The isolated effect of age on the risk of COVID-19 severe outcomes: a systematic review with meta-analysis.

INTRODUCTION: Increased 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 hospitalisation, admission to intensive care unit (ICU), mechanical ventilation and death. METHODS: This review was based on an umbrella review, in which Pubmed, Embase and preprint databases were searched on 10 December 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 Grades of Recommendations, Assessment, Development, and Evaluation framework. RESULTS: Seventy studies met our inclusion criteria (case mortality: n=14, in-hospital mortality: n=44, hospitalisation: 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 to 1.054; ES case mortality=1.074, 95% CI 1.061 to 1.087), while the risk of hospitalisation increased by 3.4% per age year (ES=1.034, 95% CI 1.021 to 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 hospitalisation. CONCLUSIONS: Our results show a best-possible quantification of the increase in COVID-19 disease severity due to age. Rather than implementing age thresholds, prevention programmes 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.

The Age-Related Risk of Severe Outcomes Due to COVID-19 Infection: A Rapid Review, Meta-Analysis, and Meta-Regression.

Increased age appears to be a strong risk factor for COVID-19 severe outcomes. However, studies do not sufficiently consider the age-dependency of other important factors influencing the course of disease. The aim of this review was to quantify the isolated effect of age on severe COVID-19 outcomes. We searched Pubmed to find relevant studies published in 2020. Two independent reviewers evaluated them using predefined inclusion and exclusion criteria. We extracted the results and assessed seven domains of bias for each study. After adjusting for important age-related risk factors, the isolated effect of age was estimated using meta-regression. Twelve studies met our inclusion criteria: four studies for COVID-19 disease severity, seven for mortality, and one for admission to ICU. The crude effect of age (5.2% and 13.4% higher risk of disease severity and death per age year, respectively) substantially decreased when adjusting for important age-dependent risk factors (diabetes, hypertension, coronary heart disease/cerebrovascular disease, compromised immunity, previous respiratory disease, renal disease). Adjusting for all six comorbidities indicates a 2.7% risk increase for disease severity (two studies), and no additional risk of death per year of age (five studies). The indication of a rather weak influence of age on COVID-19 disease severity after adjustment for important age-dependent risk factors should be taken in consideration when implementing age-related preventative measures (e.g., age-dependent work restrictions).