A confluence of acute and chronic diseases: Risk factors among Covid-19 patients

face masks

Covid-19 is a highly contagious infectious disease caused by the newly emerged virus, SARS-CoV-2. The virus rapidly spread and was declared a pandemic by the World Health Organization on 11 March 2020. By 26 May 2020, worldwide confirmed cases reached 5,543,439 with 347,836 deaths.1

There is no doubt that Covid-19 is a dangerous and deadly disease. But not everyone infected with SARS-CoV-2 experiences severe symptoms. For some, symptoms are mild. For others, they are non-existent.

In large part, severity of the disease depends on certain risk factors. The Agency for Health Research and Quality defines risk as “the possibility of suffering harm or loss; danger”.2 Furthermore, literature says: “A risk factor can be considered a type of correlate. It is associated with an increased probability of an outcome, usually an unpleasant one.”3 There are two conditions for a risk factor, which (1) occurs before the outcome and (2) can be categorized into either high or low subgroups. There are absolute versus relative risks (Table 1).
 

TABLE 1 Risk measures.

Term Meaning Definition
AR Absolute risk Number of events in a group / Number of subjects in the same group
RR Relative risk Risk of event in the treatment group / Risk of event in the control group


This article briefly summarizes what we currently know about Covid-19 risk factors, based on government information, medical literature, and several published studies.

Noncommunicable diseases as risk factors for Covid-19 severity

Severe illness can occur in any age group and even in healthy individuals. Adults with advanced age and noncommunicable diseases (NCDs) are more prone to have a severe form of Covid-19. NCDs, also known as chronic diseases, have four main types: cardiovascular diseases, cancers, chronic respiratory diseases, and diabetes.4 Thus, it is critical to understand the relationship between Covid-19 and NCDs.

According to the US Centers for Disease Control and Prevention (CDC), the following people are more likely to develop serious complications from Covid-19: (1) aged 65 and older, (2) living in a nursing home or long-term care facility, or (3) with underlying medical problems like chronic lung disease or moderate to severe asthma, serious heart conditions, immunocompromise, severe obesity, poorly controlled diabetes, renal failure, or liver disease.5

Several peer-reviewed articles from China,6 the UK,7 US,8 and Italy,9 as well as an editorial in the British Medical Journal (BMJ),10 have identified multiple NCDs as comorbid conditions with Covid-19 (Table 2). Here, a comorbid condition or a comorbidity refers to “the presence of one or more diseases or disorders in addition to a primary disease or disorder”.2
 

TABLE 2 Top comorbid conditions for Covid-19 based on four studies, where percent (%) means the percentage of confirmed cases.

China study UK study US study Italy study
n = 44,672 n = 20,133 n = 5,700 n = 355

Hypertension (12.8%)
Cardiovascular diseases (4.2%)

Chronic cardiac disease (30.9%)
Uncomplicated diabetes (20.7%)
Non-asthmatic chronic pulmonary disease (17.7%)
Chronic kidney disease (16.2%)
Asthma (14.5%)
Dementia (13.5%)
Chronic neurological disorder (11.3%)
Obesity (10.5%)

Hypertension (56.6%)
Obesity (41.7%)
Diabetes (33.8%)

Diabetes (35.5%)
Ischemic heart disease (30.0%)
Atrial fibrillation (24.5%)
Active cancer (20.3%)
Stroke (9.6%)
Dementia (6.8%)


In these four studies, the risk factors for either confirmed or deceased patients with Covid-19 were assessed. The data sources were observational, which might have limitations through different outcomes measures.

In China, among 44,672 individuals with confirmed Covid-19, hypertension (12.8%) and cardiovascular diseases (4.2%) were the top two co-existing conditions for those being hospitalized. Furthermore, those patients had increased illness severity and fatality rate (10.5% for those with cardiovascular diseases; 6.0% for those with hypertension). In contrast, the fatality rate was only 0.9% for those without any comorbidity.6

In the UK, among 20,133 Covid-19 patients (median age 73; 40.0% female patients) admitted to 208 hospitals in England, Wales and Scotland, being male and of increased age appear to be associated with more serious Covid-19-related hospital admissions and even mortality. Among 77.5% of the patients with comorbidities, the top ones were chronic cardiac disease (30.9%), uncomplicated diabetes (20.7%), non-asthmatic chronic pulmonary disease (17.7%), chronic kidney disease (16.2%), asthma (14.5%), dementia (13.5%), chronic neurological disorder (11.3%), and obesity (10.5%). This large study was conducted by ISARIC4C, a consortium with researchers from Imperial College London, the University of Liverpool, and the University of Edinburgh.7

