COVID-19 Laboratory Testing Guide

COVID-19 Laboratory Testing Guide siemens-healthineers.com/covid-19 What is COVID-19? Sign or symptom % of patients COVID-19 (coronavirus disease 2019) is the Fever 83–99 disease resulting from infection with a newly emerged coronavirus named SARS-CoV-2 (severe Cough 59–82 acute respiratory syndrome coronavirus 2).1 Fatigue 44–70 Coronaviruses are a family of RNA viruses usually Sputum production 28–33 found in animals. Mutations in the virus can result Shortness of breath 31–40 in human infection and subsequent spread.2 Myalgia (muscle aches) 11–35 SARS-CoV-2 is closely related to the SARS virus Table 1. Range and percent of symptoms seen in identified in 2003 (SARS-CoV-1) and (to a lesser confirmed COVID-19 infections.13 degree) the MERS-CoV virus from 2012. All three In some populations, a loss of taste or smell is also can produce a severe respiratory syndrome and a widely reported symptom.10 Molecular testing associated mortality.2-4 While both SARS-CoV-1 specific for the SARS-CoV-2 RNA is used to confirm and the MERS-CoV viruses seem to have a higher presence of the virus, and serology testing can comparative rate of mortality (especially identify antibodies to the virus.11,12 In addition, MERS-CoV), the newly emerged SARS-CoV-2 antibody testing is a promising approach to assess appears much more infectious, with significant prevalence of infection and potentially identify human-to-human transmission.5-7 Asymptomatic immunity. It remains to be confirmed whether individuals may transmit the virus, challenging antibodies to SARS-CoV-2 offer protection infection control.8,9 Its rapid spread has produced (immunity) from subsequent exposure. a true global pandemic. Conclusion: Diagnosis of COVID-19: Testing is critical to differentiate COVID-19 from Diagnosis cannot be made solely on signs or other respiratory disease such as influenza or RSV symptoms as these overlap with other respiratory (respiratory syncytial virus). Widespread testing illness, so confirmation of the presence of the will both inform a COVID-19 diagnosis and aid a virus is essential. Table 1 describes the range greater understanding of disease prevalence, and percent of symptoms seen in confirmed especially in infections that are asymptomatic. COVID-19 infections. SIEMENS Healthineers Clinical classification and transmission of COVID-1914-26 Clinical classification Incubation period Patients with Progression median 5 days, mild symptoms …may progress range 1–27 days in week 1… in week 2 may be rapid and sudden. Human-to-human Possible transmission transmission during asymptomatic phase 4–6 days before Possible transmission after the onset of symptoms. remission of the symptoms Possible Highest risk of transmission Possible transmission during symptomatic phase transmission Disease spectrum Asymptomatic Symptomatic Remission No symptoms Mild to Moderate Severe Critical 1.2–17.6% 80% 10–15% 2–5% Infectious virus can be No signs (mild) or some • Respiratory distress of • Respiratory failure shed, viral loads may signs (moderate) of ≥30 breath per minute requiring mechanical be comparable to pneumonia on imaging • Oxygen saturation ventilation symptomatic patients ≤93% at rest • Shock • PaO2/FiO2 ≤300 mmHg • Any organ failure • Lung lesion progression requiring ICU care >50% in 24–48h • Case/fatality rate current estimation 0.3 to 4% Course of patients at risk and/or infected by COVID-1914-26 Identification of high risk patients Patient triage2,3,4 Diagnosis • Age >55 years Epidemiologic surveillance Virus detection: • Any age with severe obesity BMI >40 Laboratory testing: • Molecular testing (RT-PCR) • Pre-existing pulmonary disease (chronic lung • RT-PCR Imaging: disease or moderate to severe asthma, COPD, • Anti-SARS-CoV-2 antibodies lung cancer, pulmonary hypertension, • Chest CT emphysema (smoking, A1AT deficiency)) • Ultrasound • • Chronic kidney disease X-ray • Diabetes • History of: + Recovery Monitoring hypertension (treated and untreated) – cardiovascular