Respiratory viruses in pregnancy—a timely warning
Authors: Priya Venkatesan
Journal: The Lancet Microbe (2020)

This year has seen a huge increase in awareness of respiratory infectious diseases and vulnerable population groups in whom such diseases might be more severe. Pregnant women are one such vulnerable group. A 2012 review of data for influenza virus infections showed that pregnant women and their unborn babies are at an increased risk for severe complications compared with the general population, including cardiopulmonary events and neonatal complications, but the reasons underlying the increased risk are still not fully understood. However, a new preclinical study in pregnant mice might offer specific clues to why this increased severity occurs. The investigators showed that infection with influenza A virus caused changes in the maternal vasculature of pregnant mice, causing widespread dissemination of the virus to major maternal blood vessels resulting in a peripheral vascular storm of elevated proinflammatory and antiviral mediators. The consequences of this vascular storm included maternal vascular dysfunction and resulting restriction of placental and intrauterine growth. By contrast, influenza A virus infection in non-pregnant mice did not cause changes in blood vessels or vascular inflammation, and the virus and inflammatory response remained localised to the lungs. Denise Jamieson (Emory University, Atlanta, GA, USA) commented “It has never been entirely clear why pregnant women are more at risk for severe disease from influenza. While there are many issues with extrapolating these findings from mice to humans, [this study] does raise questions about potential mechanisms for increased severity”. Sonja Rasmussen (University of Florida College of Medicine, FL, USA) agreed, stating “This study provides important insights, which, if replicated in humans, might suggest better ways to treat women infected with influenza during pregnancy”. The preclinical study also serves as a timely reminder of the importance of influenza vaccination for pregnant women this year, particularly given the ongoing COVID-19 pandemic. Not only could two major virus outbreaks cause undue stress on health-care systems, but also COVID-19 infection itself seems to cause severe complications in pregnant women. A study from the US Centers for Disease Control and Prevention (CDC) of pregnant versus non-pregnant women from Jan 22 to June 7, 2020, showed that 2587 (31·5%) of 8207 pregnant women with confirmed COVID-19 were admitted to hospital compared with 4840 (5·8%) of 83 205 non-pregnant women with COVID-19, and pregnant women were more likely to be admitted to an intensive care unit (adjusted risk ratio 1·5, 95% CI 1·2–1·8) and receive mechanical ventilation (1·7, 1·2–2·4). In addition, a small Swedish study found a higher incidence of ICU admission among pregnant or post-partum women with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (14·4 [95% CI 7·3–23·4] per 100 000) versus non-pregnant women in the same age group (2·5 [1·8–3·5] per 100 000) in the study period, whereas a systematic review of 339 women in two studies showed that the risk of pre-term birth was higher in pregnant women with COVID-19 than in pregnant women without the disease (odds ratio 3·0, 95% CI 1·15–7·85). Based on current data, CDC are advising that pregnant individuals might be at increased risk for severe illness with COVID-19 compared with non-pregnant individuals, and at increased risk of pre-term birth. Jamieson commented “I think there is now compelling evidence that pregnant women are more severely affected by COVID-19. Pregnant women who are overweight or have other underlying medical conditions are even more severely affected”. Rasmussen added “The data we have now suggest that pregnant women are at increased risk for severe complications from COVID-19, when compared [with] non-pregnant women of childbearing age. It's important that pregnant women do what they can to avoid getting infected with COVID-19—wear a mask, keep at least 6 feet from individuals outside of their family, and wash their hands”. Pregnant women potentially also need to be included in clinical trials for COVID-19 vaccines so that data are available on how the vaccines work and to be sure they are safe during pregnancy. Another reason for the importance of pregnant women avoiding influenza this year is that co-infection with both influenza and COVID-19 could have severe adverse effects. Data from Public Health England recently shared on a preprint server indicates that patients in the general population in England co-infected with influenza and SARS-CoV-2 between January and April, 2020, had a greater risk of death than those infected with SARS-CoV-2 alone (adjusted odds ratio 5·92, 95% CI 3·21–10·91), and were more at risk of severe illness. As Jamieson commented “It is more important than ever that pregnant women get immunised against influenza this year. The combined effects of influenza and COVID-19 could potentially be devastating”.