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

M Mendoza, I Garcia-Ruiz, N Maiz, C Rodo, P Garcia-Manau, B Serrano, R M Lopez-Martinez, J Balcells, N Fernandez-Hidalgo, E Carreras, A Suy, M Mendoza, I Garcia-Ruiz, N Maiz, C Rodo, P Garcia-Manau, B Serrano, R M Lopez-Martinez, J Balcells, N Fernandez-Hidalgo, E Carreras, A Suy

Abstract

Objectives: To investigate the incidence of clinical, ultrasonographic and biochemical findings related to pre-eclampsia (PE) in pregnancies with COVID-19, and to assess their accuracy to differentiate between PE and the PE-like features associated with COVID-19.

Design: A prospective, observational study.

Setting: Tertiary referral hospital.

Participants: Singleton pregnancies with COVID-19 at >20+0 weeks.

Methods: Forty-two consecutive pregnancies were recruited and classified into two groups: severe and non-severe COVID-19, according to the occurrence of severe pneumonia. Uterine artery pulsatility index (UtAPI) and angiogenic factors (soluble fms-like tyrosine kinase-1/placental growth factor [sFlt-1/PlGF]) were assessed in women with suspected PE.

Main outcome measures: Incidence of signs and symptoms related to PE, such as hypertension, proteinuria, thrombocytopenia, elevated liver enzymes, abnormal UtAPI and increased sFlt-1/PlGF.

Results: Thirty-four cases were classified as non-severe and 8 as severe COVID-19. Five (11.9%) women presented signs and symptoms of PE, all five being among the severe COVID-19 cases (62.5%). However, abnormal sFlt-1/PlGF and UtAPI could only be demonstrated in one case. One case remained pregnant after recovery from severe pneumonia and had a spontaneous resolution of the PE-like syndrome.

Conclusions: Pregnant women with severe COVID-19 can develop a PE-like syndrome that might be distinguished from actual PE by sFlt-1/PlGF, LDH and UtAPI assessment. Healthcare providers should be aware of its existence and monitor pregnancies with suspected pre-eclampsia with caution.

Tweetable abstract: This study shows that a pre-eclampsia-like syndrome could be present in some pregnancies with severe COVID-19.

Keywords: Angiogenic factors; COVID-19; PlGF; SARS; SARS-CoV-2; pre-eclampsia; pre-eclampsia-like syndrome; pregnancy; sFlt-1.

© 2020 Royal College of Obstetricians and Gynaecologists.

Figures

Figure 1
Figure 1
Evolution of ALT, AST, proteinuria and mean arterial blood pressure in pregnant women with COVID‐19 before (A), during (B) and after (C) severe pneumonia. The bottom and top edges of each box represent the first and third quartiles, respectively, the band within the box represents the median value and the whiskers represent values that are 1.5 times the interquartile range. Median values and interquartile range of each variable are displayed.

