Testing and Diagnosis

1. How to test for COVID-19?

2. Who to test for COVID-19?

3. Where to test for COVID-19?

How to Test for COVID-19?

The decision to test for COVID-19 is based on both clinical and epidemiological factors and an assessment of the likelihood of infection [1]
COVID-19 Specific Tests:
- RT-PCR
- Chest X-ray & CT scans
- Lung ultrasonography
RT-PCR:
- Specimens to be collected from symptomatic patients and contacts [1]:

RT-PCR (cont'd)
- An analysis of serial RT-PCR assays and CT scans demonstrated that 60-93% of patients had initial positive chest CT consistent with COVID-19 before the initial positive RT-PCR results. Further, 42% of patients showed improvement of follow-up chest CT scans beforeRT-PCR results turned negative [4]
- Thus, a single negative RT-PCR does not exclude COVID-19, especially If obtained via NP or early on in disease course, and the sensitivity may not be as good as CT scans for COVID-19 [6]
- COVID-19 RT-PCR is believed to have high specificity, but sensitivity may be as low as 60-70%; thus patients with pneumonia due to COVID-19 may have lung abnormalities on chest CT but a negative initial RT-PCR [5,7]
Chest X-ray (CXR) and CT scans
- Sensitivity of CXR (59%) is lower than CT scan (86%) [8]
- CT scanning on 15 healthcare workers exposed to COVID-19 before they became symptomatic revealed ground-glass opacification on 14/15 healthcare workers [9]
- CT scan abnormalities may appear even before symptoms [6]
Lung ultrasonography
- Can be used as a supplementary method to CT, but not replace CT [10]:
- Using ultrasound, COVID-19 foci are mainly observed in the posterior fields in both lungs, especially the posterior and inferior fields
- Ultrasound is superior to CT in showing smaller peripulmonary lesions and pleural and peripulmonary effusion; CT shows more clear and complete intrapulmonary and apical lesions than ultrasound

Who to Test for COVID-19?

This will vary from jurisdiction to jurisdiction based on public health recommendations. Notably, detection of other respiratory viruses does not rule out COVID-19; about 5% of patients with COVID-19 may be co-infected with other pathogens [3]
- Canada
  - Alberta
    - Testing will be prioritized for the following groups:
      - People who are hospitalized with respiratory illness
      - Residents of Continuing Care and other similar facilities
      - People who returned from travelling outside Canada between March 8 and March 12 (before the self-isolation protocols were in place)
      - Healthcare workers with respiratory symptoms
  - Sources & useful links:
  - British Columbia
    - Testing will be prioritized for the following groups:
      - Hospitalized, or likely to be hospitalized
      - Health Care Workers
      - Residents of long-term care facilities
      - Part of an investigation of a cluster or outbreak
    - Sources & useful links:
      - BC Centre for Disease Control: Testing
      - BC COVID-19 Support App & Self-Assessment Tool
  - Ontario
    - At this time, there are no criteria for testing and all specimens will be tested if submitted. However, where there are shortages of testing supplies, the following groups should be prioritized for testing to inform public health and clinical management of these individuals:
      - Symptomatic healthcare workers (regardless of care delivery setting) and staff who work in health care facilities
      - Symptomatic residents and staff in Long-Term Care facilities and retirement homes and other institutional settings e.g. homeless shelter (as per outbreak guidance)
      - Hospitalized patients admitted with respiratory symptoms (new or exacerbated)
      - Symptomatic members of remote, isolated, rural and/or indigenous communities
      - Symptomatic travellers identified at a point of entry to Canada
    - Sources & useful links:
      - COVID-19 Quick Reference Public Health Guidance on Testing and Clearance
      - Ontario Ministry of Health and Long-Term Care Guidance Documents (for: primary care providers in a community setting, acute care, home and community providers, long-term care, paramedic services, independent health facilities, labs, pharmacies, and occupational health and safety):
      - Ontario COVID-19 Self-Assessment Tool
      - Toronto COVID-19 Self-Assessment Tool (HRH, NYGH, SHSC)
- United Kingdom
  - Priorities for testing:
    - Prioritization
      - Group 1 (test first): patient requiring critical care for the management of pneumonia, acute respiratory distress syndrome (ARDS) or influenza-like illness (ILI)*, or an alternative indication of severe illness has been provided
      - Group 2: all other patients requiring admission to hospital** for management of pneumonia, ARDS, or ILI
      - Group 3: clusters of disease in residential or care settings (e.g. long-term care facilities and prisons)
        
