The isolated effect of age on the risk of COVID-19 severe outcomes: a systematic review with meta-analysis
Authors: Starke Karla Romero , Reissig David , Petereit-Haack Gabriela , Schmauder Stefanie , Nienhaus Albert , Seidler Andreas 
Published: May 2021

AbstractIntroductionIncreased age has been reported to be a factor for COVID-19 severe outcomes. However, many studies do not consider the age-dependency of comorbidities, which influence the course of disease. Protection strategies often target individuals after a certain age, which may not necessarily be evidence-based. The aim of this review was to quantify the isolated effect of age on hospitalization, admission to ICU, mechanical ventilation, and death.MethodsThis review was based on an umbrella review, in which Pubmed, Embase, and pre-print databases were searched on December 10, 2020 for relevant reviews on COVID-19 disease severity. Two independent reviewers evaluated the primary studies using predefined inclusion and exclusion criteria. The results were extracted, and each study was assessed for risk of bias. The isolated effect of age was estimated by meta-analysis, and the quality of evidence was assessed using GRADE.ResultsSeventy studies met our inclusion criteria (case mortality n=14, in-hospital mortality n=44, hospitalization n=16, admission to ICU n=12, mechanical ventilation n=7). The risk of in-hospital and case mortality increased per age year by 5.7% and 7.4%, respectively (Effect Size (ES) in-hospital mortality=1.057, 95% CI:1.038-1.054; ES case mortality= 1.074, 95% CI:1.061-1.087), while the risk of hospitalization increased by 3.4% per age year (ES=1.034, 95% CI:1.021-1.048). No increased risk was observed for ICU admission and intubation by age year. There was no evidence of a specific age threshold at which the risk accelerates considerably. The confidence of evidence was high for mortality and hospitalization.ConclusionsOur results show a best-possible quantification of the increase in COVID-19 disease severity due to age. Rather than implementing age thresholds, prevention programs should consider the continuous increase in risk. There is a need for continuous, high-quality research and “living” reviews to evaluate the evidence throughout the pandemic, as results may change due to varying circumstances.What is already known?Increasing age and comorbidities are risk factors for COVID-19 severe outcomes, such as hospitalization and mortality. However, comorbidities such as diabetes, cardiovascular disease, chronic pulmonary diseases increase with age, and the isolated effect of age on COVID-19 disease severity is not known.What are the new findings?The risk of COVID-19 disease severity due to the isolated effect of age increases by age year and no specific age threshold was observed.A best possible quantification of the increase in risk of COVID-19 severe outcomes due to age has been done.What do the new findings imply?Any workplace restrictions targeting a particular older age group are rather arbitrary, and may contribute to ageism in the society.If scores are to be built to assess an individual’s risk for COVID-19 severe outcomes in workplace settings, these should be based on per-age increases.