COVID-19 Response ECHO for Oregon Clinicians Session 6 March 18, 2021

COVID-19 Response ECHO for
Oregon Clinicians

Session 6 March 18, 2021

Introduction to COVID-19 ECHO
• Everyone is muted
• Use the Chat Box to submit questions/comments/share links & resources

   • We will strive to select questions directly relevant to the presentations for asking during the session,
     but will not be able to address all questions. Questions not directly answered will be collated and
     used in the planning of future sessions

• All sessions will be recorded and available for viewing after the session within 24
  hours
• Resources and transcript of today’s chat box, PowerPoint slides, and video
  recording will be posted on our ECHO Network website at
  www.connect.oregonechonetwork.org (where you registered)
• PLEASE fill out the post-session survey that you’ll receive by email today

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COVID-19 ECHO Faculty
Facilitator: Eric Wiser, M.D. (OHSU Gabriel Park)

Supporting Faculty:
Holly Tse, M.D. (Legacy Health, Medical Director of Medical Home)
Jay Richards, D.O. (Aviva Health, Chief Medical Officer)
Shelby Lee Freed, M.S.N, F.N.P.-B.C. (OHSU Richmond Clinic)
Tom Jeanne, M.D., MPH (OHA, Deputy State Health Officer and Deputy State
Epidemiologist)

Program Support
Tuesday Graham, B.S. (OEN Project Manager)
Miriam Wolf, B.S. (OEN Program Coordinator)

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Today’s Agenda
• OHA Update

• Brief Q & A for OHA

• Specialty Presentation: Testing – Yassmine Akkari, PhD, Legacy
  Lab

• Brief Q & A for Yassmine Akkari

                                                               4

Oregon Health Authority
COVID-19 Update
March 18, 2021

Tom Jeanne, MD, MPH
Ariel Smits, MD

                          5

Oregon Health Authority
COVID-19 Update
March 18, 2021

Tom Jeanne, MD, MPH
Ariel Smits, MD, MPH

                          6

COVID-19 in Oregon

    As of March 17:

    • 160,259 total cases
    • 8,945 hospitalized cases
    • 2,349 deaths

7

Weekly COVID-19 Report

For the week of March 8–March 14
• 2,272 new cases were recorded, a 14% decrease from two weeks ago
• 130 new hospitalizations, a 21% decrease from two weeks ago
• 26 Oregonians died in association with COVID-19, a 54% decrease from
  two weeks ago

From March 7–March 13
• 94,079 tests for COVID-19
• 3.6% of test results were positive last week

                                                                         8

Declining Surge in Hospital COVID-19 Census

9                                                 9

Vaccination Data Dashboard   (https://covidvaccine.oregon.gov)

                                                                 10

11

Testing Update

                 12

Testing Trends

           From 2/28–3/6, estimated testing volume was 118,847 and percent
           positivity was 2.1% (goal ≤ 5%)

13

Testing Needs and Gap Analysis

14

Testing Strategy Updates

     Expanding testing access with new federal funding:
        1. Bridging exposed contacts to testing through mail-in testing resources
           • OHA would cover cost for uninsured
        2. Expanding CBO partnerships to plan and assist at testing events
           • This work is currently being done voluntarily
           • OHA would fund CBOs for their collaboration with this essential work
        3. Expanding CBO partnerships to understanding testing barriers in
           disproportionately impacted communities
           • OHA would fund CBOs to gather detailed information that could inform public health efforts
        4. Supporting targeted testing of disproportionately impacted populations
           through regional framework
           • Reimbursement for testing of uninsured populations
        5. Supporting OHA mobile testing

15

Regional Testing Framework Progress

     190 low-barrier testing events to date and over 23,000 tested
     MSFW H2A/B visa testing initiated
          • Will be offered to all farms upon arrival of workers
     Asked by HHS testing provider to function as a testing mentor to other states
     Regional Testing Partners identified for all regions
          •   Region 1: OHSU
          •   Region 2: Santiam Hospital
          •   Region 3: McKenzie-Willamette
          •   Region 5: Asante
          •   Region 6: One Community Health
          •   Region 7: Sky Lakes
          •   Region 9: Grande Ronde
     Mobile capacity
          • OHSU received 3 vans: 1 operational, otherwise retrofitting
          • OHA received 4 vans: retrofitting
          • 3 CBO partners will receive vans
                •   HIV Alliance: Lane/Marion/Douglas/Josephine
                •   Neighborhood Health Care: Clackamas/Wash.
                •   White Bird Clinic: Lane

