COVID-19: Update for NPs and PAs Learning Objectives Describe - - PowerPoint PPT Presentation

COVID-19: Update for NPs and PAs

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• Describe what is currently known about COVID-19 epidemiology and transmission
• Assess current COVID-19 diagnostic strategies
• Discuss evolving therapeutic approaches to COVID-19

Learning Objectives

Epidemiology and Transmission

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Global Incidence (11/19/2020)

Johns Hopkins University & Medicine. gisanddata.maps.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299423467b48e9ecf6. Accessed Nov 19, 2020.

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US Average Daily Cases/100,000 in the Past 7 Days (11/19/20)

The New York Times. www.nytimes.com/interactive/2020/us/coronavirus-us-cases.html?action=click&auth=login- email&login=email&module=Top%20Stories&pgtype=Homepage#map. Accessed Nov 19, 2020.

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Percent of New Tests That Are Positive, State by State (11/19/2020)

Johns Hopkins University & Medicine. coronavirus.jhu.edu/testing/tracker/map/percent-positive. Accessed Nov 19, 2020.

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• Why rapid and global spread?

‒ Asymptomatic shedding

• Estimates 25% to 79% of infected?
• Role of asymptomatic cases affecting

models/forecasts

Transmission and Contagiousness

Centers for Disease Control and Prevention. www.cdc.gov/coronavirus/2019-ncov/travelers/travel-during-covid19.html. Accessed Oct 29, 2020.

• Third wave in the US—worries about

this winter’s respiratory season? High-risk environments? ‒ Mass gatherings ‒ Family gatherings/holidays ‒ Universities, schools ‒ Bars, restaurants ‒ Travel

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–5 –4 –3 –2 –1 1 2 3 4 5 6 7 8 9 10 11 12 13 14

When Are You Most Infectious?

Meyerowitz EA et al. Ann Intern Med. 2020;M20-5008: online ahead of print.

Infectiousness Most Least Days Relative to Symptom Onset Cycle Threshold

10 15 20 25 30 35 40 Symptomatic Respiratory tract viral load with time >33 cycle threshold (generally not infectious)

Period of infectiousness

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• Human sneeze or cough: 0.1 to 1000 microns
• Respiratory droplets: Mostly 5 to 10 microns
• Some aerosols: <5.0 microns
• Silent shedders as main drivers

‒ Estimates up to 79% ‒ lnfectious up to 6 days before symptoms

• 6 ft doesn’t account for particles ≤1 micron

‒ May be insufficient if indoors with poor circulation

• Uncovered intense coughs: ≥20 ft
• Universal masking as best weapon

‒ Surgical masks reduce transmission

The Physics of Transmission

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• A few may infect many others

‒ Most may not infect anyone else ‒ 10% of infected → 80% of cases?

• More likely to occur with

‒ Closed spaces with poor ventilation ‒ Crowds ‒ Close contact ‒ Shouting, singing, heavy breathing

Superspreading Events

Enserink M. Science 2020; vis.sciencemag.org/covid-clusters/. Accessed November 16, 2020. Meyerowitz EA et al. Ann Intern Med. 2020:[epub ahead of print].

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What About in a Household?

Madewell ZJ, et al. medRxiv. 2020:preprint.

• Meta-analysis of 40 studies

‒ Secondary attack rate 18.8% (95% CI, 15.4% to 22.2%)

• Higher for spouse/partner
• Lower for other household members
• Variable, depending on environmental factors
• Rates only lower if mask wearing and social distancing in household

‒ Strongly suggested for high-risk people

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Preventing Transmission: The 3 Best Things You Can Do

aOR = adjusted odds ratio. Chu DK, et al. Lancet. 2020;395(10242):1973-1987.

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Range of COronaVIrus Disease-2019

Ghandi RT et al. N Eng J Med. 2020;383:1757-1766.

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Age and Gender Mortality Risks

Mallapaty S. Nature. 2020;585:16-17.

Diagnosis

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Test Sensitivity Varies With Time Since Symptom Onset

Image created with biorender.com.

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COVID-19 Diagnostic Test Through RT-PCR

PCR = polymerase chain reaction; RNA =ribonucleic acid ; RT-PCR = reverse transcription PCR; qPCR = quantitative PCR. Image created with biorender.com.

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• False negatives

‒ Range 2% to 37% ‒ Depends on stage of illness, technique acquiring sample ‒ May need to repeat test if clinically suspicious

• Pooled testing

‒ May reduce costs by batching ‒ Positive pool = all in that pool need individual testing delay ‒ Not widely used ‒ Most useful if community rates are declining and low

PCR “Turkey Talk”

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• Emerging
• Likely less sensitive than nasopharyngeal swab

‒ Detects only ~90%

• No tests widely available
• Decreases barrier to testing

‒ Who is most contagious?

