Iron metabolism and lymphocyte characterisation during Covid-19 infection in ICU patients: an observational cohort study
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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 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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Cites
van der Togt, H. (2003) · Journal of Network and Computer Applications · doi:10.1016/s1084-8045(02)00061-9 · Cited by 302,548
Zhou, F., Yu, T., Du, R., Fan, G., Liu, Y., Liu, Z., Xiang, J., Wang, Y., Song, B., Gu, X., et al. (2020) · The Lancet · doi:10.1016/s0140-6736(20)30566-3 · Cited by 27,263 · cited 6× · see citing works
“It resulted to be the first severely elevated biomarker together with lymphopenia [1]: thus, its early dosage in at-home symptomatic patients might be extremely useful in individuating those who can benefit of early hospital admission.”
BackgroundInfluentialRuan, Q., Yang, K., Wang, W., Jiang, L., & Song, J. (2020) · Intensive Care Medicine · doi:10.1007/s00134-020-05991-x · Cited by 4,898 · cited 5× · see citing works
“The already described survival predictors in general hospital population (LDH, troponin, CRP and D-dimer) Data are all expressed as median, interquartile range between brackets and number of measured cases in the second line Data are all expressed as median, interquartile range between brackets and number of measured…”
BackgroundInfluentialHepcidin Regulates Cellular Iron Efflux by Binding to Ferroportin and Inducing Its Internalization
Nemeth, E., Tuttle, M. S., Powelson, J., Vaughn, M. B., Donovan, A., Ward, D. M., Ganz, T., & Kaplan, J. (2004) · Science · doi:10.1126/science.1104742 · Cited by 4,803 · see citing works
Dysregulation of Immune Response in Patients With Coronavirus 2019 (COVID-19) in Wuhan, China
Qin, C., Zhou, L., Hu, Z., Zhang, S., Yang, S., Tao, Y., Xie, C., Ma, K., Shang, K., Wang, W., et al. (2020) · Clinical Infectious Diseases · doi:10.1093/cid/ciaa248 · Cited by 4,775 · see citing works
COVID-19 pneumonia: different respiratory treatments for different phenotypes?
Gattinoni, L., Chiumello, D., Caironi, P., Busana, M., Romitti, F., Brazzi, L., & Camporota, L. (2020) · Intensive Care Medicine · doi:10.1007/s00134-020-06033-2 · Cited by 1,858 · see citing works
Weiss, G., Ganz, T., & Goodnough, L. T. (2019) · Blood · doi:10.1182/blood-2018-06-856500 · Cited by 1,219 · see citing works
Iron in infection and immunity
Cassat, J. E., & Skaar, E. P. (2013) · Cell Host & Microbe · doi:10.1016/j.chom.2013.04.010 · Cited by 1,214 · see citing works
Characteristics of Peripheral Lymphocyte Subset Alteration in COVID-19 Pneumonia
Wang, F., Nie, J., Wang, H., Zhao, Q., Xiong, Y., Deng, L., Song, S., Ma, Z., Mo, P., & Zhang, Y. (2020) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiaa150 · Cited by 1,125 · see citing works
Serum Transferrin Receptor and Its Ratio to Serum Ferritin in the Diagnosis of Iron Deficiency
Punnonen, K., Irjala, K., & Rajamäki, A. (1997) · Blood · doi:10.1182/blood.v89.3.1052 · Cited by 859 · see citing works
Hepcidin and the iron-infection axis
Drakesmith, H., & Prentice, A. M. (2012) · Science · doi:10.1126/science.1224577 · Cited by 686 · see citing works
Lymphopenia in severe coronavirus disease-2019 (COVID-19): systematic review and meta-analysis
Huang, I., & Pranata, R. (2020) · Journal of Intensive Care · doi:10.1186/s40560-020-00453-4 · Cited by 662 · see citing works
Ganz, T. (2019) · New England Journal of Medicine · doi:10.1056/nejmra1804281 · Cited by 589 · see citing works
Platelet‐to‐lymphocyte ratio is associated with prognosis in patients with coronavirus disease‐19
Qu, R., Ling, Y., Zhang, Y., Wei, L., Chen, X., Li, X., Liu, X., Liu, H., Guo, Z., Ren, H., et al. (2020) · Journal of Medical Virology · doi:10.1002/jmv.25767 · Cited by 583 · cited 1× · see citing works
“Severity at the moment of ICU admission was quantified with two parameters: mean PaO2/FiO2 ratio [18] during the first 24 h (PFmed) and platelet-tolymphocyte ratio [19] (PLR) on the day of ICU admission (data reported on Table 1).”
