Sept. 25, 2020 El l ie Sukerman, MD

COVID-19 UpdatesOHSU

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Objectives

• Differentiate testing strategies

• Describe testing technologies and performance

• Discuss current treatment guidelinesOHSU

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Diagnostic vs. Screening Testing

• Diagnostic– Patients with signs/sxs consistent with COVID-19 or– Asymptomatic but with known or suspected exposure

• Screening– Identify infected, asymptomatic cases without known

or suspected exposure

https://www.cdc.gov/coronavirus/2019-ncov/lab/resources/antigen-tests-guidelines.html. Accessed 8/22/20.

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Testing TechnologiesMolecular Tests Antigen Tests Antibody Tests

AKA: • Diagnostic tests

• Viral tests

• Nucleic acid

amplification (NAAT)

• RT-PCR

• LAMP

• Rapid

diagnostic test

• Note, some

molecular tests

are also rapid

tests

• Serology

testing

Site of

collection

• NP, nasal, throat swab

• Saliva

• NP or nasal

swab

• Finger stick or

blood draw

Time to

results

• ~1h for rapid tests

• 1+ days for “slow” tests

• 1h or less • Point of care up

to a few days

https://www.cdc.gov/coronavirus/2019-ncov/lab/resources/antigen-tests-guidelines.html. Accessed 9/20/20.

https://www.fda.gov/consumers/consumer-updates/coronavirus-testing-basics. Accessed 8/25/20.

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NAAT Testing

• Sn likely 70-98% -> false negatives up to ~30%

• Factors affecting false negative rate include timing of sample collection and quality of sampling

• Sp high (~98-99%)

Arevalo-Rodriguez, et al. False-negative results of initial RT-PCR assays for COVID-19: a systematic review. medrxiv.org. 4/21/20.

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Testing Interpretation

• Take into account test characteristics and pre-test probability

• A ”positive” PCR test has more weight than a negative test due to

the test’s high Sp but moderate Sn

• If high clinical suspicion for COVID-19 but the initial test is

negative -> repeat testing

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The persistent positive PCR

Gombar S, Chang M, Hogan CA, et al. J Clin Virol. 2020;129:104477.

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Viral shedding vs. infectious virus

Van Kampen, et al. (Preprint) Medrxiv. 2020.

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Persistent Positive PCR

• Test-based strategy for discontinuation of transmission-based precautions or isolation no longer recommended

• Resulted in prolonged isolation or delayed return to work for those who continue to shed virus but are no longer infectious

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Duration of Isolation and Precautions

• COVID-19, isolation and precautions can generally be discontinued when:– 10d after symptom onset*– Resolution of fever for at least 24h without fever-reducing

medications– Symptom improvement

• For those with asymptomatic infection, isolation and precautions can be discontinued 10d after the date of the 1st

positive PCR test

*consider extending duration of isolation and precautions up to 20d after symptom onset

https://www.cdc.gov/coronavirus/2019-ncov/hcp/duration-isolation.html. Accessed 9/20/20.

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Antigen Tests

NAAT/PCR

Tests

Antigen Tests

Sensitivity High Moderate

Specificity High High

Time to results ≤1h to days Minutes

Cost Moderate Low

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Potential Role of Antigen Tests• Diagnostic testing

– Early in course of infection when viral loads high and people are most infectious

– Persons with known exposure

• Screening testing– High-risk congregate settings where repeat testing

could quickly identify infection leading to rapid infection prevention and control intervention

https://www.cdc.gov/coronavirus/2019-ncov/lab/resources/antigen-tests-guidelines.html Accessed 8/23/20.

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Availability of Antigen Tests

• 4 assays with FDA EUA as of 9/20/20

• Use of these tests for diagnostic or screening testing requires FDA EUA

https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-

devices/vitro-diagnostics-euas#individual-antigen. Accessed 9/20/20.

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Antibody (Ab) Testing

• Not recommended for dx or exclusion of infection

• Should not be used to determine immunity or inform decisions to discontinue physical distancing or PPE

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Timing of Ab Testing

Sethuraman, N., et al. (2020). "Interpreting Diagnostic Tests for SARS-CoV-2." JAMA.

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Timing of Ab Testing

• Consider IgG testing if high clinical suspicion with repeatedly negative PCR results BUT…

• Best sensitivity at 3-4 weeks after sx onset

https://www.idsociety.org/practice-guideline/covid-19-guideline-serology/. Accessed 8/23/20.

