COVID-19 remains a health care concern despite the end of the pandemic. Patients with cardiovascular disease (CVD) are at a higher risk for developing severe COVID-19 complications. Studies investigating the COVID-19 clinical characteristics in pulmonary arterial hypertension (PAH) patients have reported discordant conclusions so far. In this review, we summarize the literature pertaining to the clinical presentation of COVID-19 in patients with PAH. In addition, we discuss common pathological aspects and disease mechanisms between PAH and COVID-19. We present an overview of the different types of PAH-approved therapy and their potential utilization as a treatment in the context of COVID-19. Moreover, we summarize the clinical trials that assessed the safety and efficiency of PAH-approved drugs in COVID-19 patients. Finally, we conclude with proposals for prospective research studies.

Pulmonary hypertension (PH) is a serious and life-threatening disease characterized by elevated mean arterial pressure and pulmonary vascular resistance. COVID-19 may exacerbate PH, as evidenced by higher mortality rates among those with PH. The objective of this study was to understand the unique burdens that the COVID-19 pandemic has placed upon families of children living with PH.

Participants were recruited online through the "Families of children with pulmonary hypertension" Facebook group and asked to complete a survey about their experiences during the COVID-19 pandemic.

A total of 139 parents/caregivers of children living with PH completed the online survey. Almost all (85.6%) of parents/caregivers had received the COVID-19 vaccine, though only 59.7% reported a willingness to vaccinate their child with PH against COVID-19. Over 75% of parents/caregivers felt that they practiced preventative measures (e.g., wearing a facemask, social distancing, and avoiding gatherings) more than those in the community where they live. They also reported several hardships related to caring for their child with PH during the pandemic such as financial duress, loss of work, and affording treatment costs.

These findings indicate that parents/caregivers of children at higher risk for COVID-19 complications may be more willing to act on clinical recommendations themselves as proxy for protecting those at high risk. The economic, emotional and social impacts of COVID-19 are significantly greater for high-risk individuals.

Respiratory tract infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first occurred in Wuhan, China, in December 2019 and was declared as a pandemic by WHO. The interaction between the 2019 coronavirus disease (COVID-19) and pulmonary hypertension (PH) in children is not widely known. Phosphodiesterase-5 inhibitors (PDEI), one class of drugs used to treat PH, including sildenafil, can suppress angiotensin type I (AT-1) receptor expression. Furthermore, it reduces proinflammatory cytokines and infiltrates the alveolar, inhibits endothelial and smooth muscle transition, mesenchymal cells in the pulmonary artery, and prevents clotting and thrombosis complications. Sildenafil has shown positive effects by diverting the blood flow to the lungs in such a way that ventilation is adequate and can also be anti-inflammatory.

The Coronavirus disease 2019 (COVID-19) pandemic has severely affected the lives of people around the world, especially some patients with severe chronic diseases. This study aims to evaluate the impact of the COVID-19 outbreak from December 2019 to April 2020 on treating patients with PH. A questionnaire regarding the medical condition of PH patients during the COVID-19 pandemic was designed by PH diagnostic experts in The First Affiliated Hospital of Guangzhou Medical University, China Respiratory Center. One hundred and fifty-six subjects with PH from non-Hubei regions in China were invited to participate in this survey online. 63.4% (n = 99) of them had difficulty seeing a doctor, and the main reason was fear of contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the hospital. Medical treatment was affected in 25% (n = 39) of patients, and who lived in rural areas, and discontinued medical therapy for financial reasons were at a higher risk of medical treatment being affected. Patients who reduced nutrition, and had difficulty seeing a doctor were more likely to get deteriorated. During the epidemic, the hospitalization rate of PH patients was 33.33%. Patients with aggravated PH had a high risk of hospitalization (odds ratio [OR] = 2.844), while patients who visited a doctor during the epidemic reduced the risk of hospitalization (OR = 0.33). In conclusion, during the COVID-19 pandemic, PH patients had difficulty seeing a doctor, and their medical treatment was affected, even worsened, and increased the risk of hospitalization.

