Can Intensive Insulin Therapy Improve Outcomes of COVID-19 Patients
Condition: COVID-19; Dysglycemia
MeSH terms: COVID-19
Study type: Interventional
Phase: Phase 1

Summary: 
      Evaluation of the reciprocal relation between hyperglycemia/diabetes mellitus (HG/DM) and
      COVID-19 disease and the effect of mode of insulin therapy; intensive (IIT) or conventional
      (CIT) on patients' outcomes All patients admitted to the quarantine hospitals with
      mild-severe COVID disease were evaluated using the COVID-GRAM Critical Illness Risk Score and
      gave blood samples for estimation of random blood glucose. Diabetic patients and non-diabetic
      patients with persistent HG were randomly divided according to mode of IT. Patients who were
      free HG were included as control normoglycemic (NG) patients. Study outcomes included the
      incidence of progress to critical illness and mortality rate (MR), and the effect of IT on
      such outcomes
    

Detailed description: 
      All patients admitted to the quarantine department at Benha University hospital and
      quarantine hospitals all over the Qalyubia Governorate were eligible for evaluation for
      exclusion criteria. Taking on the precautions according to the instruction of the Ministry of
      Health on dealing with suspected or confirmed COVID patients and with the application of
      conditions of Infection Control Programs and considering the personal protective equipment,
      clinical, radiological, and laboratory evaluation were undertaken.

        1. COVID-19 disease severity grading Patients were categorized according to the guidelines
           of the National Institutes of Health (NIH) and patients with pre-symptomatic infection
           or critical disease severity were excluded, while patients with mild-to-severe disease
           severity grade were enrolled in the study: Mild disease was defined as the presence of
           any of the signs and symptoms of COVID-19 without shortness of breath, dyspnea, or
           abnormal chest imaging. The moderate disease was determined by the presence of evidence
           of lower respiratory disease during clinical assessment or imaging, but oxygen
           saturation (SpO2) was ≥94% on room air at sea level. Patients were diagnosed as having
           the severe disease if SpO2 was <94% on room air at sea level, a ratio of arterial
           partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) <300 mm Hg,
           respiratory frequency >30 breaths/min, or lung infiltrates >50% (10).

        2. Diagnosis of hyperglycemia Stress hyperglycemia was defined according to the American
           Association of Clinical Endocrinologists and American Diabetes Association Consensus
           Statement on Inpatient Glycemic Control, as transient BG level at the time of admission
           >140 mg/dl that subsided on relief of stress and apprehension, but if BG persisted >140
           mg/dl at 6-hr after admission it is persistent hyperglycemia and needs intervention
           (11). For diagnosis of hyperglycemia and determination of baseline BG level of diabetic
           patients blood samples were obtained at admission and 6-hr thereafter for non-diabetic
           and put in a tube containing sodium fluoride (2 mg sodium fluoride/ ml blood) to prevent
           glycolysis till estimation of BG levels using glucose oxidase method (12).

        3. COVID-GRAM Critical Illness Risk Score At the time of admission, the risk for
           progression to critical COVID-19 illness was evaluated by one of the authors and the
           determined risk remained uncovered till the end of the study for comparative purposes.
           The risk of progression to critical illness depended on the three outcomes defined by
           Liang et al. (13) as admission to the ICU, need for invasive mechanical ventilation
           (IMV), or death. The risk of progression to critical illness was determined
           qualitatively as low, medium, or high and quantitatively as risk percentage using the
           COVID-GRAM Critical Illness Risk (CG-CIR) Score that can be computed depending on
           clinical, radiological, and laboratory findings at the time of admission using an online
           calculator (14).

      Patients' grouping

        -  Diabetic group: includes patients with definite DM and maintained on anti-diabetic
           therapy, either oral hypoglycemic or insulin therapy. Patients were divided according to
           the type of DM as T1D or T2D groups.

        -  Non-diabetic group: included patients who denied any history of DM or receiving
           antidiabetic therapy and were categorized as normoglycemic (NG) if their at admission
           random BG was <140 mg/dl or had stress hyperglycemia that disappeared at the 6-hr
           estimation of BG (NG Group), and hyperglycemic if their at admission BG level was >140
           mg/dl and persisted at 6-hr estimation (HG Group).
    

Intervention name(s): Insulin; Subcutaneous Insulin
Intervention type(s): Drug; Drug
Intervention description(s): Preparation: 50 IU of rapidly acting insulin in 50 ml of 0.9% saline solution was delivered through a 50-ml syringe-driven pump.
Monitoring: The insulin dose was adjusted to whole-blood glucose levels using glucometer every hour and insulin infusion was continued till BG level (Targeted level) was 80-110 mg, and then BG levels were estimated four-hourly
Insulin dose was titrated according to the Leuven titration protocol (15); Insulin dose was titrated according to the Blood glucose level
monitoring according to glucose in urine
Intervention MeSH terms: Insulin; Insulin, Globin Zinc
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Treatment