Unravelling the debate on heme effects in COVID-19 infections

Hopp, Marie-Thérèse; Domingo‐Fernándéz, Daniel; Gadiya, Yojana; Detzel, Milena S.; Schmalohr, Benjamin Franz; Steinbock, Francèl; Imhof, Diana; Hofmann-Apitius, Martin

doi:10.1101/2020.06.09.142125

Cited by 11 publications

(12 citation statements)

References 71 publications

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“…We only found two genes that were completely discordant, thus completely oppositely regulated in COVID-19 and non-COVID-19 viral infections: Aconitase1 ( ACO1 ) is over-expressed in COVID-19 and under-expressed in non-COVID-19 viral infections and Atlastin GTPase 3 ( ATL3 ) is over-expressed in non-COVID-19 viral infections and under-expressed in COVID-19. Interestingly, ACO1 is involved in iron metabolism, and heme appears to be interlinked with COVID-19 pathophysiology ( Hopp et al., 2020 ). ATL3 is required for endoplasmic reticulum (ER) membrane junctions and may be linked to viral replication sites ( Monel et al., 2019 ).…”

Section: Resultsmentioning

confidence: 99%

Transcriptomic similarities and differences in host response between SARS-CoV-2 and other viral infections

Thair¹,

He²,

Hasin-Brumshtein³

et al. 2021

iScience

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Section: Resultsmentioning

confidence: 99%

Transcriptomic similarities and differences in host response between SARS-CoV-2 and other viral infections

Thair¹,

He²,

Hasin-Brumshtein³

et al. 2021

iScience

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“…We only found two genes that were completely discordant, thus completely oppositely regulated in COVID-19 and non-COVID-19 viral infections: Aconitase1 ( ACO1 ) over-expressed in COVID-19 and under-expressed in non-COVID-19 viral infections and Atlastin GTPase 3 ( ATL3 ) over-expressed in non-COVID-19 viral infections and under-expressed in COVID-19. Interestingly, ACO1 is involved in iron metabolism, and heme appears to be interlinked with COVID-19 pathophysiology 43 . ATL3 is required for endoplasmic reticulum (ER) membrane junctions and may be linked to viral replication sites 44 .…”

Section: Resultsmentioning

confidence: 99%

Transcriptomic Similarities and Differences in Host Response between SARS-CoV-2 and Other Viral Infections

Thair¹,

He²,

Hasin-Brumshtein³

et al. 2020

Preprint

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COVID-19 is a pandemic that shares certain clinical characteristics with other acute viral infections. Here, we studied the whole-blood transcriptomic host response to SARS-CoV-2 and compared it with other viral infections to understand similarities and differences in host response. Using RNAseq we profiled peripheral blood from 24 healthy controls and 62 prospectively enrolled patients with community-acquired lower respiratory tract infection by SARS-Cov-2 within the first 24 hours of hospital admission. We also compiled and curated 23 independent studies that profiled 1,855 blood samples from patients with one of six viruses (influenza, RSV, HRV, ebola, Dengue, and SARS-CoV-1). We show gene expression changes in peripheral blood in patients with COVID-19 versus healthy controls are highly correlated with changes in response to other viral infections (r=0.74, p<0.001). However, two genes, ACO1 and ATL3, show significantly opposite changes between conditions. Pathway analysis in patients with COVID-19 or other viral infections versus healthy controls identified similar pathways including neutrophil activation, innate immune response, immune response to viral infection, and cytokine production for over-expressed genes. Conversely, for under-expressed genes, pathways indicated repression of lymphocyte differentiation and T cell activation. When comparing transcriptome profiles of patients with COVID-19 directly with those with other viral infections, we found 114 and 302 genes were over- or under-expressed, respectively, during COVID-19. Pathways analysis did not identify any significant pathways in these genes, suggesting novel responses to further study. Statistical deconvolution using immunoStates found that M1 macrophages, plasmacytoid dendritic cells, CD14+ monocytes, CD4+ T cells, and total B cells showed change consistently in the same direction across all viral infections including COVID-19. Those that increased in COVID-19 but decreased in non-COVID-19 viral infections were CD56bright NK cells, M2 macrophages, and total NK cells. The concordant and discordant responses mapped out here provide a window to explore the pathophysiology of COVID-19 versus other viral infections and show clear differences in signaling pathways and cellularity as part of the host response to SARS-CoV-2.

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“…In the current state of research, there is no explanation for the decrease in hemoglobin levels in COVID-19. 12 The rapid change in red blood cells may be thought to be due to decreased production or hemolysis. However, it is not known whether the SARS-CoV-2 virus causes hemolysis.…”

Section: Discussionmentioning

confidence: 99%

“…CD147, the new receptor of the spike protein of the SARS-CoV-2 virus, is an adhesion molecule expressed at all stages during the differentiation and maturation of erythrocytes. 12 The reason for the development of anemia in patients may be the Red blood cell distribution width measures the variation in the volumes of red blood cells (RBC). Since erythrocytes characteristically decrease in cellular volume throughout their lifetime, the persistence of these older, smaller cells increases the volume variance and causes an increase in RDW.…”

Section: Discussionmentioning

confidence: 99%

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The relationship between serum erythropoietin, hepcidin, and haptoglobin levels with disease severity and other biochemical values in patients with COVID‐19

Yağcı

Serin

Acicbe

et al. 2021

Int J Lab Hematology

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Introduction Studies have shown that iron metabolism is affected by coronavirus disease 19 (COVID‐19), which has spread worldwide and has become a global health problem. Our study aimed to evaluate the relationship between COVID‐19 and serum erythropoietin (EPO), hepcidin, and haptoglobin (Hpt) levels with disease severity, and other biochemical values. Methods Fifty nine COVID‐19 patients hospitalized in the intensive care unit (ICU) and wards in our hospital between March and June 2020 and 19 healthy volunteers were included in the study. Participants were divided into mild, severe, and critical disease severity groups. Group mean values were analyzed with SPSS according to disease severity, mortality, and intubation status. Results Hemoglobin (Hb) levels were significantly lower in the critical patient group ( P < .0001) and deceased group ( P < .0001). The red blood cell distribution width‐coefficient of variation (RDW‐CV) and ferritin values were significantly higher in the intubated ( P = .001, P = .005) and deceased ( P = .014, P = .003) groups. Ferritin values were positively correlated with disease severity ( P < .0001). Serum iron levels were lower in the patient group compared with the reference range. ( P < .0001). It was found that the transferrin saturation (TfSat) was lower in the patient group compared with the control group ( P < .0001). It was found that the mean EPO of the deceased was lower than the control group and the survived patient group ( P = .035). Hepcidin levels were found to be significantly lower in the patient group ( P < .0001). Hpt values were found to be significantly lower in the intubated group ( P = .004) and the deceased group ( P = .042). Conclusion In our study, while serum iron and hepcidin levels decreased in patients diagnosed with COVID‐19, we found that EPO and Hpt levels were significantly lower in critical and deceased patient groups. Our study is the first study examining EPO and Hpt levels in patients diagnosed with COVID‐19.

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Unravelling the debate on heme effects in COVID-19 infections

Cited by 11 publications

References 71 publications

Transcriptomic similarities and differences in host response between SARS-CoV-2 and other viral infections

Transcriptomic similarities and differences in host response between SARS-CoV-2 and other viral infections

Transcriptomic Similarities and Differences in Host Response between SARS-CoV-2 and Other Viral Infections

The relationship between serum erythropoietin, hepcidin, and haptoglobin levels with disease severity and other biochemical values in patients with COVID‐19

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