Saliva-Based Tests: Is Drool Good?

Service RF. www.sciencemag.org/news/2020/08/new-drool-based-tests-are-replacing-dreaded-coronavirus-nasal-swab. Accessed Oct 30, 2020.

A woman spits into a tube so that her saliva can be tested for the presence of novel

• coronavirus. UNIVERSITY OF ILLINOIS, URBANA-CHAMPAIGN.

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Adapted from Campbell IM. commons.wikimedia.org/wiki/File:Diagnostic_Medical_Dipstick.png. Accessed Oct 29, 2020.

Antigen Testing

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Rapid Testing

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• Antigen tests

‒ For early diagnosis in symptomatic patients ‒ Not for screening (clinical studies in progress) ‒ Negative result should be followed up with a molecular assay

Molecular vs Antigen Tests

Centers for Disease Control and Prevention. www.cdc.gov/coronavirus/2019-ncov/lab/resources/antigen-tests-guidelines.html#table2. Accessed Oct 29, 2020.

Factor RT-PCR Tests Antigen Tests Intended use Detect current infection Detect current infection Analyte detected Viral RNA Viral antigens Specimen type(s) Nasal swab, sputum, saliva Nasal swab Sensitivity High Moderate Specificity High High Test complexity Varies Relatively easy Authorized for point of care Most not Yes Turnaround time 15 min to >2 days ~15 min Cost Moderate Low

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Date: Mon 19 Oct 2020 17:01 From: Salerno, Reynolds (CDC/DDPHSS/CSELS/DLS) <…@cdc.gov> We are working on a number of studies with different partners to evaluate the performance of all of the widely available antigen tests on asymptomatic persons. The FDA authorizations for these tests are limited to their use on symptomatic persons. We will share data as soon as we are able. Ren Salerno CDC Atlanta, GA (POSTED TO EIN NETWORK)

Can the Role of Antigen Tests Be Widened?

• Uncertain
• Tests hard to obtain (most purchased by

the government)

• FDA EUA: only for symptomatic patients
• Low sensitivity

‒ If repeated, increased false positive tests ‒ Asymptomatic screening—likely with lower sensitivity as pretest probability lower

EUA = Emergency Use Authorization.

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• Positive test may reflect exposure

to other coronaviruses

• Positive test should not be taken

as evidence of immunity

• Positive test does not mean a

COVID-19 diagnosis

SARS-CoV-Antibody Testing

ACE-2 = angiotensin-converting enzyme 2. Image created with biorender.com.

Therapeutics

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Remdesivir: Results From the ACTT-1 Trial—Now FDA Approved

• IV; only for hospitalized patients
• 31% faster recovery vs placebo (P <0.001, 10 days vs 15 days)
• Appears safe
• Mechanically ventilated or ECMO patients don’t appear to

benefit

• Oxygen-requiring (largest group) had most benefit
• FDA-approved Oct 2020 for ≥12 years of age
• New EUA for children <12 years of age

ACTT-1 = stage 1 of Adaptive Covid-19 Treatment Trial. Beigel JH, et al. N Engl J Med. 2020:NEJMoa2007764. doi:10.1056/NEJMoa2007764. [Epub ahead of print.].

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COVID-19: Immune Modulation Therapy

Ingraham et al. Lancet Resp Med. 2020: DOI.org/10.1016/s2213-2600(20)30226-5. Tay et al. Nat Rev Immunolo. 2020: doi.org/10.1038/s41577-020-0311-8.

• IL6R: Tocilizumab,

sarilumab

• JAK: Baricitinib,

ruxolitinib

• IL-1: Canakinumab,

anakinra

• BTK Inhibitor:

Ibrutinib

• Steroids

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• Target: hyperinflammatory state, trial halted
• UK trial

‒ 2104 vs 4321 controls

• NNT to avoid 1 death

‒ Ventilated patients: 8

• Mortality rate 40% → 28%

‒ On oxygen: 25

• Mortality rate 25% → 20%

‒ No benefit if not on oxygen, trend toward worsening

Dexamethasone: Results From the RECOVERY Trial

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NNT = number needed to treat; RECOVERY = Randomized Evaluation of Covid-19 Therapy. Horby P, et al. N Engl J Med. 2020:NEJMoa2021436.doi:10.1056/NEJMoa2021436. [Epub ahead of print.].

