Age-Adjusted Associations Between Comorbidity and Outcomes of COVID-19: A Review of the Evidence From the Early Stages of the Pandemic

Abstract

Objectives: Early in the COVID-19 pandemic, people with underlying comorbidities were overrepresented in hospitalised cases of COVID-19, but the relationship between comorbidity and COVID-19 outcomes was complicated by potential confounding by age. This review therefore sought to characterise the international evidence base available in the early stages of the pandemic on the association between comorbidities and progression to severe disease, critical care, or death, after accounting for age, among hospitalised patients with COVID-19. Methods: We conducted a rapid, comprehensive review of the literature (to 14 May 2020), to assess the international evidence on the age-adjusted association between comorbidities and severe COVID-19 progression or death, among hospitalised COVID-19 patients - the only population for whom studies were available at that time. Results: After screening 1,100 studies, we identified 14 eligible for inclusion. Overall, evidence for obesity and cancer increasing risk of severe disease or death was most consistent. Most studies found that having at least one of obesity, diabetes mellitus, hypertension, heart disease, cancer, or chronic lung disease was significantly associated with worse outcomes following hospitalisation. Associations were more consistent for mortality than other outcomes. Increasing numbers of comorbidities and obesity both showed a dose-response relationship. Quality and reporting were suboptimal in these rapidly conducted studies, and there was a clear need for additional studies using population-based samples. Conclusions: This review summarises the most robust evidence on this topic that was available in the first few months of the pandemic. It was clear at this early stage that COVID-19 would go on to exacerbate existing health inequalities unless actions were taken to reduce pre-existing vulnerabilities and target control measures to protect groups with chronic health conditions.

Keywords: COVID-19; chronic disease; comorbidity; coronavirus; review.

Figure 1

Flowchart of progression of studies through the review of age-adjusted associations between comorbidity and outcomes of COVID-19 in the early stages of the pandemic.

Figure 2

Forest plot of study estimates of the association between comorbidities and COVID-19 mortality among hospitalized patients. Reference category for each comorbidity is the absence of that comorbidity, except where stated otherwise. HR, hazard ratio (red); OR, odds ratio (blue); CI, confidence interval; BMI, body mass index; COPD, chronic obstructive pulmonary disease. All estimates adjusted for age. Additionally adjusted for: sex [s]; other comorbidities [c]; ethnicity [e]; deprivation [d]. *95% CI not reported, but back-calculated from reported p-value.

Figure 3

Forest plot of study estimates of the association between comorbidities and composite severe endpoint (death, intensive care unit admission, severe or critical symptoms, or invasive mechanical ventilation) among hospitalized COVID-19 patients in the early stages of the pandemic. Reference category for each comorbidity is the absence of that comorbidity, except where stated otherwise. ICU, intensive care unit; HR, hazard ratio; OR, odds ratio; CI, confidence interval; COPD, chronic obstructive pulmonary disease. All estimates adjusted for age. Additionally adjusted for: smoking [sm]; sex [s]; other comorbidities [c]; ethnicity [e].

Figure 4

Forest plot of study estimates of the association between comorbidities and progression to severe disease or intensive care unit admission among hospitalized COVID-19 patients in the early stages of the pandemic. Reference category for each comorbidity is the absence of that comorbidity, except where stated otherwise. ICU, intensive care unit; OR, odds ratio; CI, confidence interval; BMI, body mass index; COPD, chronic obstructive pulmonary disease; MI, myocardial infarction. All estimates adjusted for age. Additionally adjusted for: sex [s]; other comorbidities [c]; ethnicity [e].

Figure 5

Forest plot of study estimates of the association between comorbidities and invasive mechanical ventilation among hospitalized COVID-19 patients in the early stages of the pandemic. Reference category for each comorbidity is the absence of that comorbidity, except where stated otherwise. OR, odds ratio; CI, confidence interval; BMI, body mass index; COPD, chronic obstructive pulmonary disease; CVD, cardiovascular disease. All estimates adjusted for age. Additionally adjusted for: sex [s]; other comorbidities [c]; ethnicity [e].