Buyers Guide

Testing for COVID-19

What is COVID-19 Testing and Why is it So Important?

The virus SARS-CoV-2 that causes COVID-19 is a new coronavirus that has spread to almost every country in the world, and the impact on the health and economies has already been devastating.  

 

Until there is a vaccine, the ability to test people for current or past infection will be central to economic and policy-making decisions for global health, safety, and financial recovery. 

 

Testing for the SARS-CoV-2, the virus that causes COVID-19 disease is important to achieve the following: 

  1. Determine who is currently infected as a basis for isolation and infection prevention and control procedures within and outside healthcare facilities
  2. Guide the clinical management of those with symptoms suggestive of COVID-19 
  3. Enable contact tracing 
  4. Build a more complete picture of the epidemic by understanding who has already been infected, transmission rates, and mortality rates  
  5. Understand more about disease severity
  6. Learn more about immunity 

Currently, the global testing demand exceeds capacity, which challenges the availability of timely and accurate results.   The global spread of COVID-19 has led to an enormous demand for expanding testing capabilities, shortages in molecular testing reagents.  Until accurate rapid tests are more widely available, there is still global reliance on testing that requires expensive and complex materials, equipment, and expertise, especially challenging in resource-constrained settings.

 

There are different types of tests that serve different functions and have unique advantages and disadvantages.  They all give a result based on a snapshot in time. Furthermore, testing for COVID-19 is a rapidly changing topic, and very dependent on the COVID-19 profile within the community, available laboratory resources, and local priorities.  Protocols for testing and development of new types of testing methodologies are changing, and local policies, guidelines, and resources will drive those priorities.  Additional information and resources can be found here: Foundation for Innovative New Diagnostics and World Health Organization.

Type of COVID-19 (SARS-CoV-2) Tests

Molecular
(PCR, RT-RNA, NAAT)
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Purpose:
  • Diagnose current infection by detecting genetic material from virus SARS-CoV-2 which causes COVID-19
Sample:
  • Nasal or throat swab
How it Work:
  • Series of chemical reactions to extract and copy genetic material, if there is no infection, there will be no genetic material to copy
Advantages:
  • Used to isolate and treat people with infection, and prevent further transmission through contact tracing.  Very accurate
Disadvantages:
  • Relies on expensive laboratory equipment, infrastructure, and skilled technicians. Susceptible to backlogs and slower time to result (hours to days).  A negative result does not mean there is immunity
Serologic (Antibody)
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Purpose:
  • Determines past or recent infection by detecting antibodies produced by immune system
Sample:
  • Blood draw
How it Work:
  • If immune system has produced antibodies, they will bind to the SARS-CoV-2 virus
Advantages:
  • Identifies people who might have immunity and give more information about the virus spread and impact
Disadvantages:
  • Because antibodies take time to produce, can miss very recent infection.  Still unclear how long immunity lasts
Antigen
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Purpose:
  • Diagnose current infection by detecting antigens, which are pieces of the virus that the immune system recognizes.  Newest type
Sample:
  • Nasal swab
How it Work:
  • Chemicals fragment SARS-CoV-2 and antibodies will attach to the antigen if present
Advantages:
  • Provides same information (diagnosis of current infection) as the Molecular (PCR) test but within minutes and does not need central laboratory
Disadvantages:
  • Would still need confirmation through molecular tests

For additional detail about COVID-19 tests read more here.

Key Considerations for Selecting COVID-19 Tests


Key Considerations When Selecting a Test

Selecting the appropriate COVID-19 test will be based on a number of factors, including the risks of COVID-19 in the community, available resources, and what information the healthcare workers and patients want to know.

  • Accuracy and validation. Sensitivity and Specificity are the two indices used to evaluate the accuracy of a test.  Sensitivity is the ability to detect SARS-CoV-2 in known positive samples.  Specificity is the ability to avoid falsely detecting SARS-CoV-2 in samples known to be negative. Validation studies are required to assess both.   Depending on the accuracy of the test, a confirmation laboratory test may be required.
  • What is “Proprietary” and What is Not. Nasopharyngeal swabs are the most common way to collect samples and do not need to be specific. RNA can be extracted from samples using any standard extraction protocols or kits. Transport medium are also generic. What is proprietary will be the cartridges, “test” kits, and reagents specific to the genetic sequence to be used.
  • Number of steps and complexity in laboratory testing. Molecular (PCR) testing specifically includes many steps and materials:  specimen collection materials, packaging materials, reagents, supplies, equipment and laboratory protocols. There is potential for error or contamination if the test is not run in a highly clean and controlled environment with carefully produced reagents and skilled technicians.
  • Safety procedures. Adequate standard operating procedures (SOPs) and sufficient staff training are necessary and all health care and laboratory workers should adhere to rigorously to infection prevention and control guidelines.
  • Availability of PCR Machines. Large PCR machines in centralized laboratories, and smaller ones that while expensive, are designed for rapid RT-PCR tests that can be conducted in small machines at point of care or near care. These include platforms from Abbott, one from ThermoFisher and another from Cepheid, called the GenXpert platform. These platforms are physical devices located in a laboratory that has to adhere to specific standards. The most common PCR platform in low- and middle-income countries (LMIC) is the GenXpert platform. GenXpert is commonly used for TB testing and HIV viral load testing.

More Information On Types of COVID-19 Tests: What They Do and How They Work

There are two different types of COVID-19 testing during this pandemic: Molecular and Serologic. Both types of tests are valuable, though they tell us slightly different things.  A third type, antigen test, is under development but not yet available in a sufficiently accurate, or scalable product. 