16

Regional Testing Framework Progress

Distributed 750,000+ tests to partners statewide, including:
   • Abbott BinaxNOW rapid point-of-care testing
      • 402,600 BinaxNOW tests distributed to 246 testing partners including critical access,
        primary care, LTCFs
      • Strategic reserve for K-12 testing
   • Abbott IDNOW rapid point-of-care testing
      • 44 testing platforms and 70,000 tests distributed to testing partners
      • Strategically distributed to areas of limited testing capacity and disproportionately affected
        populations
   • Thermofisher high-volume laboratory testing
      • 8 testing platforms and 310,000 tests distributed to large healthcare testing partners
Building additional testing capacity in Oregon at UO, OSU, OHSU

                                                                                                         17

School Testing

School Testing

     CDC issued new Operational Strategy for K-12 schools
        • Recommends that all students and staff who develop symptoms at school or experience an
          exposure be referred for testing
            • Oregon could meet by mandating the K-12 testing project in all schools
            • Oregon could meet by asking schools to refer out to community testing resources, but these do not
              exist in all areas
            • Access could be guaranteed through the first strategy, not through the second
        • Screening may or may not be implemented
     K-12 Testing in Oregon’s Schools project — over 800 registered
        • Testing offered to all public and private K-12 schools
        • Testing required under the following circumstances:
            • K-12 schools operating in-person in counties above advisory metrics
            • K-12 outdoor contact sports opening in High or Extreme levels

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School Testing in Oregon

A school testing administrator is assigned to perform and log all on-site
COVID-19 testing
• School nurse or trained medical professional if available
• Otherwise, anyone who is trained; does not need to be a medical
  professional
• Must complete all required online training modules for the BinaxNOW
  point-of-care antigen test and carefully review all training regarding PPE
• No CLIA-waiver application needed

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School Testing in Oregon

Oregon’s school testing program is currently for symptomatic and exposed
students and school staff only
• Screening using antigen testing is low-yield
     • Sensitivity of antigen tests is low in asymptomatic people
• People more likely to be infected are less likely to participate
• Positive tests that subsequently have a negative molecular test are
  confusing

Funding forthcoming ($10B) from HHS for surveillance testing in schools
using a regional framework
     • Identifying laboratory partners now; no operational plan yet

                                                                           21

School Testing in Oregon

Oregon’s school testing program is currently for symptomatic and exposed students and
school staff only
• BinaxNOW antigen tests
      •   84.6% sensitivity (90.6% for specimens with Ct

School Testing in Oregon

• See Healthcare Partner Resources page for resources on school testing
    • https://healthoregon.org/coronavirushcp

                                                                          23

What is a Given Test’s Sensitivity and Specificity?

• How to look up manufacturer-reported performance characteristics of any
  COVID-19 test with FDA EUA
    • https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-
      emergency-use-authorizations-medical-devices/vitro-diagnostics-euas
    • Find the right table
    • Search in search box for test name
    • Click the IFU link. Clinical performance section is typically near bottom
    • Be sure to note the comparator used (usually PCR, which is not a perfect
      gold standard!)

