2020 Symposia Series 1
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
COVID-19 • Transmission • Diagnostics • Therapeutics • Prevention 4
US Incidence Rates (5/11/2020) Johns Hopkins University & Medicine. coronavirus.jhu.edu/us-map. Accessed May 11, 2020 5
Transmission
COVID-19 Is Spread Chiefly by Droplets • Droplet ‒ 3 to 6 feet ‒ Contaminates surfaces/fomites ‒ Hand to face • Airborne ‒ Especially with intubation, suctioning, close exposure ‒ ? Aerosolization of tissue containing virus • Other routes ‒ Fecal, nosocomial, ?perinatal Centers for Disease Control and Prevention. www.cdc.gov/coronavirus/2019-ncov/hcp/infection-control-recommendations.html#adhere. Accessed April 26, 2020. 7
Transmission and Contagiousness • Why rapid and global spread? ‒ Asymptomatic shedding • Estimates 25% to 50% of infected (CDC/NIAID)? • Role of asymptomatic cases affecting models/forecasts • USC-LA County study 4/20/20: COVID-19 infections far exceed confirmed cases ‒ 4.1% of county’s adult population has antibodies to the virus ‒ Adjusting to statistical margin of error: between 2.8% and 5.6% have antibody • Thus, between 221,000 and 442,000 adults in the county have had the infection • 28 to 55 times higher than the 7994 confirmed cases reported to the county by the time of the study in early April CDC = Centers for Disease Control and Prevention. Redfield R. CDC; Fauci A. NIAID/NIH. County of Los Angeles Public Health news release. April 20, 2020. Available at publichealth.lacounty.gov/phcommon/public/media/mediapubhpdetail.cfm?prid=2328. 8
COVID-19: PPE for Healthcare Personnel — CDC Guidelines Centers for Disease Control and Prevention. www.cdc.gov/coronavirus/2019-ncov/downloads/COVID-19_PPE_illustrations-p.pdf. Accessed April 15, 2020. 9
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. doi: https://doi.org/10.1016/j.healun.2020.03.012. 11
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%) • May be heralding ‒ Shortness of breath at onset (31%) ‒ Hemoptysis ‒ Chills – 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. 12 N Engl J Med . 2020;382:727-733.
Hospitalization Rates and Characteristics of Patients Hospitalized With Laboratory-Confirmed COVID-19 • COVID-NET • 14 states • Mar 1-30, 2020 • By age group Kim GS, et al. MMWR Morb Mortal Wkly Rep . 2020;69:458-464. 13
COVID-19: US Hospitalizations • 1482 patients Higher hospitalization rates in • certain patients ‒ ≥50 years (74.5%) ⎻ Black ‒ Male (54.4%) ‒ Underlying health conditions (89.3%) • Hypertension (49.7%) • Obesity (48.3%) • Chronic lung disease (34.8%) • Diabetes (28.3%) • Cardiovascular disease (27.8%) Kim GS, et al. MMWR Morb Mortal Wkly Rep . 2020;69:458-464. 14
CDC: Priorities for Testing Patients With Suspected COVID-19 Infection • High priority: nucleic acid or antigen testing ⎻ Hospitalized patients ⎻ Healthcare facility workers, others in congregate living settings, first responders with symptoms ⎻ High priority patients • With COVID-19 symptoms • Asymptomatic people if from a racial or ethnic minority group disproportionately affected by adverse COVID-19 outcomes ⎻ African Americans, Hispanics and Latinos, some American Indian tribes (eg, Navajo) Centers for Disease Control and Prevention. www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-criteria.html. Accessed May 5, 2020. 15
CDC: Priorities for Testing Patients With Suspected COVID- 19 Infection (cont’d) • Asymptomatic people who are prioritized by clinicians or public health departments ‒ Public health monitoring ‒ Sentinel surveillance ‒ Comorbidities or disability ‒ Residence in congregate housing, homeless shelter, or long-term care facility • Recommendations for antibody testing ‒ CDC has no recommendations for diagnostic purposes Centers for Disease Control and Prevention. www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-criteria.html. Accessed May 5, 2020. 16
Diagnostics • • Rapid molecular diagnostic tests Increasing testing capacity, but still limited in many places ‒ Cepheid COVID GeneXpert, <45 minutes • Issues with sensitivity of NP swabs ‒ 70 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 17 NP = nasopharyngeal.
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 April 29, 2020; Auwaerter P. Expert Opinion. 2020. 18
Therapeutics
Many Investigational Therapeutic and Preventive Approaches Kupferschmidt K, Cohen J. Science . 2020;367:1412-1413. 20
Remdesivir: Potential Repurposed Drug Candidate for COVID-19 Source: microbenotes.com/remdesivir/. Accessed May 5,2020. Image created with biorender.com. 21
Remdesivir in Adults With Severe COVID-19: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial • N = 237 patients, halted • Confirmed infection, 12 days or fewer of symptoms, lung involvement • Remdesivir 200 mg day 1, then 100 mg IV daily vs placebo Findings : • No clinical improvement (subgroup <10 days with trend) • No difference in mortality (subgroup <10 days with trend) • No effect on viral load in upper or lower respiratory tracts Wang Y, et al. Lancet. Published online April 29, 2020. doi.org/10.1016/S0140-6736(20)31022-9. Accessed May 5, 2020 22
Adaptive COVID-19 Treatment Trial (ACTT): Remdesivir • Sponsor: National Institute of Allergy and Infectious Diseases • Randomized, controlled trial studying remdesivir vs placebo (began 2/21/20) • 1063 patients from 68 sites (47 in US; 21 from Europe and Asia) Preliminary results • Patients who received remdesivir had 31% faster time to recovery than those who received placebo ( P <0.001) • Median time to recovery: 11 days for patients treated with remdesivir vs 15 days for those who received placebo • Survival benefit? ‒ Mortality rate of 8.0% for the group receiving remdesivir vs 11.6% for the placebo group ( P = 0.059) www.nih.gov/news-events/news-releases/nih-clinical-trial-shows-remdesivir-accelerates-recovery-advanced-covid-19. Accessed April 29, 2020. 23
Prevention
Rationale for Social Distancing 25
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 • Most advanced candidates now in clinical Recombinant protein 40 Peptide-based development Virus-like particle ‒ mRNA-1273 (Moderna) 9 2 DNA ‒ Ad5-nCoV (CanSino Biologicals) 30 7 RNA 5 ‒ INO-4800 (Inovio) Unknown 2 4 ‒ LV-SMENP-DC and pathogen-specific aAPC 20 (Shenzhen Geno-Immune Medical Institute) 8 2 2 • Many others have indicated plans to initiate 4 22 6 10 human testing in 2020 (eg, J&J, phase 1 testing 2 anticipated Oct. 2020) 9 4 2 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]. 26
2020 Symposia Series 1
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