key: cord-0915789-tb2ida6n
authors: Naeh, Amir; Berezowsky, Alexandra; Yudin, Mark H.; Dhalla, Irfan A.; Berger, Howard
title: Preeclampsia-like syndrome in a pregnant patient with Coronavirus Disease 2019 (COVID-19)
date: 2021-10-12
journal: J Obstet Gynaecol Can
DOI: 10.1016/j.jogc.2021.09.015
sha: c17ffc3622a6a91d23260967355bbb0f0190f3f0
doc_id: 915789
cord_uid: tb2ida6n

Background Hypertension, proteinuria, and hepatic dysfunction have been described as manifestations of coronavirus disease 2019 (COVID-19) and are generally accepted as poor prognostic factors. However, these same findings can also occur in pregnant women with preeclampsia, thus creating a diagnostic challenge. Case We report a case of COVID-19 infection in an otherwise healthy pregnant patient with secondary hypertension, proteinuria, and significant hepatic dysfunction. Maternal placental growth factor (PlGF) testing was used to rule out preeclampsia. The patient received supportive care and improved significantly. She went on to have a spontaneous vaginal term delivery of a healthy male baby. Conclusion COVID-19 infection in pregnancy may present as preeclampsia-like syndrome. PlGF testing can be used to differentiate preeclampsia from COVID-19 and facilitate appropriate management.

accepted as poor prognostic factors. However, these same findings can also occur in pregnant women with preeclampsia, thus creating a diagnostic challenge.

We report a case of COVID-19 infection in an otherwise healthy pregnant patient with secondary hypertension, proteinuria, and significant hepatic dysfunction.

Maternal placental growth factor (PlGF) testing was used to rule out preeclampsia.

The patient received supportive care and improved significantly. She went on to have a spontaneous vaginal term delivery of a healthy male baby. Hypertension, proteinuria and hepatic dysfunction have been described as manifestations of COVID-19 infection [3] [4] [5] . However, these same findings can also occur in pregnant women that develop preeclampsia, thus creating a diagnostic challenge.

We report a case of COVID-19 in an otherwise healthy pregnant patient with secondary hypertension and significant hepatic dysfunction and discuss the differential diagnosis, investigations and management strategy.

A healthy 39-year-old, gravida 5 para 1, presented at 26+4 weeks of gestation with progressively worsening dry cough and dyspnea that began approximately 5 days prior to admission. On presentation, she was afebrile with a blood pressure of 152\132, heart rate of 141 bpm, respiratory rate of 20\min, and oxygen saturation of Obstetric ultrasound demonstrated an active baby, with normal Doppler flows. She was admitted to an internal medicine ward and was started on prophylactic dose of low molecular weight heparin. COVID-19 was confirmed by a nasopharyngeal swab.

Initially, she continued to have ongoing dyspnea with O2 desaturation on walk test.

She received IM betamethasone for fetal lung maturity followed by IV dexamethasone daily. Her blood pressure subsequently normalized without medical therapy, however, repeat laboratory studies showed progressive increase in hepatic enzymes with AST of 1154 U\L and ALT of 864 U\L, hemoglobin levels decreased to 85 g\L with LDH of 1018 U\L and albumin-creatine ratio was 9.5. Platelets, creatinine, bile acids, complement (C3, C4), anti-nuclear antibody and peripheral blood smear were normal.

Given the evolving clinical picture, a multidisciplinary discussion was conducted between the general internal medicine, maternal-fetal medicine and infectious disease teams: While the initial hypertension, anemia, severe hepatic dysfunction and proteinuria could all be related to COVID -19, the possible diagnosis of preeclampsia with severe features could not be ruled out. Furthermore, diagnosis of preeclampsia with severe features would require different management, including treatment with magnesium sulfate and ultimately, preterm delivery, with the potential for significant neonatal complications secondary to prematurity. To differentiate between these two entities, it was decided to test maternal Placental growth factor (PLGF), which was reported as 158 pg\mL (normal > 100 pg/ml), a value that rules out preeclampsia with very high negative predictive value 6 .

