Presented in collaboration with Nebraska ICAP, Nebraska DHHS HAI - PowerPoint PPT Presentation

Presented in collaboration with Nebraska ICAP, Nebraska DHHS HAI Team, Nebraska Medicine, and The University of Nebraska Medical Center Moderated by Mounica Soma Panelists: Dr. Trevor Van Schooneveld Angie Vasa, RN, BSN Guidance and responses were provided based on information Kate Tyner, RN, BSN, CIC known on 6/2/2020 and may become out of date. Guidance is Margaret Drake, MT(ASCP),CIC being updated rapidly, so users should look to CDC and Teri Fitzgerald RN, BSN, CIC jurisdictional guidance for updates. Dr. Ishrat Kamal-Ahmed

Questions and Answer Session Use the QA box in the webinar platform to type a question. Questions will be read aloud by the moderator If your question is not answered during the webinar, please either e-mail it to NE ICAP or call during our office hours to speak with one of our IPs A transcript of the discussion will be made available on the ICAP website https://icap.nebraskamed.com/coronavirus/ https://icap.nebraskamed.com/covid-19-webinars/ Panelists today are: Dr. Trevor Van Schooneveld tvanscho@unmc.edu Kate Tyner, RN, BSN, CIC ltyner@nebraskamed.com Margaret Drake, MT(ASCP),CIC Margaret.Drake@Nebraska.gov Teri Fitzgerald RN, BSN, CIC tfitzgerald@nebraskamed.com Angie Vasa, RN, BSN avasa@nebraskamed.com Dr. Ishrat Kamal-Ahmed Ishrat.Kamal-Ahmed@nebraska.gov

Testing for SARS-CoV-2 Trevor Van Schooneveld, MD Associate Professor, Infectious Diseases 6/2/20

Testing for SARS-CoV-2 Trevor Van Schooneveld, MD Associate Professor, Infectious Diseases 6/2/20

How do you diagnose viral infections? • Clinically – symptom-based How to • Imaging Diagnose • Serology – IgM, IgA, IgG COVID-19 • Rapid tests – antigen or antibodies • Culture • Molecular Testing

Clinical Diagnosis • Hospitalized Chinese - mostly older (63% >50 yo), 63% male • HCW - mostly younger (55% <45 yo), 73% female Symptoms Hospitalized Chinese (N=140) US HCW (N=9282) Fever, cough, or SOB NA 92% Cough 80% 78% Fever 87% 68% SOB 38% 41% Myalgia 21% 66% Headache 8% 65% Sore Throat 5% 38% Diarrhea, Nausea/vomiting 2%/1% 32%/20% Loss of Smell or Taste NA 16% Runny Nose 4% 12% Huang, C, et al. Lancet . 2020;395:497. Chen, N, et al. Lancet . 2020;395:507-13. CDC. MMWR . 2020;69:477-81.

• CXR insensitive for diagnosis • Typical CT findings should prompt testing • CT changes occur within 0-4 days after symptoms and peak around day 6-13 with improvement around day 14 Imaging in COVID-19 • CT progression: • Initial phase  bilateral multilobar ground-glass opacification (GGO) with peripheral or posterior distribution, mainly in the lower lobes • Progression  GGO into multifocal consolidative opacities, septal thickening, and development of a crazy paving pattern Salehi S, et al. AJR. 2020;215:1-7 Simpson S, et al. Radiology: CT Imaging, 2020;2 https://doi.org/10.1148/ryct.2020200152

Testing Primer • The sensitivity of a test means how well it can correctly identify those who have COVID-19 infection • The specificity of a test means how well it can correctly identify those who do not have COVID-19 infection • The positive predictive value of a test is the likelihood that a positive test result indicates that a person is truly positive for COVID-19 infection. • The negative predictive value of a test is the likelihood that a negative test result indicates that a person is truly negative for COVID-19 infection.

Tests Available • Molecular Tests (PCR, NAAT) • Amplify RNA of the virus • Use Case = Diagnosis of acute infection • Antigen Tests • Detect viral antigens • Don’t amplify • Use Case = Rapid diagnosis of acute infection • Serology • Detect antibodies made by the immune system • Detected after acute infection develops • Use Case = defining previous infection, population prevalence • Culture • Grow the virus • Slow and not widely available • Use Case = Defining infectivity period

Serologic Response in Severe and Mild Serology COVID-19 Infection (N=23) • What we know • Robust and rapid serologic response of IgM, IgA and IgG • IgM rises within 5-7 days symptom onset • Seropositivity at 14 days: IgM (88-94%), IgG (94-100%) • NM Serology Performance (IgG assay) • 0-5 days illness onset – 25% agreement • 6-14 days – 90% agreement • >15 days – 94.5% agreement • Specificity 99.3% • 16/214 positive (7.8%) To, K, et al. Lancet. 2020 https://doi.org/10.1016/S1473-3099(20)30196-1

Serology Questions What we don’t know • Utility in diagnosing acute infection? • IgG poor early • IgM assay cross-reactivity • Performance in mild disease? • Performance in asymptomatic? • The false positive question • Is a positive serology protective against subsequent infection and for how long?

