Public Health COVID-19 Response February 13, 2021

Panelists: Dr. Erin Narus, CAPT Kara King, Dr. Coleman Cutchins

Presentation Objectives

• List at least 3 recent developments regarding COVID-19 and discuss their importance in clinical management of the disease.

• Analyze current data on COVID-19 vaccine safety and efficacy data. • Discuss updates on PCR tests, serology, and test shortages.

• Discuss lessons learned from statewide (phase 1a) COVID-19 vaccination efforts including vaccine confidence and hesitancy in the community.

Pre-Session Assessment

1. How do mRNA vaccines work?

a. a weakened, inactivated virus is put into our bodies and we build an immune response

b. they teach our cells how to make a protein that triggers an immune response inside our bodies

c. the mRNA becomes a part of the host DNA

d. the mechanism is unknown

Pre-Session Assessment

2. What test can be used to diagnose SARS Co-2 infection

a. Lab based Rt PCR

b. Antigen test via NP swab

c. Chest Ct wit contrast

d. Antibody test

e. Just A and B

f. All of the above

Pre-Session Assessment

3. How many SARS-CoV-2 vaccines are currently approved by FDA for administration in the United States?

a. 0

b. 1

c. 2

d. 3

COVID-19

• Overview and Epidemiology

• Management

• Prevention

• Alaska’s Response

COVID-19 Update Coleman Cutchins, PharmD, BCPS

COVID-19 Snapshot in Time

• The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to propagate across the United States and worldwide.

• US cases are approaching 28 million and 500,000 deaths

Coronavirus COVID-19 (2019-nCoV) (arcgis.com)

COVID-19 – How it all begin

• 2019: • Novel coronavirus identified in Wuhan, China

• February 2020: • WHO designated coronavirus disease 2019 as “COVID-19”

• Virus that causes COVID-19 identified as SARS-CoV-2

Wuhan Flight Anniversary Plane landed in Anchorage Jan. 28, 2020, departed several hours later

• Flight carrying repatriated Americans from Wuhan, China, landed around 9:30 p.m. Tuesday, Jan. 28, 2020 and departed around 2:15 am, Jan. 29, 2020.

• Patients disembarked at the North Terminal for U.S. Customs processing and health screenings by the USPHS, CDC, the Anchorage Health Department and DHSS.

Hermoine Dickey, 8, rides in a car on her way to a U.S. evacuation flight Tuesday (Priscilla Dickey via AP)

COVID-19 Clinical Manifestations

• Incubation period • 4-5 days average, can be 14+ days

• Initial presentation • Cough

• Fever

• Headache

• Diarrhea

• Sore throat

• Taste/smell abnormalities

• Myalgias

COVID-19 Presentation

• Asymptomatic infections • Estimates vary but most agree that >50% of spread occurs from people that

are asymptomatic at the time.

• Symptomatic infections • Range from mild to critical; most infections are not severe

• Mild: ~80%

• Severe (dyspnea, hypoxia, >50% lung involvement): 14%

• Critical (respiratory failure, shock, multi-organ dysfunction): 5%

• 2.3% overall case fatality rate

COVID-19

• Risk Factors for severe illness • advanced age • certain underlying medical

comorbidities

• Comorbidities • Cardiovascular disease • Diabetes mellitus • Hypertension • Chronic lung disease • Cancer • Chronic kidney disease • Obesity • Smoking

• Lab abnormalities – associated with worse outcomes • Lymphopenia • Thrombocytopenia • ↑ liver enzymes • ↑ lactate dehydrogenase (LDH) • ↑ inflammatory markers • ↑ D-dimer • ↑ prothrombin time (PT) • ↑ troponin • ↑ creatine phosphokinase (CPK) • Acute kidney injury

COVID-19 Course and Complications

• Respiratory failure

• Cardiac and cardiovascular complications

• Thromboembolic complications

• Neurologic complications

• Inflammatory complications

• Secondary infections

• Post acute, “long COVID”

Alaskans + Underlying Conditions

2%

5%

6%

8%

32%

Chronic kidney disease

Heart conditions

COPD

Diabetes

Obesity

Smoking

1 or more conditions

26% are former smokers 20% smoke now

43% have 1 condition 24% have 2+ conditions

46%

67%

Most Alaska adults have at least one ongoing condition that increases their chances of

getting seriously ill or hospitalized with COVID-19.

