In December 2019, cases of pneumonia of unknown cause first started to appear in Wuhan in China; subsequently, a new coronavirus was soon identified as the cause of the illness, now known as Coronavirus Disease 2019 (COVID-19). Since then, infections have been confirmed worldwide in numerous countries, with the number of cases steadily rising. The aim of the present review is to provide an overview of the new severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) and, in particular, to deduce from it potential risks and complications for pregnant patients. For this purpose, the available literature on cases of infection in pregnancy during the SARS epidemic of 2002/2003, the MERS (Middle East respiratory syndrome) epidemic ongoing since 2012, as well as recent publications on cases infected with SARS-CoV-2 in pregnancy are reviewed and reported. Based on the literature available at the moment, it can be assumed that the clinical course of COVID-19 disease may be complicated by pregnancy which could be associated with a higher mortality rate. It may also be assumed at the moment that transmission from mother to child in utero is unlikely. Breastfeeding is possible once infection has been excluded or the disease declared cured.

Introduction International studies on preterm birth rates during COVID-19 lockdowns report different results. This study examines preterm birth rates during lockdown periods and the impact of the mobility changes of the population in Bavaria, Germany. Material and Methods This is a secondary analysis of centrally collected data on preterm births in Bavaria from 2010 to 2020. Preterm births (< 37 weeks) in singleton and twin pregnancies during two lockdowns were compared with corresponding periods in 2010 – 2019. Fisherʼs exact test was used to compare raw prevalence between groups. Potential effects of two fixed lockdown periods and of variable changes in population mobility on preterm birth rates in 2020 were examined using additive logistic regression models, adjusting for long-term and seasonal trends. Results Unadjusted preterm birth rates in 2020 were significantly lower for singleton pregnancies during the two lockdown periods (Lockdown 1: 5.71% vs. 6.41%; OR 0.88; p < 0.001; Lockdown 2: 5.71% vs. 6.60%; OR = 0.86; p < 0.001). However, these effects could not be confirmed after adjusting for long-term trends (Lockdown 1: adj. OR = 0.99; p = 0.73; Lockdown 2: adj. OR = 0.96; p = 0.24). For twin pregnancies, differences during lockdown were less marked (Lockdown 1: 52.99% vs. 56.26%; OR = 0.88; p = 0.15; Lockdown 2: 58.06% vs. 58.91%; OR = 0.97; p = 0.70). Reduced population mobility had no significant impact on preterm birth rates in singleton pregnancies (p = 0.14) but did have an impact on twin pregnancies (p = 0.02). Conclusions Reduced preterm birth rates during both lockdown periods in 2020 were observed for singleton and twin pregnancies. However, these effects are reduced when adjusting for long-term and seasonal trends. Reduced population mobility was associated with lower preterm birth rates in twin pregnancies. Einleitung Internationale Studien zu Frühgeburtenraten während den COVID-19-Lockdowns kommen zu unterschiedlichen Ergebnissen. Diese Studie untersucht die Frühgeburtenraten während den Lockdowns sowie die Auswirkungen von Änderungen der Bevölkerungsmobilität in Bayern auf die Frühgeburtenraten. Material und Methoden Es handelt sich um eine Sekundäranalyse von zentral erhobenen Daten zu Frühgeburten in Bayern zwischen 2010 und 2020. Die Frühgeburten (< 37. Schwangerschaftswoche) bei Einlings- und Zwillingsschwangerschaften, die in der Zeit der beiden Lockdowns auftraten, wurden den Frühgeburten in den Vergleichszeiträume der Jahre 2010 – 2019 gegenübergestellt. Die Rohprävalenzen der Gruppen wurden mit dem exakten Test nach Fisher verglichen. Additive logistische Regressionsmodelle wurden eingesetzt, um die potenziellen Auswirkungen von 2 Lockdowns sowie von Änderungen der Bevölkerungsmobilität auf die Frühgeburtenraten im Jahre 2020 zu untersuchen. Die Effekte wurden dann zusätzlich auf langfristige und saisonbedingte Trends adjustiert. Ergebnisse Die unbereinigten Frühgeburtenraten von Einlingsschwangerschaften während den 2 Lockdowns im Jahre 2020 waren signifikant niedriger (Lockdown 1: 5,71% vs. 6,41%; OR 0,88; p < 0,001; Lockdown 2: 5,71% vs. 6,60%; OR = 0,86; p < 0,001). Nachdem die Effekte auf langfristige und saisonbedingte Trends adjustiert worden waren, konnten die Auswirkungen aber nicht bestätigt werden (Lockdown 1: ber. OR = 0,99; p = 0,73; Lockdown 2: ber. OR = 0,96; p = 0,24). Die Unterschiede während der Lockdownzeiträume waren bei Zwillingsschwangerschaften weniger ausgeprägt (Lockdown 1: 52,99% vs. 56,26%; OR = 0,88; p = 0,15; Lockdown 2: 58,06% vs. 58,91%; OR = 0,97; p = 0,70). Eine geringere Bevölkerungsmobilität hatte keine signifikanten Auswirkungen auf die Frühgeburtenraten bei Einlingsschwangerschaften (p = 0,14), dafür aber auf die Frühgeburtenraten bei Zwillingsschwangerschaften (p = 0,02). Schlussfolgerungen Es wurden niedrigere Frühgeburtenraten bei Einlings- und Zwillingsschwangerschaften während den beiden Lockdowns im Jahre 2020 beobachtet. Diese Effekte wurden teilweise gemindert, wenn sie auf langfristige und saisonale Trends adjustiert wurden. Die geringere Bevölkerungsmobilität war mit einer niedrigeren Frühgeburtenrate bei Zwillingsschwangerschaften assoziiert. ^* Joint senior authors. Received: 04 April 2022 Accepted after revision: 19 May 2022 Article published online: 15 July 2022 © 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/) Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Atherosclerotic lesions preferentially develop at bifurcations, characterized by non-uniform shear stress (SS). The aim of this study was to investigate SS-induced endothelial activation, focusing on stress-regulated mitogen-activated protein kinases (MAPK) and downstream signaling, and its relation to gap junction proteins, Connexins (Cxs). Human umbilical vein endothelial cells were exposed to flow (“mechanical stimulation”) and stimulated with TNF-α (“inflammatory stimulation”). Phosphorylated levels of MAPKs (c-Jun N-terminal kinase (JNK1/2), extracellular signal-regulated kinase (ERK), and p38 kinase (p38K)) were quantified by flow cytometry, showing the activation of JNK1/2 and ERK. THP-1 cell adhesion under non-uniform SS was suppressed by the inhibition of JNK1/2, not of ERK. Immunofluorescence staining and quantitative real-time PCR demonstrated an induction of c-Jun and c-Fos and of Cx43 in endothelial cells by non-uniform SS, and the latter was abolished by JNK1/2 inhibition. Furthermore, plaque inflammation was analyzed in human carotid plaques (n = 40) using immunohistochemistry and quanti-gene RNA-assays, revealing elevated Cx43⁺ cell counts in vulnerable compared to stable plaques. Cx43⁺ cell burden in the plaque shoulder correlated with intraplaque neovascularization and lipid core size, while an inverse correlation was observed with fibrous cap thickness. Our results constitute the first report that JNK1/2 mediates Cx43 mechanoinduction in endothelial cells by atheroprone shear stress and that Cx43 is expressed in human carotid plaques. The correlation of Cx43⁺ cell counts with markers of plaque vulnerability implies its contribution to plaque progression.

Retention of circulating lipoproteins by their interaction with extracellular matrix molecules has been suggested as an underlying mechanism for atherosclerosis. We investigated the role of glypican-4 (GPC4), a heparan sulfate (HS) proteoglycan, in the development of endothelial dysfunction and plaque progression; Expression of GPC4 and HS was investigated in human umbilical vein/artery endothelial cells (HUVECs/HUAECs) using flow cytometry, qPCR, and immunofluorescent staining. Leukocyte adhesion was determined in HUVECs in bifurcation chamber slides under dynamic flow. The association between the degree of inflammation and GPC4, HS, and syndecan-4 expressions was analyzed in human carotid plaques; GPC4 was expressed in HUVECs/HUAECs. In HUVECs, GPC4 protein expression was higher in laminar than in non-uniform shear stress regions after a 1-day or 10-day flow (p < 0.01 each). The HS expression was higher under laminar flow after a 1 day (p < 0.001). Monocytic THP-1 cell adhesion to HUVECs was facilitated by GPC4 knock-down (p < 0.001) without affecting adhesion molecule expression. GPC4 and HS expression was lower in more-inflamed than in less-inflamed plaque shoulders (p < 0.05, each), especially in vulnerable plaque sections; Reduced expression of GPC4 was associated with atherogenic conditions, suggesting the involvement of GPC4 in both early and advanced stages of atherosclerosis.