key: cord-0701886-wbuasbf5
authors: Madden, Nigel; Emeruwa, Ukachi N.; Polin, Melanie; Bejerano, Shai; Gyamfi-Bannerman, Cynthia; Booker, Whitney A.
title: SARS-CoV-2 and hypertensive disease in pregnancy
date: 2021-09-25
journal: Am J Obstet Gynecol MFM
DOI: 10.1016/j.ajogmf.2021.100496
sha: 08e648e90aaf790bcfbabf21163e32b4bca460f1
doc_id: 701886
cord_uid: wbuasbf5

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the increased release of placental trophoblastic debris into the maternal circulation, stimulating the systemic inflammatory response and resulting in wide-spread endothelial dysfunction. 2, 3 Similarly, the infection caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is characterized by a substantial inflammatory response. 4 Given the commonalities in the pathogenesis of both SARS-CoV-2 infection and HPD we sought to evaluate this relationship further. Our primary objectives were to evaluate differences in the rates of HDP and hypertensive disease severity in SARS-CoV-2-versus SARS-CoV-2+ patients.

We conducted a retrospective chart review of all patients who had pre-admission SARS-CoV-2 nasal polymerase chain reaction testing at Columbia University Irving Medical Center-affiliated Labor and Delivery (L&D) units between March and June 2020. Patients with a history of chronic hypertension and multiple gestations were excluded.

The primary exposure was SARS-CoV-2 infection status on routine admission testing to L&D. The primary outcome was overall rates of HDP including gestational hypertension (gHTN), pre-eclampsia (PEC) without severe features, and PEC with severe features. A primary sub-analysis evaluated the group of patients with a HDP to determine whether hypertensive disease severity differed by SARS-CoV-2 testing status. A secondary sub-analysis evaluated the group of patients who tested SARS-CoV-2+ to determine whether symptom status differed in those with a HDP as compared to those without.

Univariable analyses for continuous variables were conducted using parametric or nonparametric tests as appropriate. Categorical or binary variables were analyzed with chi-square test or Fisher's exact test as appropriate. Multivariable analyses were conducted using logistic regression models to adjust for statistically significant potential confounders.

Our primary analysis included 1,649 patients, 1,498 (90.8%) who tested SARS-CoV-2-and 151 (9.2%) who tested SARS-CoV-2+. SARS-CoV-2+ patients were younger (28 ± 6 vs. 31 ± 6 years, P<0.01), less likely to be AMA (17.2 vs. 29.8%, P<0.01), had a higher proportion of Hispanic patients (72.8 vs. 52.1%, P<0.01), and were more likely to have public insurance (75.7 vs. 45.9%, P<0.01).

Overall rates of HDP were higher in SARS-CoV-2+ patients (21.2 vs. 8.7%, P<0.01, Table 1 ).

Specifically, SARS-CoV-2+ patients had higher rates of gHTN (10.6 vs. 3.7%, P<0.01) and PEC without severe features (4.6 vs. 1.3%, P<0.01). These differences remained significant on multivariable regression analysis. Rates of PEC with severe features did not differ significantly between the two groups (6.0 vs. 3.7%, P=0.17, Table 1 ). The first sub-analysis included 163 women with a diagnosis of HDP, 32 (19.6%) were SARS-CoV-2+ and 131 (80.4%) were SARS-CoV-2-.

SARS-CoV-2+ and SARS-CoV-2-patients did not differ significantly on variables assessing hypertensive disease severity (Table 1) . Final analysis included 151 SARS-CoV-2+ patients, 32 (21.2%) who were diagnosed with a HDP and 119 (78.8%) who did not have a HDP. Patients who had a HDP were less likely to be asymptomatic (31.2 vs. 71.4%, P<0.01) and more likely to have experienced SARS-CoV-2 symptoms prior to presentation (37.5 vs. 13.4%, P<0.01).

There are several notable commonalities in the pathophysiologies of HDP and SARS-CoV-2 infection with the activation of the systemic inflammatory response and endothelial dysfunction playing prominent roles in both. [2] [3] [4] Our results show that patients who were SARS-CoV-2+ had significantly higher rates of HDP including gHTN and PEC without severe features as compared to SARS-CoV-2patients. Rates of PEC with severe features and severity of HDP did not differ in our cohort of patients with largely asymptomatic or mild SARS-CoV-2 infection. This is in contrast to the results from a recent review of the literature including 790,954 pregnant women showed that the risk of PEC was significantly higher among 15,524 pregnant women with SARS-CoV-2 infection as compared to those without (7.0% vs 4.8%; OR 1.62, 95% CI 1.45-1.82; 26 studies), as was the risk of PEC with severe features (6.9% vs. 4.9%; OR 1.76, 95% CI 1.18-2.63; 7 studies, 11,019 women). 5 Our study also showed that patients with a HDP were also more likely to experience symptoms of SARS-CoV-2.

These results, in the context of significant similarities in disease mechanism, suggest that the acute inflammation of the SARS-CoV-2 infection may mimic hypertensive disease in pregnancy and contribute to increased rates and indicate a need for increased monitoring for hypertensive disease in patients who are SARS-CoV-2+.

Further research is needed in order to better understand how to differentiate between true hypertensive disease of pregnancy and the effects of the acute inflammatory state of the SARS-CoV-2 infection.

Furthermore, the implications of this possible overlap in regards to antenatal testing and surveillance, optimal timing of delivery, prevention of unindicated iatrogenic preterm delivery, and management of subsequent pregnancies need to be elucidated.

Disclosure Statement: Dr. Gyamfi-Bannerman has funding from NICHD, NHLBI, and was compensated for a talk for Medela. Shai Bejerano is partially supported by NIH grants (RF1AG056111 and R01DK116603).

Findings were previously presented as an Oral Presentation at the Society for Maternal Fetal Medicine 41st Annual Pregnancy Meeting; January 25-30th, 2021 (Abstract #32).

Conde-Agudelo A, Romero R. SARS-COV-2 infection during pregnancy and risk of preeclampsia: a systematic review and meta-analysis. Am J Obstet Gynecol 2021. 

Epidemiology of pre-eclampsia and the other hypertensive disorders of pregnancy

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