MethodWong, R., Wu, A., To, K.-F., Lee, N., Lam, C., Wong, C., Chan, P. K., Ng, M., Yu, L., Hui, D., et al. (2003) · British medical journal · doi:10.1136/bmj.326.7403.1358 · Cited by 566 · see citing works
Mild versus severe COVID-19: Laboratory markers
Velavan, T., & Meyer, C. (2020) · International Journal of Infectious Diseases · doi:10.1016/j.ijid.2020.04.061 · Cited by 554 · see citing works
Elevated interleukin‐6 and severe COVID‐19: A meta‐analysis
Aziz, M., Fatima, R., & Assaly, R. (2020) · Journal of Medical Virology · doi:10.1002/jmv.25948 · Cited by 515 · cited 1× · see citing works
“Due to laboratory restrictions, just 9 patients were tested for interleukin-6 (IL6) only on the day of admission [17].”
BackgroundViral infection and iron metabolism
Drakesmith, H., & Prentice, A. (2008) · Nature Reviews Microbiology · doi:10.1038/nrmicro1930 · Cited by 469 · see citing works
Wan, S.-X., Yi, Q., Fan, S., Lv, J.-L., Zhang, X.-X., Guo, L., Lang, C.-H., Xiao, Q., Xiao, K., Yi, Z.-J., et al. (2020) · British Journal of Haematology · doi:10.1111/bjh.16659 · Cited by 299 · see citing works
He, Z., Zhao, C., Dong, Q., Zhuang, H., Song, S., Peng, G., & Dwyer, D. E. (2005) · International Journal of Infectious Diseases · doi:10.1016/j.ijid.2004.07.014 · Cited by 257 · see citing works
Chen, J., & Subbarao, K. (2007) · Annual Review of Immunology · doi:10.1146/annurev.immunol.25.022106.141706 · Cited by 252 · see citing works
Bisset, L. R., Lung, T. L., Kaelin, M., Ludwig, E., & Dubs, R. (2004) · European Journal of Haematology · doi:10.1046/j.0902-4441.2003.00199.x · Cited by 249 · see citing works
Iron: Innocent bystander or vicious culprit in COVID-19 pathogenesis?
Edeas, M., Saleh, J., & Peyssonnaux, C. (2020) · International Journal of Infectious Diseases · doi:10.1016/j.ijid.2020.05.110 · Cited by 194 · cited 1× · see citing works
“The role of dysregulated iron response in Covid-19 has been recently reviewed [26].”
BackgroundLiu, W., Zhang, S.-P., Nekhai, S., & Liu, S.-J. (2020) · Current Clinical Microbiology Reports · doi:10.1007/s40588-020-00140-w · Cited by 135 · cited 1× · see citing works
“Iron metabolism has been repeatedly proposed as a potential therapeutic target during infections [31, 32].”
BackgroundDecreased T cell populations contribute to the increased severity of COVID-19
Liu, R., Wang, Y., Li, J., Han, H. W., Xia, Z., Liu, F., Wu, K., Yang, L., Liu, X., & Zhu, C. (2020) · Clinica Chimica Acta · doi:10.1016/j.cca.2020.05.019 · Cited by 106 · see citing works
SARS‐CoV‐2, the Virus that Causes COVID‐19: Cytometry and the New Challenge for Global Health
Cossarizza, A., Biasi, S. D., Guaraldi, G., Girardis, M., & Mussini, C. (2020) · Cytometry Part A · doi:10.1002/cyto.a.24002 · Cited by 103 · see citing works
Clinicolaboratory study of 25 fatal cases of COVID-19 in Wuhan
Tu, W., Cao, J., Yu, L., Hu, X., & Liu, Q. (2020) · Intensive Care Medicine · doi:10.1007/s00134-020-06023-4 · Cited by 83 · cited 1× · see citing works
“IL6 elevation is lower than reported by other studies on critically ill Covid-19 patients [21].”
ResultCoordination chemistry and biology of chelators for the treatment of iron overload disorders
Bernhardt, P. V. (2007) · Dalton Transactions · doi:10.1039/b708133b · Cited by 82 · see citing works
Wang, W.-K., Chen, S.-Y., Liu, I.-J., Kao, C., Chen, H.-L., Chiang, B., Wang, J.-T., Sheng, W.-H., Hsueh, P., Yang, C.-F., et al. (2004) · Clinical Infectious Diseases · doi:10.1086/423808 · Cited by 80 · see citing works
Commentary: Could iron chelators prove to be useful as an adjunct to COVID-19 Treatment Regimens?
