The excellent AEPC position paper of Skaiste Sendzikaite et al. CY 2021 ^{Reference Sendzikaite, Heying, Milanesi, Hanseus and Michel-Behnke1} describes the cardiovascular consequences of the highly contagious SARS-CoV2 in children, especially those with associated CHDs. The clinical symptoms of SARS-CoV2 infection in children range from asymptomatic disorders to severe (paediatric) inflammatory multisystem syndrome, which in some cases corresponds to systemic vasculitis. Immune dysregulation and pathogen-induced “cytokine storm” in COVID-19 have been described in detail. ^{Reference Feigenbaum and June2} Two partially overlapping phenotypes associated with severe COVID-19 infection were found: on the one hand, acute respiratory distress syndrome ^{Reference Wu, Chen and Cai3} and, on the other hand, a predominant microvascular disease, which is classified as endotheliopathy in connection with generalised coagulopathy. ^{Reference Varga, Flammer and Steiger4} The latter can lead to multiple (vital) organ dysfunction and ultimately to failure. Fortunately, severe symptomatic COVID-19 infection by the wild-type is rare in children. Additionally, a paediatric acute respiratory distress syndrome phenotype is less common than vasculopathy including a “Kawasaki-like” syndrome. ^{Reference Viner and Whittaker5} The “Alpha”-variant (B.1.1.7) or other mutations (Beta-, Gamma-, Delta-variants) seem to be more contagious and infectious, particularly in people under the age of 20 years. ^{Reference Swann, Holden and Turtle6} Furthermore, the spike variants have an increased affinity of binding to human angiotensin converting enzyme 2. ^{Reference Ramanathan, Ferguson, Miao and Khavari7} Given the therapeutic options, it is a little too short to address especially acute cardiovascular management issues by citing a comprehensive guidance document developed for adults during the COVID-19 pandemic. ⁸ An important aspect that the COVID pandemic has in common with the general situation in the cardiovascular treatment of children is the lack of evidence-based data, which is why hypothesis-driven therapy is required. From my point of view, COVID-19-associated cardiovascular manifestations, in particular coronary involvement, are reminiscent of a Parvo B19 infection, which in the sense of vasculitis preferably affects the microvascular endothelial cells, followed by a secondary myocarditis phenotype. ^{Reference Klingel, Sauter, Bock, Szalay, Schnorr and Kandolf9} This differs from a classic Kawasaki syndrome, in which the epicardial coronary arteries are preferentially affected and are rarely associated with sequalae myocarditis. However, this does not mean that initial medical treatment, including high-dose immunoglobulin therapy, should be withheld. ^{Reference Hu, Ma, Wei and Fang10} In addition, as described by the authors, ^{Reference Sendzikaite, Heying, Milanesi, Hanseus and Michel-Behnke1} infants seem to have a higher risk for a more severe clinical course of a vasculitis-like infection. A fulminant acute myocardial necrosis and mononuclear cell infiltration were observed, but only rarely virus particles in myocardial tissue, ^{Reference Tavazzi, Pellegrini and Maurelli11} but certainly in the endothelium. ^{Reference Lowenstein and Solomon12} The mutant change is associated not only with a higher infectivity but obviously also with a more intense virus load. The endothelium as the primary target is more severely affected. A transient “endothelial stunning” of the “wild-type” seems to be changed to an endothelial injury, which also requires longer time for regeneration. The cardiovascular sequelae become more intense. The profile of seriously ill patients with myocarditis-like or ischaemic heart failure with reduced ejection fraction corresponding to clinical picture of tachypnoea and elevated troponin and natriuretic peptide levels appear more frequently. To what extent there is a separation or even an increased overlap with patients with a dominant phenotype of pulmonary dysfunction, which is characterised by dyspnoea and reduced arterial oxygen saturation (hypoxemia), is currently open. ^{Reference Swann, Holden and Turtle13} In any case, knowledge about the entry, replication, and innate immune activation of viruses has increased, including the involvement of several distinct Toll-like-receptors and subsequent pathways in SARS-CoV-2 pathogenesis. ^{Reference Onofrio, Caraglia, Facchini, Margherita, De Placido and Buonerba14} With regard to the consequences of COVID-19-associated endothelial disease, however, the therapeutic potential has not been fully exploited. It can be postulated that COVID endotheliopathy leads to an inhibition of the innate endothelial nitric oxide-synthetase-dependent production of nitric oxide and in particular cyclooxygenase-related prostacyclin production with subsequent hypercoagulopathy and finally vascular obstruction. ^{Reference Lowenstein and Solomon12,Reference Gladka and Maack15} In-situ thrombosis formation can be monitored by elevated D-dimer levels, which are closely linked to mortality and morbidity. ^{Reference Tang, Li, Wang and Sun16} In this pathophysiological context, the therapeutic potentials of prostacyclin currently seem to receive too less attention. ^{Reference Sarkar, Mondal and Torequl Islam17,Reference Weiss, Peters and Alhazzani18} The guidelines do not recommend a therapeutic replacement of substances, which are lacking due to endogenous endothelial dysfunction or even damage. ^{Reference Sendzikaite, Heying, Milanesi, Hanseus and Michel-Behnke1,8,Reference Sarkar, Mondal and Torequl Islam17} In contrast to a disrupted endothelial nitric oxide pathway, prostacyclin can easily be replaced since it has been available for decades. From the paediatric point of view, prostacyclin is available as ilomedin or epoprostenol both administrable by continuous intravenous infusion at doses of 1–2 ng/kg/minute or 5-(10) ng/kg/minute, respectively. This dose range is safe, but effective. It can be monitored by subsequent decrease of D-dimer and concerning the coronary involvement by falling troponin levels. Based on previous experience with prostacyclin treatment in life-threatening paediatric “purpura fulminans”, partly together with substitution of activated protein-C, ^{Reference Mueller, Ehrenthal, Hafner and Schranz19} we also used successfully ilomedin, but currently only anecdotally in infants with paediatric inflammatory multisystem syndrome (PIMS). It can be hypothesised that prostacyclin infusion is a promising replacement therapy, suitable for COVID-19-associated microvascular diseases with thrombotic and ischaemic consequences. Prostacyclin combines platelet inhibition and support of microvascular function, which is not limited to pulmonary circulation. A Danish study on the use of ilomedin (1 ng/kg/min) in COVID-patients is planned and already started in adults. ^{Reference Johansson, Bestle, Søe-Jensen, Kristiansen, Stensballe, Clausen and Perner20} In contrast to prostacyclin, which is not yet generally used, low-dosed acetyl salicylic acid has proven to be beneficial in moderately to severely ill COVID-19 patients, if prophylactically applicated. ^{Reference Viecca, Radovanovic, Forleo and Santu21} Adapted to follow-up treatment for Kawasaki syndrome and from COVID-19 patients with a history of elevated troponin-I and D-dimer levels, low-dose aspirin (1–2 mg kg once a day) is recommended for follow-up treatment for 3–6 months. ^{Reference McCrindle, Rowley and Newburger22} In patients with an additional myocarditis phenotype, we also combine low-dose aspirin with clopidogrel for 3 months, which is not proved, yet.