The Long and the Short of It: Is “Long COVID” More Than Slow Resolution of the Acute Disease?

Abstract

1 Simpson RJ, McKie AT. Iron and oxygen sensing: a tale of 2 interacting elements? Metallomics 2015;7:223–231. 2 Yu Y, Kovacevic Z, Richardson DR. Tuning cell cycle regulation with an iron key. Cell Cycle 2007;6:1982–1994. 3 Rhodes CJ, Howard LS, Busbridge M, Ashby D, Kondili E, Gibbs JS, et al. Iron deficiency and raised hepcidin in idiopathic pulmonary arterial hypertension: clinical prevalence, outcomes, and mechanistic insights. J Am Coll Cardiol 2011;58:300–309. 4 Lakhal-Littleton S, Crosby A, Frise MC, Mohammad G, Carr CA, Loick PAM, et al. Intracellular iron deficiency in pulmonary arterial smooth muscle cells induces pulmonary arterial hypertension in mice. Proc Natl Acad Sci USA 2019;116:13122–13130. 5 Lee JW, Ko J, Ju C, Eltzschig HK. Hypoxia signaling in human diseases and therapeutic targets. Exp Mol Med 2019;51:1–13. 6 Cotroneo E, Ashek A, Wang L, Wharton J, Dubois O, Bozorgi S, et al. Iron homeostasis and pulmonary hypertension: iron deficiency leads to pulmonary vascular remodeling in the rat. Circ Res 2015;116:1680–1690. 7 Anker SD, Comin Colet J, Filippatos G, Willenheimer R, Dickstein K, Drexler H, et al.; FAIR-HF Trial Investigators. Ferric carboxymaltose in patients with heart failure and iron deficiency. N Engl J Med 2009;361:2436–2448. 8 Ruiter G, Lankhorst S, Boonstra A, Postmus PE, Zweegman S, Westerhof N, et al. Iron deficiency is common in idiopathic pulmonary arterial hypertension. Eur Respir J 2011;37:1386–1391. 9 Viethen T, Gerhardt F, Dumitrescu D, Knoop-Busch S, ten Freyhaus H, Rudolph TK, et al. Ferric carboxymaltose improves exercise capacity and quality of life in patients with pulmonary arterial hypertension and iron deficiency: a pilot study. Int J Cardiol 2014;175:233–239. 10 Ruiter G, Manders E, Happ e CM, Schalij I, Groepenhoff H, Howard LS, et al. Intravenous iron therapy in patients with idiopathic pulmonary arterial hypertension and iron deficiency. Pulm Circ 2015;5:466–472. 11 Smith TG, Balanos GM, Croft QP, Talbot NP, Dorrington KL, Ratcliffe PJ, et al. The increase in pulmonary arterial pressure caused by hypoxia depends on iron status. J Physiol 2008;586:5999–6005. 12 Gali e N, Hoeper MM, Humbert M, Torbicki A, Vachiery JL, Barbera JA, et al.; ESC Committee for Practice Guidelines (CPG). Guidelines for the diagnosis and treatment of pulmonary hypertension: the task force for the diagnosis and treatment of pulmonary hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS), endorsed by the International Society of Heart and Lung Transplantation (ISHLT). Eur Heart J 2009;30:2493–2537. 13 Howard LSGE, He J, Watson GMJ, Huang L, Wharton J, Luo Q, et al. Supplementation with iron in pulmonary arterial hypertension: two randomized crossover trials. Ann Am Thorac Soc. 2021;18:981–988. 14 Malope BI, MacPhail AP, Alberts M, Hiss DC. The ratio of serum transferrin receptor and serum ferritin in the diagnosis of iron status. Br J Haematol 2001;115:84–89. 15 Bonnet S, Michelakis ED, Porter CJ, Andrade-Navarro MA, Th ebaud B, Bonnet S, et al. An abnormal mitochondrial-hypoxia inducible factor1alpha-Kv channel pathway disrupts oxygen sensing and triggers pulmonary arterial hypertension in fawn hooded rats: similarities to human pulmonary arterial hypertension. Circulation 2006;113:2630–2641. 16 Smith KA, Waypa GB, Dudley VJ, Budinger GRS, Abdala-Valencia H, Bartom E, et al. Role of hypoxia-inducible factors in regulating right ventricular function and remodeling during chronic hypoxia-induced pulmonary hypertension. Am J Respir Cell Mol Biol 2020;63:652–664. 17 Mole DR. Iron homeostasis and its interaction with prolyl hydroxylases. Antioxid Redox Signal 2010;12:445–458.