Dalamaga, Μ., Karampela, Ι., & Mantzoros, C. S. (2020) · Metabolism · doi:10.1016/j.metabol.2020.154260 · Cited by 79 · see citing works
Rawahi, A. A., Alhinai, F., Doig, C. J., Ball, C. G., Dixon, E., Xiao, Z. J., & Kirkpatrick, A. W. (2019) · Critical Care · doi:10.1186/s13054-019-2669-1 · Cited by 70 · see citing works
Iron Metabolism: An Emerging Therapeutic Target in Critical Illness
Litton, E., & Lim, J. (2019) · Critical Care · doi:10.1186/s13054-019-2373-1 · Cited by 66 · see citing works
Human macrophage ferroportin biology and the basis for the ferroportin disease
Sabelli, M., Montosi, G., Garuti, C., Caleffi, A., Oliveto, S., Biffo, S., & Pietrangelo, A. (2016) · Hepatology · doi:10.1002/hep.29007 · Cited by 58 · see citing works
Stites, S. W., Nelson, M. E., & Wesselius, L. J. (1995) · Chest · doi:10.1378/chest.107.6.1681 · Cited by 42 · see citing works
Influence of mild infections on iron status parameters in women of reproductive age
Eskeland, B., Baerheim, A., Ulvik, R., & Hunskaar, S. (2002) · Scandinavian Journal of Primary Health Care · doi:10.1080/028134302317282752 · Cited by 34
Pathogens, Metabolic Adaptation, and Human Diseases—An Iron-Thrifty Genetic Model
Pietrangelo, A. (2015) · Gastroenterology · doi:10.1053/j.gastro.2015.08.003 · Cited by 18 · see citing works
Flagged first, then by citations
4 of the 40 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Ferritin in the coronavirus disease 2019 (COVID‐19): A systematic review and meta‐analysis
Cheng, L., Li, H., Li, L., Liu, C., Yan, S., Chen, H., & Li, Y. (2020) · Journal of Clinical Laboratory Analysis · doi:10.1002/jcla.23618 · Cited by 390 · see citing works
Emerging Telemedicine Tools for Remote COVID-19 Diagnosis, Monitoring, and Management
Lukas, H., Xu, C., Yu, Y., & Gao, W. F. (2020) · ACS Nano · doi:10.1021/acsnano.0c08494 · Cited by 267 · see citing works
Galmés, S., Serra, F. A., & Palou, A. (2020) · Nutrients · doi:10.3390/nu12092738 · Cited by 179 · see citing works
The Role of Nutrition in COVID-19 Susceptibility and Severity of Disease: A Systematic Review
James, P. T., Ali, Z., Armitage, A. E., Bonell, A., Cerami, C., Drakesmith, H., Jobe, M., Jones, K. S., Liew, Z., Moore, S. E., et al. (2021) · The Journal of Nutrition · doi:10.1093/jn/nxab059 · Cited by 147 · see citing works
Could nutrition modulate COVID-19 susceptibility and severity of disease? A systematic review
James, P. T., Ali, Z., Armitage, A. E., Bonell, A., Cerami, C., Drakesmith, H., Jobe, M., Jones, K. S., Liew, Z., Moore, S. E., et al. (2020) · doi:10.1101/2020.10.19.20214395 · Cited by 147 · see citing works
Coronavirus Disease 2019 as Cause of Viral Sepsis: A Systematic Review and Meta-Analysis*
Karakike, E., Giamarellos‐Bourboulis, E. J., Kyprianou, M., Fleischmann-Struzek, C., Pletz, M. W., Netea, M. G., Reinhart, K., & Kyriazopoulou, E. (2021) · Critical Care Medicine · doi:10.1097/ccm.0000000000005195 · Cited by 182 · see citing works
“Only five studies reported the exact number of patients meeting Sepsis-3 criteria (106, 118, 129, 133, 144), and for another eight studies, this was later provided by the authors (23, 24, 26, 35, 38, 71, 72, 101).”
BackgroundQin, R., He, L., Yang, Z., Jia, N., Chen, R., Xie, J., Fu, W., Chen, H., Lin, X., Huang, R., et al. (2022) · Clinical Reviews in Allergy & Immunology · doi:10.1007/s12016-021-08908-8 · Cited by 93 · see citing works
Serum Zinc, Copper, and Other Biometals Are Associated with COVID-19 Severity Markers
Skalny, A., Timashev, P., Aschner, M., Aaseth, J., Chernova, L., Belyaev, V. E., Grabeklis, A., Notova, S., Lobinski, R., Tsatsakis, A., et al. (2021) · Metabolites · doi:10.3390/metabo11040244 · Cited by 76
Zeng, H., Yang, Q., Yuan, P., Wang, X., & Cheng, L. (2021) · The FASEB Journal · doi:10.1096/fj.202002346rr · Cited by 86 · see citing works
Lactoferrin as Antiviral Treatment in COVID-19 Management: Preliminary Evidence
Campione, E., Lanna, C., Cosio, T., Rosa, L., Conte, M., Iacovelli, F., Romeo, A., Falconi, M., Vecchio, C. D., Franchin, E., et al. (2021) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph182010985 · Cited by 66 · see citing works
“This has been reported to be relevant in COVID-19 for assessing disease severity and patient outcome [69,70].”
