A Call for Comprehension of the Relationship Between Diabetes and the Novel SARS-CoV-2.

Over 3.5 million global cases of Covid-19 have been confirmed, causing worldwide devastation and intensifying the burden of disease for those with existing comorbidities (WHO report-94, Roser 2020).

COVID-19 is a respiratory tract infection that presents complicated clinical picture: a mild illness with symptoms of the upper respiratory tract at the onset, followed by a mild pneumonia which, in some cases, can lead to severe Acute Respiratory Distress Syndrome (ARDS) and/or sepsis, which can be fatal. This descent into ARDS is significantly more frequent in elderly patients with comorbidities, such as Diabetes and Cardiovascular Disease (CVD). This is an issue that is challenging healthcare systems worldwide, particularly in more developed countries with an aging population and a high incidence of chronic pathologies related to lifestyle (Gabutti 2020).

For this reason, The Journal of Diabetes is issuing a call for submissions of commentaries, original articles, and case reports regarding issues with COVID-19 in patients with diabetes, as well as descriptions of basic aspects of the interrelationships between diabetes and the novel CoV, to improve the comprehension of the disease and support physicians in the care of fragile patients (Bloomgarden 2020).

Compared to previous SARS-CoV and MERS-CoV epidemics, COVID-19 leads more readily to respiratory failure and death in susceptible patients. The abnormal immune response observed in diabetic patients is responsible for the worsening clinical picture (Wang 2020).

It is therefore crucial that risk factors that lead to a worsened prognosis from COVID-19 are defined. Particularly for fragile patients, early recognition is essential for swift initiation of preventive measures and supportive treatments to avoid the complications that have resulted in higher levels fatality today than has ever been witnessed before  (Heymann 2020).

Although it is hard to estimate the real risk of death of a disease during the outbreak, the Case Fatality Rate (CFR), a value not adjusted to the total cases but only to diagnosed individuals, is taken as an indication of a disease fatality in a certain situation. Observing the CFR data from COVID-19 pandemic and comparing with the data from past coronavirus epidemics – SARS and MERS – the relevance of chronic comorbidities in severe patients leaps out.

The CFR for populations within China, based on their health status or underlying health condition (in the period up to February 11th, 2020), was equal to 8% and 14.8% in subjects aged between 70 and 79 years and in patients aged > 80 years, respectively. Notably, CFR was higher in subjects with comorbidities. In detail, CFR was equal to 10.5% in patients with cardiovascular diseases, 7.3% in diabetic individuals, followed by patients with chronic respiratory disease, hypertension and tumours with a CFR of 6.3%, 6.0% and 5.6%, respectively (Wu 2020).

A systematic review and meta-analysis described the prevalence of comorbidities in 46,248 patients infected with COVID-19 in China. The most prevalent comorbidities were hypertension (17%) and diabetes (8%), followed by CVD (5%) and respiratory system diseases (2%). Generally, age was a determinant risk factor for severe disease and patients with more comorbidities displayed the most severe outcomes (Yang 2020).

A retrospective study on 1,590 hospitalized patients in China confirmed that subjects with any comorbidity have poorer clinical outcomes than those without, with Diabetes being a leading cause of complications. Also, a higher number of comorbidities correlated with poorest clinical outcomes (Guan 2020).

Further studies, performed on patients hospitalized with severe COVID-19 symptoms, confirmed that chronic comorbidities are prognostic factors for poor outcomes and death, with diabetes and hypertension ranking first (Grasselli 2020, Singh 2020, Zhou 2020).

Thus, epidemiological studies suggest that Diabetes, as well as hypertension, CVD and respiratory system disease, may be related to the pathogenesis of COVID-19. The reason might lie in the proinflammatory state and the attenuation of the innate immune response – just some of the features these chronic diseases share with the SARS-CoV-2 infection (Yang 2020). Accordingly, a recent study analysed the clinical data of patients with viral pneumonia and found that the absolute count levels of CD3+ T cell, CD3+ CD8+ T cell and CD3+ CD4+ T cell in the death group were significantly lower than those in the survival group, suggesting the abnormal rise in inflammatory factors was crucial for dismal prognosis and death (Guo 2019).

Diabetes, in particular, involves the abnormal accumulation of activated innate immune cells in metabolic tissues that leads to the excessive release of inflammatory mediators - particularly IL-1β and TNFα (causing systemic insulin resistance and β-cell damage), possibly worsening the aberrant immune response and cytokine storm observed during viral pneumonia (Odegaard 2012).

As already observed in the MERS disease, metabolic disorders may cause immunodepression through impaired macrophage and lymphocyte function, which in turn may render individuals more vulnerable to disease complications (Badawi 2016).

Ageing also plays a role in worsening the prognosis in diabetic patients with COVID-19.

In fact, ageing causes an impairment of T- and B-cell function with increased production of type 2 cytokines that could lead to reduced control of viral replication and more prolonged pro-inflammatory responses, adding further damage to the clinical picture of diabetic patients (Zhou 2020).

A strong response to the call for increased scientific and epidemiological research/ evidence on COVID-19 patients with diabetes, could provide useful clinical support for physicians in managing these fragile patients.