References

    1. WHO Director‐General's opening remarks at the media briefing on COVID‐19. 2020. []. Accessed 12 March 2020.
    1. Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID‐19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. JAMA 2020; published online Feb 24. 10.1001/jama.2020.2648
    1. Cai Q, Huang D, Yu H, Zhu Z, Xia Z, Su Y, et al. Characteristics of liver tests in COVID‐19 patients. J Hepatol 2020; published online Apr 13. 10.1016/j.jhep.2020.04.006
    1. Cheng Y, Luo R, Wang K, Zhang M, Wang Z, Dong L, et al. Kidney disease is associated with in‐hospital death of patients with COVID‐19. Kidney Int 2020; published online Mar 20. 10.1016/j.kint.2020.03.005
    1. Kreutz R, Algharably EAE‐H, Azizi M, Dobrowolski P, Guzik T, Januszewicz A, et al. Hypertension, the renin‐angiotensin system, and the risk of lower respiratory tract infections and lung injury: implications for COVID‐19. Cardiovasc Res 2020; published online Apr 15. 10.1093/cvr/cvaa097
    1. Lippi G, Plebani M, Henry BM. Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID‐19) infections: a meta‐analysis. Clin Chim Acta 2020;506:145–8.
    1. Gheblawi M, Wang K, Viveiros A, Nguyen Q, Zhong J‐C, Turner AJ, et al. Angiotensin converting enzyme 2: SARS‐CoV‐2 receptor and regulator of the renin‐angiotensin system. Circ Res 2020; published online Apr 8. 10.1161/CIRCRESAHA.120.317015
    1. Liu PP, Blet A, Smyth D, Li H. The science underlying COVID‐19: implications for the cardiovascular system. Circulation 2020; published online Apr 15. 10.1161/CIRCULATIONAHA.120.047549
    1. Turpin CA, Sakyi SA, Owiredu WKBA, Ephraim RKD, Anto EO. Association between adverse pregnancy outcome and imbalance in angiogenic regulators and oxidative stress biomarkers in gestational hypertension and preeclampsia. BMC Pregnancy Childbirth 2015;15:189.
    1. American College of Obstetricians and Gynecologists, Task Force on Hypertension in Pregnancy . Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists' task force on hypertension in pregnancy. Obstet Gynecol 2013;122:1122–31.
    1. Di Mascio D, Khalil A, Saccone G, Rizzo G, Buca D, Liberati M, et al. Outcome of coronavirus spectrum infections (SARS, MERS, COVID 1–19) during pregnancy: a systematic review and meta‐analysis. Am J Obstet Gynecol MFM 2020). 2, 100107 10.1016/j.ajogmf.2020.100107
    1. World Health Organization . Clinical management of severe acute respiratory infection when novel coronavirus (nCoV) infection is suspected: interim guidance. 2020. []. Accessed 11 March 2020.
    1. Haram K, Svendsen E, Abildgaard U. The HELLP syndrome: clinical issues and management. A review. BMC Pregnancy Childbirth 2009;9:8.
    1. Martin AM, Bindra R, Curcio P, Cicero S, Nicolaides KH. Screening for pre‐eclampsia and fetal growth restriction by uterine artery Doppler at 11–14 weeks of gestation. Ultrasound Obstet Gynecol 2001;18:583–6.
    1. Schiettecatte J, Russcher H, Anckaert E, Mees M, Leeser B, Tirelli AS, et al. Multicenter evaluation of the first automated Elecsys sFlt‐1 and PlGF assays in normal pregnancies and preeclampsia. Clin Biochem 2010;43:768–70.
    1. Gómez O, Figueras F, Fernández S, Bennasar M, Martínez JM, Puerto B, et al. Reference ranges for uterine artery mean pulsatility index at 11–41 weeks of gestation. Ultrasound Obstet Gynecol 2008;32:128–32.
    1. Verlohren S, Herraiz I, Lapaire O, Schlembach D, Moertl M, Zeisler H, et al. The sFlt‐1/PlGF ratio in different types of hypertensive pregnancy disorders and its prognostic potential in preeclamptic patients. Am J Obstet Gynecol. 2012;206:58.e1–8.
    1. Stepan H, Herraiz I, Schlembach D, Verlohren S, Brennecke S, Chantraine F, et al. Implementation of the sFlt‐1/PlGF ratio for prediction and diagnosis of pre‐eclampsia in singleton pregnancy: implications for clinical practice. Ultrasound Obstet Gynecol 2015;45:241–6.
    1. Paules C, Youssef L, Rovira C, Crovetto F, Nadal A, Peguero A, et al. Distinctive patterns of placental lesions in pre‐eclampsia vs small‐for‐gestational age and their association with fetoplacental Doppler. Ultrasound Obstet Gynecol 2019;54:609–16.
    1. Zeisler H, Llurba E, Chantraine F, Vatish M, Staff AC, Sennström M, et al. Predictive value of the sFlt‐1:PlGF ratio in women with suspected preeclampsia. N Engl J Med 2016;374:13–22.
    1. 1 Recommendations | PlGF‐based testing to help diagnose suspected pre‐eclampsia (Triage PlGF test, Elecsys immunoassay sFlt‐1/PlGF ratio, DELFIA Xpress PlGF 1‐2‐3 test, and BRAHMS sFlt‐1 Kryptor/BRAHMS PlGF plus Kryptor PE ratio). NICE Guidance. []. Accessed 28 March 2020.
    1. Sibai BM. Imitators of severe pre‐eclampsia. Semin Perinatol 2009;33:196–205.
    1. Inversetti A, Serafini A, Manzoni MF, Dolcetta Capuzzo A, Valsecchi L, Candiani M. Severe hypothyroidism causing pre‐eclampsia‐like syndrome. Case Rep Endocrinol 2012;2012:586056.
    1. Rolfo A, Attini R, Nuzzo AM, Piazzese A, Parisi S, Ferraresi M, et al. Chronic kidney disease may be differentially diagnosed from preeclampsia by serum biomarkers. Kidney Int 2013;83:177–81.
    1. Hirashima C, Ogoyama M, Abe M, Shiraishi S, Sugase T, Niki T, et al. Clinical usefulness of serum levels of soluble fms‐like tyrosine kinase 1/placental growth factor ratio to rule out preeclampsia in women with new‐onset lupus nephritis during pregnancy. CEN Case Rep 2019;8:95–100.
    1. Levine RJ, Maynard SE, Qian C, Lim K‐H, England LJ, Yu KF, et al. Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med 2004;350:672–83.
    1. Hung TH, Skepper JN, Burton GJ. In vitro ischemia‐reperfusion injury in term human placenta as a model for oxidative stress in pathological pregnancies. Am J Pathol 2001;159:1031–43.
    1. Pijnenborg R, Vercruysse L, Verbist L, Van Assche FA. Interaction of interstitial trophoblast with placental bed capillaries and venules of normotensive and pre‐eclamptic pregnancies. Placenta 1998;19:569–75.

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