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COVID-19: Who to Test and When? CME / ABIM MOC / CE

CME Author: Shanthi Voorn, PhD

Posted: 4/2/2020
Note: This is the twelfth of a series of clinical briefs on the coronavirus outbreak. The information on this subject is continually
evolving. The content within this activity serves as a historical reference to the information that was available at the time of this
publication. We continue to add to the collection of activities on this subject as new information becomes available.

Clinical Context
As the world watches the number of confirmed cases of COVID-19 increase exponentially in both number and geographical
reach, healthcare professionals are faced with an anticipated strain on the healthcare system. Not since the 1918 Influenza A
virus (H1N1) pandemic have we been faced with a global healthcare crisis on this scale. SARS-CoV-2 is a novel strain of
coronavirus that emerged from the Wuhan province in China and has escalated to a staggering number of cases and deaths in a
matter of months. The situation has been evolving on a daily basis, with about 200 countries affected.[1]

As of March 11, 2020, WHO Director-General Tedros Adhanom Ghebreyesus declared COVID-19 a pandemic,[2] and many
countries have taken precautionary measures by restricting travel, closing schools, and canceling large events. Everyday life has
changed for many people across the globe, with 'social or physical distancing' becoming requisite in order to prevent transmission
of the virus.

There have been tremendous efforts globally to limit the spread of disease. By slowing the pace at which the virus spreads, we
are buying time for the healthcare system to implement the necessary measures to handle an influx of severe COVID-19
infections. By using our knowledge of other well-characterized, highly contagious viral diseases, such as influenza, we can get a
better understanding of how to prepare for a pandemic.[3]

Synopsis and Perspective

Influenza and SARS-CoV-2 are different viruses, resulting in different diseases, but both have the potential for pandemic
proportions. The figure below, which has been popularized in social media, shows how to mitigate the spread of a pandemic with
or without intervention. These interventions include nonpharmaceutical measures such as social distancing and quarantine.
During this initial period of outbreak, diagnosis and surveillance are imperative as a means to control the disease.

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Figure 1. Goals of community mitigation for pandemic influenza adapted from CDC.[4]

Who to Test?

Symptoms

The WHO Joint Mission has reported comprehensive results according to 55,924 laboratory confirmed cases, as shown in Table
1.

Table 1. WHO-China Joint Mission Report of COVID-19 Symptoms

Symptom Percentage

Fever 87.9%

Dry cough 67.7%

Fatigue 38.1%

Sputum production 33.4%

Shortness of breath 18.6%

Sore throat 13.9%

Headache 13.6%

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Myalgia or arthralgia 14.8%

Chills 11.4%

Nausea or vomiting 5.0%

Diarrhea 3.7%

Hemoptysis 0.9%

Conjunctival congestion 0.8%

WHO.[5]

These symptoms are nonspecific and can range from asymptomatic, mild, moderate, to severe. On average, symptoms appear 5
to 6 days after infection, with an incubation period range of 1 to 14 days. People age 60 years and older with underlying
conditions such as hypertension, diabetes, cardiovascular disease, chronic respiratory disease, and cancer are at highest risk for
severe disease and death.[5] Other signs and symptoms are trouble breathing, persistent pain or pressure in the chest, new
confusion or inability to arouse, and bluish lips or face. More recently, there has been anecdotal evidence from several countries
that report anosmia, hyposmia, and dysgeusia as symptoms of COVID-19. The American Academy of Otolaryngology-Head and
Neck Surgery has recently stated that these symptoms should also be added as screening tools for COVID-19 cases.[6]

Criteria for Testing

Criteria for testing differ from country to country, and they may not be standardized. The WHO has provided guidance for
surveillance and laboratory testing, and the case definitions are listed below.

Table 2. WHO Case Definitions for Surveillance

A patient with acute respiratory illness that includes fever and at least one sign/symptom of
respiratory disease (e.g., cough, shortness of breath), AND with no other etiology that fully
explains the clinical presentation AND a history of travel to or residence in a country/area or
territory reporting local transmission of COVID-19 disease during the 14 days prior to symptom
Suspected onset
case A patient with any acute respiratory illness AND who has been a contact of a confirmed or
probable case COVID-19 disease in the last 14 days prior to onset of symptoms
A patient with severe acute respiratory infection (fever and at least one sign/symptom of
respiratory disease [e.g., cough, shortness of breath]) AND who requires hospitalization AND who
has no other etiology that fully explains the clinical presentation

Probable
case A suspect case for whom testing for COVID-19 is inconclusive

Confirmed A person with laboratory confirmation of COVID-19 infection, irrespective of clinical signs and
case symptoms

WHO.[7]

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As the disease spreads, the criteria for testing, diagnostic procedures, and surveillance practices may change, therefore it is
important to keep up to date with local epidemiology and regional or national health authority recommendations. Some criteria
may be more important, depending on the situation. For example, travel history is crucial in the first few cases within a
community; however, as the virus spreads, the value of the travel history becomes more limited.