BackgroundIron and iron-related proteins in COVID-19
Suriawinata, E., & Mehta, K. J. (2022) · Clinical and Experimental Medicine · doi:10.1007/s10238-022-00851-y · Cited by 69 · see citing works
“While the levels on days 15–18 were within the normal range, alterations on previous days spanned the lower end of the spectrum of the normal range [57].”
BackgroundInfluentialAssociation between iron status and the risk of adverse outcomes in COVID-19
Lv, Y.-L., Chen, L.-K., Liang, X.-L., Liu, X.-H., Gao, M., Wang, Q., Wei, Q., & Liu, L.-G. (2020) · Clinical Nutrition · doi:10.1016/j.clnu.2020.11.033 · Cited by 52 · see citing works
“A longitudinal observation study of ICU patients showed that serum iron increased to a normal range during their hospitalization [40].”
Moisă, E., Corneci, D., Negoita, S., Filimon, C. R., Serbu, A., Negutu, M., & Grințescu, I. (2021) · Biomedicines · doi:10.3390/biomedicines9111656 · Cited by 48 · see citing works
“documented that lymphopenia reaches a nadir in day 2 of ICU stay, but the CD4/CD8 ratio is conserved [20].”
BackgroundAnalysis of Iron and Iron-Interacting Protein Dynamics During T-Cell Activation
Teh, M. R., Frost, J. N., Armitage, A. E., & Drakesmith, H. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.714613 · Cited by 52 · see citing works
Osman, E. E. A., Rehemtulla, A., & Neamati, N. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c00518 · Cited by 51 · see citing works
Sánchez-Zuno, G. A., González-Estévez, G., Matuz-Flores, M. G., Macedo-Ojeda, G., Hernández-Bello, J., Mora-Mora, J., Perez-Guerrero, E. E., García-Chagollán, M., Vega-Magaña, N., Turrubiates-Hernández, F. J., et al. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10112378 · Cited by 43 · see citing works
“These biomarkers are directly correlated with the coagulation, metabolism, hepatic, and renal function alterations in COVID-19 [7].”
BackgroundA Review on the Serum Electrolytes and Trace Elements Role in the Pathophysiology of COVID-19
Taheri, M., Bahrami, A., Habibi, P., & Nouri, F. (2020) · Biological Trace Element Research · doi:10.1007/s12011-020-02377-4 · Cited by 47 · see citing works
“On the other hand, it has been reported that COVID-19 patients with acute respiratory distress syndrome have low serum levels of Iron and intubation them [37].”
BackgroundCOVID-19-Related Coagulopathy—Is Transferrin a Missing Link?
McLaughlin, K.-M., Bechtel, M., Bojkova, D., Münch, C., Ciesek, S., Wass, M., Michaelis, M., & Cinatl, J. (2020) · bioRxiv · doi:10.3390/diagnostics10080539 · Cited by 33 · see citing works
“Moreover, a rise of transferrin levels was observed in patients during COVID-19 disease progression [18].”
Gastrointestinal symptoms, pathophysiology, and treatment in COVID-19
Zhang, J., Garrett, S., & Sun, J. (2020) · Genes and Diseases · doi:10.1016/j.gendis.2020.08.013 · Cited by 32 · see citing works
“In COVID-19 patients, the metabolic alterations were also detectable in the recycle system.(90,91) By performing proteomic and metabolomic profiling of sera from COVID-19 (n Z 46) and control individuals (n Z 53), Shen et al revealed characteristic protein and metabolite changes in the sera of severe COVID-19 patients…”
Iron Chelator or Iron Supplement Consumption in COVID-19? The Role of Iron with Severity Infection
Bastin, A., Shiri, H., Zanganeh, S., Fooladi, S., Momeni‐Moghaddam, M. A., Mehrabani, M., & Nematollahi, M. H. (2021) · Biological Trace Element Research · doi:10.1007/s12011-021-03048-8 · Cited by 33 · see citing works
Iron and iron-related proteins in alcohol consumers: cellular and clinical aspects
Ferrao, K., Ali, N., & Mehta, K. J. (2022) · Journal of Molecular Medicine · doi:10.1007/s00109-022-02254-8 · Cited by 37 · see citing works
“Iron levels return to normal within 7–10 days [56].”