                                                                                  24

SARS-CoV-2
Sequencing

SARS-CoV-2 Sequencing in Oregon

• Sequencing can inform public health response; unknown clinical
  significance
• Academic laboratories in Oregon are doing sequencing
• The Oregon State Public Health Laboratory (OSPHL) will offer whole
  genome sequencing for COVID-19 beginning in March 2021
• All labs that are sequencing are to submit results to GISAID open-source
  repository

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Forthcoming Guidance from OHA

Criteria for requesting COVID-19 sequencing at OSPHL
• No cost at OSPHL, but must meet one or more of these criteria:
   • Individual with history of international travel in the 14 days prior to the onset of COVID-19
   • Individual meeting CDC vaccine breakthrough case definition
   • Specimen with result on the Thermo Fisher TaqPath and Linea COVID-19 Assay Kit with spike
     gene target failure
• Specimen criteria
   • Received at OSPHL within 7 days of collection
   • For specimens tested with PCR, only specimens with a cycle threshold (Ct) value ≤ 28
     should be submitted for sequencing
   • For specimens which have been tested using a method which does not report Ct values,
     submit original material if acceptable for testing at OSPHL
   • If no residual sample is available, submit the extract if available or collect a second specimen
     for sequencing

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Variant case counts in Oregon

As of March 17, 2021            CDC’s new variant categories:
Variants of concern             Variant of Interest
                                   • Currently B.1.526,   B.1.525, P.2
• B.1.1.7 (UK): 17
• P.1. (Brazil/Japan): 1        Variant of Concern
                                   • Currently B.1.1.7,
                                                     P.1, B.1.351,
• B.1.351 (South Africa): 0          B.1.427, B.1.429
• B.1.427 (California): 0       Variant of High Consequence
• B.1.429 (California): 0          • None in the U.S. right now

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COVID-19
Literature
Updates

BinaxNOW Rapid Antigen Testing

     Prince-Guerra et al; January 22, 2021 MMWR 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.
        • 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
        • Near 100% specificity for both asymptomatic and symptomatic
        • Advantages:
           • Results in 15-30 minutes
           • Lower requirement for resources
           • High specificity and high PPV in settings of high pretest probability (e.g., providing testing
             to symptomatic persons, to persons with a known COVID-19 exposure or where
             community transmission is high).

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BinaxNOW Rapid Antigen Testing

     Disadvantage: Low sensitivity
        • Community testing strategies focused on preventing transmission using antigen
          testing should consider serial testing to improve sensitivity.
        • When the pretest probability for receiving positive SARS-CoV-2 test results is
          elevated (e.g. for symptomatic persons or for persons with a known COVID-19
          exposure), a negative antigen test result should be confirmed by NAAT.
        • Asymptomatic persons who receive a positive BinaxNOW antigen test result in a
          setting with a high risk for adverse consequences resulting from false-positive results
          (e.g. in long-term care facilities) should also receive confirmatory testing by NAAT.
     Unknown performance with viral variants

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Questions &
Answers

Questions

Moderated by Jay Richards, D.O.

Covid-19 Testing at Legacy Health:
      March 2021 Updates
       Yassmine Akkari, PhD, FACMG
 Scientific Director, Cytogenetics and Molecular Pathology

Facts about Viruses

                    All viruses mutate
                    Genetic changes in the viral genome happen as the virus makes new
                     copies of itself to spread and thrive. Most are inconsequential, few can
                     even be harmful to the virus' survival, but some can make it more
                     infectious or threatening to its host.

                    Long latency periods, increased viral load, and extended sickness
                     duration allows for viruses to mutate more readily

                  Safety measures to decrease transmission are
                   effective in reducing the mutation rates of viruses

March 19, 2021                                                                                  LEGACY HEALTH   35

3/19/2021   LEGACY HEALTH   36

SARS-CoV-2 Around the World
               The WHO uses information from reported unusual/adverse case trends to continually
                sequence the COVID-19 viral genome and tracking increased transmissibility [Global
                Initiative on Sharing All Influenza Database (GISAID)]

               December 2019: first variant in China
               February 2020: A D614G mutation emerged in early February, and by June 2020, it was
                the main circulating strain globally.
                 >   While the D614G variant had increased transmissibility, it did not cause more severe illness or alter the effectiveness
                     of existing laboratory diagnostics, therapeutics, vaccines, or public health preventive measures

               August 2020: “Cluster 5” was in identified in North Jutland, Denmark. It has a combination
                of mutations not previously observed.
                 >   To date, following extensive investigation and surveillance, Danish authorities have identified only 12 human cases
                     of the Cluster 5 variant in September 2020, and it does not appear to have spread widely

