Hyperglycemia and Hydroxychloroquine, Obesity Paradox, Bariatric Surgery, and Hospitalization Rates

April 17, 2020

Hyperglycemia, Hydroxychloroquine, and the COVID-19 Epidemic

Theoretical review

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. 

Does COVID-19 Disprove the Obesity Paradox in ARDS?


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:

  • Under normal circumstances obese patients are presumed to be at greater risk and therefore get admitted to the hospital and have care escalated sooner.  This has not been possible during the current pandemic. 
  • Proning which has been found to be successful in some COVID-19 trials is more difficult in patients who suffer from obesity.

Recommendations for Metabolic and Bariatric Surgery During the COVID-19 Pandemic from IFSO


Recommendations issued by International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO) 

  • All elective surgical and endoscopic cases for metabolic and bariatric surgery should be postponed during the pandemic.
  • The body temperature of all patients upon arrival at endoscopy units, clinics or inpatient wards should be checked and documented.
  • Only emergency surgeries for treating severe complications of bariatric surgery are recommended during the COVID-19 pandemic
  • For any suspected or confirmed COVID-19 cases during the pandemic, emergency surgery can be offered after considering conservative treatment. The surgery should be performed in negative pressure rooms and isolation precautions should be taken.
  • metabolic and bariatric surgeries for patients who were diagnosed and recovered from COVID-19 should be evaluated by a multidisciplinary team. Diet and lifestyle modifications should be advised before surgical treatment.
  • Clinic and hospital visits are not recommended.
  • All face-to-face academic activities and conferences should be cancelled or postponed.

Risk factors for severity and mortality in adult COVID-19 inpatients in Wuhan

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.

Hospitalization Rates and Characteristics of Patients Hospitalized with Laboratory-Confirmed Coronavirus Disease 2019 - COVID-NET, 14 States, March 1-30, 2020

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.