SARS-CoV-2 is a novel coronavirus that was identified in late 2019 as the causative agent of COVID-19 (aka coronavirus disease 2019). On March 11, 2020, the World Health Organization (WHO) declared the world-wide outbreak of COVID-19 a pandemic. This document summarizes the most recent knowledge regarding the biology, epidemiology, diagnosis, and management of COVID-19

Carlos, Graham

Dela Cruz, Charles S.

Gross, Jane E.

Jamil, Shazia

Mark, Nick

Pasnick, Susan

American Journal of Respiratory and Critical Care Medicine

English

IUPUIScholarWorks

American Thoracic SocietyPUBLIC HEALTH | INFORMATION SERIESHEALTHCARE PROVIDER EDUCATION RAPID RESPONSEwww.thoracic.orgCLIP AND COPYBiology	■ SARS-CoV-2 is single-stranded RNA, enveloped virus that likely spread to humans from a zoonotic source, possibly bats or pangolins1.	■ It is believed to spread from person to person via respiratory droplet nuclei2.	■ Other routes of infection (e.g. contact, enteric) are possible as the virus can persist on surfaces and is shed in feces, but it is unclear if these are significant means of spread.2,3	■ There is evidence of transmission by asymptomatic individuals4.	■ The virus binds to the ACE2 receptor on type II pneumocytes. However, the role of Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers (ARBs) as treatments or risk factors for disease is unclear5. 	■ The reported incubation time is 3-12 days with a median duration of viral shedding of 20 days6,7.	■ There is evidence that the virus changes over time. There may be multiple strains of SARS-CoV-2 in circulation8.EpidemiologyCharacteristics such as the attack rate (% of individuals in an at-risk population who acquire the infection), R0 (R naught, the expected number of cases directly generated by one case in a population where all individuals are susceptible to infection), and case fatality rate (CFR, % of infected individuals who die) are contextual. That is, they depend on factors such as testing rate, population density, and control strategies that vary from location to location. These factors may also change over time. Table 1 summarizes reported epidemiologic characteristics of SARS-CoV-29.Table 1: Reported epidemiologic characteristics of SARS-CoV-2.Attack rate: 30-40% (community, in China)R0: 2-4 (lower with containment)Case fatality rate 1.5% USA, 3.4% overall worldwideIncubation time 3-14 daysViral shedding Median 20 daysClinical PresentationSymptoms may vary from mild cough to fulminant respiratory failure. Positive tests have also been obtained from asymptomatic patients. Table 2 lists the estimated frequency of symptoms observed to date10:Table 2: Frequency of Symptoms in COVID-19Symptom Percent of patients with symptomCough 50-80%Fever 85% (only 45% febrile on presentation)Fatigue 69.6%Dyspnea 20-40%URI symptoms 15%GI symptoms (nausea, vomiting, diarrhea)10%Diagnosis and Management of COVID-19 DiseaseSARS-CoV-2 is a novel coronavirus that was identified in late 2019 as the causative agent of COVID-19 (aka coronavirus disease 2019). On March 11, 2020, the World Health Organization (WHO) declared the world-wide outbreak of COVID-19 a pandemic. This document summarizes the most recent knowledge regarding the biology, epidemiology, diagnosis, and management of COVID-19. Am J Respir Crit Care Med 2020 [online ahead of print]Public Health Information Series © 2020 American Thoracic SocietyNIAID-RMLPage 1 of 4 AJRCCM Articles in Press. Published March 30, 2020 as 10.1164/rccm.2020C1  Copyright © 2020 by the American Thoracic Society American Thoracic SocietyPUBLIC HEALTH | INFORMATION SERIESHEALTHCARE PROVIDER EDUCATION RAPID RESPONSEwww.thoracic.orgLaboratory FindingsThe following lab abnormalities have been observed in patients with COVID-1910:	■ Complete blood count: normal WBC, leukopenia, lymphopenia (80%+), thrombocytopenia	■ Chemistries: elevated BUN/creatinine, elevated AST, ALT, and Total bilirubin	■ Inflammatory markers: normal or low