Pregnancy and iron deficiency anemia are associated with COVID-19 severity: a retrospective cohort study from Gaza

INTRODUCTION COVID-19 poses significant risks to pregnant women, with pregnancy recognized as a risk factor for severe disease. This vulnerability may be exacerbated by iron deficiency anemia (IDA) due to impaired immune function, reduced oxygen transport, and altered coagulation and endothelial function. METHODS A retrospective cohort study of 271 unvaccinated, otherwise healthy women aged 18-38 with COVID-19 was conducted at Al-Shifa Hospital, Gaza (2021). Pregnant (n = 97) and nonpregnant (n = 174) groups were stratified by IDA, investigating the impact of pregnancy and IDA on the severity of COVID-19. Iron deficiency was determined by transferrin saturation levels <20% measured during acute infection, whereas ferritin levels were not available. RESULTS Overall pregnancy was significantly associated with COVID-19 severity (p < 0.001), with pregnant women having higher odds of critical illness (OR = 4.61, 95% CI 2.27-9.39, p < 0.001) and death (OR = 5.25, 95% CI 1.91-14.44, p = 0.001) compared with moderate illness. All deaths were due to acute respiratory distress syndrome; no venous thromboembolism cases occurred. IDA was associated with COVID-19 severity in both pregnant (p = 0.015) and non-pregnant (p = 0.002) women. In a multivariable model including pregnancy, IDA was associated with higher odds of severe (OR = 3.57, 95% CI 1.97-6.48, p < 0.001), critical (OR = 2.25, 95% CI 1.09-4.64, p = 0.029), and fatal illness (OR = 7.23, 95% CI 1.96-26.74, p = 0.003) compared with moderate illness. CONCLUSION This study suggests that among young, otherwise healthy, unvaccinated women with COVID-19, pregnancy and IDA are associated with increased COVID-19 severity. However, interpretation requires caution considering the small number of events, particularly deaths, and the assessment of iron status during acute infection using transferrin saturation alone without ferritin measurements, which limits the ability to distinguish preexisting iron deficiency from inflammation-related changes in iron metabolism.