CURRENT AND FUTURE IMPACTS PANELISTS: Carlos del Rio, MD Guillermo - - PowerPoint PPT Presentation

COVID-19 AND DIABETES: CURRENT AND FUTURE IMPACTS

PANELISTS:

• Carlos del Rio, MD
• Guillermo Umpierrez, MD
• Mohammed K. Ali, MD, MSc, MBA
• Shivani Agarwal, MD

MODERATOR:

• K.M. Venkat Narayan, MD, MSc, MBA

GCDTR is funded by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institute of Health (P30DK111024)

FRAMING QUESTIONS

1) Are people with diabetes truly at higher risk for COVID-19? If so, why? 2) Are people with diabetes truly at higher risk for COVID-19 complications (hospitalization, ICU admission, ARDS, pneumonia, death)? If so, why? 3) Will COVID increase diabetes disparities? If so, why, and in whom? 4) What are the challenges and solutions for diabetes prevention and care in the COVID era? 5) What specific public health and clinical guidelines are needed for people at risk of or with diabetes to deal with the risk of COVID? 6) What can we learn about COVID and diabetes through global collaboration?

CO COron

• naVirus Infec

ectiou

• us Disease

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CARLOS DEL RIO, MD EMORY UNIVERSITY

CarlosdelRio7

https://www.eurekalert.org/multimedia/pub/226254. php?from=457812. German Primate Center

ACE2 receptors: Lungs Heart GI Kidneys

“Wuhan p pneu eumon

• nia”

Wuhan, a city in central China, is the capital of Hubei province. 31 December 2019: WHO China Country Office was informed of cases

• f pneumonia of unknown etiology detected in Wuhan.

07 January 2020: Chinese authorities identified a novel coronavirus (2019-nCoV) as the probable causative agent.

• Disease now named COVID-19 by WHO
• Virus named SARS-CoV-2

(https://www.biorxiv.org/content/10.1101/2020.02.07.937862v1)

As of April 3, 2020: > 1,000,000 confirmed cases and > 54,000 deaths

• Three cases > 100,000 cases: USA (245,380); Spain (117,710) & Italy (115,242)

Human to Human transmission driving the epidemic Significant risk to Healthcare workers

Current Status of the COVID-19

(March 27, 2020)

Global case numbers: > 1,000,000 cases & > 54,000 deaths

• https://gisanddata.maps.arcgis.com/apps/opsdashboard/index.html#/bda759

4740fd40299423467b48e9ecf6

• https://www.worldometers.info/coronavirus/

US case numbers: > 245,000 cases and > 6,000 deaths

• https://www.cdc.gov/coronavirus/2019-ncov/cases-in-us.html

Expon

• nen

ential g growth….> 6 600,000 cases es The r rapid gr growth th in t the n e number of case ses

• Took 67 days from the first reported case to reach the first 100,000
• cases. Then…
• 11 days for the second 100,000 cases
• 4 days for the third 100,000 cases
• 3 days for the fourth 100, 000 cases
• 2 days for the fifth 100,000 cases
• 1 day for the sixth 100,000 cases

Source: WHO

COVID-19 C 19 CASES I IN N THE HE U U.S. .

https://w /www.worldometer ers.info/coronavi virus/country/us/

COVID-19 Cases & deaths per capita by county (as of April 2, 2020)

https://public.flourish.studio/visualisation/1759890/

COV OVID-19 C 19 CASES I IN T THE U U.S.

https://www.nytimes.com/interactive/2020/us/coronavirus-us-cases.html#states

State Cases Per 100,000 pop Deaths Per 100,000 pop Mortality New York 92,770 472.9 2,653 13.5 2.8% New Jersey 25,590 288.1 539 6.1 2.1% California 10,925 27.9 243 0.6 2.2% Michigan 10,791 108.4 417 4.2 3.8% Louisiana 9,150 196.2 310 6.6 3.3% Florida 9,000 43.7 144 0.7 1.6% Massachusetts 8,966 131.3 154 2.3 1.7% Illinois 7,695 60.0 165 1.3 2.1% Pennsylvania 7,016 54.9 90 0.7 1.3% Washington 6,585 90.3 300 4.1 4.5% Georgia 5,444 52.9 176 1.7 3.2%

COV OVID-19 T Tran ansmission

• n

Respiratory secretions - main mode of transmission

• Spread through respiratory droplets in the

air and that land on surfaces

• Transmission from people ~ 24 – 48 hrs

before onset of symptoms occurs Stool – unlikely to be a source Perinatal – no transmission observed

Tang JW et al, J Hosp Infect 2006; 64:100-14.