        * ILI: fever 37.8°C
        
        **admission to hospital: a hospital practitioner has decided that admission to hospital is required with an expectation that the patient will need to stay at least one night.
  - Repeat Testing
    - If patient is producing sputum or is intubated, obtain samples from both lower respiratory tract and upper respiratory tract
    - If a suitable lower respiratory tract sample is negative, repeat tests are not needed
  - Step down testing
    - Priority testing for viral clearance should focus on:
      - Severely immunocompromised patients being stepped down to a setting where isolation is not possible
        (repeated, for example, at fortnightly intervals)
      - Patients being discharged to a residential or care facility
      - Patients who require multiple repeat healthcare admissions and attendances (such as those with ongoing cancer treatment)
  - Sources and useful links
- United States
  - CDC recommendation for priorities for testing [2]:
    - Patients with severe symptoms such as difficulty breathing should seek care immediately
    - Older adults and those with severe underlying chronic medical conditions (e.g. heart disease, lung disease, diabetes, etc.) are at higher risk for developing serious complications from COVID-19, should contact their physician early even if mild illness
    - Hospitalized patients who have signs and symptoms
    - Any individuals, including healthcare personnel, who have had close contact with a suspect or laboratory-confirmed COVID-19 patient within 14 days of symptom onset, or have a history of travel from affected geographic areas within 14 days of symptom onset
    - Mildly ill patients should be encouraged to stay at home and contact their healthcare provider via phone regarding clinical management
      - Clinicians are strongly encouraged to test for other causes of respiratory illness (e.g. influenza) [2]
  - New York
    - Testing for COVID-19 shall be authorized by a healthcare provider when:
      - An individual has come within proximate contact (same classroom, office, or gatherings) of another person known to be positive; or
      - An individual has traveled to a country that the CDC has issued a Level 2 or Level 3 Travel Health Notice, and shows symptoms of illness; or
      - An individual is quarantined (mandatory or precautionary) and has shown symptoms of COVID-19 illness; or
      - An individual is symptomatic and has not tested positive for any other infection; or
      - Other cases where the facts and circumstances warrant as determined by the treating clinician in consultation with state and local department of health officials.
    - Sources & useful links:
      - New York State COVID-19 Testing

Where to Test for COVID-19?

Alberta
- Zone Emergency Operation Centres (ZEOCs) have now been established in each zone. Clinics should contact their Primary Care Networks (PCNs) for guidance on how the response is being organized in their zone. PCNs are communicating regularly with the ZEOCs [11]
British Columbia
- A list of community collection centres can be downloaded from Provincial Health Services Authority Staff COVID-19 Testing
Ontario
- Ontario COVID-19 Assessment Centres (OMA EPR) (most updated source; will need OMA membership to access list of Assessment Centres)
- COVID-19 Assessment Centres in the Greater Toronto Area and Southern Ontario

References

(1). Laboratory testing for 2019 novel coronavirus (2019-nCoV) in suspected human cases (accessed Mar 19, 2020).

(2) CDC. Coronavirus Disease 2019 (COVID-19) (accessed Mar 18, 2020).

(3) Wang, M.; Wu, Q.; Xu, W.; Qiao, B.; Wang, J.; Zheng, H.; Jiang, S.; Mei, J.; Wu, Z.; Deng, Y.; Zhou, F.; Wu, W.; Zhang, Y.; Lv, Z.; Huang, J.; Guo, X.; Feng, L.; Xia, Z.; Li, D.; Xu, Z.; Liu, T.; Zhang, P.; Tong, Y.; Li, Y. Clinical Diagnosis of 8274 Samples with 2019-Novel Coronavirus in Wuhan. medRxiv 2020, 2020.02.12.20022327.

(4) Ai, T.; Yang, Z.; Hou, H.; Zhan, C.; Chen, C.; Lv, W.; Tao, Q.; Sun, Z.; Xia, L. Correlation of Chest CT and RT-PCR Testing in Coronavirus Disease 2019 (COVID-19) in China: A Report of 1014 Cases. Radiology 2020, 200642.

(5) Kanne, J. P.; Little, B. P.; Chung, J. H.; Elicker, B. M.; Ketai, L. H. Essentials for Radiologists on COVID-19: An Update—Radiology Scientific Expert Panel. Radiology 2020, 200527.

(6) COVID-19. EMCrit Project.

(7) Fang, Y.; Zhang, H.; Xie, J.; Lin, M.; Ying, L.; Pang, P.; Ji, W. Sensitivity of Chest CT for COVID-19: Comparison to RT-PCR. Radiology 2020, 200432.

(8) Guan, W.; Ni, Z.; Hu, Y.; Liang, W.; Ou, C.; He, J.; Liu, L.; Shan, H.; Lei, C.; Hui, D. S. C.; Du, B.; Li, L.; Zeng, G.; Yuen, K.-Y.; Chen, R.; Tang, C.; Wang, T.; Chen, P.; Xiang, J.; Li, S.; Wang, J.; Liang, Z.; Peng, Y.; Wei, L.; Liu, Y.; Hu, Y.; Peng, P.; Wang, J.; Liu, J.; Chen, Z.; Li, G.; Zheng, Z.; Qiu, S.; Luo, J.; Ye, C.; Zhu, S.; Zhong, N. Clinical Characteristics of Coronavirus Disease 2019 in China. N. Engl. J. Med. 2020, 0 (0), null.

(9) Shi, H.; Han, X.; Jiang, N.; Cao, Y.; Alwalid, O.; Gu, J.; Fan, Y.; Zheng, C. Radiological Findings from 81 Patients with COVID-19 Pneumonia in Wuhan, China: A Descriptive Study. Lancet Infect. Dis. 2020.

(10) Huang, Y.; Wang, S.; Liu, Y.; Zhang, Y.; Zheng, C.; Zheng, Y.; Zhang, C.; Min, W.; Zhou, H.; Yu, M.; Hu, M. A Preliminary Study on the Ultrasonic Manifestations of Peripulmonary Lesions of Non-Critical Novel Coronavirus Pneumonia (COVID-19); SSRN Scholarly Paper ID 3544750; Social Science Research Network: Rochester, NY, 2020. https://doi.org/10.2139/ssrn.3544750.

(11) AHS. COVID-19 Frequently Asked Questions for Primary Care. https://www.albertahealthservices.ca/assets/info/ppih/if-ppih-covid-19-primary-care-faq.pdf (accessed April 2, 2020).