procalcitonin, high C-reactive protein and ferritin	■ Miscellaneous: elevated D-dimer, interleukin -6, and lactate dehydrogenaseImaging:Imaging findings are frequently absent on presentation and should not be used for diagnosis of COVID. Many patients have normal imaging at the time of presentation, but the following abnormalities have been reported (Figure 1)10:	■ Chest X-ray: bilateral, peripheral, patchy opacities	■ Chest CT scan: bilateral ground glass opacities, crazy paving, and consolidation. Not routinely recommended to avoid unnecessary exposure during transport	■ Point-of-care ultrasound: B-lines, pleural line thickening, consolidations with air bronchograms. Assessment of cardiac function is also usefulFigure 1: COVID-19 Imaging. (A) CXR showing bilateral peripheral opacities, (B) Chest CT showing diffuse ground glass with a peripheral predominance, (C) point of care lung ultrasound showing predominance of B-lines in patients with COVID-19. Images courtesy of Dr. Nick Mark.Diagnostic Testing and Reporting:Lack of availability has hampered testing to date, but testing capacity is increasing quickly. The following recommendations have been made regarding diagnostic testing and reporting11,12.	■ Send nasopharyngeal swab for SARS-CoV-2 polymerase chain reaction testing (RT-PCR). Check with your local facility regarding test characteristics, including sensitivity and specificity	■ Differentiating SARS-CoV-2 from other circulating respiratory viruses is important, particularly Influenza, therefore consider testing of usual respiratory pathogens. Co-infection has also been reported	■ Do not order sputum induction	■ Avoid bronchoscopy unless absolutely indicated  ◆ If indicated, follow current recommendations for bronchoscopy in suspected COVID-19 patients as recommended by the American Association for Bronchology and Interventional Pulmonology13	■ PFTs or spirometry are not indicated in these patients. In addition, ATS and American College of Occupational and Environmental Medicine has recommended against doing routine outpatient PFTs for concerns of spread	■ Notify your local health department of positive casesIsolation and Infection Control for Confirmed and Suspected Cases:Recommendations for isolation and infection control are evolving as more is learned about the SARS-CoV-2 virus. Current best practices include:	■ Place all suspected patients in droplet masks during assessment and when in transit	■ If cohorting is required due to resource limitation, keep patients 2 meters apart in a single room	■ Restrict visitors	■ Try to avoid room entry unless essential; try to move equipment (e.g. IV pumps) out of the room	■ Hand hygiene: 20+ seconds with soap and or 60-95% alcohol containing hand gel	■ Use appropriate PPE in the correct sequence, including14:  ◆ Standard precautions ◆ Contact precautions  ◆ Droplet precautions with eye protection ◆ PLUS airborne precautions for aerosolizing procedures such as intubation, extubation, non-invasive positive pressure ventilation (NIPPV), open circuit suctioning, bronchoscopy, and aerosol treatmentsPage 2 of 4 AJRCCM Articles in Press. Published March 30, 2020 as 10.1164/rccm.2020C1  Copyright © 2020 by the American Thoracic Society PUBLIC HEALTH | INFORMATION SERIESHEALTHCARE PROVIDER EDUCATION RAPID RESPONSEAmerican Thoracic SocietyPUBLIC HEALTH | INFORMATION SERIESHEALTHCARE PROVIDER EDUCATION RAPID RESPONSEwww.thoracic.org	■ N95 masks must be fit tested	■ All Healthcare professionals must be trained in how to properly don, use, and doff PPE in a manner to prevent self-contamination	■ If available, consider powered air-purifying respirator (PAPRs) or controlled air purifying respirators (CAPRs).  ◆ Use of tight-fitting respirators require fit testing, but use of loose-fitting respirators does not require fit testing15General Treatment RecommendationsThe following treatment strategies are recommended based on experience to-date. Of note, these are suggestions and should not replace clinical judgement at the bedside.	