Iron metabolism and lymphocyte subpopulations during Covid-19 infection in ICU patients: an observational cohort study and a narrative review of clinical practice.

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. Little is known about clinical management of severe forms of Covid-19. Methods: we performed an observational study during the peak of pandemic in our intensive care unit, serially 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. Trend over time were tested with Kruskall-Wallis analysis. Results: All patients show hyperferritinemia, and its dosage might be helpful in individuating patients developing hemophagocytic lymphohistiocytosis (we observed 1 case). 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. D-dimer is constantly 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 and provide a narrative review of our clinical experience about critical Covid-19 patients. D-dimer is constantly elevated in our ICU population and increases from admission to a maximum on day 3 to 6 of ICU stay (median 6820 µg/L; IQR 6619 µg/L) Conclusions: iron metabolism and lymphopenia are key clinical features of Covid-19 patients in the ICU setting and have been specifically described in this paper. Keywords – MeSH repository (3-10): Iron, COVID-19, SARS-CoV-2, Coronavirus, Critical Care, Lymphocytes, Lymphopenia, Ferritins, Immunity, Coagulation.