disease – liver disease – Epidemiologic surveillance transplants or other immunosuppression Laboratory testing: – (ex. cancer treatment) Laboratory testing: • Arterial blood gas Anti-SARS-CoV-2 • • • All patients with HIV Complete blood count antibodies (IgG, IgM) • Acute phase proteins, • Patients with endocrine pathologies inflammation & coagulation • Use of biologic drugs Confirm immunization • Liver, kidney, cardiac function biomarkers • Additional testing related to comorbidities Imaging: • Chest CT (ground glass opacification) • Ultrasound • X-ray The essential role of laboratory diagnostics in SARS-CoV-2 infection14-26 Essential lab testing Frequent laboratory abnormalities in patients with COVID-19* Daily labs CBC with differential (trend total lymphocyte count) Comprehensive metabolic panel: Decreased Increased • Electrolytes: Na, K, Total CO2, Chloride Blood Aspartate • Total protein and Albumin Neutrophil count aminotransferase (AST) • Creatinine lymphocyte count (35–75%) Erythrocyte sedimentation rate (ESR; up to 85%) Total bilirubin • Bilirubin, ALT, AST CPK (total creatine kinase) Albumin (50–98%) C-reactive protein Cardiac troponin Lactate (CRP; 75–93%) D-dimer, Ferritin, CRP, ESR, LDH, Cardiac troponin Hemoglobin Procalcitonin (6–25%) Risk (41–50%) Lactate dehydrogenase stratification (LDH; 27–92%) Prothrombin time (PT) Alanine aminotransferase (ALT) D-dimer (36–43%) Viral serologies HBV, HCV, HIV 1/2/O *Approximate percentage of patients Additional essential lab testing Test Potential clinical significance Arterial blood gas pH, PaCO2, PaO2, and aHCO3 For ventilator adjustments Hematology Lymphopenia with atypical lymphocytes Decreased immunological response to the virus Leukocytosis, Neutrophilia, low eosinophils Bacterial (super) infection Thrombocytopenia: Platelet count Consumption (disseminated) coagulopathy Hemostasis Prothrombin time, D-Dimer Activation of blood coagulation and/or disseminated coagulopathy PT and D-dimer are significant predictors of disease severity Inflammation/Infection CRP, Ferritin, IL6, TNFα, SAA Severe viral infection/viremia Procalcitonin Bacterial (super) infection Cardiac High-sensitivity troponin, CK-MB, BNP/NT-proBNP Increased levels may be associated with higher mortality† Liver Albumin, ALT, AST, Bilirubin Impairment of liver function, Liver injury Renal Creatinine, Cystatin C Kidney injury †This information represents a potential novel clinical utility. Data have not been reviewed by FDA or any other regulatory agency Impact of Comorbidities on COVID-19 Patients Patients with comorbidities (like diabetes mellitus, hypertension, cardiovascular, chronic lung and chronic kidney disease) are particularly susceptible to COVID-19 infection and are likely to have more severe illness14-26 Comorbidities Additional testing Impact of COVID-19 Cardiovascular Troponin, Natriuretic peptides, CKMB Precipitates cardiac complications like: acute heart failure, disease myocardial infarction, myocardial injury, cardiac arrest. Challenges for patients on dialysis, in particular, in-center Chronic kidney Blood: Creatinine, Cystatin C, eGFR hemodialysis; uremic patients are particularly vulnerable to disease Urine: Albumin infection and may exhibit greater variations in clinical symptoms and infectivity. Heart/liver/kidney Immunosuppressant Drugs: Mycophenolate, transplant Cyclosporine, Tacrolimus, Sirolimus, Everolimus Patients may be more vulnerable due to immunocompromised status. Viral Hepatitis B serologies (anti-HBs, anti-HBc, and HBsAg) Viral serologies assist in interpretation of ALT elevations, present in ~25% of COVID-19 patients. HIV patients may get severe side effects co-infection Hepatitis C serology (anti-HCV), unless positive in past HIV 1/2/O, CD4 count when taking Tocilizumab (drug being used for COVID-19 pneumonia).