COVID-19 and hemolysis, elevated liver enzymes and thrombocytopenia syndrome in pregnant women - association or causation?

Pregnant women are among the high-risk population for severe coronavirus disease 2019 (COVID-19) with unfavorable peripartum outcomes and increased incidence of preterm births. Hemolysis, the elevation of liver enzymes, and low platelet count (HELLP) syndrome and severe preeclampsia are among the leading causes of maternal mortality. Evidence supports a higher odd of pre-eclampsia in women with COVID-19, given overlapping pathophysiology. Involvement of angiotensin-converting enzyme 2 receptors by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for the entry to the host cells and its downregulation cause dysregulation of the renin-angiotensin-aldosterone system. The overexpression of Angiotensin II mediated via p38 Mitogen-Activated Protein Kinase pathways can cause vasoconstriction and uninhibited platelet aggregation, which may be another common link between COVID-19 and HELLP syndrome. On PubMed search from January 1, 2020, to July 30, 2022, we found 18 studies on of SARS-COV-2 infection with HELLP Syndrome. Most of these studies are case reports or series, did not perform histopathology analysis of the placenta, or measured biomarkers linked to pre-eclampsia/HELLP syndrome. Hence, the relationship between SARS-CoV-2 infection and HELLP syndrome is inconclusive in these studies. We intend to perform a mini-review of the published literature on HELLP syndrome and COVID-19 to test the hypothesis on association vs causation, and gaps in the current evidence and propose an area of future research.