BackgroundAnalysis of COVID-19 prevention and treatment in Taiwan
Chiu, Y.-J., Chiang, J.-H., Fu, C.-W., Hour, M., Ha, H.-A., Kuo, S., Lin, J.-J., Cheng, C.-C., Tsai, S., Lo, Y.-S., et al. (2021) · BioMedicine · doi:10.37796/2211-8039.1185 · Cited by 29
Tojo, K., Sugawara, Y., Oi, Y., Ogawa, F., Higurashi, T., Yoshimura, Y., Miyata, N., Hayami, H., Yamaguchi, Y., Ishikawa, Y., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-92921-6 · Cited by 28 · see citing works
Tojo, K., Sugawara, Y., Oi, Y., Ogawa, F., Higurashi, T., Yoshimura, Y., Miyata, N., Hayami, H., Yamaguchi, Y., Ishikawa, Y., et al. (2021) · doi:10.1101/2021.02.19.21252061 · Cited by 28 · see citing works
Association of iron-related biomarkers with severity and mortality in COVID-19 patients
Yadav, D., Kumar, P. K., Tomo, S., Sankanagoudar, S., Charan, J., Purohit, A. H. L., Nag, V., Bhatia, P. K., Singh, K., Dutt, N., et al. (2022) · Journal of Trace Elements in Medicine and Biology · doi:10.1016/j.jtemb.2022.127075 · Cited by 28 · see citing works
“Many recent studies had reported similar reports, with a significant decrease of iron levels in severe patients [19,20,32,33].”
The Relationship Between Hepcidin-Mediated Iron Dysmetabolism and COVID-19 Severity: A Meta-Analysis
Peng, D., Gao, Y., Zhang, L., Liu, Z., Wang, H., & Liu, Y. (2022) · Frontiers in Public Health · doi:10.3389/fpubh.2022.881412 · Cited by 26 · see citing works
Iron as an emerging therapeutic target in critically ill patients
Grangé, C., Lux, F., Brichart, T., David, L., Couturier, A., Leaf, D., Allaouchiche, B., & Tillement, O. (2023) · Critical Care · doi:10.1186/s13054-023-04759-1 · Cited by 22 · see citing works
Nassar, Y. H., Mokhtar, A., Elhadidy, A., Elsayed, M., Mostafa, F., Rady, A., El-adawy, A., Elshazly, M., Saeed, M., Mokhtar, S., et al. (2021) · Journal of Infection and Public Health · doi:10.1016/j.jiph.2021.06.012 · Cited by 21
Kontoghiorghes, G. J. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23126735 · Cited by 16 · see citing works
Adaptive immunity and vaccination – iron in the spotlight
Preston, A. E., Drakesmith, H., & Frost, J. N. (2021) · Immunotherapy Advances · doi:10.1093/immadv/ltab007 · Cited by 20 · see citing works
COVID-19, ferrosenescence and neurodegeneration, a mini-review
Sfera, A., Osorio, C. P., Maguire, G. A., Rahman, L., Jafri, A., Cummings, M. A., & Maldonado, J. C. (2020) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2020.110230 · Cited by 21 · see citing works
COVID-19 and iron deficiency anemia: relationships of pathogenesis and therapy
Gromova, O., Torshin, I., Shapovalova, Y. O., Kurtser, M., & Chuchalin, A. G. (2020) · Obstetrics Gynecology and Reproduction · doi:10.17749/2313-7347/ob.gyn.rep.2020.179 · Cited by 14
“Например, анализ пациентов с инфекцией COVID-19, поступивших в отделение интенсивной терапии (ОИТ), показал, что у них снижено насыщение трансферрина в среднем на 9 % [27].”
Campione, E., Lanna, C., Cosio, T., Rosa, L., Conte, M., Iacovelli, F., Romeo, A., Falconi, M., Vecchio, C. D., Franchin, E., et al. (2020) · bioRxiv · doi:10.1101/2020.08.11.244996 · Cited by 12 · see citing works
“In COVID-19, it has been reported to be relevant for assessing disease severity and patients outcome(Bolondi et al., 2020; Kappert et al., 2020).”
