Impact of COVID-19 Infection on the Course of Pregnancy and Fetal-neonatal Outcomes

Coronaviruses are a large family of viruses known to cause illnesses ranging from the common cold to more serious illnesses such as Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS). They are positive-stranded RNA viruses, with a corona-like appearance under the electron microscope, whose primary target cells are the epithelial cells of the respiratory and gastrointestinal tract. The 2019/20 COVID-19 respiratory disease pandemic, caused by a coronavirus, began in December 2019 in the city of Wuhan, the capital of the Chinese province of Hubei, which has subsequently spread to several countries around the world. In early January 2020, health authorities identified the virus responsible for the epidemic, designating it, initially as "Coronavirus 2019-nCoV" but later with the official name of "SARS-CoV-2". To date, seven Coronaviruses have been shown to be capable of infecting humans: Common Human Coronaviruses: HCoV-OC43 and HCoV-HKU1 (Betacoronavirus) and HCoV-229E and HCoV-NL63 (Alphacoronavirus); they can cause common colds but also severe lower respiratory tract infections; other human coronaviruses (Betacoronaviruses): SARS-CoV, MERS-CoV and 2019-nCoV (now referred to as SARS-CoV-2).

SARS-CoV-2 is therefore the seventh virus of the same family that involves humans, spreads through respiratory droplets and direct contact. The most common symptoms of the disease include fever, cough, asthenia or myalgia, wheezing and headache, and the most serious complication is acute respiratory distress syndrome (ARDS). The new coronavirus has continued to spread to multiple countries and continents so much so that the outbreak was declared a public health emergency of international concern (PHEIC) by the World Health Organization (WHO) on January 30, 2020.

In the first phase of world emergency, characterized by high morbidity and mortality, scientific interest has been mainly focused on the study of the transmission mechanisms of the infection, diagnostic tools and therapies for ARDS, especially in elderly patients and with co-morbidities. Interest has rapidly spread to other categories of patients and in particular to pregnancy, on which the virus could impact in different ways, with consequences for both the mother and the fetus.

During pregnancy, different changes in the immune system and adaptive changes affecting organs and systems are observed in relation to the gestational period, among which those affecting the respiratory system are highlighted, particularly evident in the third trimester including, upper airway mucosal edema induced by elevated levels of estrogen and progesterone, elevation of the diaphragm and consequent limited lung expansion, and high oxygen consumption, all conditions that increase the susceptibility of pregnant women to respiratory insults.

The maternal immune system during pregnancy undergoes specific adaptations aimed at establishing and maintaining a fetal allogeneic tolerance while preserving the ability to protect against external infectious agents. It goes from a pro-inflammatory state in the first trimester (important for implantation and placentation) to an anti-inflammatory state in the second trimester (necessary for fetal growth), and finally returns to a pro-inflammatory state again in the third trimester and during childbirth. In addition, innate immunity cells, that is, NK cells and monocytes respond more actively to viral insults, while the adaptive immune response is down-regulated (Hong Liu et al). As for CD4 + (Th) T cells, involved in the regulation of the inflammatory response through the production of cytokines, there is a shift in the maternal immune response from Th1 (with pro-inflammatory action) towards Th2 (with anti-inflammatory action ), a crucial modification for maintaining maternal-fetal tolerance (Wegmannetal et al.).