Clinical Characteristics of COVID-19

Incubation period is ~5 days (range = 2 – 14 days) ~80 % have mild illness (~80%)

• fever (83 – 98%)
• cough (76 – 82%)
• myalgia or fatigue (11 – 44%)

~ 30% of hospitalized patients required intensive care

• 5-10% require mechanical ventilation

No approved medication

• NIH clinical trials have started

Supportive care has been very successful for most patients

Risk factors for severe disease

Age >55 Underlying pulmonary disease Cardiovascular disease Hypertension Diabetes Immunocompromise (history of transplant, HIV regardless of CD4 count, use of biologics) Physical exam findings including RR>24, HR>125, oxygen saturation <90% on room air Elevated D-dimer CPK > 2x ULN CRP >100 LDH >245 Elevated troponin Lymphopenia <0.8 x103cells/minute Platelet count <100 Ferritin >300

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30566-3/fulltext

COVID-19 Mortality

What about ICU and mechanical ventilation?

• A machine that helps a patient breathe

(ventilate) when he/she cannot breathe on their

• wn for any reason.
• 2,704 US hospitals have ICU services (51.4% of

all US hospitals) – 74% in metropolitan areas.

• There are ~ 96,596 ICU beds in the US (16.7% of

all hospital bed)

• This is 34.7 per 100,000 population
• 25,157 step-down beds & 1,183 burn beds
• ICU occupancy rates are ~ 66.6%
• US hospitals have ~ 100,000 ventilators and

there are ~ 12,700 in the SNS

Testing for COVID-19

Testing by detecting RNA of virus:

• Nasopharyngeal swab and Throat swab
• Lower respiratory sample if possible

Until recently only available at CDC

• Now available in all state laboratories

Commercial labs (ej: Quest, LabCorp, ViraCor) also performing testing Time from sample acquisition to test result is still longer than desired Supplies and throughput still an issue Still needed: greater ability to obtain testing without coming to hospital or busy clinic

Personal Protective Equipment

Gown Gloves N-95 Respirator Face Shield Personal Protective Equipment are Single Use Only Discard after leaving the patient room and perform hand hygiene

Challenges in Infection Prevention

In the case of 2019-nCoV, the difficulty in controlling the virus includes:

• presence of many mild infections: difficulty in identifying and

isolating cases at an early stage

• limited resources for isolation of cases and quarantine of their close

contacts

• Training needed to donning and duffing PPE
• Great video from NETEC: https://www.youtube.com/watch?v=bG6zISnenPg

Protective efficiencies:

• N95 mask = 89.6%
• Surgical mask = 33.3%
• Bandana = 11.3%
• Dust mask = 6.1%
• universal mask use could reduce

infections by around 10 percent

Abaluck, J at al. The Case for Universal Cloth Mask Adoption and Policies to Increase Supply of Medical Masks for Health Workers (April 2, 2020). Available at SSRN: https://ssrn.com/abstract= :

Non-pharmacologic measures

• Border screenings/closures
• Little value at this point
• Mass gatherings
• Important to prevent them – may have significant impact on conferences and sporting event
• In Atlanta the NCAA Basketball final 4 and the Decennial Conference in Infection Prevention
• Public transportation
• Potential place for spread
• School closures
• Have to be implemented early to have impact
• Isolation of infected
• Critically important, need testing to identify those infected!

