COVID-19’s interaction with co-morbidities poses a major threatJune 10, 2020
The crosstalk between communicable diseases (CDs) and noncommunicable diseases (NCDs) is not completely understood, but with COVID-19, NCDs have emerged as major comorbidities. Usually the term “pandemic” is used for infectious diseases, but NCDs such as diabetes, hypertension and vascular diseases have also been described as pandemics. There are almost 2.2 billion people who are overweight worldwide, with a two-fold increase in the past three decades. Metabolic risk factors that promote the development of metabolic disease and contribute to their progress include obesity, inflammation, oxidative stress, endothelial dysfunction, insulin resistance, deregulated lipid and glucose metabolism, subclinical atherosclerosis, vascular diseases and diabetes. Inflammation and oxidative stress seem to be the common denominator between COVID-19 and NCDs. However, there is limited information regarding clinical presentations and outcomes of patients requiring hospitalisation with this illness.
A retrospective cohort study from Wuhan, China involving 191 patients showed that 91 (48%) of them had hypertension, followed by diabetes (36 or 19%) and coronary artery disease (15 or 8%) (Zhou F et al Lancet Mar 2020;395(10229)). However, there are many differences in the epidemiology of NCDs in China, USA and India, especially in risk factors, including smoking rates. Richardson S et al (JAMA April 2020) included a total of 5,700 patients with a median age of 63 years in their study. The cohort showed that the most common comorbidities were hypertension 56.5%, obesity 41.7% and diabetes 33.8%. The Charlson comorbidity index was 4, suggesting that the survival rate was 53% for patients with significant co-morbidity burden.
Role of anticoagulation therapies
The 1918 Spanish Flu (H1N1) affected over 500 million globally and more than 50 million died within the two-year cycle. In comparison, NCDs, mainly vascular associated diseases, resulted in the death of 18 million people worldwide in 2016 alone. In India, there are 257 million people with hypertension and 73 million with diabetes. They are now at high risk of COVID-19 infection.
Swiss researchers have also found hypertension (23.7%), diabetes (22%) and cerebrovascular disease (22%) highly represented co-morbidities among COVID-19 patients. During the current conditions of high infectivity of COVID-19, it has been observed globally that 89% of these patients have at least one comorbidity. Several studies also have shown increased D-dimer levels and myocardial injury due to plaque rupture, cytokine storm, coronary spasm, microthrombi and endothelial lesions. The molecular mechanisms associated with such provocation of cardiac injury can be understood due to coagulopathy. In COVID-19 patients, there is elevated fibrinogen and D-dimer, suggesting that anticoagulation therapies such as low molecular weight heparin (LMWH) and tissue plasminogen activator may show better prognosis.
It is also seen that around 70% of patients who die due to COVID-19 seem to have Disseminated Intravascular Coagulation (DIC), potentially due to pro-thrombotic DIC, pulmonary congestion, venous thromboembolism and microvascular occlusion by thrombosis. In such situations, it is important to note that monitoring of specific biomarkers such as clotting factors, fibrinogen etc. can help in identifying patients who may benefit from anticoagulation therapies rather than antiplatelet therapies.
In the case of uncontrolled diabetes, the innate immunity is already compromised, thereby allowing the unhindered proliferation of virus within the host. Even short-term hyperglycemia may reduce the innate immunity and also exaggerate pro-inflammatory cytokine production, including IL-6, IL-1 and TNF-alpha. The functional role of angiotensin-converting enzyme 2 (ACE2) in diabetes and COVID-19 is highly evaluated and we understand that ACE2 is expressed by epithelial cells of lungs, kidney, intestine and blood vessels. In normal conditions, ACE2 breaks down angiotensin-II and I into smaller peptides called angiotensin (Ang 1-7) and angiotensin (Ang 1-9) which play an important anti-inflammatory and antioxidant role in the lungs. ACE2 expression is reduced in diabetes patients, thus potentially increasing the predisposition to COVID-19 infection. However, overexpression of ACE2 would be counterproductive in COVID-19 as the virus uses ACE2 for entry into host cells. Thus, the confounding role of ACE inhibitors can be understood. The expression of ACE2 is increased in diabetes and hypertension patients who are on ACE inhibitors, thus counteracting the effects of angiotensin I and II. This facilitates the entry of the virus and results in a severe and fatal disease.
As of April 2020, there are 115 vaccine candidates (78 confirmed and 37 unconfirmed). of which 73 are in preclinical stages. The most advanced of these are mRNA-1273 from Moderna and Ad5-nCoV from Can Sino Biologicals. These vaccines may take longer than expected. Therefore, It is important for every country to evolve a strategy to protect high risk populations, especially those with diabetes and hypertension. At this point, social distancing and good hygiene remain the most reliable ways of preventing COVID-19.