Who to Test • All persons with symptoms suspicious for COVID-19 TEST • Previously testing was prioritized due to limited capacity • Patients being hospitalized • Healthcare workers and those who work in healthcare environments • Ambulatory patients at increased risk for poor outcomes or who work in high risk environments • Older adults (age ≥ 65 years) • Those who are immunocompromised or have chronic medical conditions (e.g., diabetes, chronic lung, heart, or kidney disease) • Long-term care facility residents or those who reside in other group settings (homeless shelter, group home, etc.) • Public safety workers and first responders • Persons performing duties or administering care in settings where spread of COVID19 would be particularly disadvantageous: group homes, prisons, assisted living facilities, long term care, etc.

Testing Asymptomatic Persons • Molecular tests • Pre-organ transplant, bone marrow transplant • Not generally recommended outside of outbreak investigation • LTCF, group settings, etc. • Being done widely… • Admission screening • Likely low yield and potentially inaccurate in low prevalence settings • Pre-procedural • Much debate, yield very low (false +?), potentially to preserve PPE • Post-exposure testing not generally recommended • When and how often? • A negative doesn’t rule out subsequent development of disease • Serology • May be a role • Define population prevalence, determine retrospectively if infected, monitor healthcare workers, determine incidence of asymptomatic infection

How to Test

Rapid Testing • CLIA waived tests • Results in 5-15 minutes • Molecular • Antigen and serologic coming • Performance parameters undefined • Reports of decreased sensitivity • Useful early in infection • Good for ruling in, less so for ruling out • Urgent care, ED, clinic??

Molecular Tests in Use at NM • Numerous platforms available • Nebraska Medicine currently using the following (TAT <18 hours) • Roche Cobas 6800 (COV19) • Laboratory developed test (NECoV19) • Regional Lab using a third platform • NPHL using the CDC designed assay • Increasing capacity and batching • Rapid testing (TAT <4 hours) • Biofire SARS-CoV-2 only • Biofire Respiratory Pathogen Panel with SARS-CoV-2 (coming soon) • Cepheid

2019-20 2003 Li X, et al. J Pharma Analysis. 2020; https://doi.org/10.1016/j.jpha.2020.03.001

Roche assay NPHL assay Roche assay NM Assay NM Assay Li X, et al. J Pharma Analysis. 2020; https://doi.org/10.1016/j.jpha.2020.03.001

Test Results Interpretation • Slight variations in how results are reported based on targets • Understand what is being reported at your facility • Roche (E- and ORF1a-) • E- and ORF1a- not detected = COVID Not Detected • E- and ORF1a- detected = COVID Detected • Only E- detected = Presumptive positive • E- is same in SARS-CoV-1 but this virus is not circulating • Invalid – test didn’t work  Repeat swab • NE COV Test (E- and N-) • E- not detected = Not Detected • E- detected  Will be retested on next run for both E- and N- • If either detected = COVID Detected • If neither detected = Inconclusive  Repeat swab

How good is the test? • Depends on how well you did the swab • Depends on the assay • Depends on where you are in the illness course Should I Get • Early in the illness upper airway viral levels Two Tests in are very high but begin to decline after 7 days • Numerous reports of patients presenting Symptomatic with typical symptoms and especially pneumonia and having a negative initial NP Person but then a second NP or lower respiratory tract specimen being positive Does our experience help us?

Inpatient Repeat Testing • Reviewed all inpatient repeat Characteristic Results (N=226) testing 3/10/20-4/21/20 where Median Age (range) 60 (1-94) initial result was negative or Male 57% inconclusive Median Time Between 1 st 1.0, 2.9 • Utilized both Roche and NM assay and 2 nd Test and 2 nd and 3 rd Test (days) • Primarily NP Time from Symptom • 99% first test, 94% second, 74% third Onset to First Test Negative Inconclusive Positive 1-7 days 73% 1 st Test 93% (209) 7% (17) 0% (0) 8-14 days 12% N=226 >14 days 2% 2 nd Test 98.5% (223) 1% (2) 0.5% (1) Asymptomatic Screening 13% N=226 3 rd Test 97% (32) 0% (0) 3% (1) N=33