DHSS Insights Blog: http://dhss.alaska.gov/dph/Epi/id/Pages/COVID-19/blog/default.aspx

COVID-19 Data Summary February 9, 2021

COVID-19 Data Summary Updated through

TOTAL CONFIRMED COVID BEDS OCCUPIED DAILY TESTS WITH POSITIVE RESULTS

COVID-19 CASES BY ONSET DATE

COVID-19 Status Report February 9, 2021

2.52%

Alaska and U.S. – Current Situation CASES

CDC Data Cases Per Capita – Last 7 Days Alaska: 20/100K 12th lowest case rate in nation per capita

Alaska and U.S. – Current Situation

DEATHS CDC Data Deaths Per Capita – Alaska: 37/100K Third lowest death rate in nation

TESTING Johns Hopkins Alaska: 2.52% percent positivity Fourth lowest among states Second most tested state per capita

Alaska and U.S. – Pandemic to Date

Alaska and U.S. – Current Situation

Thank you, Alaskans!

20

Alaskans have come together: providers and volunteers, families and friends, municipal and tribal leader. Alaskans have risen to the challenge in the most amazing ways.

Testing and Contact Tracing

21

• Workforce expanded to about 500 contact tracers.

• Cases called the day they are entered into the database.

• Average statewide of three days between testing and a call from a contact tracer.

• Only about 2% decline to participate after picking up a contact tracer’s call.

COVID Testing/Diagnosis

Testing and Diagnosis

• Diagnostic test is the gold standard for diagnosis of SARS CoV-2 infection • IDSA: “Clinical assessment alone is not accurate in predicting COVID-19

diagnosis.”

• Availability is better than it had been at any point in the pandemic • Getting commercial availability of ID NOW devices and cartridges

• Commercial labs both in AK and out of state consistently <24 hr Turn around time (TAT)

• Antigen tests are widely available

• Anticipate CUE to be available soon

• CEPHEID is still greatly scarce.

https://jamanetwork.com/journals/jama/fullarticle/2765837?fbclid=IwAR0YkCSstgR3sNX6h3902etQ1bMmtyYgbejNxNcqfX6vG3uYPKVCD_UItms

JAMA May, 6 2020Interpreting Diagnostic Tests for SARS-CoV-2

Types of tests –Diagnostic (Swabs)

• Molecular - Detects the RNA of the SARS CoV-2 virus • Send to lab

• high volume

• NAAT, PCR, THERMOFISHER, ROCHE, HOLOGIC,….

• Turn around time, most places in AK TAT <48 hours, some places <24 hrs

• Expensive ($75-$150+)

• Best option when testing groups of people

• At home options (FULGENT, VAULT, LAB CORP,…)

• Rapid • low volume, 20min -> 1 hr

• PCR, Isothermal NAAT, ABBOTT ID NOW, CEPHEID GENEXPERT, BIOFIRE, CUE,...

• Expensive (~$45-$300+)

Ct Values (Cycle Threshold)

• SARS CoV-2 PCR is a qualitative “yes or No” test • Inverse correlation between the amount of virus in the sample and the Ct but

not designed to determine viral load. • Many things can lead to a lower amount of virus in a sample

• Poor/incomplete collection, • Improper storage/transport. • Viral load is not static but a measurement at a single point in time

• In terms of Ct values, Ct values are and only comparable within one given assay

• Many of the SARS CoV-2 PCR platforms do not have the ability to report a Ct, particularly the “walk away” platforms used at many high-capacity commercial labs.

