The outbreak of a new viral infection in Wuhan, a city in Habei Province, China, became evident in December 2019. The origin of the infection appeared to be a seafood market and it seems likely that the COVID-19 virus crossed from animals to humans. It was soon clear that serious lung disease and increased mortality were possible consequences of acquiring this infection. The disease proved highly contagious and quickly spread to cause a global pandemic, arriving in the UK in late January 2020 (Seewoodhary and Oozageer, 2020).
The nature of COVID-19 virus
The virus responsible for the disease known as COVID-19 was identified as SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), which belongs to the coronavirus group of viruses that commonly cause mild upper respiratory disease. Structurally the coronaviruses are composed of a single-strand of RNA surrounded by a lipid envelope that appears spherical under an electron microscope with a crown or ‘corona’ of spikes on the surface. Coronaviruses were also responsible for the epidemics of SARS-CoV in 2002 in China and MERS-CoV in 2012 in Saudi Arabia (BMJ Best Practice, 2020).
Diabetes and the risk of severe COVID-19 infection
For most individuals who contract COVID-19, the disease is mild to moderate. Older people are disproportionately affected with serious disease, while children appear less likely to experience serious illness (Qiu et al, 2020). So far, there is little evidence that COVID-19 is associated with worse outcomes in pregnancy but vertical transmission cannot be excluded (Chen et al, 2020).
A number of conditions are linked to increased severity of disease and poorer outcomes including both type 1 diabetes (T1 DM) and type 2 diabetes (T2 DM) (Table 1) (Jordan et al, 2020; Wu et al, 2020; Wu and McGoogan, 2020).
Table 1. Risk factors for severe COVID-19 infection
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An extensive study from Wuhan, reported by the China Centre for Disease Control (summarised by Wu and McCoogan, 2020), included 1102 confirmed cases of COVID-19 in people with diabetes. Of these, 80 people died, giving a diabetes case fatality rate of 7.3%, well above the overall case fatality rate of 2.3%.
In a retrospective case series of consecutive hospitalised people with COVID-19 reported by Wang et al, 22% of patients admitted to the intensive care unit (ICU) had diabetes compared to 6% having diabetes among non-ICU patients (Wang et al, 2020), consistent with diabetes being associated with more severe disease.
A systematic review and meta-analysis confirmed diabetes as an important co-morbidity in those presenting with COVID-19 infection (Yang et al, 2020). Poorly controlled hyperglycaemia is associated with worse outcomes, as is the presence of diabetic complications and other co-morbidities (Hillson, 2020).
Why are people with diabetes at higher risk of serious infection from COVID-19?
Hyperglycaemia provides a conducive environment for viral replication. Hyperglycaemia also weakens the response of the immune system in numerous ways. Lymphocyte activity is impaired as is the mobility and phagocytic ability of neutrophils. The antioxidant system is suppressed, rendering cells more susceptible to oxidative stress, and glycation of immunoglobulins (glucose molecules attaching to proteins) damages the function of antibodies (Casqueiro et al, 2012; Shaw, 2020).
Acute illness triggers release of stress hormones (cortisol, glucagon, adrenalin) that drive hyperglycaemia and release the brakes on lipolysis (and ketone body formation) that may precipitate a diabetic crisis, such as diabetic ketoacidosis in T1 DM or hyperosmolar hyperglycaemic state in T2 DM.
Avoiding infection
Health professionals should encourage people with diabetes to diligently practice careful hygiene and maintain social distancing (American Diabetes Association, 2020; International Diabetes Federation, 2020). People with diabetes will need to plan ahead to ensure an adequate supply of medication and glucose testing equipment. Maintaining good glycaemic control reduces the risk of severe infection. Diabetes UK (2020) provides useful information on its website in regard to work, school and travel.
Clinical presentation of COVID-19 infection
Some key features of COVID-19 infection are listed in Table 2, but it is important to recognise that there is wide individual variation in symptoms. There is clearly overlap with other respiratory infections, notably influenza, and symptoms can range from a mild upper respiratory infection (even asyptomatic) to a severe viral pneumonia and life-threatening acute respiratory distress syndrome (BMJ Best Practice, 2020). The damage caused by COVID-19 may be due both to the direct effects of the virus and the response of the immune system to the virus (production of inflammatory mediators – a cytokine storm).
Table 2. Symptoms associated with COVID-19 infection
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Greater severity of infection may be indicated by breathing difficulty, chest tightness and pain, and confusion or unexpected drowsiness (BMJ Best Practice, 2020; American Diabetes Association, 2020). Signs to look for include tachycardia, tachypnoea with use of accessory muscles of respiration, hypotension, falling oxygen saturations, central cyanosis and abnormal findings on chest auscultation.
The incubation period for COVID-19 is usually around 3 to 7 days, but for a few people it may be as long as 14 days after exposure before symptoms appear (International Diabetes Federation, 2020).
Blood glucose levels are likely to rise in those with diabetes with COVID-19 infection.
Action to take with suspected infection
People with diabetes should follow the same general advice as others. They should avoid rushing to the GP or local hospital to reduce the risk of transmission to others. If symptoms are not severe then guidance can be found on the NHS 111 online coronavirus service (NHS 111 online, 2020). In the case of severe symptoms or if people are unable to get help online, they should phone NHS 111 for advice on how to proceed; if circumstances are life-threatening patients should call 999 for an ambulance.
