2020 Symposia Series 2
COVID-19: Update for NPs and PAs
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 3
US Incidence Rates (6/04/2020) • US Cases: 1,851,520 • US Deaths: 107,175 Key Concerns • Transmission • Diagnosis • Therapeutics • Prevention Johns Hopkins University & Medicine. coronavirus.jhu.edu/us-map. Accessed June 4, 2020. 4
US Incidence Rates (6/04/2020) cont’d Source: Wikimedia Commons. 5
TRANSMISSION Clustering is a COVID Puzzle • 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 Kupferschmidt K. Science 2020;368:808-09. 6
TRANSMISSION Clustering is a COVID Puzzle (cont’d) • Reproduction number (R 0 ) • Another factor important (k) ‒ Dispersion factor: how much an infection ‒ SARS-CoV-2 = ~ 3.0 if not socially distancing clusters • But, some spread lots, others not at all • Lower k values = more transmission comes • Healthy people make droplets when from fewer people talking, some >> others • SARS-CoV-1 → 0.16 ‒ Indoor risk in Japan 19x than outdoor • MERS-CoV → 0.25 risk ‒ People with more social contacts • H1N1 1918 influenza → 1.0 • SARS-CoV-2 varying estimates ‒ k = 0.1 (10% cases = 80% of spread) Kupferschmidt K. Science 2020;368:808-09; Lloyd-Smith JO, et al. Nature 2005; 438:355-359. 7
TRANSMISSION Masks Reduce Airborne 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 Prather KA et al. Science 10.1126/science.abc6197 (2020). 8
TRANSMISSION Masks Reduce Airborne Transmission (cont’d) • 6 feet doesn’t account for particles 1 micron or 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 Prather KA et al. Science 10.1126/science.abc6197 (2020). 9
TRANSMISSION Masks Reduce Airborne Transmission (cont’d) • Covid-19 Deaths ‒ Fatalities among confirmed coronavirus cases in Hong Kong and Singapore are extremely low 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. Prather KA et al. Science 10.1126/science.abc6197 (2020). 10
TRANSMISSION What Do We Know About COVID-19 Immunity? • 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?) Alshukiari AN et al. Emerg Infect Dis . 2016;22:1113-1115; Long QX et al, Nat Med 2020;10.1038/s41591-020-0897-1. 11
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. 12
TRANSMISSION Transmission and Contagiousness • 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 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. 13
DIAGNOSIS Range of COVID-19 Disease States and Potential Therapeutic Targets ARDS = acute respiratory distress syndrome; CRP = C-reactive protein; IL = interleukin; JAK = Janus kinase; LDH = lactate dehydrogenase; SIRS = systemic inflammatory response syndrome. Siddiqi HK, Mehra MR. J Heart Lung Transplant. 2020;39:405-407. 14
DIAGNOSIS Clinical Presentations • • Descriptions mostly limited to Less common symptoms hospitalized patients ‒ Pharyngitis ‒ Loss of taste/smell • Signs, symptoms ‒ Headache ‒ Fever (46%-98%) ‒ Productive cough ‒ Cough (46%-82%, usually dry) ‒ GI symptoms ‒ Myalgia or fatigue (11%-44%) ‒ Shortness of breath at onset (31%) • May be heralding ‒ Chills ‒ 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]; 15 Zhu N, et al. N Engl J Med . 2020;382:727-733.
DIAGNOSIS Diagnostics • • Increasing testing capacity, but still Rapid molecular diagnostic tests limited in many places ‒ Cepheid COVID GeneXpert, <45 minutes • Issues with sensitivity of NP swabs ‒ 75% to 85%? • Need for additional • High clinical suspicion ? need for test • Is (+) later in course reflective of ‒ Abbott ID Now COVID, infectiousness? <5 min (+), <15 min ( – ) • Lower vs upper samples 16 NP = nasopharyngeal.
DIAGNOSIS Diagnostics (cont’d) • 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 Food and Drug Administration. www.fda.gov. Accessed May 27 2020; Auwaerter P. Expert Opinion. 2020. 17
THERAPEUTICS Many Investigational Therapeutic and Preventive Approaches Kupferschmidt K, Cohen J. Science . 2020;367:1412-1413. 18
THERAPEUTICS Remdesivir: Potential Repurposed Drug Candidate for COVID-19 www.microbenotes.com/remdesivir/. Accessed May 27,2020. Image created with biorender.com. 19
THERAPEUTICS 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. 20 Beigel JH, et al. N Engl J Med . May 22. doi: 10.1056/NEJMoa2007764. [Epub ahead of print].
PREVENTION COVID-19: Vaccines in Development 60 Live attenuated virus Several Vaccines in Development 2 Inactivated • 115 candidates 50 Non-replicating viral vector 5 • >90 currently at exploratory or preclinical stages Replicating viral vector Number of Projects 8 ‒ 10 in human trials Recombinant protein 40 Peptide-based • Most advanced candidates now in clinical Virus-like particle development 9 2 DNA ‒ mRNA-1273 (Moderna) 30 7 RNA 5 ‒ Ad5-nCoV (CanSino Biologicals) Unknown 2 4 ‒ INO-4800 (Inovio) 20 ‒ LV-SMENP-DC and pathogen-specific aAPC 8 2 2 (Shenzhen Geno-Immune Medical Institute) 4 22 6 10 • Many others have indicated plans to initiate 2 human testing in 2020 (eg, J&J, phase 1 testing 9 4 2 anticipated Oct. 2020) 2 0 Exploratory Exploratory Preclinical Phase I (confirmed) (unconfirmed) Current Stage of Development Thanh LT, et al. Nat Rev Drug Discov . 2020 [Epub ahead of print]. 21
PREVENTION Clinical Phase Vaccine Candidates for COVID-19 www.microbenotes.com. Accessed May 27,2020. Image created with biorender.com. 22
PREVENTION Moderna Announces Positive Interim Phase 1 Data for its mRNA Vaccine (mRNA-1273) Against Novel Coronavirus 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 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. 23
PREVENTION 24
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