Over the next few days, the patient's condition improved. Her dyspnea resolved, with normalization of oxygen saturation on room air. AST and ALT levels gradually declined to 331 U\L and 343 U\L respectively and the patient was discharged on day 13 for outpatient follow-up.

During her outpatient follow up AST and ALT continued to decline and eventually normalized. Blood pressure measurements and serial US scans for fetal growth were normal. She went on to have a spontaneous vaginal delivery of a healthy 3880 g male baby at 39+2 weeks gestation.

Data regarding the effect of COVID-19 on pregnancy course and outcomes continues to accumulate as the pandemic spreads. Recent studies have demonstrated that pregnant women with COVID-19 are at increased risk for severe disease, mechanical ventilation and ICU admission 1,2 . COVID-19 in pregnancy also significantly increases the risk for preterm delivery and maternal death 7 .

Hepatic dysfunction is a common finding in COVID-19 and is considered a poor prognostic factor 3 .

Proteinuria is also a common manifestation of COVID-19 and is considered a risk factor for a severe disease 5 . New-onset hypertension has also been described in COVID-19 4 . Endothelial dysfunction has been suggested as the mechanism for both manifestations: The SARS-CoV-2 coronavirus accesses host cells via binding to angiotensin-converting enzyme 2, expressed in endothelial cells, and can cause endothelial dysfunction resulting in hypertension, kidney injury and proteinuria, as well as diabetes and thrombosis 8 .

Nevertheless, new-onset hypertension, proteinuria and severe hepatic dysfunction are also clinical manifestations of preeclampsia 9 , and therefore differentiating between preeclampsia and COVID-19 in pregnancy can be challenging. Moreover, management strategies are different: while the treatment of severe COVID-19 infection consists of steroids, antiviral drugs and supportive care, treatment of preeclampsia with severe features is usually delivery 9 . An increased incidence of preeclampsia has been reported among pregnant women with COVID-19 7 . However, it is possible that some of those cases were misdiagnosed as preeclampsia, and thus potentially contributing to the high incidence of provider initiated preterm delivery in COVID-19 pregnant patients 1,2 .

PLGF is a placental-related angiogenic marker which is considered highly specific for preeclampsia. Women with preeclampsia are characterized with low-levels of PlGF and high levels of sFlt-1\PlGF ratio. Thus, PLGF can be used to distinguish between these two entities, with levels > 100 pg\mL ruling out preeclampsia with a high degree of certainty 6 . Additional support for the use of PLGF in this situation can be found in a recent publication by Mendoa et al 10 who described a preeclampsia-like syndrome in 5 of 42 (12%) COVID-19 pregnant women with severe disease, and used sFlt-1\PlGF ratio to rule out preeclampsia in four of those cases.

COVID-19 infection in pregnancy can present with manifestations imitating preeclampsia. Greater awareness of this situation, along with possible use of PLGF as an ancillary test, can assist in ruling out preeclampsia and thus, avoid unnecessary provider initiated preterm delivery with improved neonatal outcomes. Additional studies are needed to further investigate the association between COVID-19, preeclampsia and the preeclampsia-like syndrome described in this report.

The patient provided consent for publication (REB#21-077).

Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta-analysis

Liver injury is associated with severe coronavirus disease 2019 (COVID-19) infection: A systematic review and metaanalysis of retrospective studies

COVID-19 and late-onset hypertension with hyporeninaemic hypoaldosteronism

Incidence and risk factors of kidney impairment on patients with COVID-19: A meta-analysis of 10180 patients

Predictive Value of the sFlt-1:PlGF Ratio in Women with Suspected Preeclampsia

Outcome of coronavirus spectrum infections (SARS, MERS, COVID-19) during pregnancy: a systematic review and meta-analysis

Thrombosis, Kidney Failure, and Diabetes: Is COVID-19 an

Report of the American College of Obstetricians and Gynecologists' Task Force on Hypertension in Pregnancy

Pre-eclampsia-like syndrome induced by severe COVID-19: a prospective observational study