The COVID-19 Saga: Diagnostics and the Test Kit Dilemma

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INTRODUCTION: The War against COVID 19 continues. We will now be talking about its detection and Diagnosis, a Quick Summary: 

The standard diagnostic measure is by reverse transcription polymerase chain reaction (rRT-PCR) from a nasopharyngeal or throat swab. Without this, a combination of symptoms, risk factors and chest CT scan findings showing features of Pneumonia provides a likely candidate for COVID19 infection. 

DIAGNOSTICS

The WHO has published several protocols for the disease. The standard method of testing is rRT-PCR, and can be done on respiratory samples obtained through nasopharyngeal swab or sputum sample. Results are generally available within a few hours to two days. Blood test can be used but require two blood samples taken two weeks apart, which makes the test having little immediate value. Zhongnan Hospital of Wuhan University realeased diagnostic guidelines based on clinical features and epidemiological risk involving identifying people with two of the following symptoms in addition to a history of travel to Wuhan or contact with infected people: fever, imaging features of pneumonia, normal or reduced white blood cell count, or reduced lymphocyte count.

Hong Kong has set up a scheme where suspected patients can stay at home and given a specimen tube that they can spit on and send back. They can then get the test results after awhile. The British NHS has announced that it will start testing suspected cases at home, which removes the risk of a patient infecting others if they come to a hospital or having to disinfect an ambulance if one is used. In South Korea there are drive-through centers for testing, making them the fastest most extensive in testing people in any country.

China and US had problems with reliability early on in the outbreak. Along with Australia, these countries were unable to supply enough kits as recommended by Health experts, in contrast to South Korea’s broad availability that helped reduce the spread of the virus.
A timeline of Test Kits produced by global companies.

One of the early tests was developed in Berlin in January, which formed the basis of the 250 000 kits distributed by WHO.

On January 28, South Korean company Kogenebiotech developed a PCR based test kit named PowerChek, which looks for the “E” gene shared by all betacoronavirus and the RdRp gene specific to SARS-CoV-2. Solgent and Seegene developed test kits named DiaPlexQ and Allplex, respectively in February. In the US, the CDC is distributing the (2019-nCoV) Real-Time RT-PCR Diagnostic Panel to public health labs through the International Reagent Resource. As of March 5, LabCorp announced nationwide availability of COVID-19 testing based on RT-PCR, and as of March 9, Quest Diagnostics similarly made nationwide COVID-19 testing available

On March 12, Mayo Clinic was reported to have developed a test kit and on March 13, Roche Diagnostics received FDA approval for a test which could be performed within 3.5 hours, thus allowing one machine to do approximately 4,128 tests in a 24-hour period.

Immunoassays

As of 26th of February 2020, there were no antibody tests though efforts of developing them are ongoing.

On 28 February, South Korean company PCL filed a request to the MFDS of South Korea for their antibody detection kit, COVID-19 Ag GICA Rapid that claims to make a diagnosis within 10 minutes.

On 8 March, Taiwan’s Academia Sinica announced that they have generated a monoclonal antibody that specifically binds to the N protein of SARS CoV 2, and further developing this into a test kit would yield tests as fast as 15 to 20 minutes.

In USA, Biomedics in North Carolina developed a rapid antibody test that detects IgM and IgG antibodies using blood drawn from veins / finger pricks that could get test results in 15 minutes. They are waiting for FDA approval.

(Left) Typical CT manifestation. A case of a 38-year-old male with fever, dry cough, shortness of breath for 3 days.
(Right)  CT imaging of rapid progression stage. A case of a 50 years old female with anorexia, fatigue, muscle soreness, nasal congestion and runny nose for 1 week, sore and itching throat for 2 days.
(Left) Typical CT manifestation. A case of a 38-year-old male with fever, dry cough, shortness of breath for 3 days.
(Right) CT imaging of rapid progression stage. A case of a 50 years old female with anorexia, fatigue, muscle soreness, nasal congestion and runny nose for 1 week, sore and itching throat for 2 days.

To help identify and characterize lung pathology, a Chest CT scan may be used. Systemic review of the Chest CT findings in 919 patients described the typical early manifestation of COVID19 as “Bilateral multilobular ground glass opacification with peripheral or posterior distribution”. These findings were either patchy or diffuse, with subpleural dominance, crazy pavings and in later stages, consolidation.

Initially, the lesions are confined to one lung, but as the disease progresses, it manifest in both lungs.

These findings however are non-specific, and are also found in other types of pneumonia. A study by Chinese radiologists demonstrated 72-94% sensitivity and 24-94% specificity in differentiating COVID19 from other types of viral pneumonia through CT imaging and claimed the most discriminating features are peripheral distribution, ground glass opacity and vascular thickening.  Based on this study it can be concluded that chest CT had a high sensitivity but moderate specificity for COVID19. A correlation study found that CT scan’s sensitivity was greater at 98% compared to RT-PCR at 71% but this study is limited to Wuhan China, therefore is not generalizable.

