COVID-19  and Metabolic Syndrome – An Association too Difficult to Ignore

Deep Dutta,¹ Gagan Priya² and Ameya Joshi³

1. Department of Endocrinology, Center for Endocrinology Diabetes Arthritis & Rheumatism (CEDAR)
   Superspecialty Clinics, Dwarka, New Delhi, India
2. Consultant Endocrinologist, Fortis Hospital, Mohali, Punjab, India
3. Consultant, Department of Endocrinology, Bhaktivedanta Hospital, Maharashtra, India

The pandemic of novel coronavirus disease 2019 (COVID-19) has been a global catastrophe, the nadir of which is yet to be fathomed. The rapidity of its spread across the globe, and the variable mortality in different countries is an enigma. Its symptoms span a spectrum ranging from mild, self-limiting flu to frank pneumonia, acute respiratory distress syndrome and death. A greater percentage of people have died in Europe than in Asia. There have been suggestions that elderly, frail people, people living with diabetes and hypertension – the two main components of metabolic syndrome – and people with comorbidities have worse clinical and survival outcomes. This article presents the current data on clinical outcomes of COVID-19 infection in people living with metabolic syndrome.

Viral flu and metabolic syndrome – the epidemiology

Historically, viral flu has not been kind to people living with metabolic syndrome. Diabetes was one of the major risk factors for increased morbidity and mortality in people infected with H1N1 Influenza – a pandemic, severe acute respiratory syndrome (SARS) coronavirus – and middle east respiratory syndrome coronavirus (MERSCoV).^1,2 Variable glycaemic control, poor glycaemic legacy, burden of end organ damage, impaired and altered immunity all contribute to poor clinical outcomes in people living with diabetes. Hence, all major guidelines routinely recommend that all people above 2 years of age be immunized with the influenza vaccine and the pneumococcal vaccine.

COVID-19 and metabolic syndrome – the epidemiology

A recent meta-analysis from China involving 46,248 patients showed that the most prevalent co-morbidity in people infected by COVID-19 was  hypertension (17±7, 95% confidence interval [CI] 14–22%) followed by diabetes (8±6, 95% CI 6–11%), cardiovascular diseases (5±4, 95% CI 4–7%) and respiratory diseases (2±0, 95% CI 1–3%), which surprisingly comes much later than the components of metabolic syndrome.³ Patients with severe disease were 2.36 times more likely to have hypertension (95% CI 1.46–3.83), 2.46 times like to have respiratory disease (95% CI 1.76–3.44) and 3.42 times likely to have underlying cardiovascular disease (95% CI 1.88–6.22), as compared to those with mild disease not needing hospital admission.³ In a cohort of 54 critically ill patients admitted with COVID-19 pneumonia in China, 44.4%, 24.1% and 14.8% patients had pre-existing hypertension, diabetes and coronary heart disease, respectively.⁴ Of these, 44.4% of patients were complicated with myocardial injury as evidenced by raised cardiac enzymes, and N-terminal pro-B-type natriuretic peptide. These patients had a very high mortality of 48.1%.⁴ In another cohort of 131 patients with COVID-19 infection admitted at a hospital in Wuhan, hypertension was the most common associated comorbidity (30%), followed by diabetes (19%) and coronary artery disease (8%).⁵

COVID-19 and metabolic syndrome – molecular insights

Previous pathogenic coronaviruses like the SARS virus have been demonstrated to bind to their target cells through angiotensin-converting enzyme 2 (ACE2), which is expressed by epithelial cells of the lung, kidneys, intestines and blood vessels,⁶ the expression of which are upregulated in people being treated with ACE inhibitors and angiotensin II type-I receptor blockers (ARBs), which are in fact the drugs of choice of treating hypertension in metabolic syndrome. Other medications which have been linked to increased ACE2 expression include ibuprofen and thiazolidinediones, namely pioglitazone.⁷ At this juncture, it would be premature to recommend not to use ACE inhibitors or ARBs for managing hypertension in people with metabolic syndrome and diabetes. This is because the above hypothesis is purely theoretical. Increased ACE2 expression, on the contrary, has been found to be beneficial and has been linked to reduced inflammation in the lungs and is a potential area of therapy in people living with inflammatory lung disease.⁷ Also people with different ACE2 polymorphisms would further complicate the picture. However, this remains an area of active research and the picture is likely to be clearer in the near future.

Current status of pharmacotherapy for hypertension and diabetes in COVID-19

As of today, ensuring a good blood pressure control and blood glucose control is of primary importance in ensuring better outcomes in people with COVID-19 infection. How we achieve the goal is of lesser importance. Insulin remains the mainstay of therapy for diabetes in sick patients admitted to hospitals. There is no rationale for sudden stoppage of ACEI and ARBs in people with hypertension, metabolic syndrom, coronary artery disease and COVID-19 infection. These drugs have proven benefits in improving cardiovascular outcomes. Sudden stoppage without adequate coverage of alternate pharmacotherapy may precipitate hypertensive crisis or a cardiovascular event in these patients. As of today, the American Heart Association (AHA), the European Society of Cardiology (ESC) and the International Society of Hypertension (ISH) recommend to continue use of ACEI and ARBs in managing hypertension in metabolic syndrome with COVID-19 infection, in view of lack of concrete adverse data.^8–10

Reference

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Support: No funding was received in the publication of this insight article.

Published: 20 March 2020