Types of tests – Diagnostic (Swabs)

• Antigen - Detects surface proteins of SARS CoV-2 virus • Rapid (<30min), low volume (but higher volume then rapid molecular)

• Some require a device (QUIDEL, BD)

• Some don’t (BINAX, CARESTART)

• Many are Nasopharyngeal

• Most evidence (and EUAs) for use in symptomatic

• Less expensive ($15-$50)

• Less sensitive, even less so in asymptomatic • Require frequent testing

Evaluation of Abbott BinaxNOW Rapid Antigen Test for SARS-CoV-2 Infection at Two Community-Based Testing Sites — Pima County, Arizona, November 3–17, 2020

• CDC – MMWR January 22, 2021 / 70(3);100–105

• 'Sensitivity of the BinaxNOW antigen test, compared with polymerase chain reaction testing, was lower when used to test specimens from asymptomatic (35.8%) than from symptomatic (64.2%) persons, but specificity was high. Sensitivity was higher for culture-positive specimens (92.6% and 78.6% for those from symptomatic and asymptomatic persons, respectively); however, some antigen test-negative specimens had culturable virus.'

Antibody – not diagnostic (blood)

• Test for the presence of antibodies, 1-3 weeks post exposure

• Should NOT be used for diagnosis or rule out of infection

• All results should be considered presumptive and currently no recommendations to use antibody to guide clinical decision making

• Can be rapid or lab processed, greatly vary in cost and TAT

• Performance also highly variable and some tests cross react

• Antibody response is not the bodies only defense (B cells)

SARS-CoV-2 Genomic Sequencing

Questions about variants

• How widely have these new variants spread? • Spread more easily from person-to-person

• How does the disease caused by these new variants differ from the disease caused by other variants that are currently circulating? • Cause milder or more severe disease in people

• How do these variants affect existing therapies, vaccines, and tests? o Are they detected by currently available viral tests?

o Do they respond to medicines currently being used to treat people for COVID-19?

o Will they change the effectiveness of COVID-19 vaccines?

~3-4%

January 8, 2021

Spike Mutations Mutation What we know

69/70 del -histidine, -valine

N-terminal mutation, six nucleotide deletion in spike resulting in double deletion of 2 aa, present >3,000 sequences worldwide, multiple lineages. Found to occur with other mutations in receptor binding domain (Y453F, N501Y, N439K, D614G)

K417N lysine to asparagine

Part of a trio of mutations in the RBD of B.1.351 variant

N439K asparagine to lysine

No evidence of increased transmission, may be capable of escape from neutralizing activity of some monoclonal antibodies.

L452R leucine to arginine

First described in California. Provides better binding affinity to human receptor.

Y453F tyrosine to phenylalanine

Associated with mink-human infections, risen independently multiple times in several countries. Provides better binding affinity to human receptor, ACE2

E484K glutamic acid to lysine

Part of a trio of mutations in the RBD of B.1.351 variant. May affect neutralization by some polyclonal and monoclonal antibodies.

N501Y asparagine to tyrosine

Found in multiple lineages. Demonstrates increased binding affinity to ACE2. Affects conformation of receptor-binding domain.

D614G aspartic acid to glycine

C-terminal mutation, might provide greater stability to the S protein, associated with enhanced viral transmission, present in most Alaska viruses we’ve sequenced.

P681H aspartic acid to glycine

Near the S1/S2 furin cleavage site. This mutation has also emerged spontaneously multiple times. https://covariants.org/variants

B.1.1.7 UK Variant

B.1.351 South African Variant

P.1/P.2 Brazilian Variant

Variants of Concern in the U.S.

Variant B.1.1.7 (20I/501Y.V1)

B.1.351 (20H/501Y.V2)

P.1 (20J/501Y.V3)

# of Cases in U.S. 467 (32 states) 3 (2 states) 1

# of Cases in AK 1 0 0

Protein mutations 18 (50% spike) 8 (62.5% spike) 22 (50% spike)

Spike mutations N501Y N501Y N501Y

D614G K417N K417N

69/70 deletion E484K E484K

6 others… D614G D614G

A701V 8 others…

https://www.cdc.gov/mmwr/volumes/70/wr/mm7003e2.htm#T1_down

COVID-19 Variant Strains

Priority Specimens

• Travelers

• Rural specimens

• Outbreaks

• Vaccinated

http://dhss.alaska.gov/dph/Epi/id/SiteAssets/Pages/HumanCoV/AKCOVIDTestingGuidance.pdf

COVID-19 Therapeutic Options

Remdesivir • FDA EUA May 1, 2020, Approved October 22, 2020

• Early was allocated by the Federal government, now commercially avaialble

• First medication approved for use in adult and pediatric patients 12 years of age and older and weighing at least 40 kg for the treatment of COVID-19 requiring hospitalization.