               December 2020: the SARS-CoV-2 VOC 202012/01 (Variant of Concern, year 2020, month
                12, variant 01) emerged in South East England. This variant contains 23 nucleotide
                substitutions. B.1.1.7
                 >   Preliminary epidemiologic, modelling, phylogenetic and clinical findings suggest that SARS-CoV-2 VOC 202012/01
                     has increased transmissibility but no change in disease severity

               December 18th, 2020: South Africa reports the emergence of 501Y.V2, because of a
                N501Y mutation
                 >   It is was shown to be associated with a higher viral load, which may suggest potential for increased transmissibility.
                     No clear evidence of the new variant being associated with more severe disease or worse outcomes

3/19/2021                                                                                                                                      LEGACY HEALTH   37

How does the occurrence of these
        variants affect our testing methodology?

3/19/2021                                    LEGACY HEALTH
                                                        38

LLS Reported      LLS Reported
                                                                 FDA EUA                        SARS CoV-2        SARS CoV-2            TAT
                                                                                 Acceptable      Sensitivity       Specificity
     Method       Platform      Reagent   Test Components                        Specimen
                                                              (Manufacturer's       Type
                                                               Package Insert)                                                   (Received testing Lab
                                                                                                                                     to Resulted)

                                                                           NP swab,               100.0%             100.0%
Molecular PCR     Cepheid                  Flu A, Flu B, RSV,
                                 4 in 1                       Symptomatic nasal wash/

Testing Methodology

3/19/2021                 LEGACY HEALTH   40

Testing Methodology:
            RT-PCR

3/19/2021                          LEGACY HEALTH   41

Legacy Laboratory Services: COVID-19 Testing

                                       Roche 6800 Platform

             ORF1a gene

             Altona Diagnostics
             Roche MagNA Pure 96
             Roche MagNA Pure LC
             Roche cobas z 480
                                   S Gene

3/19/2021                                                    LEGACY HEALTH   42

COVID-19 Testing at Hospital Sites:

             Xpert® Xpress SARS-CoV-2
             Cepheid
               > Emergency departments
               > Inpatients
               > 1 hour turnaround time

3/19/2021                                 LEGACY HEALTH   43

“Analytical” Versus “Clinical” Sensitivity
              Analytical Sensitivity:
                 > Ability of an assay to detect pathogen when present in a clinical
                   specimen

              Clinical Sensitivity:
                 > Ability of a test to identify a patient’s overall infected status
                 > reflects various other factors that include the specimen-site and
                   method of collection, in conjunction with the burden of organism as a
                   function of anatomic location, disease severity, and time symptomatic
                   (and variability of these factors from individual to individual).

3/19/2021                                                                                  LEGACY HEALTH   44

Analytical Sensitivity: Legacy Results

                Reference material purchased from Exact Diagnostics
                Standard and 12 COVID-19 blind specimens (OSPHL Method Evaluation
               Panel for nCoV-2019 RT-PCR) sent from the Oregon State Health Lab
                5 positive samples obtained from the University of Washington (UW)
               Virology laboratory
                Patient and contrived samples (30 positives and 41 negatives)

                100% Concordance

3/19/2021                                                                             LEGACY HEALTH   45

Limit of Detection for the PCR Test

               Roche 6800: 100 viral copies/ml

               Cepheid: 250 Copies/ml

3/19/2021                                         LEGACY HEALTH   46

Cross-Reactivity (Specificity)

               •   1 Bordetella parapertussis positive
               •   1 RSV positive
               •   1 RSV/Influenza A H1 2009 positive
               •   1 Coronavirus HKU1
               •   2 Coronavirus OC43
               •   1 Coronavirus NL63
               •   5 Human Metapneumovirus
               •   2 Coronavirus not typed
               •   1 adenovirus/Coronavirus (not typed)/Human Metapneumovirus

