King Abdul-aziz University (PG Scholarship)

 Diabetes mellitus and Hypertension are Risk Factors for COVID-19 

•  Recent studies reported people with co-morbidities are more risk for the infection of the novel coronavirus-19 specially patients with  hypertension , diabetes mellitus and cardiovascular diseases .

Angiotensin Converting Enzyme Inhibitors ACEIs :

• Angiotensin  converting enzyme 2 (ACE2)  is a surface membrane receptor for SARS coronavirus (SARS-coV) the virus directly bind to the ACE2 receptor through the spike glycoprotein (S protein) .  The affinity between ACE2 and the receptor binding domain (RBD) of SARS-coV2 is 10 to 20 times greater than that with RBD of SARS-coV. 
• ACE2 was reported to be widely  expressed in various organ system includes the cardiovascular system , kidney , brain and lungs . This  may explain why some covid-19 patients died of multiple organ failure. 
• Angiotensin converting enzyme inhibitors (ACEIs) could act as a potential risk factor for fatal  novel corona virus COVID-19  that by up regulating ACE2 . ACE2 plays important role in Renin angiotensin system (RAS) , Ang -2 promotes atherosclerosis in CVS and promotes inflammation , oxidative stress and migration of endothelial cells and vascular smooth muscle cells.
•  It has reported that plasma glucose levels and diabetes are independent predictors mortality and morbidity in patients with SARS . In china study revealed that of the 41 COVID-19 patients 32% of them underlying diseases , and among which 20% diabetes . therefore, these diabetic patients might be at increased risk of COVID-19 and have a poorer prognosis. 

Recent Studies :

• Most of the recent available studies have shown that diabetes mellitus as a distinctive co-morbidity is associated with sever disease, acute respiratory distress syndrome and increased mortality . Of 1099 confirmed cases of COVID-19  in china, 173 had sever diseases  , patients with severe diseases had a higher prevalence of diabetes mellitus (16.2%) as compared to those with non-severe diseases (5.7%).
• In the largest series reported by the Chinese center for disease control and prevention comprising of 72,314 cases of COVID-19, patients with diabetes mellitus had higher mortality (7.3% in DM  Vs 2.3% overall). 
•  Diabetes mellitus is characterized by exaggerated pro-inflammatory cytokine response , notably interleukin (IL)-1, IL-6 and tumor necrosis factor (TNF)-alpha , in the absence of immune-stimulation so this may be further exaggerated in response to a stimulus as seen in patients with COVID-19 complicated by acute respiratory distress syndrome (ADRS) . 
• ACE2 has protective effect on many diseases with reduced expression of ACE2 , such as hypertension , diabetes mellitus and cardiovascular diseases because it antagonize the function of ang-2.
•  The role of angiotensin converting enzyme-2 in the association between diabetes mellitus and COVID-19 is sensible. ACE2 is type 1 integral membrane glycoprotein that is constitutively expressed by the epithelial cells of the lung , kidney and blood vessels.
• ACE2 expression in reduced in patients with diabetes mellitus possibly due to glycosylation, this might explain the increased predisposition to sever lung injury and ADRS with COVID-19  .  Even over expression of ACE2 might be counterproductive in COVID-19. 
• The most distinguishing study reported  co-morbidities of 32 non-survivors from a group of 52 ICU patients with COVID-19 , were cerebrovascular diseases (22%) and diabetes (22%) . The expression of ACE2 is substantially increased in patients with type1  or type2 diabetes mellitus ,  who are treated with ACE inhibitors and angiotensin receptor blockers (ARBs) . High blood pressure / hypertension is also treated with ACE inhibitors and ARBs , which result in an up-regulation of ACE2. 
•  On the other hand ACE can be increased by thiazolidindiones e.g pioglitazone and Ibuprofen . A study suggested that ACE2 expression is increased in diabetes and treatment with ACE inhibitors and ARBs increases ACE2 expression  , the increased expression of ACE2 would facilitate the infection with COVID-19 . Therefore the study hypothesized that diabetes and hypertension treatment with ACE2-stimulating drugs increase the risk of developing severe and even fatal COVID-19  . Overall the study suggested that patients with CVDs , hypertension or diabetes , who are treated with ACE2 increasing drugs , are at higher risk for severe COVID-19 infection , therefore  should be monitored ACE2-modulating medication.