■ Fluid-sparing resuscitation	■ Empiric antibiotics if suspicion for secondary infection	■ Due to concerns for aerosol spread, nebulizers should be converted to MDIs	■ WHO has not recommended against the use of Non-steroidal anti-inflammatory agents. Clinicians should consider alternatives if concerns exist	■ Initiating or discontinuing ACE-I and ARBs have been an area of intense discussion. The American College of Cardiology, American Heart Association and Heart Failure Society of America’s joint statement recommends against discontinuing ACE-I and ARBs in patients with COVID-19	■ Monitor for and treat cardiomyopathy and cardiogenic shock which have been reported as a late complication of COVID-19. Point-of-care ultrasound may be useful in identifying patients with this complication	■ Corticosteroids are not recommended except when required for other indications such as asthma or COPD exacerbations, refractory shock or evidence of cytokine stormManagement of Hypoxemic Respiratory FailureThese are suggestions and should not replace clinical judgement at the bedside.	■ Oxygen by nasal cannula OR simple mask OR non-rebreather masks	■ Consider early intubation to avoid use of aerosolizing NIPPV and emergent intubations	■ Use rapid-sequence intubation. Avoid bag-mask valve if possible due to risk of droplet spread	■ Avoid direct laryngoscopy to distance provider from patient. Use video laryngoscopy where possible	■ Connect suction and capnography in advance to avoid circuit breaks	■ Minimize circuit breaks and use high-efficiency particulate air (HEPA) filters between endotracheal tubes and CO2 detectors	■ Use lung-protective ventilation strategies per ARDSnet protocol. Prone and paralyze as needed	■ Patients will likely require a prolonged duration of mechanical ventilation	■ Extracorporeal Membrane Oxygenation (ECMO) can be considered but is associated with a high mortality rate16	■ Monitor for and treat cardiomyopathy and cardiogenic shock which have been reported as a late complication of COVID-19. Point-of-care ultrasound as well as BNP levels may be useful in identifying patients with this complication ◆ In a recent case series from Washington, 33% of patients developed cardiomyopathy17Investigational TherapiesInformation on registered clinical trials for COVID-19 in the United States is available at: https://clinicaltrials.gov/	■ No US Food and Drug Administration (FDA)-approved drugs specifically for the treatment of patients with COVID-19 currently exist. Drugs currently approved for other indications as well as investigational drugs are being studied in clinical trials17 	■ FDA approved drugs that may be used off-label ◆ Chloroquine or Hydroxychloroquine—blocks viral entry into the endosome; in vitro data suggests some utility but data from RCTs is lacking	■ Investigational agents available in the U.S. Avoid prophylactic use ◆ Remdesivir—anti-viral nucleotide analog 	■ Other drugs ◆ Lopinavir/ritonavir—anti-viral protease inhibitors; recent negative RCT19Page 3 of 4 AJRCCM Articles in Press. Published March 30, 2020 as 10.1164/rccm.2020C1  Copyright © 2020 by the American Thoracic Society American Thoracic SocietyPUBLIC HEALTH | INFORMATION SERIESHEALTHCARE PROVIDER EDUCATION RAPID RESPONSEwww.thoracic.org ◆ Tocilizumab—IL-6 inhibitor and may have a role in cytokine storm and for patients in shockPrognosisBased on experience in China, 80% of patients have mild symptoms, 15% moderate, and 5% severe (requiring mechanical ventilation). Most patients deteriorate gradually with a median of 9 days from symptom onset to ICU admission. Pregnant women and children appear to have a better prognosis. The following factors have been associated with worse outcomes:	■ Increasing age	■ Comorbidities including diabetes, cardiovascular disease (including hypertension), and chronic lung disease	■ Higher admission sequential organ failure assessment (SOFA) score	■ Laboratory abnormalities: elevated D-dimer, ferritin, and troponinControl StrategiesThe following strategies are recommended to slow the rate of SARS-CoV-2 spread: 	■ Contact tracing	■ Social /Physical distancing	■ Quarantine of suspected cases and exposed individuals	■ Travel restrictionsAuthors: Shazia Jamil, MD, Scripps Clinic and University of California, San DiegoNick Mark, MD, University of WashingtonGraham Carlos, MD, Indiana UniversityCharles S. Dela Cruz, MD, PhD, Yale UniversityJane E Gross, MD, PhD, National Jewish HealthSusan Pasnick, MD, MidCentral DHB, New ZealandReviewers:Vidya Krishnan, MDMarianna Sockrider, MD, DrPHKevin Wilson, MDReferences:1. Peng Z, et al. “A pneumonia outbreak associated with a new coronavirus of probable bat origin.” Nature: 579, 270-273(2020).2. https://www.cdc.gov/coronavirus/2019-ncov/prepare/transmission.html?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fcoronavirus%2F2019-ncov%2Fabout%2Ftransmission.html (accessed 3/20/2020).3. Xiao F, et al. “Evidence for gastrointestingal infection of SARS-CoV-2.” Gastroenterology (2020), doi: https://doi.org/10.1053/j.gastro.2020.02.055.4.  Wu D, et al. “The SARS-CoV-2 outbreak: what we know.” International Journal of Infectious Diseases (2020), doi: https://doi.org/10.1016/j.ijid.2020.03.004.5. http://www.nephjc.com/news/covidace2 (accessed 3/21/2020).6. Lauer S, et al. “The Incubation Period of Coronavirus Disease 2019 (COVID-19) from Publicly Reported Confirmed Cases: Estimation and Application.” Annals of Internal Medicine: 10 March 2020.7. Zhou F, et al. “Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a restrospective cohort study. Lancet. 2020 Mar 11. pii: S0140-6736(20)30566-3. doi: 10.1016/S0140-6736(20)30566-3. 8. Xiaolu Tang, Changcheng Wu, Xiang Li, Yuhe Song, Xinmin Yao, Xinkai Wu, Yuange Duan, Hong Zhang, Yirong Wang, Zhaohui Qian, Jie Cui, Jian Lu, On the origin and continuing evolution of SARS-CoV-2, National Science Review, nwaa036, https://doi.org/10.1093/nsr/nwaa0369. https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200306-sitrep-46-covid-19.pdf?sfvrsn=96b04adf_2 (accessed 3/21/2020).10. Guan W, et al. “Clinical Characteristics of Coronavirus Disease 2019 in China.” NEJM. DOI: 10.1056/NEJMoa2002032.11. https://www.cdc.gov/coronavirus/2019-nCoV/lab/guidelines-clinical-specimens.html (accessed 3/21/2020)12. https://aabronchology.org/2020/03/12/2020-aabip-statement-on-bronchoscopy-covid-19-infection/ (accessed 3/21/2020)13. https://aabronchology.org/2020/03/12/2020-aabip-statement-on-bronchoscopy-covid-19-infection/ (accessed 3/23/2020)14. https://www.cdc.gov/coronavirus/2019-ncov/infection-control/control-recommendations.html (accessed 3/21/2020)15. Board on Health Sciences Policy; Institute of Medicine. The Use and Effectiveness of Powered Air Purifying Respirators in Health Care: Workshop Summary. Washington (DC): National Academies Press (US); 2015 May 7. 2, Defining PAPRs and Current Standards. Available from: https://www.ncbi.nlm.nih.gov/books/NBK294223/16. Henry B. “COVID-19, ECMO, and lymphomenia: a word of caution.” Lancet: DOI:https://doi.org/10.1016/S2213-2600(20)30119-3.17. Arentz M, Yim E, Klaff L, et al. Characteristics and Outcomes of 21 Critically Ill Patients With COVID-19 in Washington State. JAMA. Published online March 19, 2020. doi:10.1001/jama.2020.432618. https://www.cdc.gov/coronavirus/2019-ncov/hcp/therapeutic-options.html (accessed 3/23/2020)19. Cao B, Wang Y, Wen D, et al. A trial of lopinavir–ritonavir in adults hospitalized with severe Covid-19. N Engl J Med. DOI: 10.1056/NEJMoa2001282.Page 4 of 4 AJRCCM Articles in Press. Published March 30, 2020 as 10.1164/rccm.2020C1  Copyright © 2020 by the American Thoracic Society 

Diagnosis and Management of COVID-19 Disease

https://scholarworks.iupui.edu/bitstream/1805/22758/1/Jamil-2020-Diagnosis.pdf

Diagnosis and Management of COVID-19 Disease

Abstract

Similar works

Full text

Available Versions

IUPUIScholarWorks