ACE2 and COVID - presentation on a theory that could cause varying levels of disease severity
It appears from literature published from the SARS epidemic and early data from COVID-19 that viral entry occurs through binding to ACE2 in various epithelial tissues. It appears that glycosylation of both the viral protein and ACE2 increases affinity for binding that this may be a factor in the increased risk of poor outcomes in patients with uncontrolled hyperglycemia and diabetes.
“By reducing levels of glycosylated ACE2 target in the target lung
tissue by glycemic control, this could possibly reduce the number of glycosylated viral
binding sites in the lung, and hence possibly ameliorate some of the inflammation and
symptoms of COVID-19 disease.”
Hyperglycemia induced or worsened by corticosteroids has led to a recent review that recommended against their use in COVID-pneumonia.
Bottom line: Hyperglycemia appears to lead to increased levels of glycosylated ACE2 in various tissues and could be responsible for increased disease severity.
However, higher ACE2 has also been found to be protective in other tissues and it may be that it is the glycosylation and not the total ACE2 levels that confer increased risk for progression of disease.
It is possible that hydroxychloroquine and chloroquine could be helpful in COVD-19 by blunting some of the immune response and decreasing glycosylation of the ACE2 receptor.
Past studies have shown that obesity leads to decreased mortality from ARDS known as the obesity paradox. However, a number of studies have found that with COVID-19, obesity is a risk factor for poor outcomes. Hypotheses raised for this apparent contradiction are:
Recommendations issued by International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO)
Ambispective cohort study
Patients with COVID-19 admitted to Tongji Hospital from January 26, 2020 to February 5, 2020 were retrospectively enrolled and followed-up until March 3, 2020. 549 total patients were included in the study with 269 patients identified as severe cases. Patients over 65 years of age were almost twice as likely to develop severe disease as patients under age 65. Compared with nonsevere cases, severe cases exhibited more comorbidities, including chronic obstructive pulmonary disease (4.8% vs. 1.4%, p=0.026), coronary heart disease (10.4% vs. 2.2%, p<0.001), hypertension (38.7% 241 vs. 22.2%, p<0.001), and diabetes (19.3% vs. 11.1%, p=0.009) respectively. No difference in severity was found in patients who were taking ACEI or ARBS. However, hypertension was the only comorbidity associated with the severity of 383 COVID-19 after adjustment for age, sex and smoking status
Hyperglycemia (adjusted 318 HR 1.8; 95% CI 1.1-2.8) was among the factors associated with mortality in severe cases. However, hypertension was the only comorbidity associated with the severity of 383 COVID-19 after adjustment for age, sex and smoking status.
This is a population-based surveillance for laboratory-confirmed COVID-19–associated hospitalizations in the United States by the COVID-19–Associated Hospitalization Surveillance Network (COVID-NET). This report presents age-stratified COVID-19–associated hospitalization rates for patients admitted during March 1–28, 2020, and clinical data on patients admitted during March 1–30, 2020, the first month of U.S. surveillance.
Data from 1,482 hospitalized patients was examined. Not all patients had data on underlying conditions available, but for those that did - 89.3% had one or more underlying conditions; the most common were hypertension (49.7%), obesity (48.3%), chronic lung disease (34.6%), diabetes mellitus (28.3%), and cardiovascular disease (27.8%). Data from this study also suggests that COVID-19 is disproportionately impacting men and African-Americans.These results are overall consistent prior studies in the US and other countries.