key: cord-0751169-7k6yojge authors: Skarstein Kolberg, Espen title: ACE2, COVID19 and serum ACE as a possible biomarker to predict severity of disease date: 2020-04-02 journal: J Clin Virol DOI: 10.1016/j.jcv.2020.104350 sha: 0fd60c231b28076c5195a8b611873708adc454ad doc_id: 751169 cord_uid: 7k6yojge nan Letter to the editor ACE2, COVID19 and serum ACE as a possible biomarker to predict severity of disease Preliminary epidemiological data indicates that symptomatic Coronavirus disease 2019 in children is uncommon. In a cohort of 44 672 confirmed cases in China, only 1% were younger than 10 years of age [1] . This could suggest that children are less susceptible to infection, or that infection in children leads to asymptomatic or mild disease that remains largely undetected. Cellular entry of SARS-CoV-2, the causative agent for COVID-19, is facilitated by binding of viral spike proteins to Angiotensin Converting Enzyme 2 (ACE2) receptors on host membranes [2] . This raises the possibility that susceptibility to infection is related to expression of the target ACE2 receptor in virally exposed epithelium [2] . However, a complex too much/too soon relationship is at play here, as the related SARS-CoV virus has been shown to downregulate ACE2 after cell entry, a factor contributing to the severe lung pathologies associated with infection with this virus [3] . Evidence suggest that there is a counter-regulatory relationship between ACE2 and its homologue, Angiotensin Converting Enzyme (ACE), as they take part in opposite axes in the Renin-Angiotensin-System (RAS). For example, drugs that inhibit ACE activity induces ACE2 expression [4] . Therefore, high levels of ACE could indicate low levels of ACE2, and vice versa [4] . Children have higher ACE volumes in serum than adults [5] . Considering the inverse relationship between ACE and ACE2, could this difference similarly reflect a lower degree of ACE2 expression in children compared with adults? The same study found that adolescents had higher levels of circulating ACE than adults [5] , and is interesting to note that COVID-19 in the age group 10-19 years also amounted to only 1% in the Chinese cohort [1] . It remains to be verified if the low frequency of symptomatic COVID-19 in children and adolescents can be attributed to lower levels of membrane bound ACE2 in this population. It is equally uncertain that serum ACE is inversely related to ACE2 expression in airway epithelium and other tissue. The hypothesis that serum ACE could serve as a biomarker for the severity of COVID-19 therefore hinges on the data being able to draw a line between the propositions outlined above. Should such a relationship be established, it could provide us with a powerful tool for early intervention in and triage of COVID-19 patients. Low levels of circulating ACE in symptomatic patients could predict mild disease, whereas high levels could be indicative of a more severe progression, cf. the biphasic role of ACE2 found in airway infection with the related SARS-CoV virus [3] . This work contains previously unpublished material and is not being considered for publication elsewhere. None. As this letter presents a theoretical hypothesis and contains no patient data, approval from the regional committees for medical and health research ethics in Norway was not required. The author declares no conflict of interest. Characteristics of and important lessons from the Coronavirus Disease 2019 (COVID-19) Outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention Receptor recognition by novel coronavirus from Wuhan: an analysis based on decade-long structural studies of SARS A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury The vasoprotective axes of the renin-angiotensin system: physiological relevance and therapeutic implications in cardiovascular, hypertensive and kidney diseases Serum angiotensin-converting enzyme activity in normal children and in those with sarcoidosis I would like to thank my colleagues for their support and for providing a fertile environment for discussing ideas and theories.