Iron: Innocent bystander or vicious culprit in COVID-19 pathogenesis?

Edeas, Marvin; Saleh, Jumana; Peyssonnaux, Carole

doi:10.1016/j.ijid.2020.05.110

Cited by 166 publications

(185 citation statements)

References 28 publications

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“…Serum iron and TfSat are known to decrease early after infections, inhibiting iron availability to the pathogen, but then return to almost-normal values within 7-10 days [24,25]. The role of dysregulated iron response in Covid-19 has been recently reviewed [26].…”

Section: Discussionmentioning

confidence: 99%

Iron metabolism and lymphocyte characterisation during Covid-19 infection in ICU patients: an observational cohort study

et al. 2020

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Background: Iron metabolism and immune response to SARS-CoV-2 have not been described yet in intensive care patients, although they are likely involved in Covid-19 pathogenesis. Methods: We performed an observational study during the peak of pandemic in our intensive care unit, dosing Ddimer, C-reactive protein, troponin T, lactate dehydrogenase, ferritin, serum iron, transferrin, transferrin saturation, transferrin soluble receptor, lymphocyte count and NK, CD3, CD4, CD8 and B subgroups of 31 patients during the first 2 weeks of their ICU stay. Correlation with mortality and severity at the time of admission was tested with the Spearman coefficient and Mann-Whitney test. Trends over time were tested with the Kruskal-Wallis analysis. Results: Lymphopenia is severe and constant, with a nadir on day 2 of ICU stay (median 0.555 10 9 /L; interquartile range (IQR) 0.450 10 9 /L); all lymphocytic subgroups are dramatically reduced in critically ill patients, while CD4/CD8 ratio remains normal. Neither ferritin nor lymphocyte count follows significant trends in ICU patients. Transferrin saturation is extremely reduced at ICU admission (median 9%; IQR 7%), then significantly increases at days 3 to 6 (median 33%, IQR 26.5%, p value 0.026). The same trend is observed with serum iron levels (median 25.5 μg/L, IQR 69 μg/L at admission; median 73 μg/L, IQR 56 μg/L on days 3 to 6) without reaching statistical significance. Hyperferritinemia is constant during intensive care stay: however, its dosage might be helpful in individuating patients developing haemophagocytic lymphohistiocytosis. D-dimer is elevated and progressively increases from admission (median 1319 μg/L; IQR 1285 μg/L) to days 3 to 6 (median 6820 μg/L; IQR 6619 μg/L), despite not reaching significant results. We describe trends of all the abovementioned parameters during ICU stay. Conclusions: The description of iron metabolism and lymphocyte count in Covid-19 patients admitted to the intensive care unit provided with this paper might allow a wider understanding of SARS-CoV-2 pathophysiology.

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Section: Discussionmentioning

confidence: 99%

Iron metabolism and lymphocyte characterisation during Covid-19 infection in ICU patients: an observational cohort study

et al. 2020

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“…Among then, manganese has been reported of playing a important role in innate immune activation and host anti-viral defense, as it released from organelles into the cytosol upon virus infection and facilitates the activation of cGAS and STING signaling [27]. For iron, systemic dysregulation resulted from COVID-19 hyperin ammation has been recently reviewed [28]. Serum iron level was reported as a potential predictor of COVID-19 severity and mortality [29].…”

Section: Discussionmentioning

confidence: 99%

Associations of blood essential and toxic metal(loid)s with both disease severity and mortality in patients with COVID-19: a retrospective study

