On March 11, 2020, WHO declared the severe acute respiratory syndrome coronavirus 2
(SARS-CoV-2) which causes the illness COVID-19, a pandemic. As of June 9, 2020, over 408,000 lives have been lost to the virus and over 112,000 were US deaths. Currently, there are over 1.9 million confirmed US cases.1 It is estimated that for every one person infected with the novel coronavirus that an additional 2.4 – 3.6 others will become infected.2,3 Currently, researchers are still gleaning valuable and important insights regarding viral transmission, asymptomatic cases and specific factors that result in higher risk for the disease and serious outcomes. Researchers have documented certain comorbidities being associated with heightened risk of hospitalization and even death.
Comorbidities and Risk
A study published in JAMA that spanned 5,700 hospitalized COVID-19 patients in New York City found the most common comorbidities to be: obesity, hypertension and diabetes.4 Of their sample, 57% were comorbid with hypertension, 42% obesity and 34% diabetes . A prospective observational cohort study of 20,133 patients in the UK also investigated common comorbidities. The most common comorbidities of those hospitalized in this study include chronic cardiac disease (31%), uncomplicated diabetes (21%) and non-asthmatic chronic pulmonary disease (18%).5 Comorbidities that were associated with mortality in hospitals included: cardiac disease, non-asthmatic pulmonary disease, kidney disease, liver disease, malignancy, obesity, and dementia.5 In a recent study (n=10) that used minimally invasive autopsies to confirm disease and associated conditions present, the authors found that most common conditions included: systemic arterial hypertension, diabetes mellitus and chronic cardiopathy.6 A study of 1,590 individuals in China found that the most common comorbidities for being a confirmed COVID-19 hospitalized case included hypertension and diabetes.7
Diabetes and Hazard
Hazard ratios are often used by epidemiologists to measure how often an outcome or event happens in one group in comparison to another, through time. In many of the aforementioned studies, the authors used hazard ratios to determine which comorbidities were associated with certain outcomes such as admission to ICU, invasive ventilation and/or death. A hazard ratio of 1 means there is no difference between the two groups for the outcome being compared. A hazard ratio above 1 indicates increased risk and below 1 suggests less risk. For example, when using a hazard ratio to measure the event of death between two groups, a hazard ratio of 4 indicates there is 4 times the risk of experiencing death as the comparison group.
In the UK study which looks at a sample of 20,133 hospitalized patients, while diabetes is one of the most common comorbidities, it is weakly associated with mortality. In Figure 1. we see the hazard ratio for diabetes is measured at 1.06 with a confidence interval that includes 1; however obesity was observed with a highly statistically significant hazard ratio of 1.33. Other significantly elevated risks include liver disease with a hazard ratio of 1.51, 95%CI (1.21-1.88) and dementia has a 1.40 hazard ratio, 95%CI (1.28-1.52). Additionally, an age of 80 years or greater has the most elevated risk of death with a hazard ratio of 11.09. Individuals who are 80 years are greater than 11 times the risk of death from a covid-19 infection as compared to infected individuals who were less than 50 years old.
In the study from China which examines 1590 hospitalized COVID-19 patients, we see a hazard ratio that measures the events of admission to ICU, invasive ventilation or death. While this study does not measure the outcome of mortality alone, but rather includes other outcomes such as ICU admission and ventilation, the hazard ratio for diabetes is unsurprisingly higher and 1.59 in this sample (Figure 2.).7 However, we also see hazard ratios inflate for other diseases such as malignant tumor (3.5) and COPD (2.7).
While diabetes may not be strongly associated with mortality, it is one of the most common comorbidities for COVID-19 patients and is associated with severe disease.
Figure 1. UK Study Examining 20,133 Hospitalized Individuals (Docherty, et al, 2020)
Multivariable Cox proportional hazards model (age, sex, and major comorbidities), where hazard is death. Patients who were discharged were kept in the risk set (n=15 194; No of events=3911)
Figure 2. China Study Examining 1590 Hospitalized Patients (author)
“Predictors of the composite end-points in the proportional hazards model. Hazard ratio (95% confidence interval) are shown for the risk factors associated with the composite end-points (admission to intensive care unit, invasive ventilation or death). The comorbidities were classified according to the organ systems as well as the number. The scale bar indicates the hazard ratio. Cox proportional hazard regression models were applied to determine the potential risk factors associated with the composite end-points, with the hazard ratio (95% confidence interval) being reported. The model has been adjusted with age and smoking status.”
While measuring the events of admission to intensive care unit, invasive ventilation or death, it is important to note that having one comorbidity results in a hazard ratio of 1.79 and having 2 or more comorbidities increases the ratio to 2.59.7 It is clear that underlying health conditions and having more than 1, increases the risk for severe disease.
Current Recommendations for Higher Risk Individuals
The CDC states that people who are at high-risk of severe illness include: individuals 65 and older, nursing home and long term care residents, people of all ages who have underlying health conditions such as: asthma, chronic lung disease, serious heart conditions, immunocompromised, severe obesity, diabetes, chronic kidney disease undergoing dialysis, liver disease.8 Recent modeling results suggest that more than 7% of the US population or greater than 23 million people are at risk of a severe covid-19 infection.9
For individuals who are at higher risk of severe illness from COVID-19 the CDC recommends: staying home, frequent hand washing, remaining 6 feet away from others, cleaning and disinfecting high touch surfaces and avoiding all cruise and non-essential air travel.10 The CDC has also created a detailed list that provides recommendations for specific underlying conditions that include activities like continuing medications and treatment.
Looking forward, it is important to leverage existing infection prevention and control measures for higher risk populations. Those with comorbidities are well documented in the literature for being associated with more severe illness. In addition to CDC recommendations for higher risk populations, we encourage creativity in solutions that expand upon prevention efforts.
1. COVID-19 Map. Johns Hopkins Coronavirus Resource Center https://coronavirus.jhu.edu/map.html.
2. Li, R. et al. Substantial undocumented infection facilitates the rapid dissemination of novel coronavirus (SARS-CoV-2). Science 368, 489–493 (2020).
3. PETERSEN, E. & GÖKENGİN, D. SARS-CoV-2 epidemiology and control, different scenarios for Turkey. Turk J Med Sci 50, 509–514 (2020).
4. Richardson, S. et al. Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area. JAMA 323, 2052–2059 (2020).
5. Docherty, A. B. et al. Features of 20 133 UK patients in hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: prospective observational cohort study. BMJ 369, (2020).
6. Nunes Duarte‐Neto, A. et al. Pulmonary and systemic involvement of COVID‐19 assessed by ultrasound‐guided minimally invasive autopsy. Histopathology (2020) doi:10.1111/his.14160.
7. Guan, W. et al. Comorbidity and its impact on 1590 patients with COVID-19 in China: a nationwide analysis. Eur Respir J 55, (2020).
8. CDC. Coronavirus Disease 2019 (COVID-19). Centers for Disease Control and Prevention https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/groups-at-higher-risk.html (2020).
9. Clark, A. et al. Global, regional, and national estimates of the population at increased risk of severe COVID-19 due to underlying health conditions in 2020: a modelling study. The Lancet Global Health (2020) doi:10.1016/S2214-109X(20)30264-3.
10. What You Can Do if You are at Higher Risk of Severe Illness from COVID-19. 1.