Coronavirus Disease 2019 (COVID-19) is caused by the novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) - the culprit of an ongoing pandemic responsible for the loss of over 3 million lives worldwide within a year and a half. While the majority of SARS-CoV-2 infected people develop no or mild symptoms, some become severely ill and may die from COVID-19-related complications. In this review, we compile and comment on a number of biomarkers that have been identified and are expected to enhance the detection, protection and treatment of individuals at high risk of developing severe illnesses, as well as enable the monitoring of COVID-19 prognosis and responsiveness to therapeutic interventions. Consistent with the emerging notion that the majority of COVID-19 deaths occur in older and frail individuals, we researched the scientific literature and report the identification of a subset of COVID-19 biomarkers indicative of increased vulnerability to developing severe COVID-19 in older and frail patients. Mechanistically, increased frailty results from reduced disease tolerance, a phenomenon aggravated by ageing and comorbidities. While biomarkers of ageing and frailty may predict COVID-19 severity, biomarkers of disease tolerance may predict resistance to COVID-19 with socio-economic factors such as access to adequate health care remaining as major non-biomolecular influencers of COVID-19 outcomes. Graphical Abstract Figure: Biomarkers of ageing and frailty may predict COVID-19 severity as both conditions are associated with reduced disease tolerance - the host’s defense mechanisms to limit tissue damage or reduce immunopathology induced by the infection with a pathogen. While these biomolecular markers inform about the baseline ground for exacerbated viral infection, inflammaging and pre-existing comorbidities, which are common at advanced ages, as well as socio-economic conditions that affect people in underdeveloped nations and underserved communities of developed nations appear to be strong influencers of COVID-19 trajectory - particularly in older and frail individuals.ga1