Hypertensive disorders of pregnancy, especially preeclampsia (PE), represent main contributors to maternal mortality and morbidity worldwide and most significantly in low and middle-income populations [[1], [2]]. During the COVID-19 pandemic, these populations have also been disproportionately affected by severe infections due to delays in healthcare, difficulties in testing and managing the disease, restricted availability of intensive care units, and inadequate management of complications, all aggravated by low access to vaccination. Outcomes are particularly striking for COVID-19 infections during pregnancy and postpartum, with increased numbers reported for maternal morbidity and mortality not only due to the challenges with healthcare, but also because of pregnancy itself as a risk factor for severe disease[[3], [4], [5]].

The association between COVID-19 and PE has been recently highlighted by different studies, showing increased frequencies of PE among cases of COVID-19[6]. The rationale to explain such findings is based on the similar pathophysiology and clinical presentation of both conditions[7].

PE is a syndrome with multisystemic organ involvement associated with inflammation and endothelial damage. Plasma concentrations of pro-angiogenic/anti-angiogenic factors released by the placental syncytiotrophoblast have been identified as markers of disease progression. In PE, soluble fms-like tyrosine kinase 1 (sFlt-1, an anti-angiogenic protein) increases, and placental growth factor (PlGF, a pro-angiogenic protein) decreases. Therefore, sFlt-1 and PlGF directly and inversely correlate, respectively, with disease onset [[8], [9], [10]]. COVID-19 has a few similarities as it also presents with multi-organ involvement and extensive inflammation and endothelial damage, therefore the differential diagnosis can be challenging especially in severe acute respiratory syndrome (SARS) cases, leading to what has been referred to as “PE-like syndrome”[11], [12].

Adequate diagnosis is key in ascertaining appropriate clinical management, especially in cases of preterm gestation since the decision on the timing of delivery has a significant impact on perinatal outcomes. Because clinical parameters of hypertension, proteinuria, and target organ damage can be similar, biomarkers could be a useful tool in distinguishing and guiding such decision-making for cases that involve COVID-19 and preeclampsia [13]. The sFlt-1/PlGF ratio at a threshold of below 38 can provide reassurance for the absence of PE at that given time, as well as indicate a low likelihood of onset in the following week. However, there are still uncertainties about the levels of biomarkers in COVID-19 cases given previous reports of high values of sFlt-1 in patients with COVID-19 pneumonia vs. COVID-19 without pneumonia [8].

Therefore, the aim of this study was to analyze sFlt-1 and PlGF concentrations and their ratio in pregnant/postpartum women with suspected COVID-19, and further investigate conditions associated with the increased ratio (sFlt-1/PlGF>38), including preeclampsia and severe COVID-19 cases.