As physician office customers begin undertaking diagnosis and care of COVID-19 patients, there are a lot of questions they’ll need help answering.
By Jim Poggi
As the 2020/2021 respiratory season unfolds, we have a very different environment from prior seasons. We have a new respiratory pathogen, SARS CoV-2. In addition to being new, it occurred off cycle from typical respiratory season pathogens. It is also far more contagious than influenza, group A strep and RSV. As of November, 2020, it has created a worldwide pandemic, with over 54 million infections and 1.3 million deaths worldwide. In the United States, we have experienced 11 million cases and 246,000 deaths as of press time. And its severity is less predictable on the individual patient than influenza and other well-known respiratory pathogens.
The current pandemic has had a dramatic negative impact on economies around the world. Preventive measures including avoidance of social settings has had an unexpected impact on emotional health and well-being related to isolation and lack of typical social contact. As a result, the pressure on prevention, diagnosis and treatment has reached unprecedented levels. In this article we will focus on lab diagnosis.
Testing for the virus has changed the face of respiratory testing in fundamental ways. In the early days of the pandemic, many physician practices closed to help blunt the spread of the disease. In addition, the first diagnostic tests for SARS CoV-2 used RT-PCR technology, which is technically complex and not widely available in physician office laboratories. So, for most of the first eight months of the pandemic, physician practices were not highly involved in diagnosis or patient care. Hospitals and new testing sites such as “drive through” testing locations performed most of the early testing. The emphasis on safety and reducing the spread of COVID-19 has had a far greater impact on testing sites than any respiratory disease in recent years. Traditional physician office testing is just beginning to become more widespread based on availability of easier to use and more familiar antigen diagnostic tests from well-established lab manufacturers.
As our physician office customers begin undertaking diagnosis and care of COVID-19 patients, there are a lot of questions coming your way. This information, along with ongoing communication with your key respiratory test kit manufacturers is intended to help you answer some of those questions and enhance your value as a consultant to our customers.
Which tests are out there and what is their primary use?
For past respiratory seasons, while we have had visually read lateral flow tests, followed by reader based lateral flow tests and more recently molecular tests for influenza, strep and RSV, we always had diagnostic tests. We did not have tests specifically intended to detect antibodies in patients with previous infections. For COVID-19, both diagnostic and antibody tests are important and for different reasons. Diagnostic tests fulfill their traditional purpose: to inform the caregiver whether the patient is currently infected. The new antibody tests are used by public health and large healthcare systems to determine the spread and prevalence of the infection in our communities and country as a whole. The range of test types, testing technologies and intended use of these tests has increased rapidly this year. There are more than 200 total tests approved under Emergency Use Authorization as of November, 2020 and the list is growing daily. As noted in a previous column, we have never seen as many sample types with nasal and nasopharyngeal swabs used, along with whole and capillary blood, saliva and stool samples.
| Test Methodology | Detects? | Used for | Sensitivity | Specificity | Test format | Applicability in POL? |
| RT-PCR | The RNA of the virus | Diagnosis of COVID-19 infection | High | High | Instrument/reagent | Limited |
| Antigen Tests | Viral antigens | Diagnosis of COVID-19 infection | Moderate | High | Reader/reagent ELISA/reagent | High |
| Antibody Tests | Antibodies produced as a result of a previous infection | Determination of community spread; population prevalence of the disease | Moderate; varies by antibody | Moderate; varies by antibody | Instrument/reagent Reader/reagent Lateral flow visual read | Moderate/high |
Understanding test performance and its relationship with disease prevalence
There is new emphasis being placed on understanding how well the new COVID-19 tests are preforming. The reasons include the proliferation on new suppliers and tests as well as the use of Emergency Use Authorizations in place of the more rigorous 510(k) process. Given the speed of spread of COVID-19 and the large range of new test types, there has been insufficient time and effort devoted to comparisons of tests within each type of testing technology. As a result, there’s a good deal of confusion about how well tests are diagnosing COVID-19 in general, as well as the inherent performance of specific tests. The data is just being generated, and there are a number of claims of both false negative and false positive tests being reported in the press and peer reviewed literature. It’s clear that we are just beginning to understand how well current tests are performing. Manufacturers are stepping up to the plate to provide far more data in the instructions for use for these tests, including limits of detection and performance expectations related to disease prevalence. This more comprehensive data set is likely to filter into IFU documents for other infectious disease tests as well and provide better guidance than previously available.
Your manufacturer rep and the data their company provides is the best, most complete and accurate source of this information. With concerns about quality of test results high and questions about “which test types and manufacturers provide best results?”, your customers are sure to ask you for advice and help. Here is some quick, simple to understand guidance:
Sensitivity and specificity are inherent elements of the specific test and are not impacted by disease prevalence. Positive predictive and negative predictive values, on the other hand, are dependent on disease prevalence and as a result, when disease prevalence is high, positive predictive value (true positives) is high and false negatives are low. When disease prevalence is low, positive predictive value drops and false negatives are observed. High sensitivity fosters improved true positives and rises with increased levels of prevalence. High specificity helps reduce false positives and improves with increased levels of prevalence. The perfect assay would be close to 100% for both; with lower incidence diseases, specificity is the more important measure.
You and your key respiratory test kit manufacturers have the most daunting challenges yet this respiratory season. You need to balance test performance, ease of use, availability of instruments and reagents and provide sound consultative advice to physician practices needing to provide a safe, patient friendly and effective program for diagnosis and treatment of COVID-19. We are all counting on you.