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• No RCTs support use

(early terminations or Phase II) ‒ Li et al; Gharbharan et al; Agarwal et al (PLACID, n = 464)

Convalescent Plasma

RCT = randomized controlled trial. US Food & Drug Administration. www.fda.gov/news-events/press-announcements/fda-issues-emergency-use-authorization-convalescent-plasma- potential-promising-covid-19-treatment. Accessed Oct 29, 2020.

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• 76 patients
• 7-day mortality if…

‒ ≤3 hospital days

• 8.7% (95% CI 8.3%-9.2%)

‒ ≥4 hospital days

• 11.9% (11.4%-12.2%) , P < 0.001
• 30-day mortality

‒ 21.6% vs 26.7%, P <0.0001

Preliminary Data from Convalescent Plasma Expanded Access Program Adjusted Mortality—Graded Dose Effect (High vs Low Titer)

• High titer vs low titer

– 7-day mortality

• 8.9% (6.8%, 11.7%) vs 13.7%

(11.1%, 16.8%), P = 0.048

• 30-day mortality

– High titer, pooled 0.77 (0.63-0.94) for 30 days

Joyner JM, et al. medRxiv. 2020:doi:10.1101/2020.08.12.20169359. Preprint.

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Passive Antibody Therapy: Advantages and Disadvantages

Abraham, J. Nat Rev Immunol. 2020: doi.org/10.1038/s41577-02—0365-7.

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• Multiple Agents Under Development (ACTIV-2)
• Lilly Antibody: LYCoV555

‒ Treatment of early illness ‒ Endpoint – Admission or ER Visit: 1.7 percent (5/302) of LY-CoV555 vs 6 percent (9/150) of placebo patients ‒ 8% developed resistance to antibody

• Regeneron Combination

‒ Outpatient study – focus on reducing viral load and time to alleviation of symptoms ‒ REGN-COV2 rapidly reduced viral load through Day 7 in seronegative patients

• 0.51 log10 copies/mL greater reduction (p = 0.0049) in patients treated with high dose, and a 0.23

log10 copies/mL greater reduction (p = 0.20) in patients treated with low dose, compared to placebo ‒ Faster improvement in symptoms

• 13 days in placebo, 8 days in high dose (p = 0.22), and 6 days in low dose (p = 0.09)

‒ Fewer medically attended visits post-dose

• 15.2% of placebo-treated patients, 7.7% of patients treated with high dose and 4.9% of patients

treated with low dose required additional medical visits.

COVID-19: Monoclonal Antibodies

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COVID-19: Monoclonal Antibodies

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LYCoV555 (Bamlanivimab): Results From the BLAZE-1 Trial

BLAZE-1 = Blocking Viral Attachment and Cell Entry with SARS-CoV-2 Neutralizing Antibodies. Chen P et al. N Engl J Med. 2020. DOI: 10.1056/NEJMoa2029849.

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LYCoV555 (Bamlanivimab): Results From the BLAZE-1 Trial (cont’d)

Chen P et al. N Engl J Med. 2020. DOI: 10.1056/NEJMoa2029849.

Change From Baseline Symptom Score Hospitalization*

Vaccines

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The COVID-19 Vaccine Race (11/19/20)

• >300 candidate vaccines
• Vaccines in Phase 3 trials

– SSSBioNTech/Pfizer (mRNA) – Moderna (mRNA) – Murdoch (BCG vaccine) – J&J (Ad26) – Novavax (protein based) – Oxford/AstraZeneca (ChAdOx1) – CanSinoBio (Ad5)* – Gamaleya (Ad5/Ad26)* – Sinovac (inactivated)* – Sinopharm (inactivated)* – Wuhan Inst/Sinopharm (inactivated)*

*Approved for early or limited use in China, Russia, or United Arab Emirates. Corum J, et al. www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html?action=click&module=RelatedLinks&pgtype=Article. Accessed Nov 19, 2020.

All require two injections except:

• J&J and CanSinoBio (single injection)

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Who Have Built the Biggest Vaccine Portfolios?

Gross A, Bott I. www.ft.com/content/e5012891-58da-4a4f-8a05-182adf3ba0e2. Accessed Oct 29, 2020.

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COVID-19: RNA/DNA and Viral Vaccines

“These are the Top Coronavirus Vaccines to Watch.” Washington Post. 13 October 2020.

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COVID-19: Protein Vaccines

“These are the Top Coronavirus Vaccines to Watch.” Washington Post. 13 October 2020.

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COVID-19: Time to Vaccination

National Academies of Science, Engineering, and Medicine.

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• Global effect
• Worries for this winter
• Likely only US hope = vaccines (Spring 2021)
• WEAR MASKS

Summary

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Be Sure to Visit PCE’s COVID Resource Center: Visit PCE.is/covid

Click the link at the top

• f the PCE homepage

OR