COVID-19: Update for NPs and PAs
Learning Objectives • Describe what is currently known about COVID-19 epidemiology and transmission • Assess current COVID-19 diagnostic strategies • Discuss evolving therapeutic approaches to COVID-19 2
Epidemiology and Transmission
Global Incidence (11/12/20) Johns Hopkins University & Medicine. gisanddata.maps.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299423467b48e9ecf6. Accessed Nov 12, 2020. 4
US Average Daily Cases/100,000 in the Past 7 Days (11/12/20) The New York Times. www.nytimes.com/interactive/2020/us/coronavirus-us-cases.html?action=click&auth=login- 5 email&login=email&module=Top%20Stories&pgtype=Homepage#map. Accessed Nov 12, 2020.
Percent of New Tests That Are Positive, State by State (11/12/20) Johns Hopkins University & Medicine. coronavirus.jhu.edu/testing/tracker/map/percent-positive. Accessed Nov 12, 2020. 6
Transmission and Contagiousness • • Third wave in the US — worries about Why rapid and global spread? this winter’s respiratory season? ‒ Asymptomatic shedding High-risk environments? • Estimates 25% to 79% of infected? ‒ Mass gatherings • Role of asymptomatic cases affecting ‒ Family gatherings/holidays models/forecasts ‒ Universities, schools ‒ Bars, restaurants ‒ Travel Centers for Disease Control and Prevention. www.cdc.gov/coronavirus/2019-ncov/travelers/travel-during-covid19.html. Accessed Oct 29, 2020. 7
When Are You Most Infectious? Most Symptomatic 10 Respiratory tract viral load with time >33 cycle threshold (generally not infectious) Cycle Threshold 15 Infectiousness 20 25 30 35 Period of 40 infectiousness Least – 5 – 4 – 3 – 2 – 1 7 0 1 2 3 4 5 6 8 9 10 11 12 13 14 Days Relative to Symptom Onset 8 Meyerowitz EA et al. Ann Intern Med . 2020;M20-5008: online ahead of print.
The Physics of Transmission • 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 9
Who Transmits? — The Superspreaders • Superspreaders – Biologically yield more droplets or aerosol – Loud speaking/singing • Estimates 10% to 20% of infected → 80% of cases • High viral load likely important 10 Meyerowitz EA et al. Ann Intern Med . 2020;M20-5008: online ahead of print.
What About in a Household? • 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 11 Madewell ZJ, et al. medRxiv. 2020:preprint.
Preventing Transmission: The 3 Best Things You Can Do aOR = adjusted odds ratio. 12 Chu DK, et al. Lancet . 2020;395(10242):1973-1987.
Range of CO rona VI rus D isease - 20 19 13 Paul G. Auwaerter, personal communication.
Age and Gender Mortality Risks 14 Mallapaty S. Nature . 2020;585:16-17.
Diagnosis
Test Sensitivity Varies With Time Since Symptom Onset 16 Image created with biorender.com.
COVID-19 Diagnostic Test Through RT-PCR PCR = polymerase chain reaction; RNA =ribonucleic acid ; RT-PCR = reverse transcription PCR; qPCR = quantitative PCR. 17 Image created with biorender.com.
PCR “Turkey Talk” • 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 18
Saliva-Based Tests: Is Drool Good? • Emerging • Likely less sensitive than nasopharyngeal swab ‒ Detects only ~90% • No tests widely available • Decreases barrier to testing ‒ Who is most contagious? A woman spits into a tube so that her saliva can be tested for the presence of novel coronavirus. UNIVERSITY OF ILLINOIS, URBANA-CHAMPAIGN. Service RF. www.sciencemag.org/news/2020/08/new-drool-based-tests-are-replacing-dreaded-coronavirus-nasal-swab. Accessed Oct 30, 2020. 19
Antigen Testing Adapted from Campbell IM. commons.wikimedia.org/wiki/File:Diagnostic_Medical_Dipstick.png. Accessed Oct 29, 2020. 20
Rapid Testing 21
Molecular vs Antigen Tests Factor RT-PCR Tests Antigen Tests • Antigen tests Intended use Detect current infection Detect current infection ‒ For early diagnosis in Analyte detected Viral RNA Viral antigens symptomatic patients Specimen type(s) Nasal swab, sputum, Nasal swab ‒ Not for screening saliva (clinical studies in Sensitivity High Moderate progress) Specificity High High ‒ Negative result should Test complexity Varies Relatively easy be followed up with a Authorized for Most not Yes molecular assay point of care Turnaround time 15 min to >2 days ~15 min Cost Moderate Low Centers for Disease Control and Prevention. www.cdc.gov/coronavirus/2019-ncov/lab/resources/antigen-tests-guidelines.html#table2. 22 Accessed Oct 29, 2020.
Can the Role of Antigen Tests Be Widened? • Uncertain Date: Mon 19 Oct 2020 17:01 From: Salerno, Reynolds (CDC/DDPHSS/CSELS/DLS) • Tests hard to obtain (most purchased by < …@cdc.gov > the government) • We are working on a number of studies with FDA EUA: only for symptomatic patients different partners to evaluate the performance of • Low sensitivity all of the widely available antigen tests on ‒ If repeated, increased false positive asymptomatic persons. The FDA authorizations for tests these tests are limited to their use on symptomatic persons. We will share data as soon as ‒ Asymptomatic screening — likely with we are able. lower sensitivity as pretest probability lower Ren Salerno CDC Atlanta, GA (POSTED TO EIN NETWORK) EUA = Emergency Use Authorization. 23
SARS-CoV-Antibody Testing • 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 ACE-2 = angiotensin-converting enzyme 2. 24 Image created with biorender.com.
Therapeutics
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. 26 Beigel JH, et al. N Engl J Med . 2020:NEJMoa2007764. doi:10.1056/NEJMoa2007764. [Epub ahead of print.].
Dexamethasone: Results From the RECOVERY Trial • 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 19 NNT = number needed to treat; RECOVERY = Randomized Evaluation of Covid-19 Therapy. 27 Horby P, et al. N Engl J Med . 2020:NEJMoa2021436.doi:10.1056/NEJMoa2021436. [Epub ahead of print.].
LYCoV555 (Bamlanivimab): Results From the BLAZE-1 Trial Symptom Score Hospitalization* Change From Baseline 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. 28
Convalescent Plasma • No RCTs support use (early terminations or Phase II) ‒ Li et al; Gharbharan et al; Agarwal et al (PLACID, n = 464) RCT = randomized controlled trial. US Food & Drug Administration. www.fda.gov/news-events/press-announcements/fda-issues-emergency-use-authorization-convalescent-plasma- 29 potential-promising-covid-19-treatment. Accessed Oct 29, 2020.
Preliminary Data from Convalescent Plasma Expanded Access Program Adjusted Mortality — Graded Dose Effect (High vs Low Titer) • • High titer vs low titer 76 patients – 7-day mortality • 7- day mortality if… • 8.9% (6.8%, 11.7%) vs 13.7% ‒ ≤3 hospital days (11.1%, 16.8%), P = 0.048 • 8.7% (95% CI 8.3%-9.2%) • 30-day mortality ‒ ≥4 hospital days – High titer, pooled 0.77 (0.63-0.94) • 11.9% (11.4%-12.2%) , P < 0.001 for 30 days • 30-day mortality ‒ 21.6% vs 26.7%, P <0.0001 30 Joyner JM, et al. medRxiv. 2020:doi:10.1101/2020.08.12.20169359. Preprint.
Vaccines
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