ABSTRACT
Background: To inform vaccine prioritization guidance by the National Advisory Committee on Immunization (NACI), we reviewed evidence on the magnitude of association between risk factors and severe outcomes of COVID-19. Methods: We updated our existing review by searching online databases and websites for cohort studies providing multivariate adjusted associations. One author screened studies and extracted data. Two authors estimated the magnitude of association between exposures and outcomes as little-to-no (odds, risk, or hazard ratio <2.0, or >0.50 for reduction), large (2.0-3.9, or 0.50-0.26 for reduction), or very large (>=4.0, or <=0.25 for reduction), and rated the evidence certainty using GRADE. Results: Of 7,819 unique records we included 111 reports. There is probably (moderate certainty) at least a large increase in mortality from COVID-19 among people aged 60-69 vs. <60 years (11 studies, n=517,217), with 2+ vs. no comorbidities (4 studies, n=189,608), and for people with (vs. without): Down syndrome (1 study, n>8 million), type 1 and 2 diabetes (1 study, n>8 million), end-stage kidney disease (1 study, n>8 million), epilepsy (1 study, n>8 million), motor neuron disease, multiple sclerosis, myasthenia gravis, or Huntingtons disease (as a grouping; 1 study, n>8 million). The magnitude of association with mortality is probably very large for Down syndrome and may (low certainty) be very large for age 60-69 years, and diabetes. There is probably little-to-no increase in severe outcomes with several cardiovascular and respiratory conditions, and for adult males vs. females. Interpretation: Future research should focus on risk factors where evidence is low quality (e.g., social factors) or non-existent (e.g., rare conditions), the pediatric population, combinations of comorbidities that may increase risk, and long-term outcomes. Systematic review registration: PROSPERO #CRD42021230185.