2020 Symposia Series 2 COVID-19: Update for NPs and PAs Learning - - PowerPoint PPT Presentation

2020 Symposia Series 2

COVID-19: Update for NPs and PAs

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Learning Objectives

• Describe what is currently known about COVID-19 transmission and how

to prevent it

• Assess current COVID-19 diagnostic strategies
• Discuss evolving therapeutic strategies for patients with COVID-19

infection

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US Incidence Rates (6/10/2020)

Johns Hopkins University & Medicine. coronavirus.jhu.edu/us-map. Accessed June 10, 2020.

• US Cases: 1,982,264
• US Deaths: 112,093

Key Concerns

• Transmission
• Diagnosis
• Therapeutics
• Prevention

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US Incidence Rates (6/04/2020) cont’d

Source: Wikimedia Commons.

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TRANSMISSION

• Why do some infect many and others don’t?

‒ Superspreader events

• Churches, especially with choirs
• Migrant worker dormitories
• Zumba classes
• Nursing homes
• Meatpacking plants
• Ski resorts
• Restaurants
• Hospitals
• Prisons

‒ Tendency for tightly connected >>> outdoor activities

• Remains poorly understood

Clustering is a COVID Puzzle

Kupferschmidt K. Science 2020;368:808-09.

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TRANSMISSION

• Reproduction number (R0)

‒ SARS-CoV-2 = ~ 3.0 if not socially distancing

• But, some spread lots, others not at all
• Healthy people make droplets when

talking, some >> others ‒ Indoor risk in Japan 19x than

• utdoor risk

‒ People with more social contacts

Clustering is a COVID Puzzle (cont’d)

Kupferschmidt K. Science 2020;368:808-09; Lloyd-Smith JO, et al. Nature 2005; 438:355-359.

• Another factor important (k)

‒ Dispersion factor: how much an infection clusters

• Lower k values = more transmission

comes from fewer people

• SARS-CoV-1 → 0.16
• MERS-CoV

→ 0.25

• H1N1 1918 influenza → 1.0
• SARS-CoV-2 varying estimates

‒ k = 0.1 (10% cases = 80% of spread)

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TRANSMISSION

• Human sneeze or cough

‒ 0.1 to 1000 microns

• Respiratory droplets mostly

‒ 5 to 10 microns ‒ Fall to ground, gravity (larger) or evaporate (smaller)

• Probably some aerosols?

‒ <5.0 microns ‒ May bypass protection by upper airway defenses

• Silent shedders as main drivers? Estimates up to 79%

‒ Infectious up to 6 days before symptoms

Masks Reduce Airborne Transmission

Prather KA et al. Science 10.1126/science.abc6197 (2020).

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TRANSMISSION

• 6 feet doesn’t account for particles 1 micron
• r smaller

‒ May not be sufficient if indoors with poor circulation

• Uncovered intense coughs → 20 ft. or further
• Universal masking as best weapon

‒ Surgical masks reduce transmission

Masks Reduce Airborne Transmission (cont’d)

Prather KA et al. Science 10.1126/science.abc6197 (2020).

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TRANSMISSION

• Covid-19 Deaths

‒ Fatalities among confirmed coronavirus cases in Hong Kong and Singapore are extremely low

Masks Reduce Airborne Transmission (cont’d)

Prather KA et al. Science 10.1126/science.abc6197 (2020). Note: Data as of May 26, 2020. Sources: Johns Hopkins University, New York City Department of Health and Mental Hygiene, Hong Kong Department of Health.

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TRANSMISSION

• Key questions:

‒ How durable? ‒ Lessons from other coronaviruses

• Respiratory coronaviruses (229E, NL63, OC43, HKU1), ~1 year
• SARS-CoV-1: ~3 to 4 years
• MERS-CoV: 7 to 34 months
• Is reinfection possible?
• Severe COVID-19: China

‒ 285 patients

• ~ 95% developed SARS-CoV-2 IgM antibodies by week 3
• IgG appeared later (sustained immunity?)

What Do We Know About COVID-19 Immunity?