BackgroundHarahap, I., Kuligowski, M., Schmidt, M., & Suliburska, J. (2023) · Journal of Trace Elements in Medicine and Biology · doi:10.1016/j.jtemb.2023.127183 · Cited by 12 · see citing works
Cardiac complications in patients with COVID-19: a systematic review
Brogi, E., Marino, F. V., Bertini, P., Tavazzi, G., Corradi, F., & Forfori, F. (2022) · Journal of Anesthesia Analgesia and Critical Care · doi:10.1186/s44158-022-00046-7 · Cited by 16 · see citing works
Self-citationSokolov, A., Isakova-Sivak, I., Mezhenskaya, D. A., Kostevich, V., Gorbunov, N., Elizarova, A., Matyushenko, V., Berson, Y., Grudinina, N., Kolmakov, N. N., et al. (2022) · Biometals · doi:10.1007/s10534-022-00458-6 · Cited by 11 · see citing works
“Increased serum iron, ferritin and Tf saturation in intensive care unit patients during the 3rd–6th day of COVID-19 were documented (Bolondi et al 2020).”
MethodMuhammad, J. S., ElGhazali, G. E., Shafarin, J., Mohammad, M. G., Abu-Qiyas, A., & Hamad, M. A. (2022) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2022.09.083 · Cited by 11 · see citing works
Toledano, J. M., Puche-Juárez, M., Moreno‐Fernández, J., Ochoa, J. J., & Díaz‐Castro, J. (2023) · Antioxidants · doi:10.3390/antiox12051104 · Cited by 13 · see citing works
“Anemia and hyperferritinemia have been reported as typical manifestations in hospitalized patients [53].”
BackgroundPérez-García, N., García‐González, J., Requena, M., Rodríguez-Maresca, M. Á., & Alarcón, R. (2022) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph19095354 · Cited by 9 · see citing works
“The results indicated a higher risk index for patients admitted to the ICU with a higher SOFA (Sequential Organ Failure Assessment) score and increased values of C-reactive protein [26].”
BackgroundInfluentialRolla, R., Vidali, M., Puricelli, C., Scotta, A., Pedrinelli, A., Pergolini, P., Pirisi, M., Dianzani, U., & Rigamonti, C. (2020) · International Journal of Laboratory Hematology · doi:10.1111/ijlh.13331 · Cited by 9 · see citing works
Biochemical Analysis of Ferritin and D-dimer in COVID-19 Survivors and Non-survivors
Hakami, A., Altubayqi, T., Qadah, E., Zogel, B., Alfaifi, S., Refaei, E., Sayed, A., Alhazmi, L., Sayegh, M. A., Alamer, A., et al. (2023) · Cureus · doi:10.7759/cureus.45389 · Cited by 7
“As a result, it might be beneficial in distinguishing individuals who may need hospital admission, but it is ineffective for patients who have already been admitted to the ICU [28-29].”
BackgroundIron Metabolism in the Recovery Phase of Critical Illness with a Focus on Sepsis
Zhang, X., Holbein, B. E., Zhou, J., & Lehmann, C. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25137004 · Cited by 5 · see citing works
“Then, in the later stage, generally within 7–18 days of staying in the hospital, their levels returned to normal [56].”
BackgroundLeal, K. N. D. S., Silva, A. B., Fonseca, E. K. B., Moreira, O. B. D. O., de Lemos, L. M., de Oliveira, M. A. L., Stewart, A. J., & Arruda, M. A. Z. (2024) · Journal of Trace Elements in Medicine and Biology · doi:10.1016/j.jtemb.2024.127557 · Cited by 5 · see citing works
Micronutrient Status of Critically Ill Patients with COVID-19 Pneumonia
Rozemeijer, S., Hamer, H. M., Heijboer, A. C., de Jonge, R., Jiménez, C. R., Juffermans, N. P., Dujardin, R. W. G., Girbes, A. R. J., & de Man, A. (2024) · Nutrients · doi:10.3390/nu16030385 · Cited by 5 · see citing works
Li, X., Zhang, Y., Ma, W., & Li, J.-W. (2022) · BioMed Research International · doi:10.1155/2022/6141317 · Cited by 5
“…factors, especially infections [46, 47] and drugs [48], and in a recent study, COVID-19 infection was also found to result in severe lymphopenia [49], therefore, cautions should be taken to interpret the changes of NLR in HCC patients, and additional data, particularly in fl ammation-related…”
Evaluation of perturbed iron-homeostasis in a prospective cohort of patients with COVID-19
Frost, J. N., Hamilton, F., Arnold, D., Elvers, K. T., Shah, A., Armitage, A. E., Milne, A., McKernon, J., Attwood, M., Chen, Y., et al. (2022) · Wellcome Open Research · doi:10.12688/wellcomeopenres.17904.1 · Cited by 5 · see citing works
“Further work is required to understand how the iron levels dynamically shift during SARS-CoV-2 infection in relation to therapy and in the context of disease progression (Bolondi et al., 2020; Chakurkar et al., 2021; Hippchen et al., 2020).”