In the US, among 5,700 sequentially hospitalized patients with confirmed Covid-19 (median age of 63 years; 39.7% female patients), the top comorbidities were hypertension (56.6%), obesity (41.7%), and diabetes (33.8%).8

In Italy, among 355 patients with Covid-19 who died (mean age of 79.5 years; 30.0% female patients), the mean number of pre-existing diseases was 2.7. The top comorbidities were diabetes (35.5%), ischemic heart disease (30.0%), atrial fibrillation (24.5%), active cancer (20.3%), having a history of stroke (9.6%), and dementia (6.8%). In terms of multiple comorbid conditions, patients had either three or more underlying diseases (48.5%), two diseases (25.6%), a single disease (25.1%), or no diseases (0.8%).9

What’s next

For future research, we need to better understand the mechanism of the risk factors’ effects on the severity of Covid-19. In addition, the impact of multiple comorbidities on the severity of the disease should be evaluated. Finally, ways to control for the risk factors and comorbid conditions should be explored and examined. In order to achieve these aims, high-quality and consistent data across countries are critical.10



About the authors

Tarek A. Hassan, Jorge Enrique Saenz, Jim Z. Li, Danute Ducinskiene, Joseph Imperato and Kelly H. Zou are all employees of Upjohn, a division of Pfizer.


Disclaimer

The views expressed by the authors are their own and do not necessarily represent their employer.


References

  1. Johns Hopkins University. COVID-19 Dashboard by the Center for Systems Science and Engineering (CSSE). 2020. https://www.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299423467b48e9ecf6 (accessed 26 May 2020). ^
  2. US Agency for Healthcare Research and Quality. Glossary. 2020. https://www.ahrq.gov/patients-consumers/patient-involvement/ask-your-doctor/tips-and-tools/glossary.html#R (accessed 26 May 2020). ^
  3. Offord, D. R., Kraemer, H. C. Risk factors and prevention. Evidence-Based Mental Health 2000;3:70-71. https://ebmh.bmj.com/content/ebmental/3/3/70.full.pdf (accessed 26 May 2020). ^
  4. World Health Organization. Noncommunicable diseases. 2018. https://www.who.int/news-room/fact-sheets/detail/noncommunicable-diseases (accessed 26 May 2020). ^
  5. US Centers for Disease Control and Prevention. People who are at higher risk for severe illness. 2020. https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-at-higher-risk.html (accessed 26 May 2020). ^
  6. Yang, C., Jin, Z. An acute respiratory infection runs into the most common noncommunicable epidemic-COVID-19 and cardiovascular diseases. JAMA Cardiol. 2020;10.1001/jamacardio.2020.0934. https://jamanetwork.com/journals/jamacardiology/fullarticle/2763525 (accessed 26 May 2020). ^
  7. Docherty, A. B., Harrison, E. M., Green, C. A. et al.; ISARIC4C investigators. Features of 20,133 UK patients in hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: prospective observational cohort study. BMJ. 2020 May 22;369:m1985. https://www.bmj.com/content/369/bmj.m1985 (accessed 26 May 2020). ^
  8. Richardson, S., Hirsch, J. S., Narasimhan, M. et al.; and the Northwell COVID-19 Research Consortium, Barnaby, D. P., Becker, L. B., Chelico, J. D. et al. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area. JAMA. 2020;e206775. https://jamanetwork.com/journals/jama/fullarticle/2765184 (accessed 26 May 2020). ^
  9. Onder, G., Rezza, G., Brusaferro, S. Case-fatality rate and characteristics of patients dying in relation to COVID-19 in Italy. JAMA. 2020;10.1001/jama.2020.4683. https://jamanetwork.com/journals/jama/fullarticle/2763667 (accessed 26 May 2020). ^
  10. Jordan, R. E., Adab, P., Cheng, K. K. Covid-19: risk factors for severe disease and death. BMJ. 2020;368:m1198. https://www.bmj.com/content/368/bmj.m1198 (accessed 26 May 2020). ^