Zeng

Yang

Yuan

et al. 2020

Preprint

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Background The variations and dynamics of blood essential and toxic metal(loid)s in patients with COVID-19 still remains unclear.Methods A retrospective study was performed in a cohort of confirmed COVID-19 patients for their whole blood levels of essential and/or toxic metal(loid)s including magnesium, calcium, chromium, manganese, iron, copper, zinc, arsenic, cadmium, mercury, thallium and lead according to the disease severity and outcome.Results Compared to the non-severe COVID-19 patients, Whole blood calcium, chromium and copper were higher in the severe patients, while magnesium, manganese, iron, zinc, arsenic, thallium and lead were lower. These differences were further found to be consistently existed across the clinical course since the disease onset by longitudinal analysis. Moreover, among the severe patients, chromium and cadmium were higher in the deceased group compared to the recovered group, while arsenic were found to be lower. Whole blood iron, arsenic, and age and sex were determined to be independently factors associated with the disease severity, while chromium, cadmium and the co-morbidity of cardiovascular disease were determined to be independently factors associated with the mortality.Conclusions These results suggest variations of whole blood metal(loid)s as associated factors correlated with the disease severity and mortality for COVID-19.

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“…Serum iron and TfSat are known to decrease early after infections, inhibiting iron availability to the pathogen, but then return to almost-normal values within 7-10 days [24,25] [shortened]. The role of dysregulated iron response in Covid-19 has been recently reviewed [26].…”

Section: Discussionmentioning

confidence: 99%

Iron metabolism and lymphocyte characterisation during Covid-19 infection in ICU patients: an observational cohort study.

Bolondi

Russo

Gamberini

et al. 2020

Preprint

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Abstract Background: Iron metabolism and immune response to SARS-CoV-2 have not been described yet in intensive care patients, although they are likely involved in Covid-19 pathogenesis.Methods: We performed an observational study during the peak of pandemic in our intensive care unit, dosing D-dimer, C-reactive protein, Troponin T, Lactate Dehydrogenase, Ferritin, Serum iron, Transferrin, Transferrin Saturation, Transferrin Soluble Receptor, Lymphocyte count and NK, CD3, CD4, CD8, B subgroups of 31 patients during the first two weeks of their ICU stay. Correlation with mortality and severity at the time of admission was tested with Spearman coefficient and Mann-Whitney test. Trends over time were tested with Kruskall-Wallis analysis.Results: Lymphopenia is severe and constant, with a nadir on day 2 of ICU stay (median 0.555 109/L; interquartile range (IQR) 0.450 109/L); all lymphocytic subgroups are dramatically reduced in critically ill patients, while CD4/CD8 ratio remains normal. Neither Ferritin nor lymphocyte count follow significant trends in ICU patients. Transferrin Saturation is extremely reduced at ICU admission (median 9%; IQR 7%), then significantly increases at day 3 to 6 (median 33%, IQR 26.5%, p-value 0.026). The same trend is observed with serum iron levels (median 25.5 µg/L, IQR 69 µg/L at admission; median 73 µg/L, IQR 56 µg/L on day 3 to 6) without reaching statistical significance. Hyperferritinemia is constant during intensive care stay: however, its dosage might be helpful in individuating patients developing hemophagocytic lymphohistiocytosis. D-dimer is elevated and progressively increases from admission (median 1319 µg/L; IQR 1285 µg/L) to day 3 to 6 (median 6820 µg/L; IQR 6619 µg/L), despite not reaching significant results. We describe trends of all the above mentioned parameters during ICU stay.Conclusions: The description of iron metabolism and lymphocyte count in Covid-19 patients admitted to the Intensive Care Unit provided with this paper might allow a wider understanding of SARS-CoV-2 pathophysiology.

show abstract

Iron: Innocent bystander or vicious culprit in COVID-19 pathogenesis?

Cited by 166 publications

References 28 publications

Iron metabolism and lymphocyte characterisation during Covid-19 infection in ICU patients: an observational cohort study

Iron metabolism and lymphocyte characterisation during Covid-19 infection in ICU patients: an observational cohort study

Associations of blood essential and toxic metal(loid)s with both disease severity and mortality in patients with COVID-19: a retrospective study

Iron metabolism and lymphocyte characterisation during Covid-19 infection in ICU patients: an observational cohort study.

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