Recent studies have now determined that second generation RT-PCR has successfully overcome the accuracy problem making CT scans for COVID19 not a standard test, with the CDC saying CT is not an initial screening test. But patients with Cough and shortness of breath will routinely have Chest Radiology and may have a CT scans, thus these records are still clinically useful.

THE LOCAL TEST KIT DILEMMA

As of this writing, the Philippines has 307 confirmed cases of COVID-19 [Editor’s Note: 380 as of last count], with 19 deaths and 13 recoveries.

With a population of 100 million, the country initially had only 2,000 test kits. The limited number of testing kits is surely a cause of alarm, limiting our ability to test more people for the virus. Scarcity of test kits have forced health officials to prioritize people with symptoms and/or those who have a history of exposure especially those who travelled from endemic countries. But developing reports have netizens clamoring on this statement as state officials and their families have been undergoing tests despite being asymptomatic and the limited availability of the said kits.

The DOH remains optimistic that the country will have enough test kits as it deals with the rapidly rising cases (not to mention the huge possibility of thousands of undocumented cases) of COVID 19. While foreign aid is coming, and DOH Secretary Francisco Duque III acknowledged that “Slowly, we are acquiring the capability to test many people,”. I personally think it’s hardly reassuring when the cases are “rapidly rising”

As of this writing, the country is currently waiting for the arrival of more test kits from South Korea (those from China have arrived) and the results of the field testing of the locally made UP-NIH test kits. The Food and Drug Administration (FDA) reiterates that there are no registered COVID-19 diagnostic test kits available to the public because no company has complied with the minimum set of requirements.

The only COVID-19 diagnostic test kits used now are PCR based lab kits at the Research Institute of Tropical Medicine (RITM) donated by WHO; and the University of the Philippines National Institutes of Health (UP NIH) and Department of Science and Technology (DOST) developed test kit.

With the scarcity of test kits, the public is currently in distress. We urge the citizens not to indulge on counterfeit test kits being sold online by people who are taking advantage of the pandemic. Test kits are handled by licensed professionals.

With this in mind, it’s better to heighten vigilance as there is no conclusive way for now to diagnose COVID19 outside of confirmatory tests but signs and symptoms. 

REFERENCES:

  1. DIAGNOSTICS

a. Hong Kong Tests.

“In Age of COVID-19, Hong Kong Innovates To Test And Quarantine Thousands”. NPR.org.

b. South Korean Drive Through Tests”South Korea’s Drive-Through Testing For Coronavirus Is Fast — And Free”. npr. 11 March 2020.

c. WHO and CDC 
2. A timeline of Test Kits produced by global companies

a. Korean Test KitsJeong, Sei-im (28 February 2020). “Korea approves 2 more COVID-19 detection kits for urgent use – Korea Biomedical Review”. www.koreabiomed.com (in Korean). 

b. Chinese test Kits

“BGI Sequencer, Coronavirus Molecular Assays Granted Emergency Use Approval in China”. GenomeWeb.

c. CDC test kits and Mayo Clinic Test kit references from CDC and Mayo Clinic websites respectively.

3. Immunoassays  

“Development and Clinical Application of a Rapid IgM-IgG Combined Antibody Test for SARS-CoV-2 Infection Diagnosis”. Journal of Medical Virology.

4. Chest CT scan

a. PHOTOS and Guidelines

A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version) Jin, Y., Cai, L., Cheng, Z. et al.https://mmrjournal.biomedcentral.com/articles/10.1186/s40779-020-0233-6

b. Sensitivity and Specificity of CT Scan”CT provides best diagnosis for COVID-19Science Daily. 26 February 2020.
c. CT scan Findings

Salehi, Sana; Abedi, Aidin; Balakrishnan, Sudheer; Gholamrezanezhad, Ali (14 March 2020). “Coronavirus Disease 2019 (COVID-19): A Systematic Review of Imaging Findings in 919 Patients”. American Journal of Roentgenology: 1–7.

Lee, Elaine Y. P.; Ng, Ming-Yen; Khong, Pek-Lan (24 February 2020). “COVID-19 pneumonia: what has CT taught us?”. The Lancet Infectious Diseases

5. THE LOCAL TEST KIT DILEMMA

a. Phils have only 2000 test kitshttps://www.bloomberg.com/news/articles/2020-03-10/philippines-has-just-2-000-virus-testing-kits-as-cases-rise

b. Thousands of Coronavirus Test Kits coming From South Korea and China

https://www.rappler.com/nation/254793-coronavirus-test-kits-coming-south-korea-china-march-2020

c. FDA clarifies that there is no test kits released for Public use https://www.fda.gov.ph/fda-clarifies-availabilty-of-covid-19-test-kits-in-the-country/

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