ABSTRACT
Long COVID has become a world-wide, non-communicable epidemic, caused by long-lasting multi-organ symptoms that endure for weeks or months after SARS-CoV-2 infection has already subsided. This scientific document aims to provide insight into the possible causes and therapeutic options available for the cardiovascular manifestations of long COVID. In addition to chronic fatigue, which is a common symptom of long COVID, patients may present with chest pain, ECG abnormalities, postural orthostatic tachycardia, or newly developed supraventricular or ventricular arrhythmias. Imaging of the heart and vessels has provided evidence of chronic, post-infectious peri-myocarditis with consequent left or right ventricular failure, arterial wall inflammation or micro-thrombosis in certain patient populations. Better understanding of the underlying cellular and molecular mechanisms of long COVID will aid in the development of effective treatment strategies for its cardiovascular manifestations. A number of mechanisms have been proposed, including those involving direct effects on the myocardium, micro-thrombotic damage to vessels or endothelium, or persistent inflammation. Unfortunately, existing circulating biomarkers, coagulation and inflammatory markers, are not highly predictive for either the presence or outcome of long COVID when measured 3 months after SARS-CoV-2 infection. Further studies are needed to understand underlying mechanisms, identify specific biomarkers and guide future preventive strategies or treatments to address long COVID and its cardiovascular sequelae.
ABSTRACT
Ischaemic heart disease (IHD) is a complex disorder and a leading cause of death and morbidity in both men and women. Sex, however, affects several aspects of IHD, including pathophysiology, incidence, clinical presentation, diagnosis as well as treatment and outcome. Several diseases or risk factors frequently associated with IHD can modify cellular signalling cascades, thus affecting ischaemia/reperfusion injury as well as responses to cardioprotective interventions. Importantly, the prevalence and impact of risk factors and several comorbidities differ between males and females, and their effects on IHD development and prognosis might differ according to sex. The cellular and molecular mechanisms underlying these differences are still poorly understood, and their identification might have important translational implications in the prediction or prevention of risk of IHD in men and women. Despite this, most experimental studies on IHD are still undertaken in animal models in the absence of risk factors and comorbidities, and assessment of potential sex-specific differences are largely missing. This ESC WG Position Paper will discuss: (i) the importance of sex as a biological variable in cardiovascular research, (ii) major biological mechanisms underlying sex-related differences relevant to IHD risk factors and comorbidities, (iii) prospects and pitfalls of preclinical models to investigate these associations, and finally (iv) will provide recommendations to guide future research. Although gender differences also affect IHD risk in the clinical setting, they will not be discussed in detail here.