‡ Hepatitis patients are at higher risk for liver complications. Diabetes Blood glucose Patients with diabetes who are infected with COVID-19 may see their glycemic control deteriorate during the illness. Chronic lung disease LDH Patients may be more vulnerable due to lung function insufficiency. Chronic liver disease Albumin, AST, ALT, Total Protein, Bilirubin, PT INR Patients may be more vulnerable due to liver function insufficiency. ‡PDR Tocilizumab https://www.pdr.net/drug-summary/Actemra-tocilizumab-2359#1 At Siemens Healthineers, our purpose is to enable healthcare providers References: to increase value by empowering them on their journey toward expanding 1. Lai CC, Shih TP, Ko WC, et al. Int J Antimicrob Agents. 2020 Mar;55(3):105924. precision medicine, transforming care delivery, and improving patient 2. Chen, Y. et al. J Med Virol. 2020 Apr;92(4):418-423 experience, all made possible by digitalizing healthcare. 3. Guarner J. Am J Clin Pathol. 2020 Mar 9;153(4):420-421. 4. Liu J. et al. J Med Virol. 2020;92:491–494 5. Riou J, Althous CL. Euro Surveill. 2020;25(4):2000058. An estimated 5 million patients globally benefit every day from our https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2020.25.4.2000058 innovative technologies and services in the areas of diagnostic and 6. Liu Y, Gayle AA, Wilder-Smith A, et al. J Travel Med. 2020;27(2). therapeutic imaging, laboratory diagnostics, and molecular medicine, https://doi.org/10.1093/jtm/taaa021 as well as digital health and enterprise services. 7. Guo YR et al. Mil Med Res. 2020;7(1):11. https://mmrjournal.biomedcentral.com/articles/10.1186/s40779-020-00240-0 8. Bai Y. et al. JAMA. Published online February 21, 2020. doi:10.1001/jama.2020.2565 We are a leading medical technology company with over 120 years of 9. https://www.cdc.gov/coronavirus/2019-ncov/hcp/faq.html#transmission. experience and 18,000 patents globally. Through the dedication of Accessed April 6, 2020. more than 50,000 colleagues in 75 countries, we will continue to 10. https://www.the-hospitalist.org/hospitalist/article/219556/coronavirus-updates/reports- innovate and shape the future of healthcare. increasingly-suggest-anosmia/hyposmia-can Accessed April 6, 2020. 11. https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/testing.html Accessed April 6, 2020. 12. https://www.cdc.gov/coronavirus/2019-ncov/about/testing.html Accessed April6, 2020. 13. https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-guidance-management-patients.html 14. World Health Organization. Coronavirus disease 2019 (COVID-19) Situation Report – 44. https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports 15. https://www.ifcc.org/ifcc-news/2020-03-26-ifcc-information-guide-on-covid-19/ 16. Report of the WHO-China Joint Mission on Coronavirus Disease 2019 (COVID-19) 17. March 22, 2020 Content source: National Cent Immunization and Respiratory Diseases (NCIRD) Division of Viral Diseases 18. JAMA.2020 Feb7. doi:10,1001/jama,20201585 19. Ann Transl Med 2020;8(3):48 | http://dx.doi.org/10.21037/atm.2020.02.06 20. Lippi G, PlebaniM. Laboratory abnormalities in patients with COVID-2019 infection. Clin Chem Lab Med. 2020 Mar 3. doi: 10.1515/cclm-2020-0198. 21. https://www.massgeneral.org/news/coronavirus/coronavirus-latest-updates 22. Jingyuan Liu, https://doi.org/10.1101/2020.02.10.20021584 23. Hematologic parameters in patients with COVID-19 infection 10.1002/ajh.25774 24. Ruan et al: https://doi.org/10.1007/s00134-020-05991-x 25. Boettler T et al. Care of patients with liver disease during the COVID-19 pandemic: EASL-ESCMID Position Paper. https://easl.eu/wp-content/uploads/2020/04/EASL-ESCMID- Position-Paper-on-COVID-19-and-the-liver-2-April-2020.pdf April 2, 2020. 26. ifcc.org/ifcc-news/2020-03-26-ifcc-information-guide-on-covid-19/ Siemens Healthineers Headquarters Published by Siemens Healthcare GmbH Siemens Healthcare Diagnostics Inc. Henkestr. 127 Laboratory Diagnostics 91052 Erlangen, Germany 511 Benedict Avenue Phone: +49 9131 84-0 Tarrytown, NY 10591-5005 siemens-healthineers.com USA Phone: +1 914-631-8000 Published by Siemens Healthcare Diagnostics Inc. · Order No. 31-20-14365-01-76 · 04-2020 · ©Siemens Healthcare Diagnostics Inc., 2020