A majority of cases are mild, and the recovery rate is high; therefore, many cases are recommended home isolation to minimize
the risk for spread. In the event of home isolation, it may be difficult to issue a test; however, in the beginning stages of disease
outbreak, such data is useful for understanding transmission and the development of robust guidelines. Healthcare professionals
who are in contact with suspected cases should follow local health authority guidelines regarding specimen collection.

Diagnosis

Diagnosis and surveillance procedures will also differ from country to country, and this will depend on the healthcare authority and
available resources. The WHO has provided guidance for testing SARS-CoV-2. Molecular assays for the detection of SARS-CoV-
2 have several protocols, and these are listed on the WHO website.[8] Countries that have no testing capacity can send
specimens to one of the WHO reference laboratories where the tests are processed.

Currently the focus is on nucleic acid testing to confirm the presence of the virus as efficiently as possible. Nucleic acid
amplification tests, such as real-time reverse transcriptase-polymerase chain reaction (rRT-PCR), can detect unique sequences
of viral RNA.[8] rRT-PCR tests that commercial manufacturers are distributing to state and local public health departments and
states turnaround is between 4 and 6 hours.[9] It is important to note that these tests confirm the presence of viral RNA and not a
live infectious virus.

As these diagnostic tests are new and were developed rapidly, validated test performance evaluation is needed. The evaluation of
these tests would assess sensitivity and specificity and provide reassurance against false negatives.[10]

In order to make more tests available, the FDA issued emergency authorization for use of many point-of-care (POC) SARS-CoV-2
diagnostic tests.[11] These tests have become commercially available and are meant to significantly shorten the wait time for
access to testing and results. Results from POC tests can help to accelerate clinical decision making and are needed on the front
line of medical care; however, it is important to consider the sensitivity and specificity of these new rapid diagnostic tests.

Serologic testing is also needed to further understand the true scope of disease severity.[10] Serology tests can confirm the
presence of SARS-CoV-2 antibodies, which indicate an immune response after an infection. Having a serology test would
improve the sensitivity and accuracy of a test if used in conjunction with nucleic acid testing. For example, in cases where nucleic
acid testing is negative, a serology test can support a diagnosis.

Surveillance

Healthcare infrastructure will be significantly affected as the number of infected individuals continues to rise. Surveillance
strategies will depend on how quickly and efficiently mass sample testing can be deployed. In the United States, the CDC has
centralized diagnostic testing by using standardized test kits that are sent back to the CDC for processing.[12] If there is a
shortage of test kits or reagents, and laboratory testing capacity is strained, some cases may remain undiagnosed and unaware
of their status.

COVID-19 is highly infective and can spread from human to human in early disease onset, without the presence of symptoms. In
the case of the severe acute respiratory syndrome (SARS) epidemic in 2002, transmission rarely occurred in asymptomatic
patients. This feature allowed for disease containment and the subsequent eradication of disease. In the case of COVID-19, it is
evident that interrupting transmission is a significant challenge.

Currently, most countries are employing reactive surveillance according to the presence of symptoms. In South Korea, in
response to the growing number of confirmed cases, 'drive-through' testing facilities have been launched. Individuals are tested
inside their car, in a procedure that takes a few minutes, and negative result notification is sent via text message. COVID-19--
positive individuals are contacted and directed for treatment.[13,14] This approach to identify and treat patients with COVID-19 has
led to the successful mitigation of disease spread and a reduction in the death rate.

The rate of COVID-19 spread is modifiable, which has been shown by the status of confirmed cases in different countries. A
concerted effort from both the public and public health authorities is needed for the management of outbreaks. Diagnosis and
surveillance are the crucial steps required to lessen the impact on our healthcare systems.

Highlights

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As the disease spreads, the criteria for testing, diagnostic procedures, and surveillance practices may change; therefore it
is important to keep up to date with local epidemiology and regional or national health authority recommendations. Some
criteria may be more important, depending on the situation. For example, travel history is crucial in the first few cases
within a community; however, as the virus spreads, the value of the travel history becomes more limited.
Nucleic acid amplification tests, such as rRT-PCR, can detect unique sequences of viral RNA. It is important to note that
these tests confirm the presence of viral RNA and not a live infectious virus.
As these diagnostic tests are new and were developed rapidly, validated test performance evaluation is needed. The
evaluation of these tests would assess sensitivity and specificity and provide reassurance against false negatives.
Serologic testing is also needed to further understand the true scope of disease severity.
The approach employed with SARS-CoV-2 in China and South Korea to proactively identify and treat patients with COVID-
19 has led to the successful mitigation of disease spread and a reduction in the death rate.

Clinical Implications

The WHO has provided case definitions for patients with suspected, probable, or confirmed cases of COVID-19.
Nucleic acid amplification tests, such as rRT-PCR, can detect unique sequences of viral RNA. It is important to note that
these tests confirm the presence of viral RNA and not a live infectious virus.
Clinicians should identify key actions to enhance preparedness for patients potentially infected with COVID-9, which
includes appropriate diagnosis and testing.

