Angiotensin-converting enzyme 2 (ACE2) has been established as the functional host receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the current devastating worldwide pandemic of coronavirus disease 2019 (COVID-19). ACE2 is abundantly expressed in a variety of cells residing in many different human organs. In human physiology, ACE2 is a pivotal counter-regulatory enzyme to ACE by the breakdown of angiotensin II, the central player in the renin-angiotensin-aldosterone system (RAAS) and the main substrate of ACE2. Many factors have been associated with both altered ACE2 expression and COVID-19 severity and progression, including age, sex, ethnicity, medication, and several co-morbidities, such as cardiovascular disease and metabolic syndrome. Although ACE2 is widely distributed in various human tissues and many of its determinants have been well recognised, ACE2-expressing organs do not equally participate in COVID-19 pathophysiology, implying that other mechanisms are involved in orchestrating cellular infection resulting in tissue damage. Reports of pathologic findings in tissue specimens of COVID-19 patients are rapidly emerging and confirm the established role of ACE2 expression and activity in disease pathogenesis. Identifying pathologic changes caused by SARS-CoV-2 infection is crucially important as it has major implications for understanding COVID-19 pathophysiology and the development of evidence-based treatment strategies. Currently, many interventional strategies are being explored in ongoing clinical trials, encompassing many drug classes and strategies, including antiviral drugs, biological response modifiers, and RAAS inhibitors. Ultimately, prevention is key to combat COVID-19 and appropriate measures are being taken accordingly, including development of effective vaccines. In this review, we describe the role of ACE2 in COVID-19 pathophysiology, including factors influencing ACE2 expression and activity in relation to COVID-19 severity. In addition, we discuss the relevant pathological changes resulting from SARS-CoV-2 infection. Finally, we highlight a selection of potential treatment modalities for COVID-19. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

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Angiotensin?converting enzyme 2 (ACE2), SARS?CoV?2 and the pathophysiology of coronavirus disease 2019 (COVID?19)

SARS-CoV-2 detection, viral load and infectivity over the course of an infection.

Vertical transmission of coronavirus disease 2019: a systematic review and meta-analysis.

A recent outbreak of a novel Coronavirus responsible for a Severe Acute Respiratory Syndrome (SARS-CoV-2) is spreading globally. The aim of this study was to systematically review main clinical characteristics and outcomes of SARS-CoV-2 infections in pediatric age. An electronic search was conducted in PubMed database. Papers published between 1 January and 1 May 2020 including children aged 0–18 years were selected. Sixty-two studies and three reviews were included, with a total sample size of 7480 children (2428/4660 males, 52.1%; weighted mean age 7.6 years). Patients showed mainly mild (608/1432, 42.5%) and moderate (567/1432, 39.6%) signs of the infection. About 2% of children were admitted to the pediatric intensive care unit. The most commonly described symptoms were fever (51.6%) and cough (47.3%). Laboratory findings were often unremarkable. Children underwent a chest CT scan in 73.9% of all cases, and 32.7% resulted normal. Overall, the estimated mortality was 0.08%. A higher proportion of newborns was severely ill (12%) and dyspnea was the most common reported sign (40%). Conclusion: SARS-CoV-2 affects children less severely than adults. Laboratory and radiology findings are mainly nonspecific. Larger epidemiological and clinical cohort studies are needed to better understand possible implications of COVID-19 infection in children.

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SARS-COV-2 infection in children and newborns: a systematic review.

The impact of SARS-CoV-2 infection during gestation remains unclear. Here, we analyse the viral genome on maternal and newborns nasopharyngeal swabs, vaginal swabs, maternal and umbilical cord plasma, placenta and umbilical cord biopsies, amniotic fluids and milk from 31 mothers with SARS-CoV-2 infection. In addition, we also test specific anti-SARS-CoV-2 antibodies and expression of genes involved in inflammatory responses in placentas, and in maternal and umbilical cord plasma. We detect SARS-CoV-2 genome in one umbilical cord blood and in two at-term placentas, in one vaginal mucosa and in one milk specimen. Furthermore, we report the presence of specific anti-SARS-CoV-2 IgM and IgG antibodies in one umbilical cord blood and in one milk specimen. Finally, in the three documented cases of vertical transmission, SARS-CoV-2 infection was accompanied by a strong inflammatory response. Together, these data support the hypothesis that in utero SARS-CoV-2 vertical transmission, while low, is possible. These results might help defining proper obstetric management of COVID-19 pregnant women, or putative indications for mode and timing of delivery.

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Wei Duan

Papers

Unlikely SARS-CoV-2 vertical transmission from mother to child: A case report.