BackgroundCOVID-19: A pluralistic and integrated approach for efficient management of the pandemic
Bouare, N., Minta, D. K., Dabo, A., & Gérard, C. (2022) · World Journal of Virology · doi:10.5501/wjv.v11.i1.20 · Cited by 3 · see citing works
Early predictors of intensive care unit admission among COVID-19 patients in Qatar
Abuyousef, S., Alnaimi, S. J., Omar, N. E., Elajez, R., Elmekaty, E., Abdelfattah-Arafa, E., Barazi, R., Ghasoub, R. S., Rahhal, A., Hamou, F., et al. (2024) · Frontiers in Public Health · doi:10.3389/fpubh.2024.1278046 · Cited by 6 · see citing works
Role of Metals on SARS-CoV-2 Infection: a Review of Recent Epidemiological Studies
Khan, K. M., Zimpfer, M. J., Sultana, R., Parvez, T. M., Navas-Acien, A., & Parvez, F. (2023) · Current Environmental Health Reports · doi:10.1007/s40572-023-00409-4 · Cited by 4
Double chelation of Iron through dimer formation of favipiravir: Density functional theory analysis
Ansari, M. J., Jasim, S., Abed, A., Altimari, U. S., Yasin, G., Suksatan, W., Oudaha, K. H., Kadhim, M. M., Jabbar, A. H., & Mustafa, Y. F. (2022) · Main group chemistry (Print) · doi:10.3233/mgc-210182 · Cited by 4 · see citing works
“Concentration of iron (Fe) has been seen as another challenging issue about the health system of the infected patients by coronavirus [13–15].”
Xiao, W.-Y., Zhang, L.-L., Zhang, Y., Hu, J.-J., Zhang, J., Hua, T.-F., & Yang, M. (2025) · PLoS Neglected Tropical Diseases · doi:10.1371/journal.pntd.0013104 · Cited by 3 · see citing works
“Serum ferritin levels may reflect a balance between beneficial immune responses and a harmful inflammatory overreac-tion in patients with COVID-19 [14–15], Papamanoli et al. [16] posited that serum ferritin levels up to 1,300 ng/mL potentially indicating a healthy immune response to acute…”
Kokkoris, S., Kanavou, A., Kremmydas, P., Katsaros, D., Karageorgiou, S., Gkoufa, A., Georgakopoulou, V., Spandidos, D. A., Giannopoulos, C., Kardamitsi, M., et al. (2023) · Medicine International · doi:10.3892/mi.2023.112 · Cited by 3 · see citing works
“…only in the less severe cases. additional data have also revealed marked lymphopenia over time, which is more severe in non‑survivors (17,18,26,27), suggesting that this variable may be used as a laboratory marker to distinguish patients with COVID‑19 who are at a high risk of mortality at…”
Bagheri‐Hosseinabadi, Z., Pirsadeghi, A., Ostadebrahimi, H., Sharifi, G. T. K., & Abbasifard, M. (2023) · Journal of Trace Elements in Medicine and Biology · doi:10.1016/j.jtemb.2023.127285 · Cited by 5 · see citing works
COVID-19 as cause of viral sepsis: A Systematic Review and Meta-Analysis
Karakike, E., Giamarellos-Bourboulis, E., Kyprianou, M., Fleischmann-Struzek, C., Pletz, M. W., Netea, M., Reinhart, K., & Kyriazopoulou, E. (2020) · medRxiv · doi:10.1101/2020.12.02.20242354 · Cited by 3
Zeng, H., Yang, Q. H., Yuan, P., Wang, X., & Cheng, L. (2020) · Research Square · doi:10.21203/rs.3.rs-54691/v1 · Cited by 3 · see citing works
Chen, X., Ma, B., Yang, Y., Zhang, M., & Xu, F. (2024) · BMC Pulmonary Medicine · doi:10.1186/s12890-024-03073-y · Cited by 1 · see citing works
“However, in another group of COVID-19 infected patients, the CD4 + /CD8 + T cell ratio may also be elevated due to a more pronounced reduction in CD8 + T cells than in CD3 + , CD4 + and CD8 + T lymphocytes [34].”
BackgroundАнатольевна, Ш. И., Voznyuk, I. A., Lodyagin, A. N., Васильевич, Б. Б., Timofeyeva, N. V., Pivovarova, L. P., Osipova, I. V., Polyakov, I., Ariskina, O. B., Borisenko, A. N., et al. (2021) · Russian Sklifosovsky Journal Emergency Medical Care · doi:10.23934/2223-9022-2021-10-2-259-267 · Cited by 2 · see citing works
Joshua, D., Shane, G., Gina, H., & Connor, T. (2020) · Scholarly Journal of Emergency Medicine and Critical Care · doi:10.36959/592/391 · Cited by 1 · see citing works
Iron Status in Patients with SARS-CoV-2 Infection
Cylwik, B., Gruszewska, E., Lozowicka, M., Panasiuk, A., & Chrostek, L. (2026) · Current Issues in Molecular Biology · doi:10.3390/cimb48101062
“While some authors reported elevated sTfR levels in patients admitted to the intensive care unit (ICU) compared to healthy controls, contrary to our findings, others found no significant changes in sTfR levels during a 15–18 day ICU stay [50,51].”