Molecular” (also known as RT-PCR, RNA, or “swab”) actually detects the virus so can tell who currently is infected, and is therefore diagnoses existing COVID-19. RT-PCR is a molecular diagnostic that detects the genetic viral material from a sample and is performed in a laboratory.   There are three main individual steps: an RNA extraction kit, a PCR assay mixture, and a polymerase chain reaction or PCR machine (also known as a “Thermal Cycler”) that runs the test to determine if a patient is positive or negative. These RT-PCR or “RNA” tests for COVID-19 are either manual or automated.  

 

Manual PCR Testing is when each step is done individually and is user-operated, and therefore requires a laboratory with skilled staff and adequate biosafety precautions and a “clean” room to prevent cross-contamination, etc.  These usually are done through the use of RNA “test kits” and require swabs and transport medium to protect the stability of the sample.  Advantages: This approach is currently considered the “Gold Standard” for diagnosing SARS-CoV-2, the virus that causes COVID-19 disease. There are lots of “test kits” that are available, typically they come with all the materials (except for swabs and transport medium) and can run on a variety of PCR machines, they often will designate which ones. Disadvantages: The laboratories with these PCR machines have specially trained staff and procedures to prevent contamination, and are often centralized or reference labs, so the excess demand on this capacity, as well as requirements for reagents, transport, and very specific “clean rooms” makes it challenging to do as many tests as are needed in a short turnaround time. They may also not be geographically convenient to where testing is needed.

Automated molecular assays (sometimes also called Point of Care or Near Point of Care NAT) mean that after the swab is collected, the whole process is done by a machine. These require the use of single use-disposable cartridges that hold the RT-PCR reagents and host the entire process. These cartridges contain everything that is needed (reagents etc) and therefore minimize cross-contamination between samples. Common platforms are Cepheid’s GeneXpert system, or Gene Xpress, Roche’s cobas 6800/8800 systems, Abbott’s m2000 RealTime system, and the BD MAX System. Advantages:  Simple, everything contained and automated with the cartridges; the smaller PCR Machines exist outside big lab settings and in lower level labs or facilities; they do already exist from Tuberculosis (TB) testing in many places but the cartridges have to be specific to COVID-19. Disadvantages:  Machines are still expensive, and the cartridges are still not widely available or affordable since they have to be proprietary to the PCR machine or “platform” on which they are being used.

Serologic (aka “Antibody/Antigen” or IgM/IgG) with blood sample from finger prick.  These tests detect the body’s immunological response to infection (antibodies) in a blood sample through a finger prick and do not diagnose current infection.  The presence of immunoglobulin M (IgM) antibodies indicate recent exposure to COVID-19, while the presence of immunoglobulin G (IgG) antibodies suggest later-stage infection. The rapid response serological tests typically use a technique called enzyme-linked immunological assay (ELISA). Advantages: These do not require special equipment to process the results, which allows them to be used in laboratories or at point-of-care and more useful for large-scale testing, as has been done for HIV and malaria.  Therefore, they are more “familiar” in LMICs as they are similar to “rapid tests.”  They are becoming increasingly available and are much less expensive.  Serologic “Antibody” tests are helpful if someone has been exposed through close contact, travel, or previous suspected infection. Disadvantages. These tests DO NOT tell us if someone is currently infected because antibodies are generated after infection, but they DO tell us who has been infected and who should be immune, though we don’t know how long immunity lasts.  They will likely need confirmation with PCR testing.  Although promising, many of these tests have not yet been validated and are pending regulatory approval.

Antigen Detection as a Rapid Diagnostic Test

One type of rapid diagnostic test (RDT) detects the presence of viral proteins (antigens) expressed by the COVID-19 virus, taken from a swab sample from the respiratory tract. If there is enough virus in the sample, the antigens will bind to specific antibodies fixed and produce a visual result, very quickly (under 30 minutes). The antigen(s) detected are expressed only when the virus is actively replicating; and will be useful to identify acute or early infection.   Although these may be faster than RT-PCR they may not be as sensitive and might miss the presence of COVID-19 and may therefore have to be confirmed with a PCR (molecular test).  Antigen tests are still in development and not yet widely available.

 

What Does a “Point of Care Test” Mean?

Point of Care Tests (Closer to Patients, less reliant on centralized laboratories) are intended to be used in non-laboratory settings, or closer to patients. Some of these might be molecular tests that can be used in more portable laboratories or community settings with smaller PCR machines, and others might be immunoassays or ELISA tests.  

 

What are “Rapid Diagnostic Tests (RDT)” for COVID-19?

The two types of “RDTs” for COVID-19, are “antibody” and “antigen” tests because they can produce results much more quickly than PCR tests.    One is the antibody test which only tell us about recent infection or antibody/immune response and would need confirmation tests.  The other is an antigen detection, which could be like a strip test, which are still not available.

VIA Global Health is committed to supporting health systems access affordable and appropriate medical products to improve the health in their communities. Products included in our Buyers Guides are available for purchase at VIA Global Health.

References and Acknowledgments

(1) World Health Organization, Laboratory Testing for COVID-19 Interim G

uidance. March, 2020. https://www.who.int/emergencies/diseases/novel-coronavirus-2019

(2) Foundation for Innovative New Diagnostics FIND. https://www.finddx.org/covid-19/pipeline/

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