Earn Credit

PDF Download Translations

COVID-19: chi sottoporre al test e quando?

COVID-19: ¿A quién realizarle las pruebas y cuándo?

COVID-19 : qui tester et à quel moment ?

COVID-19: em quem e quando realizar o teste?

References

1. Coronavirus disease 2019 (COVID-19): Situation report -- 66. World Health Organization (WHO) website.
https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200326-sitrep-66-covid-19.pdf?
sfvrsn=9e5b8b48_2. Published March 26, 2020. Accessed March 27, 2020.
2. WHO Director-General's opening remarks at the media briefing on COVID-19 - 11 March 2020. World Health Organization
(WHO) website. https://www.who.int/dg/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-
covid-19---11-march-2020. Published March 11, 2020. Accessed March 26, 2020.
3. Qualls N, Levitt A, Kanade N, et al; CDC Community Mitigation Guidelines Work Group. Community mitigation guidelines
to prevent pandemic influenza -- United States, 2017. MMWR Recomm Rep. 2017;66:1-34.
https://www.cdc.gov/mmwr/volumes/66/rr/rr6601a1.htm. Accessed March 26, 2020. Article full text.
4. Centers for Disease Control and Prevention (CDC). Interim pre-pandemic planning guidance: community strategy for
pandemic influenza mitigation in the United States— early, targeted, layered use of nonpharmaceutical interventions.
https://www.cdc.gov/flu/pandemic-resources/pdf/community_mitigation-sm.pdf. Published February 2007. Accessed March
26, 2020.
5. World Health Organization (WHO). Report of the WHO-China Joint Mission on coronavirus disease 2019 (COVID-19).
https://www.who.int/docs/default-source/coronaviruse/who-china-joint-mission-on-covid-19-final-report.pdf. Published
February 16-24, 2020. Accessed March 12, 2020.
6. Anosmia, hyposmia, and dysgeusia symptoms of coronavirus disease. American Academy of Otolaryngology-Head and
Neck Surgery (AAO-HNS) website. https://www.entnet.org/content/aao-hns-anosmia-hyposmia-and-dysgeusia-symptoms-
coronavirus-disease. Published March 22, 2020. Accessed March 23, 2020.
7. Global surveillance for COVID-19 disease caused by human infection with the 2019 novel coronavirus. World Health
Organization (WHO) website. https://www.who.int/publications-detail/global-surveillance-for-human-infection-with-novel-
coronavirus-(2019-ncov). Published February 27, 2020. Accessed March 13, 2020.
8. Laboratory testing for 2019 novel coronavirus (2019-nCoV) in suspected human cases. World Health Organization (WHO)
website. https://www.who.int/publications-detail/laboratory-testing-for-2019-novel-coronavirus-in-suspected-human-cases-
20200117. Published March 19, 2020. Accessed March 13, 2020.
9. Centers for Disease Control and Prevention (CDC). Testing for COVID-19. https://www.cdc.gov/coronavirus/2019-
ncov/symptoms-testing/testing.html. Published March 21, 2020. Accessed March 27, 2020.

https://www.medscape.org/viewarticle/927860_print 5/6
04/05/2020 https://www.medscape.org/viewarticle/927860_print

10. Wang P, Anderson N, Pan Y, et al. The SARS-CoV-2 outbreak: diagnosis, infection prevention, and public perception. Clin
Chem. Published online March 10. https://academic.oup.com/clinchem/advance-
article/doi/10.1093/clinchem/hvaa080/5802466. Accessed March 26, 2020.
11. Emergency Use Authorization: Emergency Use Authorization (EUA) information, and list of all current EUAs. Silver Spring,
MD: US Food and Drug Administration (FDA); https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-
regulatory-and-policy-framework/emergency-use-authorization#2019-ncov. Accessed March 29, 2020.
12. Coronavirus disease 2019 (COVID-19): FAQ for diagnostic tools and virus. Centers for Disease Control and Prevention
(CDC) website. https://www.cdc.gov/coronavirus/2019-ncov/lab/tool-virus-requests.html. Last reviewed March 6, 2020.
Accessed March 13, 2020.
13. Shin H. South Korean launches 'drive-thru' coronavirus testing facilities as demand soars. Reuters.
https://www.reuters.com/article/us-china-health-southkorea-test/south-korea-launches-drive-thru-coronavirus-testing-
facilities-as-demand-soars-idUSKCN20L1Q5, Published February 27, 2020. Accessed March 26, 2020.
14. Kwon KT, Ko JH, Shin H, et al. Drive-Through Screening Center for COVID-19: a Safe and Efficient Screening System
against Massive Community Outbreak. J Korean Med Sci. 2020;35:e123. https://jkms.org/DOIx.php?
id=10.3346/jkms.2020.35.e123. Accessed March 27, 2020. Article full text.

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