Goals of Mitigation Strategies

• Minimizing morbidity
• “Flattening” the epidemic curve

to avoid overwhelming healthcare services

• Keeping impact on economy

manageable

• Slowing progression of epidemic

to allow for vaccine and other treatment development

Social Distancing

“TO LIMIT THE SPREAD IN THE COMMUNITY WE NEED TO SPREAD THE COMMUNITY”

Social Distancing

Impact of social distancing – Mobility Index

The Emory COVID-19 Checker:

https://c19check.com Based on the answers to questions about signs and symptoms, age and other medical problems, a person is directed to guidance based on CDC guidelines and is placed into one of three categories:

• high risk - needs immediate medical

attention,

• intermediate risk - can contact their doctor for

guidance about how to best manage their illness,

• low risk - can most likely administer self-care
• r recover at home.

Conclusions

1. It is going to get worse before it gets better 2. We need to “prepare for the worst and hope for the best” 3. This is going to be long (3 -4 months) and there will be significant pain. a. We need to protect our healthcare workers but also need to be prepared as some ofour friends, family and colleagues will get infected b. We need to provide psychological support/counseling 4. We can make a difference as persons, society and healthcare system a) Help promote social distancing b) Make sure those sick with fever or respiratory symptoms stay home 5. This too shall pass, how long it lasts is really up to us

The Future

Rapid Diagnostic Test Antiviral Therapy? Identification of “Super” spreaders, most efficient transmission routes, period of infectivity, etc. Spectrum of Disease:

• asymptomatic transmission

Vaccines Understanding why outbreak occurred and prevent from happening again

https://jamanetwork.com/journals/jama/fullarticle/2760782 https://jamanetwork.com/journals/jama/fullarticle/2762510

• CDC
• https://www.cdc.gov/coronavirus/about/index.html
• WHO
• https://www.who.int/health-topics/coronavirus
• IDSA:
• https://www.idsociety.org/public-health/Novel-Coronavirus/
• National Academy of Medicine:
• https://nam.edu/coronavirus-resources/
• NYT:
• https://www.nytimes.com/live/2020/coronavirus-covid-19-03-18

Resources es

COVID-19 and Diabetes: Clinical Implications

Guillermo E. Umpierrez Professor of Medicine Emory University April 3, 2020

1. Huang et al. Journal of Microbiology, Immunology and Infection 2020 2. Chen N et al. Lancet 2020 3. Wang D et al. JAMA 2020

COVID-19 – Epidemiology and Comorbidities

Huang et al N= 41 Chen et al N=99, pneumonia Wang et al N= 138, pneumonia Study site Wuhan Wuhan Wuhan Age, years 49 (41-58) 55.5 (13.1) 56 (42-68) Men, % 73.2 67.7 75 Comorbidities (present in 30-50% of patients) CVD, % 14.6 40.4 14.5 Hypertension, % 14.6 NA 31.2 Diabetes, % 19.5 12.1 10.1 Respiratory Dis, % 2.4 1.0 2.9 Malignancy, % 2.4 1.0 7.2

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China

Onder et al. JAMA 2020

Case-Fatality Rate and Characteristics of Patients Dying in Relation to COVID-19 in Italy

Onder et al. JAMA 2020

Case-Fatality Rate and Characteristics of Patients Dying in Relation to COVID-19 in Italy

Clinical characteristics and outcomes of severe COVID-19 patients with diabetes

Total N= 193 Diabetes N= 48 No-Diabetes N=145 P-value Age, median, yr 64 (49, 73) 70 (62, 77) 60 (43, 71) ,0.001 Male, % 59.1 68.8 55.9 0.115 Symptoms Fever, % 89.6 89.6 89.7

• .98

Cough, % 69.9 77.1 67.6 0.214 Dyspnea, % 59.6 68.8 56.6 0.13 Random BG, mmol/l 11.31 (7.9-16.7) 6.56 (5.59, 8.08) <0.001 HbA1c, % 7.2 (6.7, 8.3) 5.8 (5.5, 6.1) <0.001

Dong et al. BMJ DRC, Accepted for publication Severe case was defined as including one criterion as follow: 1. respiratory rate > 30/min, 2. oxygen saturation ≤ 93%, 3. PaO2/FiO2 ≤ 300mmHg, 4.patients developed either with shock, or respiratory failure requiring mechanical ventilation, or combined with the other organ failure admission to intensive care unit (ICU).

