COVID-19 Infection in Pregnancy: PCR Cycle Thresholds, Placental Pathology, and Perinatal Outcomes

Abstract

(1) This study aimed to evaluate characteristics, perinatal outcomes, and placental pathology of pregnant women with or without SARS-CoV-2 infection in the context of maternal PCR cycle threshold (C_T) values. (2) This was a retrospective case-control study in a third-level health center in Mexico City with universal screening by RT-qPCR. The association of COVID-19 manifestations, preeclampsia, and preterm birth with maternal variables and C_T values were assessed by logistic regression models and decision trees. (3) Accordingly, 828 and 298 women had a negative and positive test, respectively. Of those positive, only 2.6% of them presented mild to moderate symptoms. Clinical characteristics between both groups of women were similar. No associations between C_T values were found for maternal features, such as pre-gestational BMI, age, and symptomatology. A significantly higher percentage of placental fibrinoid was seen with women with low C_Ts (<25; p < 0.01). Regarding perinatal outcomes, preeclampsia was found to be significantly associated with symptomatology but not with risk factors or C_T values (p < 0.01, aOR = 14.72). Moreover, 88.9% of women diagnosed with COVID-19 at <35 gestational weeks and symptomatic developed preeclampsia. (4) The data support strong guidance for pregnancies with SARS-CoV-2 infection, in particular preeclampsia and placental pathology, which need further investigation.

Keywords: SARS-CoV-2; hypertensive disorder; placenta; pregnancy.

Figure 1

Age and BMI characteristics. Maternal age was similar between women who tested positive and negative to COVID (a). Women who were overweight tended to have lower C_T values, and women with class three obesity had the lowest gestational age at triage (b).

Figure 2

Regression tree for symptom variables (cough, fever, headache, dyspnea, myalgias, rhinorrhea, diarrhea, thrombosis, neurological symptoms, arrhythmia, lethargy) and PCR test positivity. (a) shows the cross-validated error of the regression tree. Only one variable split the tree, indicating that 88% of women who tested positive had cough at triage (b). CHAID tree also had one split, and the terminal nodes indicate that cough was present in 88% of women who tested positive, whereas only 26% of those who tested positive did not have cough (c).

Figure 3

Two-way ANOVA C_T distribution between BMI categories. Women with overweight tended to have lower (non-significant) C_T values.

Figure 4

Presence of placental fibrinoid according to C_T values. (a) all patients with a positive PCR test, (b) asymptomatic patients, (c) symptomatic patients. Lower C_T values were more common in placentas from women who developed fibrinoid (a). asymptomatic patients who developed fibrinoid had either low or high C_Ts (b). All women with low C_T values (<25), who were symptomatic, developed fibrinoid (c).

Figure 5

Presence of placental fibrinoid. The hematoxylin and eosin-stained photomicrograph of the placenta shows the chorionic villi encased by massive perivillous fibrin deposition (arrowheads). Original magnification ×20.

Figure 6

QUEST trees for preterm birth (a) and preeclampsia (b). QUEST for preterm birth had only one split. Preterm birth was highly related to the development of preeclampsia; the terminal node of the tree shows that 60.8% of women who developed preeclampsia had preterm birth, whereas in women who did not develop preeclampsia, only 26% delivered preterm (a). QUEST for preeclampsia had two splits. Preeclampsia was present in 8.7% of women who tested negative or were positive asymptomatic, but 57.1% of positive and symptomatic women developed preeclampsia. Moreover, the terminal node shows that women who developed COVID before or at week 35 and who were symptomatic were more likely to develop preeclampsia (88.9%).