Hodo, E. J., Shaikh, A. P., Shaikh, N. P., Chauhan, N., Nishanthan, A. F., & Nakashidze, I. (2026) · Pharmedicine Journal · doi:10.62482/pmj.42
El-Meshad, M. S., Alwakeel, A., El-Farahaty, R. M., Nada, H. S., & Zeid, M. (2024) · Egyptian Pediatric Association Gazette · doi:10.1186/s43054-024-00330-x
Abdalla, A. E., Doha, S. A., Nashaat, S. M., El-Din, A.-H. S. A., Mohammed, S., & Hebat-Allah, N. H. (2024) · The Egyptian Journal of Haematology · doi:10.4103/ejh.ejh_2_24
Jung, B. K., Park, E. J., Kim, S. G., & Kim, J. K. (2023) · Asia-pacific Journal of Convergent Research Interchange · doi:10.47116/apjcri.2023.05.50
“Hematological parameters and inflammatory indices based on blood cell analysis are useful prognostic indicators in patients with infections and many other diseases[7][8].”
BackgroundMETİN, S., Eraybar, S., Aygün, H., & Demir, C. (2022) · Medical Science and Discovery · doi:10.36472/msd.v9i9.817
“For these processes to take place, microorganisms compete with the body's cells for iron binding (26).”
BackgroundThe role of iron and ferritin in pathophysiology and as a laboratory marker in COVID-19
Sampaio, S. C., Sacramento, G. S., & de Almeida, J. B. (2022) · REVISTA CIÊNCIAS EM SAÚDE · doi:10.21876/rcshci.v12i3.1275
Die Rolle des Eisens bei Infektionen
Nielsen, P. (2020) · MMW, Fortschritte der Medizin · doi:10.1007/s15006-020-4320-0
Li, X., Wang, S., Yu, L., Wang, X., Yan, Z., Zheng, Y., Li, Y., Liu, X., Jia, R., & Cui, L. (2020) · Research Square · doi:10.21203/rs.3.rs-60917/v1
“Typhi competes with humans for iron utilization by increasing the expression of hepcidin, which can restrict iron uptake and macrophage iron release, and the high serum hepcidin leads to hypoferremia[8]; COVID-19 infection resulted in hyperferritinemia due to cytokine storms, and serum iron transferrin saturation in i…”
Background
- Authors
- Bolondi, G., Russo, E., Gamberini, E., Circelli, A., Meca, M. C. C., Brogi, E., Viola, L., Bissoni, L., Poletti, V., & Agnoletti, V.
- Affiliations
- Ospedale “M. Bufalini” di Cesena (IT)
- Aarhus University Hospital (DK)
- Corresponding author
- Bolondi, Giuliano
- ORCID
- Venue
- World Journal of Emergency Surgery
- Published
- 2020-06-30
- Volume
- 15
- Issue
- 1
- Pages
- 41-41
- ISSN
- 1749-7922 (ISSN-L)
- PMC
- PMC7324776
- OpenAlex
- W3034768431
- Cited by
- 82
- References
- 40
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 16 · 2023: 10 · 2022: 19 · 2021: 19 · 2020: 15
- FWCI
- 2.10
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- World Journal of Emergency Surgery (publishedVersion, cc-by)
- Research Square (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Informationszentrum Lebenswissenschaften (ZB MED) (submittedVersion, cc-by)
- Funders
- University of Oxford
- Topics
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Keywords
- COVID-19 pandemic, SARS-CoV-2, iron metabolism, transferrin saturation, serum iron, ferritin, hyperferritinemia, lymphocyte subsets, CD4/CD8 ratio, natural killer cells, D-dimer, critically ill patients, intensive care, hemophagocytic lymphohistiocytosis, mortality
- MeSH terms
- Betacoronavirus, Correlation of Data, COVID-19, SARS-CoV-2, Aged, Blood Coagulation, Critical Care, Female, Humans, Intensive Care Units, Iron, Italy, Lymphocytes, Male, Middle Aged, Mortality, Pneumonia, Viral, Severity of Illness Index, Transferrin, Lymphocyte Subsets, Coronavirus Infections, Lymphocyte Count, Pandemics
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