Clinical characteristics and outcomes of severe COVID-19 patients with diabetes

Total N= 193 Diabetes N= 48 No-Diabetes N=145 P-value Comorbidities Hypertension, % 37.8 50.0 33.8 0.045 Cardio VD, % 16.1 27.1 12.4 0.016 Cerebro VD, % 4.1 10.4 2.1 0.036 CKD, % 2.1 0.0 2.8 0.54 ICU, % 47.7 66.7 41.4 0.002 Ventilator Rx, % 57 81.3 49.0 <0.01 LOS, median, % 13 (7, 16) 10 (6, 13) 13 (9, 18) 0.001 Mortality, % 56 81.3 47.6 <0.001

Dong et al. BMJ DRC, Accepted for publication

Plasma glucose levels and diabetes are independent predictors for mortality and morbidity in patients with SARS

Changes in fasting plasma glucose (FPG) levels during the clinical course of SARS survivors (n = 385) and deceased patients [n = 135 (week 0); 92 (1); 33 (2); 14 (3)

Yang et al. Diabetic Medicine. 23: 623–628, 2006 Retrospective analysis, 135 patients who had died from SARS, 385 survivors

• f SARS and 19 patients with non-SARS

pneumonia were compared Survivors Deceased

Diabetes patients with COVID-19 need better care Wuham Health Care System, Hospital admissions

Total N= 29 Age, median, yr 69 (54, 81) Target BG 7.8 -10.0 mmol/L # POC testing 881 Hyperglycemia 499 (56.6%)

• pre-prandial hyperglycemia

58 (29.4%)

• postprandial hyperglycemia

441 (64.5%) Hypoglycemia 10.3%

Dong et al. BMJ DRC, in press

Diabetes and COVID-19 Patients: Before Illness

American Diabtes Association, WWW. ADA.ORG, accessed 4/2/2020 Gather supplies:

• Get 90-day or extra refills
• Glucose testing, medications

Perform frequent BG testing during illness Phone numbers of your doctors and healthcare team, your pharmacy and your insurance provider

1.ACE/ADA Task Force on Inpatient Diabetes. Diabetes Care. 2006 & 2009 2.Diabetes Care. 2009;31(suppl 1):S1-S110..

Antihyperglycemic Therapy

I nsulin

Recommended

OADs

Not Generally Recommended

Recommendations for Managing Patients With Diabetes in the Hospital Setting

ICU: Insulin is the Most Appropriate Agent for Critically Ill Hospitalized Patients

Rapidly effective Easily titratable (up or down) No real contraindications

I V I nsulin Critically I ll Patients

Most potent glucose- lowering agent

Glucose target between 140-180 mg for most patients in the ICU

Recommended 140-180 Acceptable 110-140 Not recommended <110 Not recommended >180

Basal Plus Insulin Regimen

SSI = sliding scale insulin Umpierrez et al. Endocrine Society Guidelines. J Clin Endocrinol Metabol. 97(1):16-38, 2012 Umpierrez et al, Diabetes Care 8:2169-74, 2013 Smiley et al. J Diabetes & Its Complications 6:637-41, 2013 Pasquel et al. Lancet Diabetes & Endocrinology 2020, in press

Long-acting insulin Rapid-acting insulin

“Scheduled” (SSI only uses this component)

Basal Correction

Concerns:

• COVID Patients are presenting with significant hyperglycemia

and have evidence of insulin resistance.

• Steroid treated patients
• Large insulin requirement in ICU and non-ICU

Safety and Efficacy of Continuous Insulin Infusion in Noncritical Care Settings

Smiley et al. J Hosp Med. 2010 Apr; 5(4): 212–217.