General advice on managing COVID-19 infection at home
With suspected or proven COVID-19 infection, then people with diabetes should try to isolate as much as possible from other household members. This means not sharing the same room as others, taking meals separately and, if feasible, using a different bathroom. In the case of a shared bathroom, surfaces should be wiped down with antiseptic wipes after use. Face masks should be worn if rooms need to be shared with someone else. Rooms should be kept well ventilated by opening windows (NHS, 2020).
Hands should be regularly washed with soap and water for at least 20 seconds, or if these are not available a hand sanitiser gel should be used. Coughing and sneezing into open air should be avoided and tissues should be put in the bin and hands washed afterwards.
There are no specific treatments for COVID-19 to be offered in primary care. Good fluid intake should be encouraged and paracetamol can be used as required for fever or discomfort (BMJ Best Practice, 2020; NHS, 2020). There have been concerns that ibuprofen may aggravate symptoms, but there is no firm evidence to support this (National Institute for Health and Care Excellence [NICE], 2020). If an individual is taking an anti-inflammatory medication for another condition then whether or not to continue can be discussed with the prescriber.
Managing diabetes during COVID-19 infection
In the event of coronavirus infection (suspected or proven) the usual sick day rules apply to people with diabetes (Table 3) (Down, 2018; Diabetes UK, 2020). If diabetic ketoacidosis is suspected (Table 4), usually in T1DM, then ketones should be tested for, ideally with a fingerprick blood test (Table 5). Remember that for those taking an SGLT-2 inhibitor then the possibility of euglycaemic DKA arises, so if symptoms and signs suggest DKA then ketone testing should be undertaken even if blood glucose concentrations are not unduly raised (<14 mmol/l) (Peters et al, 2015; Rosenstock and Ferrannini, 2015; Fralick et al, 2017).
Table 3. Sick day rules
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Table 4. Symptoms and signs of diabetic ketoacidosis (DKA)
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Table 5. Blood and urine ketone test results and interpretation
| Blood ketone concentration | Urine ketones dipstick | Interpretation |
|---|---|---|
| <0.6 mmol/l | Negative | Normal range |
| 0.6–1.5 mmol/l | Trace or + | Potential problem. Keep monitoring. Seek medical advice if unwell |
| 1.5–3 mmol/l | ++ | High risk of diabetic ketoacidosis (DKA), seek medical advice urgently |
| >3 mmol/l | +++/++++ | Likely DKA. Immediate medical review needed |
Individuals also need to be aware that certain classes of medication should be temporarily stopped in acute illness (with vomiting and/or diarrhoea) to reduce the risk of dehydration and acute kidney injury. In the case of metformin there is a risk of lactic acidosis, and SGLT-2 inhibitors increase the risk of DKA. The medications implicated are listed below and can be remembered by the mnemonic SADMAN (Down, 2018).
- S: SGLT-2 inhibitors, eg dapagliflozin
- A: ACE-inhibitors, eg ramipril
- D: diuretics, eg indapamide
- M: metformin
- A: angiotensin receptor blockers, eg losartan
- N: non-steroidal anti-inflammatory drugs (NSAIDs), eg ibuprofen
Expert opinion on managing diabetes in individuals with COVID-19 infection has been published (Bornstein et al, 2020).
Long-term complications from COVID-19
It is becoming increasingly apparent that cough and shortness of breath can persist months after initial infection, with possible pathologies of fibrotic lung disease, bronchiectasis and pulmonary hypertension (Fraser, 2020). Fatigue and exercise intolerance are further consequences. Other organ systems may be chronically affected (eg heart, kidney) and mental health issues are also a concern.
People with post-acute COVID-19 will be seen in primary care. Beyond history and chest examination, they may need investigation with oxygen saturation measurement and chest X-ray. Onward referral to chest physicians may then be required (Fraser, 2020). Psychological issues will also be an important consideration in primary care.
Conclusion
Individuals with diabetes are at higher risk of experiencing severe COVID-19 disease, including increased mortality compared to those without diabetes. With suspected or proven COVID-19 disease those with diabetes should regularly monitor blood glucose and ketone levels as appropriate. In cases of severe COVID-19 disease with symptoms and signs of respiratory distress or with a hyperglycaemic crisis (diabetic ketoacidosis or hyperosmolar hyperglycaemic state) then hospital transfer will be necessary.
KEY POINTS:
- Individuals with diabetes are at higher risk of experiencing severe COVID-19 disease, including increased mortality compared to those without diabetes
- Poorly controlled glycaemia is linked to worse outcomes with COVID-19 infection
- Increasing age, male sex, BAME ethnicity, obesity, socioeconomic deprivation and chronic medical conditions are associated with increased mortality from COVID-19 infection
- To avoid COVID-19 infection people with diabetes should be rigorous in their application of hygiene measures and social distancing
- Individuals with diabetes should follow sick day rule advice during COVID-19 infection
- With suspected or proven COVID-19 disease, those with diabetes should regularly monitor blood glucose and ketone levels as appropriate
- In cases of severe COVID-19 disease with symptoms and signs of respiratory distress or with a hyperglycaemic crisis (diabetic ketoacidosis or hyperosmolar hyperglycaemic state), then hospital transfer will be necessary
- Long-term complications following COVID-19 infection are becoming apparent and will present in primary care
CPD reflective practice:
- Who would you prioritise as being at high risk of severe COVID-19 disease?
- What guidance would you give to people in regard of managing their diabetes during acute illness with COVID-19? What about those using insulin?
- In someone at risk of dehydration which medications should you be on the look out for that might need temporarily discontinuing?
- How would you identify diabetic ketoacidosis (DKA) in an individual using an SGLT-2 inhibitor for their diabetes?