Alshukiari AN et al. Emerg Infect Dis. 2016;22:1113-1115; Long QX et al, Nat Med 2020;10.1038/s41591-020-0897-1.

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TRANSMISSION

We are far from herd immunity

Popovich N et al. www.nytimes.com/interactive/2020/05/28/upshot/coronavirus-herd-immunity.html. Accessed June 4, 2020.

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TRANSMISSION

We are far from herd immunity

Popovich N et al. www.nytimes.com/interactive/2020/05/28/upshot/coronavirus-herd-immunity.html. Accessed June 4, 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
• Second wave—worries about next respiratory season? High risk events?

‒ Mass gatherings ‒ Schools, Universities

Transmission and Contagiousness

CDC = Centers for Disease Control and Prevention. Redfield R. www.cdc.gov. Accessed June 4, 2020; Fauci A. www.niaid.nih.gov. Accessed June 4, 2020.

TRANSMISSION

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Range of COVID-19 Disease States and Potential Therapeutic Targets

Siddiqi HK, Mehra MR. J Heart Lung Transplant. 2020;39:405-407. ARDS = acute respiratory distress syndrome; CRP = C-reactive protein; IL = interleukin; JAK = Janus kinase; LDH = lactate dehydrogenase; SIRS = systemic inflammatory response syndrome.

DIAGNOSIS

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• Descriptions mostly limited to

hospitalized patients

• Signs, symptoms

‒ Fever (46%-98%) ‒ Cough (46%-82%, usually dry) ‒ Myalgia or fatigue (11%-44%) ‒ Shortness of breath at onset (31%) ‒ Chills

Clinical Presentations

• Less common symptoms

‒ Pharyngitis ‒ Loss of taste/smell ‒ Headache ‒ Productive cough ‒ GI symptoms

• May be heralding

‒ Hemoptysis – Leukopenia in ~70% hospitalized patients – LDH often elevated

Chan JF, et al. Lancet. 2020;395:514-523; Huang C, et al. Lancet. 2020;395:497-506; Wang D, et al. JAMA. 2020; [Epub ahead of print]; Zhu N, et al. N Engl J Med. 2020;382:727-733.

DIAGNOSIS

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• Increasing testing capacity, but still

limited in many places

• Issues with sensitivity of NP swabs

‒ 75% to 85%?

• Need for additional
• High clinical suspicion

? need for test

• Is (+) later in course reflective of

infectiousness?

• Lower vs upper samples

Diagnostics

• Rapid molecular diagnostic tests

‒ Cepheid COVID GeneXpert, <45 minutes ‒ Abbott ID Now COVID, <5 min (+), <15 min (–)

NP = nasopharyngeal.

DIAGNOSIS

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• FDA eased approvals, allowing laboratory-developed tests (LDTs)
• Serology: “No IMMUNITY PASSPORT” likely valid at this time

‒ Many tests now available—unclear how well validated; FDA warnings ‒ Tests have not been reviewed by the FDA ‒ Negative results do not rule out COVID-19 infection (molecular needed) ‒ Results from antibody testing should not be used as the sole basis to diagnose or exclude COVID-19 infection ‒ Results from antibody testing should not be used to inform infection status or protective immunity ‒ Positive results may be due to past or present infection with non-SARS-CoV-2 coronavirus strains, such as coronavirus HKU1, NL63, OC43, or 229E

Diagnostics (cont’d)

Food and Drug Administration. www.fda.gov. Accessed May 27 2020; Auwaerter P. Expert Opinion. 2020.

DIAGNOSIS

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Many Investigational Therapeutic and Preventive Approaches

Kupferschmidt K, Cohen J. Science. 2020;367:1412-1413.

THERAPEUTICS

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www.microbenotes.com/remdesivir/. Accessed May 27,2020. Image created with biorender.com.