Retrospective analysis of 200 consecutive patients receiving CII while admitted to general medical-surgical units at Emory University Hospital. 41% receiving steroids, 16% ICU transfer

During the CII, 37% of patients experienced a BG <70 mg/dL

Hospital Use of Continuous Glucose Monitoring (CGM)

CGM in Non-ICU Insulin-Treated Patients with T2D

Gomez et al. J Diabetes Science & Technology 2016 Average daily BG measured by CGM and POC Clinical accuracy BG levels measured by CGM No differences in daily BG between CGM and POC. Higher # of hypoglycemia detected by CGM CGM than POC (55 vs 12, P < .01). Glucose measurements were clinically valid, with 91.9% of patients falling within the Clarke error grid A and B zones.

Freestyle Libre Pro Flash CGMS vs. POC Capillary Glucose Testing in Hospitalized Patients with T2D

Mean Hospital Daily Glucose Hypoglycemia by POC and CGM

Galindo et al. Diabtes Care 2020, in press Galindo et al. ADA Scientific Session 2019; Diabetes Care Under Review

COVID-19 and Diabetes: Clinical Implications

• Higher prevalence of diabetes in patients with Covid-19 infections
• Patients with diabetes have worse outcome compared to non-DM:
• Higher hospital admissions
• Among hospitalized patients:
• Higher ICU, ventilatory support and mortality
• Inpatient hyperglycemia associated with poor outcome
• Inpatient management of diabetes:
• Target BG < 180 mg/dl
• Insulin therapy is the preferred treatment regimen
• ICU: continuous insulin infusion
• Non-ICU: basal plus – bolus if needed
• Follow corticosteroid protocols
• Frequent BG monitoring (SMBG, CGM?)

Convergence of infectious & chronic diseases:

SARS-CoV-2 and Diabetes

M ohammed K Ali

Departments of Family and Preventive Medicine, Global Health, and Epidemiology

Diabetes COVI D-19

Baker et al. BMC 2011

Diabetes and I nfections

MORE SUSCEPTIBLE to and/or MORE SEVERE infxns respiratory (30% higher odds of pneumonias) urinary (2-4 fold higher urinary infections) skin, bone

• 2 billion people latent TB infection
• In diabetes:

➢3 times higher risk risk of active TB ➢70% higher risk of Rx failure or death ➢4 times higher risk of TB relapse

Joshi et al. NEJM 1999 Muller et al CID 2005

Diabetes COVI D-19

BEHAVIORS & PREVENTIVE SERVICES

Detection Counseling Lifestyle choices Utilization Patterns Medication adherence Clinical Care Quality

Providers & Hospitals

IMPACTS

Diabetes Incidence Diabetes Progression Patient-centered outcomes Patient & System Costs Unintended outcomes Disparities

Health Plans Patients

NEXT-D Network

Fragmentation Inertia Engagement Access Motivation Fear

95% 92% 81% 64% 66% 57% 27% 21%

0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% Usual Place of Care ≥2 Provider Visits in Past Year Nonsmoker Glycemic Control † BP Control LDL Cholesterol Control Combined ABC Control Combined ABC Control + Nonsmoker Proportions (%) with Diagnosed DM

85% 67% 78% 77% 58% 36% 22% 19%

0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% Usual Place of Care ≥2 Provider Visits in Past Year Nonsmoker Glycemic Control † BP Control LDL Cholesterol Control Combined ABC Control Combined ABC Control + Nonsmoker Proportions (%) with Undiagnosed DM

20.5 millio n 7.9 millio n

0.0 5.0 10.0 15.0 20.0 25.0 30.0 Total with Diabetes Population Size (millions)

Undiagnosed Diagnosed

Pr Prevention C ention Continuum

• ntinuum

53.5M 27.1M 22.7M 19.0M 5.7M 0.2M 45.2M 14.6M 10.7M 9.3M 8.7M 3.1M 0.7M 13.1M

Ali et al, JAMA Network Open, 2019

Diagnosis

Screening +/- Dx test(s) Routine checks (BP, weight, etc)

Care Outcomes Engagement

Clinical assessment and judgment of risk

Care Processes

Routine medical & family History Access to care providers Visit care provider Treatment Monitoring Care goals Treatment modification Retention in care

Ali et al, Annals of Int Med, 2014

Natural Experiment

COVID-19

mkali@emory.edu @mkali80 diabetes.emory.edu