The study investigates the effect of iron status on sepsis and the risk of severe COVID-19

In a recent article posted on medRxiv* Preprint server, researchers have shown an association between high iron status and hospitalization associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and sepsis.

study: Iron status and risk of sepsis and severe COVID-19: Mendel randomized study of 2 samples.. Image Credit: angellodeco / Shutterstock

Background

Iron is essential for various physiological functions such as metabolism, immune function, and erythropoiesis. Therefore, defects in iron status, such as iron overload and iron deficiency, can have serious health consequences. In addition, there are significant gender differences in iron status, and women are at risk of iron deficiency.

Many recent studies suggest that cellular and systemic iron regulatory pathways play an important role in protecting the host from infection. Moreover, existing reports show that iron is essential for the pathogenicity of most pathogens. Interestingly, multiple observational studies have shown an association between iron status and the likelihood of sepsis and severe SARS-CoV-2 infection. Nevertheless, inverse causality and residual confounding can distort these results.

Mendelian randomization (MR) studies can avoid these restrictions by adopting genetic variation that correlates with exposure as an instrumental parameter. However, there are no studies evaluating the function of the iron profile on the potential for SARS-CoV-2 infection in the MR paradigm, and few experiments use gender-based MR assessment to assess gender differences.

About research

The purpose of this study is to use data from a major genome-wide association study (GWAS) to be hospitalized for genetically predicted biological markers of iron status and SARS-CoV-2 infection or sepsis. It was to determine if there was a connection with. The team also used gender-based summary-level information on iron status and SARS-CoV-2 outcomes for genetically predicted iron status and CoV disease 2019 (COVID-19) -related hospitalizations. We evaluated gender differences in relation to possibility. They evaluated the results of two different COVID-19: inpatient SARS-CoV-2 patients compared to non-hospitalized patients and inpatient SARS-CoV-2 patients compared to controls from the population.

The authors conducted a two-sample MR study and used reverse dispersion weighting (IVW) techniques to genetically predicted iron biological markers (transferrin saturation (TSAT), serum iron, ferritin, and total iron binding capacity). The effect of iron binding capacity (TIBC) was quantified. ) About sepsis and the possibility of hospitalization due to COVID-19. In addition, they performed a gender stratification analysis to assess the results of COVID-19. Sensitivity analysis included weighted mode, median weighted, and MREgger.

Researchers have pointed out that it is difficult to assess the iron status of the population because none of the iron biomarkers fully reflect it. In addition, the GWAS, which generated iron biomarker data, was published in 2021 and had 246,139 participants in European ancestry. The genetic vulnerability to sepsis was obtained from the Integrated Epidemiology Unit (IEU) OpenGWAS. This included 454,764 controls characterized as explicit sepsis and 10,154 cases of sepsis, as well as summary-level data from the UK Biobank. The authors used data from Release 5 of the COVID-19 Host Genetics Initiative (HGI), an international effort to support genetic assessment of SARS-CoV-2 infection.

result

MR findings suggest that elevated genetically close iron status, as measured by elevated TSAT and serum iron levels and decreased TIBC levels, is associated with an increased likelihood of sepsis. .. In participants genetically expected to have high serum iron titers, the authors found that they were more likely to be hospitalized for SARS-CoV-2 infection than non-hospitalized COVID-19 patients. did.

An increase in one standard deviation of genetically predicted serum iron was associated with an odds ratio (OR) of 1.14 for the probability of sepsis. Estimates of ferritin were unknown, but results were confirmed by TSAT and TIBC analysis.

In addition, the team found a high risk of hospitalization associated with serum iron COVID-19, with an OR of 1.29. In addition, gender stratification revealed that hospitalization with COVID-19 associated with high iron load had an OR of 1.63 for women and 1.21 for men. Nevertheless, the accuracy of gender-based findings was very minimal to strongly support variance. In addition, sensitivity studies confirmed the major findings and found no evidence of pleiotropy bias.

Researchers hypothesize that people with high iron status may not be able to tolerate the acute iron influx found in severe infections and may be more susceptible to sepsis and COVID-19-related hospitalizations. I did. In addition, they found that iron levels affected sepsis and the likelihood of hospitalization for COVID-19. This means that pre-infection iron status interferes with the immune response to infection.

Conclusion

According to the researchers, there is no prior literature to evaluate the effect of iron profile on the occurrence or outcome of SARS-CoV-2 infection using MR analysis.

In summary, this study used extensive summary data to investigate the effect of iron status on the likelihood of severe COVID-19 and sepsis. The results of the study show an association between genetically predicted high iron status and the likelihood of sepsis-related hospitalization with evidence of an increased risk of SARS-CoV-2-related hospitalization.

To analyze gender changes in correlation, the author emphasizes the importance of gender-specific summary-level datasets. Higher iron status had a greater impact on women than men considering hospitalization associated with COVID-19.

Notably, current results call for further study of the exact association between iron status and severe infections and for assessing the potential for better management and therapeutic approaches.

*Important Notices

medRxiv Publish preliminary scientific reports that should not be considered definitive as they have not been peer-reviewed, guide clinical practice / health-related behaviors, and should not be treated as established information.