Lack of Evidence on Association between Iron Deficiency and COVID-19 Vaccine-Induced Neutralizing Humoral Immunity

Abstract

Iron is a crucial micronutrient for immunity induction in response to infections and vaccinations. This study aimed to investigate the effect of iron deficiency on COVID-19-vaccine-induced humoral immunity. We investigated the effectiveness of COVID-19 vaccines (BNT162b2, mRNA-1273, and ChAdOx nCov-2019) in iron-deficient individuals (n = 63) and provide a side-by-side comparison to healthy controls (n = 67). The presence of anti-SARS-CoV-2 spike (S) and anti-nucleocapsid (NP) IgG were assessed using in-house S- and NP-based ELISA followed by serum neutralization test (SNT). High concordance between S-based ELISA and SNT results was observed. The prevalence of neutralizing antibodies was 95.24% (60/63) in the study group and 95.52% (64/67) in the controls with no significant difference. The presence/absence of past infection, period since vaccination, vaccine type, and being iron-deficient or having iron-deficiency anemia did not exert any significant effect on the prevalence or titer of anti-SARS-CoV-2 neutralizing antibodies. NP-based ELISA identified individuals unaware of exposure to SARS-CoV-2. Moreover, absence of anti-NP IgG was noted in participants who were previously diagnosed with COVID-19 suggesting the unpredictability of after-infection immunity. To sum up, this study demonstrated an initial lack of evidence on the association between iron deficiency and the effectiveness of COVID-19-vaccine-induced neutralizing humoral immunity. Similar studies with larger sample size remain necessary to obtain comprehensive conclusions about the effect or lack of effect of iron on COVID-19-vaccine effectiveness.

Unveiling the micronutrient‐immunity puzzle in inactivated COVID‐19 vaccination: A comprehensive analysis of circulating micronutrient levels and humoral responses in healthy adults

“…[14][15][16][17][18][19][20][21][22][23][24][25] Three studies have reported no association between serum iron or selenium status, as well as concentrations of total zinc, and antibody concentrations or titers in response to COVID-19 vaccinations. [14][15][16] Nine studies have reported the associations between serum vitamin D concentrations or status (sufficient, deficient, or insufficient) and humoral responses following COVID-19 vaccinations, yet inconsistent conclusions have been reached. [17][18][19][20][21][22][23][24][25] Investigations into the influence of micronutrients on antibody binding affinity and neutralizing capacity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), crucial parameters for immune protection, are virtually non-existent.…”

“…Only a limited number of studies with sample sizes ranging from 97 to 73 254 participants have investigated the associations between circulating concentrations of micronutrients, particularly those involved in immune regulation, and humoral immune responses as well as protection following inoculation with COVID-19 vaccines. [14][15][16][17][18][19][20][21][22][23][24][25] Three studies have reported no association between serum iron or selenium status, as well as concentrations of total zinc, and antibody concentrations or titers in response to COVID-19 vaccinations. [14][15][16] Nine studies have reported the associations between serum vitamin D concentrations or status (sufficient, deficient, or insufficient) and humoral responses following COVID-19 vaccinations, yet inconsistent conclusions have been reached.…”

“…Despite enormous scientific interest in exploring various aspects related to COVID‐19 vaccination, the potential association between micronutrients and humoral responses following COVID‐19 vaccination remains understudied. Only a limited number of studies with sample sizes ranging from 97 to 73 254 participants have investigated the associations between circulating concentrations of micronutrients, particularly those involved in immune regulation, and humoral immune responses as well as protection following inoculation with COVID‐19 vaccines 14‐25 . Three studies have reported no association between serum iron or selenium status, as well as concentrations of total zinc, and antibody concentrations or titers in response to COVID‐19 vaccinations 14‐16 .…”