Cytokine Storms in the Course of COVID-19 and Haemophagocytic Lymphohistiocytosis in Pregnant and Postpartum Women

Abstract

The term 'cytokine storm' (CS) applies to a pathological autoimmune reaction when the interactions that lead to cytokine production are destabilised and may even lead to death. CS may be induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this study, we present our analysis of certain pathological processes that induce a CS in pregnant and postpartum women. We draw our attention to the similarities between the severe course of Coronavirus Disease 2019 (COVID-19) and haemophagocytic lymphohistiocytosis (HLH). It is noteworthy that many of the criteria used to diagnose HLH are described as COVID-19 mortality predictors. Cytokine storms are considered to be an important cause of death in patients with the severe course of SARS-CoV-2 infection. Due to the fact that pregnant women are in an immunosuppressive state, viral pulmonary infections are more perilous for them-possible risks include miscarriage, intrauterine growth restriction or birth before the term; sometimes ventilation support is needed. HLH should be considered in pregnant and puerperal women suffering from moderately severe to severe COVID-19 and presenting with: fever unresponsive to antibiotic therapy, cytopenia, hepatitis and hyperferritinaemia. The HLH disorder is rare and difficult to diagnose; however, its early detection could reduce patient mortality.

Keywords: COVID-19; cytokine storm; haemophagocytic lymphohistiocytosis; postpartum period; pregnancy.

Figure 1

Physiological changes in the immune system in early pregnancy. hCG-human chorionic gonadotropin; IFN-γ-interferon gamma; IL-2-interleukin 2; IL-4-interleukin 4; IL-10-interleukin 10; IL-13-interleukin 13; LT-α-lymphotoxin-alpha; TGF-β-transforming growth factor beta; Th1-type 1 T helper cells; Th2-type 2 T helper cells; Th17-T helper 17 cells; TNF-α-tumour necrosis factor; TREG-regulatory T cell.

Figure 2

The number of ACE2 receptors increases during early and mid-pregnancy. ACE2 are receptors for the entry of SARS-CoV-2 into placental cells. ACE2-angiotensin-converting enzyme-related carboxypeptidase; SARS-CoV-2-severe acute respiratory syndrome coronavirus 2.