The Impact of Iron Dyshomeostasis and Anaemia on Long-Term Pulmonary Recovery and Persisting Symptom Burden after COVID-19: A Prospective Observational Cohort Study

Abstract

Coronavirus disease 2019 (COVID-19) is frequently associated with iron dyshomeostasis. The latter is related to acute disease severity and COVID-19 convalescence. We herein describe iron dyshomeostasis at COVID-19 follow-up and its association with long-term pulmonary and symptomatic recovery. The prospective, multicentre, observational cohort study “Development of Interstitial Lung Disease (ILD) in Patients With Severe SARS-CoV-2 Infection (CovILD)” encompasses serial extensive clinical, laboratory, functional and imaging evaluations at 60, 100, 180 and 360 days after COVID-19 onset. We included 108 individuals with mild-to-critical acute COVID-19, whereas 75% presented with severe acute disease. At 60 days post-COVID-19 follow-up, hyperferritinaemia (35% of patients), iron deficiency (24% of the cohort) and anaemia (9% of the patients) were frequently found. Anaemia of inflammation (AI) was the predominant feature at early post-acute follow-up, whereas the anaemia phenotype shifted towards iron deficiency anaemia (IDA) and combinations of IDA and AI until the 360 days follow-up. The prevalence of anaemia significantly decreased over time, but iron dyshomeostasis remained a frequent finding throughout the study. Neither iron dyshomeostasis nor anaemia were related to persisting structural lung impairment, but both were associated with impaired stress resilience at long-term COVID-19 follow-up. To conclude, iron dyshomeostasis and anaemia are frequent findings after COVID-19 and may contribute to its long-term symptomatic outcome.

Iron Deficiency Anemia and COVID-19

“…These centers are highrisk places due to the referral of COVID-19 patients for diagnosis [58] and make anemic patients to a high rate of exposure to the virus and prone them to COVID-19 complications due to impaired immune function. In anemic patients, there is a lack of hemoglobin, a decrease in oxygen supply to vital organs, lymphopenia, and a malfunction of the immune system; all of these have a poor prognosis for COVID-19 [56]. Therefore, appropriate planning should be adopted to diagnose and follow up the treatment of patients with iron deficiency so that they become less exposed to the virus while receiving and following their treatments.…”

“…Along with the exacerbation of inflammatory diseases through IDA, COVID-19 can worsen anemia by affecting iron metabolism [51]. Changes in iron homeostasis and anemia are frequent findings in acute COVID-19 and post-acute COVID-19 follow-ups [56]. There are two hypotheses for the aggravation of anemia by the SARS-CoV-2 virus.…”

Long-COVID is Associated with Impaired Red Blood Cell Function

“…The pathophysiological mechanisms of Long-COVID are still under discussion and include the effects of viral persistence, inflammation, excessive blood clotting, and autoimmunity [9]. It was suggested that the hematological system is altered in Long-COVID as lower hemoglobin levels, increased D-dimers, anemia, thrombocytopenia, and lymphopenia have been reported in Long-COVID patients [10][11][12]. In addition, changes in RBCs size and morphology have been demonstrated in Long-COVID, which may contribute to impaired oxygen diffusion [13].…”

Iron deficiency and postcovid syndrome: a clinical case

“…Согласно накопленным данным, COVID-19 часто связан с дисгомеостазом железа [12]. Последнее, в свою очередь, ассоциировано с тяжестью острого заболевания и выздоровлением от COVID-19 [13]. Железо необходимо для нормальной клеточной и физиологической функции.…”

“…Позже (опубликовано в июне 2022 г.) этой же группой ученых были представлены данные (n=108) более длительного наблюдения (60, 100, 180 и 360 дней после начала заболевания), которые показали, что анемия воспаления была преобладающей чертой в раннем периоде после острого периода наблюдения, тогда как фенотип анемии сместился в сторону железодефицитной анемии (ЖДА) и комбинации ЖДА и дефицита железа до 360 дней наблюдения [13]. При этом распространенность анемии со временем снизилась, но дисгомеостаз железа оставался частым явлением на протяжении всего исследования [13].…”