The COVID-19 pandemic and related political and public health strategies have given rise to controversial discussions about general restrictions such as social distancing, adverse impact on mental health, social harm and economic damage, and the sense of pinning all hope on vaccination. SARS-CoV-2 infection covers a wide range from asymptomatic carriers via mild and moderate courses of disease to life-threatening conditions, and robust immune functions can be regarded as an efficient protective shield. By means of systemic meta-synthesis the present article elucidates inner connections between cardiorespiratory fitness (CRF) and the immune system and discusses how CRF can modulate critical co-factors such as stress, depression and metabolic syndrome. Understanding translational medicine from a public health perspective involves health education alongside steps to enhance health awareness and self-administered health promotion in the wider population. These interdisciplinary challenges call for appropriate models, which also involve arts-based activities and creative sports.