The COVID-19 infection is a double challenge for people with diabetes. Diabetes has been reported to be a risk factor for the severity of the disease and at the same time patients have to control glucose in a situation with a decreased and more variable food intake.
COVID-19 (Coronavirus Disease-2019) is caused by the coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2), which has spread quickly to more than 160 countries across the world.1 The spreading mechanism of the virus is primarily by transmission of respiratory droplets between people.1 The incubation time is on average 6–8 days, followed by 1–2 weeks of symptomatic disease. It is characterised by a wide spectrum of symptoms including coughing, fever, myalgia and respiratory problems such as viral pneumonia, and respiratory failure. In worst cases, these can lead to death.2–11 Time from first onset to hospital admission has been on the average 6–7 days.2–11 A proportion of the infected are without symptoms (yet remain infectious) or have only mild symptoms.2–11
Diabetes as a risk factor
Diabetes is a risk factor for hospitalisation and mortality of the COVID-19 infection. Diabetes was a comorbidity in 22% of 32 non-survivors in a study of 52 intensive care patients.2 In another study of 173 patients with severe disease, 16.2% had diabetes, and in further study of 140 hospitalised patients, 12% had diabetes.3,4 When comparing intensive care and non-intensive care patients with COVID-19, there appears to be a twofold increase in the incidence of patients in intensive care having diabetes.11 Mortality seems to be about threefold higher in people with diabetes compared with the general mortality of COVID-19 in China.2–11
The number of comorbidities is a predictor of mortality in COVID-19. In addition to diabetes, the other common comorbidities were hypertension, in about 20% of cases, cardiovascular disease (16%), and lung disease (6%).2–11 Indeed, people with diabetes are a high-risk group for severe disease. Notably, diabetes was also a risk factor for severe disease and mortality in the previous SARS, MERS (Middle East respiratory syndrome) coronavirus infections and the severe influenza A H1N1 pandemic in 2009.12–4
What explain the increase risk of diabetes?
It is a fact that people with diabetes are at increased risk of infections including influenza and for related complications such as secondary bacterial pneumonia. Diabetes patients have impaired immune-response to infection both in relation to cytokine profile and to changes in immune-responses including T-cell and macrophage activation.15 Poor glycaemic control impairs several aspects of the immune response to viral infection and also to the potential bacterial secondary infection in the lungs.16 It is likely that many of the patients with diabetes in China have been in poor metabolic control when infected by COVID-19.
Many patients with type 2 diabetes are obese and obesity is also a risk factor for severe infection.17–9 It was illustrated during the influenza A H1N1 epidemic in 2009 that the disease was more severe and had a longer duration in about twofold more patients with obesity who were then treated in intensive care units compared with background population.14,17,18 Specically, metabolic active abdominal obesity is associated with higher risk.17-9 The abnormal secretion of adipokines and cytokines like TNF-alfa and interferon characterise a chronic low-grade in abdominal obesity and may induce an impaired immune-response.. 17–9 People with severe abdominal obesity also have mechanical respiratory problems, with reduced ventilation of the basal lung sections increasing the risk of pneumonia as well as reduced oxygen saturation of blood.20 Obese subjects also have an increased asthma risk, and those patients with obesity and asthma have more symptoms, more frequent and severe exacerbations and reduced response to several asthma medications. 20
Lastly, late diabetic complications such as diabetic kidney disease and ischaemic heart disease may complicate the situation for people with diabetes, making them frailer and further increasing the severity of COVID-19 disease and the need for care such as acute dialysis. Some findings indicate that COVID-19 could cause acute cardiac injury with heart failure, leading to deterioration of circulation.11
The most frequent comorbidities to COVID 19 are hypertension and diabetes. Both diseases are often treated with angiotensin-converting enzymes (ACE) inhibitors. Coronavirus binds to target cells through angiotensin-converting enzyme 2 (ACE2), which expressed in the epithelial cells in the lungs, blood vessels and in the intestine.21,22 In patients treated with ACE and angiotensin II receptor blockers, expression of ACE2 is increased.23 Therefore, it has been suggested that ACE2 expression may be increased in these two groups of patients with hypertension and diabetes, which could facilitate infection with COVID-19 and increase the risk of severe disease and fatality.
Treatment of diabetes during COVID 19 infection
Poor glycaemic control is a risk factor for serious infections and adverse outcomes. However, the reverse is also true and the risk of infection, including bacterial pneumonia, can be reduced through good glycaemic control.16 The problem is that infections cause loss of glycaemic control, and treatment of hyperglycaemia is difficult during intercurrent disease with fever, unstable food intake and use of drugs like glucocorticoids in patients with respiratory problems. To maintain optimal glycaemic control requires more frequent blood glucose monitoring and continuous change in antidiabetic treatment after the measured glucose levels.
