Vaccine efficacy and iron deficiency: an intertwined pair?

Vaccines are the most effective measure to prevent deaths and illness from infectious diseases. Nevertheless, the efficacy of several paediatric vaccines is lower in low-income and middle-income countries (LMICs), where mortality from vaccine-preventable infections remains high. Vaccine efficacy can also be decreased in adults in the context of some common comorbidities. Identifying and correcting the specific causes of impaired vaccine efficacy is of substantial value to global health. Iron deficiency is the most common micronutrient deficiency worldwide, affecting more than 2 billion people, and its prevalence in LMICs could increase as food security is threatened by the COVID-19 pandemic. In this Viewpoint, we highlight evidence showing that iron deficiency limits adaptive immunity and responses to vaccines, representing an under-appreciated additional disadvantage to iron deficient populations. We propose a framework for urgent detailed studies of iron-vaccine interactions to investigate and clarify the issue. This framework includes retrospective analysis of newly available datasets derived from trials of COVID-19 and other vaccines, and prospective testing of whether nutritional iron interventions, commonly used worldwide to combat anaemia, improve vaccine performance.

Hypoferremia is Associated With Increased Hospitalization and Oxygen Demand in COVID-19 Patients.

Iron metabolism might play a crucial role in cytokine release syndrome in COVID-19 patients. Therefore, we assessed iron metabolism markers in COVID-19 patients for their ability to predict disease severity. COVID-19 patients referred to the Heidelberg University Hospital were retrospectively analyzed. Patients were divided into outpatients (cohort A, n = 204), inpatients (cohort B, n = 81), and outpatients later admitted to hospital because of health deterioration (cohort C, n = 23). Iron metabolism parameters were severely altered in patients of cohort B and C compared to cohort A. In multivariate regression analysis including age, gender, CRP and iron-related parameters only serum iron and ferritin were significantly associated with hospitalization. ROC analysis revealed an AUC for serum iron of 0.894 and an iron concentration <6 µmol/l as the best cutoff-point predicting hospitalization with a sensitivity of 94.7% and a specificity of 67.9%. When stratifying inpatients in a low- and high oxygen demand group serum iron levels differed significantly between these two groups and showed a high negative correlation with the inflammatory parameters IL-6, procalcitonin, and CRP. Unexpectedly, serum iron levels poorly correlate with hepcidin. We conclude that measurement of serum iron can help predicting the severity of COVID-19. The differences in serum iron availability observed between the low and high oxygen demand group suggest that disturbed iron metabolism likely plays a causal role in the pathophysiology leading to lung injury.