                No cross-reactivity observed

3/19/2021                                                                       LEGACY HEALTH   47

Legacy Molecular Diagnostics Covid-19 Tests
                                139,100 patients; 5.05%
             Roche 6800: Live Test
               > ORF1a gene
               > Vendor Communication: No sequences, including the UK variants, have been identified that have mutations in both
                  target regions; therefore, no impact on the performance of any cobas® SARS-CoV-2 test is anticipated.

             altona/z480: Live Test
               > S gene
               > Vendor Communication: We are aware of the SARS-CoV-2 variant under investigation (VUI-202012/01, England,
                  United Kingdom) which is defined by variant spike protein mutations: deletion 69-70, deletion 144, N501Y, A570D, D614G,
                  P681H, T716I, S982A, D1118H. These mutations do not impact the performance of the S gene detection system.

             Thermofisher: Validation in Progress
               > ORF1a/b, N, and S genes
               > Vendor Communication: If only the S gene drops out, the test is still positive. Report to the State

3/19/2021                                                                                                                     LEGACY HEALTH   48

Older Variant

                                                    Successful amplification
                                                    and extension

            New Variant
                    5’                     3’
                      TACTAGTCCTAGGAG
                                                      No amplification
                                                X     “S gene drop out”
                                 GATACTC
                            3’             5’
                                                                For illustration purposes only
3/19/2021                                                                                        LEGACY HEALTH   49

Tracking “Inconclusive” Results Daily
             3 Total runs (280 patients reported) = 3 Cobas 6800 runs, 0 Altona
              runs
             # COBAS Inconclusive results: 2
             # Altona Inconclusive results: 0
             # COBAS 6800 Positives: 22
             # Altona Positives: 0
             New Positives: 22
              New Positivity %: 7.9%
              Cumulative Test Performed: 112,422
              Cumulative Positives: 5,966
              Cumulative Positivity %: 5.3%

3/19/2021                                                                          LEGACY HEALTH   50

Thinking Ahead..

                90-day post infection and vaccine escape patients:

                  > Asymptomatic; tested as pre-op; positive test; CT values
                  > Symptomatic; sequencing to detect possible variants

3/19/2021                                                                      LEGACY HEALTH   51

The use of SARS-CoV-2 PCR cycle threshold (Ct) values for
                            clinical decision-making

                    Definition: The Ct value refers to the number of PCR
                     cycles required to amplify the targeted viral nucleic acid
                     to a detectable level that is discernable from
                     background
                    In general, low Ct values indicate a higher viral density
                     and high Ct values generally indicate a lower viral
                     density
                    Growing interest in using Ct values as a surrogate
                     measure of viral copies in clinical specimens

3/19/2021                 https://www.idsociety.org/globalassets/idsa/public-health/covid-19/idsa-amp-statement   LEGACY HEALTH   52

CAVEATS

              > Definitive data to support the predictive value of Ct values in
                these situations are lacking
              > Ct values generated by qualitative PCR assays do not reliably
                correspond to specific RNA concentrations
              > Ct values generated by qualitative PCR assays are not
                consistent across platforms
              > multiple factors other than viral load are known to affect Ct values
              > Qualitative test Ct values are not normalized to standardized
                controls of known concentration
              > respiratory specimen types are less amendable to quantitative
                PCR testing

3/19/2021                                                                              LEGACY HEALTH   53

Thank you!!

Thank you!

Serology/Antibody Test at LCL
              Beckman Dxl
              Diasorin Liaison
              Clinical utility:
                 > Detection of PCR-negative cases, especially for patients who present
                   late with a very low viral load below the detection limit of RT-PCR
                   assays, or when lower respiratory tract sampling is not possible
                 > Identification of convalescent plasma donors
                 > Epidemiologic studies of disease prevalence in the community
                 > Verification of vaccine response once antibody correlate(s) of
                   protection identified
                 > Drawbacks: false negative (early in disease course or mild disease)
                   and false positive with cross-reactivity with other Coronaviruses

3/19/2021                                                                                 LEGACY HEALTH   55

Questions

Moderated by Shelby Lee Freed, FNP

Important Reminder
Next COVID-19 Response ECHO for Oregon
               Clinicians:

Thursday, April 1 at noon: “VAERS Reporting
                   System”

oregonechonetwork.org

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