In patients with type 2 diabetes, metformin and SGLT-2 inhibitors with moderate to severe illness should be stopped. Dipeptidyl peptidase 4 (DPP-4) inhibitors and also linagliptin can be used in patients with impaired kidney function without risk of hypoglycaemia. Sulphonylureas may induce hypoglycaemia in patients with low calorie intake. The long-acting GLP-1 receptor agonist which reduces appetite in sparse-eating patients and with a half-life of 1 week cannot be stopped from day to day. In many patients with type 2 diabetes, insulin treatment will be preferred and need to be initiated, which is complicated because of the limited time for instruction and titration of insulin. Patients already treated with basal insulin will need fast-acting bolus insulin to correct hyperglycaemia. Hospitals have experience and algorithms for the treatment of patients during intercurrent disease, but the time involved for treating labile glycaemic control is a major problem in situations where time is short.
In patients with type 1 diabetes treated with basal bolus or insulin pump therapy, the insulin doses should be titrated using frequent glucose and ketone monitoring to avoid hypoglycaemia in patients with reduced food intake, and adding correctional bolus of fast-acting insulin to avoid severe hyperglycaemia and ketoacidosis.
Taken all together, patients with diabetes are a high-risk and complicated group of patients to treat for COVID19, with an increased requirement of hospitalisation. Patients with diabetes need intensive attention to reduce the risk of fatalities. Patients with diabetes should follow the general prevention advice given by the authorities thoroughly to avoid infection with COVID-19.
- Del Rio C, Malani PN. COVID-19-new insights on a rapidly changing epidemic. JAMA. 2020; doi: 10.1001/jama.2020.3072.
- Yang X, Yu Y, Xu J, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. 2020; doi: 10.1016/S2213-2600(20)30079-5.
- Guan WJ, Ni ZY, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020; doi: 10.1056/NEJMoa2002032.
- Zhang JJ, Dong X, Cao YY, et al. Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan, China. Allergy. 2020; doi: 10.1111/all.14238.
- Yang J, Zheng Y, Gou X, et al. Prevalence of comorbidities in the novel Wuhan coronavirus (COVID-19) infection: a systematic review and meta-analysis. Int J Infect Dis. 2020; pii: S1201-9712(20)30136-3. doi: 10.1016/j.ijid.2020.03.017.
- Ruan Q, Yang K, Wang W, et al. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020; doi: 10.1007/s00134-020-05991-x.
- Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020; pii: S0140-6736(20)30566-3. doi: 10.1016/S0140-6736(20)30566-3.
- Wu C, Chen X, Cai Y, et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med. 2020; doi: 10.1001/jamainternmed.2020.0994.
- Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: Summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. JAMA. 2020; doi: 10.1001/jama.2020.2648.
- Leung C. Clinical features of deaths in the novel coronavirus epidemic in China. Rev Med Virol. 2020;e2103. doi: 10.1002/rmv.2103.
- Li B, Yang J, Zhao F, et al. Prevalence and impact of cardiovascular metabolic diseases on COVID-19 in China. Clin Res Cardiol. 2020; doi: 10.1007/s00392-020-01626-9.
- Yang JK, Feng Y, Yuan MY, et al. Plasma glucose levels and diabetes are independent predictors for mortality and morbidity in patients with SARS. Diabet Med. 2006;23:623–8.
- Schoen K, Horvat N, Guerreiro NFC, et al. Spectrum of clinical and radiographic findings in patients with diagnosis of H1N1 and correlation with clinical severity. BMC Infect Dis. 2019;19:964.
- Wang W, Chen H, Li Q, et al. Fasting plasma glucose is an independent predictor for severity of H1N1 pneumonia. BMC Infect Dis. 2011;11:104.
- Ferlita S, Yegiazaryan A, Noori N et al. Type 2 diabetes mellitus and altered immune system leading to susceptibility to pathogens, especially mycobacterium tuberculosis. J Clin Med. 2019;8. pii: E2219.
- Critchley JA, Carey IM, Harris T et al. Glycemic control and risk of infections among people with type 1 or type 2 diabetes in a large primary care cohort study. Diabetes Care. 2018;41:2127–35.
- Huttunen R, Syrjänen J. Obesity and the risk and outcome of infection. Int J Obes (Lond). 2013;37:333–40.
- Honce R, Schultz-Cherry S. Impact of obesity on influenza a virus pathogenesis, immune response, and evolution. Front Immunol. 2019;10:1071.
- Almond MH, Edwards MR, Barclay WS, Johnston SL. Obesity and susceptibility to severe outcomes following respiratory viral infection. Thorax. 2013;68:684–6.
- Dixon AE, Peters U. The effect of obesity on lung function. Expert Rev Respir Med. 2018;12:755–67.
- Wan Y, Shang J, Graham R, et al. Receptor recognition by the novel coronavirus from Wuhan: An analysis based on decade-long structural studies of SARS coronavirus. J Virol. 2020;94. pii: e00127-20.
- Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020; pii: S0092-8674(20)30229-4. doi: 10.1016/j.cell.2020.02.052.
- Li XC, Zhang J, Zhuo JL. The vasoprotective axes of the renin-angiotensin system: Physiological relevance and therapeutic implications in cardiovascular, hypertensive and kidney diseases. Pharmacol Res. 2017;125:21–38.
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