Remdesivir: Potential Repurposed Drug Candidate for COVID-19 THERAPEUTICS

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Remdesivir: Potential Repurposed Drug Candidate for COVID-19

• Added data to reduced length of stay
• RDV patients 31% faster recovery vs placebo

(P <0.001, 11d vs 15 d)

• 14 d (28 d in analysis)
• No virologic data
• Appears safe
• Mechanically ventilated or ECMO patients don’t appear

to benefit

• O2 requiring (largest group) most benefit

ECMO = extracorporeal membrane oxygenation; RDV = remdesivir. Beigel JH, et al. N Engl J Med. May 22. doi: 10.1056/NEJMoa2007764. [Epub ahead of print].

THERAPEUTICS

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Several Vaccines in Development

• 115 candidates
• >90 currently at exploratory or preclinical stages

‒ 10 in human trials

• Most advanced candidates now in clinical

development ‒ mRNA-1273 (Moderna) ‒ Ad5-nCoV (CanSino Biologicals) ‒ INO-4800 (Inovio) ‒ LV-SMENP-DC and pathogen-specific aAPC (Shenzhen Geno-Immune Medical Institute)

• Many others have indicated plans to initiate

human testing in 2020 (eg, J&J, phase 1 testing anticipated Oct. 2020)

COVID-19: Vaccines in Development

Thanh LT, et al. Nat Rev Drug Discov. 2020 [Epub ahead of print].

9 22 2 4 4 8 4 2 5 2 9 7 6 8 2 5 2 2 2 2

10 20 30 40 50 60 Exploratory (confirmed) Exploratory (unconfirmed) Preclinical Phase I

Number of Projects Current Stage of Development

Live attenuated virus Inactivated Non-replicating viral vector Replicating viral vector Recombinant protein Peptide-based Virus-like particle DNA RNA Unknown

PREVENTION

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Clinical Phase Vaccine Candidates for COVID-19

www.microbenotes.com. Accessed May 27,2020. Image created with biorender.com.

PREVENTION

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Moderna Announces Positive Interim Phase 1 Data for its mRNA Vaccine (mRNA-1273) Against Novel Coronavirus

Moderna Press Release. investors.modernatx.com/news-releases/news-release-details/moderna-announces-positive-interim-phase-1-data-its- mrna-vaccine. Accessed May 27, 2020.

• After 2 doses all participants evaluated to date across the 25g and 100g dose cohorts

seroconverted with binding antibody levels at or above levels seen in convalescent sera

• mRNA-1273:

⎻ Elicited neutralizing antibody titer levels in all 8 initial participants across the 25g and 100g dose cohorts, reaching or exceeding neutralizing antibody titers generally seen in convalescent sera ⎻ Was generally safe and well tolerated ⎻ Provided full protection against viral replication in the lungs in a mouse challenge model

• Anticipated dose for Phase 3 study between 25g and 100g: expected to start in

July 2020

PREVENTION

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PREVENTION

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• BARDA & AstraZeneca

‒ Candidate AZD1222 ‒ Phase 1/Phase 2 underway ‒ Phase 3, summer 2020 start

• 30,000 volunteers
• Partnerships to make 300M doses

‒ Goal to have first vaccine delivery by Oct 2020

• Supporting 14 vaccines → narrowed to 5 (6/4/20)

‒ No partnering with Chinese vaccine efforts ‒ Moderna, Astra Zeneca/Oxford U, JNJ, Merck, Pfizer

Operation Warp Speed

PREVENTION

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• Attenuated adenovirus

‒ Spike glycoprotein insert ‒ Phase 1/Phase 2 in 1112 volunteers

• Started enrollment 4/23/20

‒ Protection from pneumonia in challenge in rhesus macaques

• 5/23/20 Prof. Adrian Hill

‒ “It’s a race against the virus disappearing, and against time…there’s a 50% chance we get no result at all”

AZD1222 aka ChAdOx1 nCoV-19

PREVENTION

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• Speed
• Safety
• Production capacity
• >110 vaccine candidates

‒ How to test that many? ‒ 10 in human trials ‒ 16% (historical average) get to FDA approval

• Durability

Vaccine Big Picture Issues

PREVENTION

2020 Symposia Series 2