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IDSA Ab Testing Guidelines

• For pediatric pts with multisystem inflammatory syndrome, suggest using IgG and PCR to provide evidence of current or past COVID-19 infection

• Suggest against IgG/IgM combination tests to detect evidence of past infection

https://www.idsociety.org/practice-guideline/covid-19-guideline-serology/. Accessed 8/23/20.

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Ab Test Performance

• False positives possible, PPV ranging 50-100%*– With low seroprevalence, PPV decreases so a

false positive may be more likely than a true positive

• False negatives may occur if testing is performed early in illness*assumes 5% seroprevalence

https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/eua-authorized-serology-

test-performance. Accessed 8/25/20.

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Re-infection Risk

• Lots of uncertainties

– Are patients with antibodies protected against reinfection?

– If so, what antibody concentration is needed to provide protection?

– Durability of protection?

• No confirmed reports of reinfection within 3mos of initial infection

https://www.cdc.gov/coronavirus/2019-ncov/hcp/duration-isolation.html. Accessed 9/20/20.

To KK, Hung IF, Ip JD, et al. Clin Infect Dis. 2020.

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Credit: davegranlund.com

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Treatment

• Remdesivir

• Steroids

• Convalescent plasma

• In the pipelineOHSU

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Remdesivir• IDSA Guidelines (as of 9/15)

– In hospitalized patients with severe* COVID-19, remdesivir is suggested over no antiviral treatment

• NIH Guidelines (last updated 7/24)– Recommend prioritizing remdesivir for use in

hospitalized pts requiring supplemental O2 but not high-flow, noninvasive or invasive ventilation or ECMO

*severe defined as: SpO2 ≤94% on room air, and those who require supplemental O2, mechanical

ventilation or ECMO

https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/#toc-8. Accessed 9/15/20.

https://files.covid19treatmentguidelines.nih.gov/guidelines/covid19treatmentguidelines.pdf. Accessed 9/20/20.

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ACTT-1 Prelim Report

• Hospitalized adults with evidence of lower respiratory tract infection

• Shorter time to recovery in remdesivir group (median 11 vs. 15d)

Time to Recovery by Subgroup*

Beigel JH, Tomashek KM, Dodd LE, et al. N Engl J Med. 2020.

*CIs not adjusted for multiplicityOHSU

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ACCT-1 PrelimEstimates of cumulative recoveries

Overall Patients Receiving O2

Mechanical Ventilation/ECMOHigh-Flow or NIPPV

Beigel JH, Tomashek KM, Dodd LE, et al. N Engl J Med. 2020.

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SIMPLE Trial

• No significant difference of 5 vs. 10d in patients with severe COVID not on mechanical ventilation/ECMO for primary endpoint of clinical status at day 14

• No placebo group

Goldman JD, Lye DCB, Hui DS, et al. N Engl J Med. 2020.

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Remdesivir in Moderate COVID-19• Statistically significant difference in clinical status at day 11 for 5d group but not

10d group vs. SOC; difference of uncertain clinical significance

Spinner CD, Gottlieb RL, Criner GJ, et al. JAMA. 2020;324(11):1048-1057.

Change in Clinical Status Over TimeOHSU

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Steroids• RECOVERY Trial Prelim report showed decreased mortality

and increased likelihood of hospital discharge for dexamethasone vs usual care

• Guidelines recommend dexamethasone 6mg daily for up to 10d for hospitalized pts with hypoxia requiring supplemental O2

• May substitute alternative glucocorticoids if dex not available

Group, R. C., et al. (2020). "Dexamethasone in Hospitalized Patients with Covid-19 - Preliminary Report." N Engl J Med.

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Convalescent Plasma

• IDSA Guidelines (as of 9/4) – Recommended only in the context of a clinical

trial

• NIH Guidelines (as of 7/17)– Insufficient data to recommend for or against use

https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/#toc-8. Accessed 9/15/20.

https://files.covid19treatmentguidelines.nih.gov/guidelines/covid19treatmentguidelines.pdf. Accessed 9/20/20.

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Convalescent Plasma (CP)

• PLACID Trial– Adults with moderate illness randomized to

CP plus standard of care (SOC) vs SOC alone

– No difference in primary outcome of progression to severe disease or all-cause mortality at 28d

Mukherjee, et al. (Preprint). medRxiv. 2020.

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Stay tuned

• ACTT-2

• Randomized, double-blind, placebo-controlled phase investigating

efficacy and safety of baricitinib + remdesivir vs. remdesivir in

hospitalized pts

• BLAZE-1

• Randomized, double-blind, placebo-controlled phase 2 evaluating

LY-CoV555 neutralizing Ab for outpatients with symptomatic

COVID-19

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Thank YouOHSU