• Nucleotide analogue, with broad-spectrum antiviral activity in vitro and in vivo against a number of viral pathogens, including SARS-CoV-2.

• Inhibits viral RNA replication via antagonism of RNA-dependent RNA polymerase. It was studied extensively during the Ebola outbreak with mixed results.

Remdesivir, continued

• Administered only as an IV infusion

• 200-mg IV loading dose, followed by 100 mg IV daily for 5–10 days or until hospital discharge.

• National Institutes of Health (NIH) treatment guidelines recommend prioritizing the limited supplies of remdesivir for use in patients who are hospitalized with COVID-19 who require supplemental oxygen but who do not require oxygen delivery through a high-flow device, noninvasive ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO) • ACTT-1 Post hoc analysis showed most benefit in hospitalized patients on low flow O2, only

group to show mortality benefit (hazard ratio, 0.30; 95% CI, 0.14 to 0.64)

https://www.nejm.org/doi/full/10.1056/NEJMoa2007764

Remdesivir, continued

• Recommendations for use: • Hospitalized and requiring supplemental oxygen: For these patients,

remdesivir can be given for 5 days or until hospital discharge (whichever occurs first). Alternatively, dexamethasone can be given in concert with remdesivir therapy or in place of remdesivir therapy.

• Hospitalized and requiring supplemental oxygen delivery through a high-flow

device or noninvasive ventilation: Remdesivir is not recommended as monotherapy but rather in conjunction with dexamethasone.

• Hospitalized and requiring invasive mechanical ventilation or

ECMO: Remdesivir is only recommended with dexamethasone in patients who have recently been intubated.

Monoclonals

• Bamlanivimab (Lilly), casirivimab + imdevimab (Regeneron), bamlanivimab + etesevimab (Lilly, EUA 2/10/2021)

• Monoclinal antibodies targeted to spike protein on SARS CoV-2

• All are given over IV infusion up to 1 hr +

• All have the same EUA criteria and no data to support one above the other

• It is recommended that sites use the monoclonal antibody product that is available.

• Combination MABs are to target variant strains. Bamlanivimab alone has decreased activity against the S. African (B1.351) strain whereas Regeneron’s combo maintained activity • Lilly recommends continuing to use bamlanivimab alone. They stated the amount of

resistance is so low that all products provide benefit.

EUA criteria

• To treat mild to moderate COVID-19 in patients not admitted to the hospital for COVID-19

• High risk is defined as patients who meet at least one of the following criteria:

• Have a body mass index (BMI) ≥35

• Have chronic kidney disease

• Have diabetes

• Have immunosuppressive disease

• Are currently receiving immunosuppressive treatment

• Are ≥65 years of age

• Are ≥55 years of age AND have: cardiovascular disease, OR hypertension, OR chronic obstructive pulmonary disease/other chronic respiratory disease.

• Are 12–17 years of age AND have: BMI ≥85th percentile for their age and gender based on CDC growth charts, OR sickle cell disease, OR congenital or acquired heart disease, OR neurodevelopmental disorders, OR a medical-related technological dependence or positive pressure ventilation (not related to COVID-19), OR asthma, reactive airway or chronic respiratory disease requiring daily medication.

• n=139

• COVID-19-related urgent care visit, emergency department assessment or hospitalization was the primary outcome 10 participants in usual care vs 1 participant in budesonide arm (difference in proportion 0.131, p=0.004).

• The number needed to treat with inhaled budesonide to reduce COVID-19 deterioration was 8.

• Clinical recovery was 1 day shorter in the budesonide arm compared to the usual care arm (median of 7 days versus 8 days p=0.007)

https://www.ashp.org/-/media/assets/pharmacy-practice/resource-centers/Coronavirus/docs/ASHP-COVID-19-Evidence-Table.ashx

COVID-19 Vaccines