza A(H1N1) pdm09 virus infection. Our results for the first time demonstrate an induction of CXCL17 specifically during pandemic influenza A(H1N1), but not COVID-19 and PTB in humans. These findings could be of great utility to differentiate influenza and COVID-19 and to predict poor prognosis specially at settings of high incidence of pandemic A(H1N1). Future studies on the role of CXCL17 not only in severe pandemic influenza, but also in seasonal influenza, COVID-19, and PTB are required to validate our results.

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confidence: 60%

CXCL17 Is a Specific Diagnostic Biomarker for Severe Pandemic Influenza A(H1N1) That Predicts Poor Clinical Outcome

et al. 2021

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“…Here we used to assess the severity of COVID-19 as previously reported (17,18). Laboratory variables that were evaluated included levels of blood routine examination (white blood cells, hemoglobin, platelet, neutrophil and lymphocyte), coagulation function (D-Dimer), biochemical examination [alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), c-reactive protein (CRP), creatinine (Cr)] and serum ferritin.…”

Section: Data Extractionmentioning

confidence: 99%

Cytokine Signature Associated With Disease Severity in COVID-19

Guo

Wang

et al. 2021

Front. Immunol.

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Coronavirus disease 2019 (COVID-19) broke out and then became a global epidemic at the end of 2019. With the increasing number of deaths, early identification of disease severity and interpretation of pathogenesis are very important. Aiming to identify biomarkers for disease severity and progression of COVID-19, 75 COVID-19 patients, 34 healthy controls and 23 patients with pandemic influenza A(H1N1) were recruited in this study. Using liquid chip technology, 48 cytokines and chemokines were examined, among which 33 were significantly elevated in COVID-19 patients compared with healthy controls. HGF and IL-1β were strongly associated with APACHE II score in the first week after disease onset. IP-10, HGF and IL-10 were correlated positively with virus titers. Cytokines were significantly correlated with creatinine, troponin I, international normalized ratio and procalcitonin within two weeks after disease onset. Univariate analyses were carried out, and 6 cytokines including G-CSF, HGF, IL-10, IL-18, M-CSF and SCGF-β were found to be associated with the severity of COVID-19. 11 kinds of cytokines could predict the severity of COVID-19, among which IP-10 and M-CSF were excellent predictors for disease severity. In conclusion, the levels of cytokines in COVID-19 were significantly correlated with the severity of the disease in the early stage, and serum cytokines could be used as warning indicators of the severity and progression of COVID-19. Early stratification of disease and intervention to reduce hypercytokinaemia may improve the prognosis of COVID-19 patients.

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“…When several immune mediators were measured in patient's plasma suffering from in uenza A (H1N1) and COVID-19, TSLP levels were signi cantly upregulated in COVID-19 patients. This fact suggests a possible contribution of TSLP in COVID-19 pathogenesis and perhaps aids differential diagnosis 125 . Besides, since TSLP concentration was reported to be higher in severely affected than in mild and moderated COVID-19 cases, it may be potentially used as a biomarker for disease severity 126 .…”

Section: Discussionmentioning

confidence: 85%

Single-nucleus lung transcriptomics and inflammatory responses in lethal COVID-19 reveal potential drugs in advanced-stage clinical trials

López‐Cortés

Guerrero²,

Ortíz-Prado

et al. 2021

Preprint

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There is pressing urgency to identify drugs that allow treating COVID-19 patients effectively. Respiratory failure is the leading cause of death in patients with severe COVID-19, and the host inflammatory response at the lungs remains poorly understood. Therefore, we retrieved data from postmortem lungs from COVID-19 patients and performed in-depth in silico analyses of single-nucleus RNA sequencing data, inflammatory protein interactome network, functional enrichment, and shortest pathways to cancer hallmark phenotypes to reveal potential therapeutic targets and drugs in advanced-stage COVID-19 clinical trials. Herein, we analyzed transcriptomics data of 719 inflammatory response genes across 19 cell types (116,313 nuclei) from lung autopsies. The functional enrichment analysis of the 233 significantly expressed genes showed that the most relevant biological annotations were: inflammatory response, innate immune response, cytokine production, interferon production, macrophage activation, thymic stromal lymphopoietin, blood coagulation, IL-1 and megakaryocytes in obesity, NLRP3 inflammasome complex, and the TLR, JAK-STAT, NF-κB, TNF, oncostatin M, AGE-RAGE signaling pathways. Subsequently, we identified 34 essential inflammatory proteins with both high-confidence protein interactions and shortest pathways to inflammation, cell death, glycolysis, and angiogenesis. Lastly, we propose five small molecules involved in advanced-stage COVID-19 clinical trials: baricitinib, pacritinib, and ruxolitinib are tyrosine-protein kinase JAK2 inhibitors, losmapimod is a MAP kinase p38 alpha inhibitor, and eritoran is a TLR4/MD-2 antagonist. After being thoroughly analyzed in COVID-19 clinical trials, these drugs can be considered for treating severe COVID-19 patients.

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Clinical and immunological factors that distinguish COVID-19 from pandemic influenza A(H1N1)

Cited by 7 publications

References 63 publications

CXCL17 Is a Specific Diagnostic Biomarker for Severe Pandemic Influenza A(H1N1) That Predicts Poor Clinical Outcome

CXCL17 Is a Specific Diagnostic Biomarker for Severe Pandemic Influenza A(H1N1) That Predicts Poor Clinical Outcome

Cytokine Signature Associated With Disease Severity in COVID-19

Single-nucleus lung transcriptomics and inflammatory responses in lethal COVID-19 reveal potential drugs in advanced-stage clinical trials

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