SARS-CoV-2 and the subsequent development of preeclampsia and preterm birth: evidence of a dose-response relationship supporting causality

Does COVID‐19 cause pre‐eclampsia?

“…In the study 28 , among the 23 cases of pre‐eclampsia diagnosed after SARS‐CoV‐2, the median interval from diagnosis of SARS‐CoV‐2 infection to diagnosis of pre‐eclampsia was 16 (interquartile range (IQR), 7–61) days. Only one other study 26 reported on the time from diagnosis of SARS‐CoV‐2 infection to diagnosis of pre‐eclampsia.…”

“…Few studies have focused on women in whom pre‐eclampsia preceded a diagnosis of SARS‐CoV‐2 infection. In one study that did 28 , among 1223 SARS‐CoV‐2‐positive pregnant women, there were 51 cases of pre‐eclampsia, of which 21 were diagnosed before SARS‐CoV‐2 infection, seven at the same gestational age as SARS‐CoV‐2 infection and 23 after SARS‐CoV‐2 infection. When the 21 women in whom pre‐eclampsia was diagnosed before SARS‐CoV‐2 infection were compared with those who did not develop pre‐eclampsia, there was a trend towards an increased risk of subsequently developing moderate or severe COVID‐19 (unadjusted RR, 2.28 (95% CI, 0.92–5.61) ( P = 0.07); adjusted RR (aRR), 1.96 (95% CI, 0.8–4.84) ( P = 0.14)).…”

SARS-CoV-2 impacts the transcriptome and epigenome at the maternal-fetal interface in pregnancy

“…Therefore, the overexpression of IFITM genes in late pregnancy can still potentially impair ST formation and function. A recent report suggests that the type I interferon response from SARS-CoV-2 infection can cause endothelial damage in the lungs by cGAS-STING activation ( 68 ), which is analogous to the placental endothelial damage observed in COVID-19 patients ( 1, 4, 69, 70 ). Taken together, we have found the aberrant expression of IFN-related genes across distinct immune cell types at the maternal-fetal interface, which is potentially detrimental to placental function and fetal health.…”

“…The situation worldwide remains dire. Evidence suggests that pregnant COVID-19 patients have worse clinical outcomes than similarly aged non-pregnant patients ( 1, 2 ). Indeed, pregnant patients show higher incidences of pneumonia, intensive care unit admission, need for invasive ventilation, need for extracorporeal membrane oxygenation, and death ( 2–4 ).…”

World Prematurity Day: it takes an NIH village to prevent preterm birth and improve treatments for preterm infants

“…Infection with SARS-CoV-2 during pregnancy is associated with an increased rate of preterm birth. The greater the severity of SARS-CoV-2, the higher the risk of preterm birth, which is thought to be related to an increase in medically indicated, rather than spontaneous, preterm birth (57). A systematic review and meta-analysis also indicated an association between SARS-CoV-2 infection during pregnancy and the odds of preeclampsia (pooled odds ratio 1.58, 95% CI 1.39-1.80; P<0.001; I 2 =0%; 11 studies) (58).…”