Pulmonary parenchymal and vascular damage are frequently reported in COVID-19 patients and can be assessed with unenhanced chest computed tomography (CT), widely used as a triaging exam. Integrating clinical data, chest CT features, and CT-derived vascular metrics, we aimed to build a predictive model of in-hospital mortality using univariate analysis (Mann-Whitney U test) and machine learning models (support vectors machines (SVM) and multilayer perceptrons (MLP)). Patients with RT-PCR-confirmed SARS-CoV-2 infection and unenhanced chest CT performed on emergency department admission were included after retrieving their outcome (discharge or death), with an 85/15% training/test dataset split. Out of 897 patients, the 229 (26%) patients who died during hospitalization had higher median pulmonary artery diameter (29.0 mm) than patients who survived (27.0 mm, p < 0.001) and higher median ascending aortic diameter (36.6 mm versus 34.0 mm, p < 0.001). SVM and MLP best models considered the same ten input features, yielding a 0.747 (precision 0.522, recall 0.800) and 0.844 (precision 0.680, recall 0.567) area under the curve, respectively. In this model integrating clinical and radiological data, pulmonary artery diameter was the third most important predictor after age and parenchymal involvement extent, contributing to reliable in-hospital mortality prediction, highlighting the value of vascular metrics in improving patient stratification.

Since the beginning of the pandemic, coronavirus disease-2019 (COVID-19) in children has shown milder cases and a better prognosis than adults. Although the respiratory tract is the primary target for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), cardiovascular involvement is emerging as one of the most significant and life-threatening complications of SARS-CoV-2 infection in adults.

To summarize the current knowledge about the potential cardiovascular involvement in pediatric COVID-19 in order to give a perspective on how to take care of them during the current pandemic emergency.

Multiple searches in MEDLINE, PubMed were performed using the search terms "COVID-19" or "SARS-CoV-2" were used in combination with "myocardial injury" or "arrhythmia" or "cardiovascular involvement" or "heart disease" or "congenital heart disease" or "pulmonary hypertension" or "long QT" or "cardiomyopathies" or "channelopathies" or "Multisystem inflammatory system" or "PMIS" or "MIS-C" or "Pediatric multisystem inflammatory syndrome" or "myocarditis" or "thromboembolism to identify articles published in English language from January 1st, 2020 until July 31st, 2020. The websites of World Health Organization, Centers for Disease control and Prevention, and the Johns Hopkins Coronavirus Resource Center were reviewed to provide up to date numbers and infection control recommendations. Reference lists from the articles were reviewed to identify additional pertinent articles. Retrieved manuscripts concerning the subject were reviewed by the authors, and the data were extracted using a standardized collection tool. Data were subsequently analyzed with descriptive statistics. For Pediatric multisystemic inflammatory syndrome temporally associated with COVID-19 (PMIS), multiple meta-analyses were conducted to summarize the pooled mean proportion of different cardiovascular variables in this population in pseudo-cohorts of observed patients.

A total of 193 articles were included. Most publications used in this review were single case reports, small case series, and observational small-sized studies or literature reviews. The meta-analysis of 16 studies with size > 10 patients and with complete data about cardiovascular involvement in children with PMIS showed that PMIS affects mostly previously healthy school-aged children and adolescents presenting with Kawasaki disease-like features and multiple organ failure with a focus on the heart, accounting for most cases of pediatric COVID-19 mortality. They frequently presented cardiogenic shock (53%), ECG alterations (27%), myocardial dysfunction (52%), and coronary artery dilation (15%). Most cases required PICU admission (75%) and inotropic support (57%), with the rare need for extracorporeal membrane oxygenation (4%). Almost all of these children wholly recovered in a few days, although rare deaths have been reported (2%). Out of PMIS cases we identified 10 articles reporting sporadic cases of myocarditis, pulmonary hypertension and cardiac arrythmias in previously healthy children. We also found another 10 studies reporting patients with pre-existing heart diseases. Most cases consisted in children with severe COVID-19 infection with full recovery after intensive care support, but cases of death were also identified. The management of different cardiac conditions are provided based on current guidelines and expert panel recommendations.

There is still scarce data about the role of cardiovascular involvement in COVID-19 in children. Based on our review, children (previously healthy or with pre-existing heart disease) with acute COVID-19 requiring hospital admission should undergo a cardiac workup and close cardiovascular monitoring to identify and treat timely life-threatening cardiac complications.