Position Paper 

The Testing Debate for COVID-19: PCR vs. Rapid Antibody Test: How Rapid Antibody Testing can Identify Potential Immune Patients Quickly 

 

Rashid A. Chotani, MD, MPH, FRCPH, Chief Science Officer & VP Medical Affairs, Carelife Medical 

Syed S. Ashraf, MD, FHM, Chief Administrative Officer, Carelife Medical 

Fatima Aziz, MD, Senior Medical Director, Carelife Medical 

Terry Clark, MD, Executive VP & Chief Medical Officer, Boston Biopharma 

Charles Haviland Mize, MD, Bear/Badger Expeditionary and Retrieval Medicine 

 Knowledge and clarity empower rational action. The COVID-19 pandemic demands a powerful response, but the absence of a clear understanding of the virus has hamstrung governments' ability to act. The COVID-19 pandemic has now affected over 200 hundred countries and caused disease in over one million, resulting in close to 53,000 deaths. According to the Johns Hopkins Coronavirus Resource Center, United States has the largest number of cases (over 245,000) with close to 6,000 deaths and an epicenter of the disease in New York State (~ 93,000 cases and over 2,500 deaths). The quarantine, staying-home and social-distancing measures instituted throughout the states will help curb the epidemic. These measures are important and powerful tools to slow viral transmission. In of themselves, however, they do not help decision-makers determine the true extent and spread of the disease, nor how best to prepare to meet it. Rapid screening for disease is the cornerstone of curbing an outbreak, because such screening affords an understanding the epidemiology of the virus. Armed with this knowledge, public health policymakers are in a stronger position to more accurately assess and implement strategically meaningful interventions. 

 

The nation struggles with the question “To Test or Not” for COVID-19. Testing for SAR-CoV-2 in the US appears to be controversial. The concerns arise from a poor understanding of the testing process and the consequences test results may have on staffing and employment. Fundamentally, however, the implications of testing are far-reaching and concern more than the single individual and a single test. Widespread testing is what enables us to discern disease incidence and prevalence, and to determine who has recovered from infection and is now immune. The faster we can clear individuals from active disease state, the faster we can mitigate the socio-economic downturn and social disruption. In order to do so, we need the ability to clearly identity the following categories of patients: 

1. Exposed and now infected (at risk) 

2. Infected but asymptomatic (infectious to others) 

3. Infected and symptomatic (sick and infectious) 

4. Infected and recovered (developed immunity) 

Testing that can place patients into one of these categories will allow us to understand if someone is contagious (shedding virus) or non-contagious (not shedding virus). Furthermore, such testing will inform us if an individual has developed a certain level of immunity. 

Multiple testing modalities are being used or have recently been developed, to include RT-PCR for viral RNA and rapid antibody testing. Neither of these tests are perfect; alone can provide neither 100% sensitivity nor specificity. PCR tests for viral presence, which can vary between patients depending viral load and the patient’s degree of exposure. Variability in viral load as well as poor swab technique during testing can lead to false negatives. Administration of the test puts staff at risk because it requires removal of a patient’s mask and can cause the patient to sneeze or cough. Furthermore, recent studies have demonstrated that PCR, which has been considered the “Gold Standard,” has a high false negative rate, up to 30%. This false negative rate suggests that a third of covid-19 suspected individuals tested negative by PCR may continue to carry and transmit COVID-19 unaware of the risk they pose to others. Moreover, PCR testing requires special equipment and special training, and can provide results only days after testing. By contrast, serologic immunoassay via IgM/IgG is a simple point-of-care, cost-effective test using a finger-stick blood drop. It provides results within minutes and can be used to conduct serial monitoring of populace to see who has been exposed to COVID-19. Importantly, antibody testing allows clinical decision makers to determine who is now clear of active disease and can return to work. 

We have been using a rapid antibody IgM/IgG test by Boston Biopharma that has been FDA-approved for sale and is under evaluation for emergency use authorization like most rapid tests available currently. After consideration of the sensitivity/specificity of the PCR test, the inherent danger of spreading the virus during the nasal swabbing, and the test’s cost and inconsistent turnaround time, we believe that a rapid antibody test is the better tool to empower our public health. The antibody test for IgM and IgG detects the humoral response (in immuno-competent people) and exposure prevalence. Known immunologic graphs correlate IgM rise with symptom development in covid-19 patients (roughly ~4-7 days since exposure event) and, additionally, the IgM response may be present in asymptomatic patients. IgG indicates longer-term immune response. 

It is important to note that no test on its own can determine patient infectious status. To be effective, testing must be conducted within a clinical screening and evaluation process. Based on our experience, antibody testing is easier to administer, is a better point-of-care (POC) tool, and adds further critical information to that of RT-PCR alone. 

Disagreement over testing methodology stems from the evolving understanding of COVID-19 and the varying knowledge of virology by those crafting the public response. It is clear that a stay-home policy without a means to survey the US population and “clear” individuals of active disease state would be detrimental to the American economy and would create further social disruption and anxiety. This toll on staffing is especially important in the healthcare setting. The use of social distancing and isolation measures in democratic nations have yielded favorable outcomes and have been able to “flatten the curve.” However, the ability to identify individuals who are IgM (-) and IgG (+) is critical if we are to return to some normalcy and reassure labor force mobility. Table 1 describes the various scenarios and the potential outcomes. 

At present, there are no definitive nor specific therapeutic agents or vaccines, despite the tremendous commitment to their research and development. While we wait, the disease continues to cause significant morbidity and mortality. Antibody testing affords another benefit: the identification of patients who have recovered from the infection and who are able to provide their own antibodies to others in the form of convalescent plasma. During the 2014 Ebola outbreak, convalescent plasma was recommended as an empirical treatment, and a protocol for treatment of Middle East Respiratory Syndrome (MERS) coronavirus with convalescent plasma was established in 2015. Other studies for viruses such as SARS-CoV, H5N1 avian influenza, and H1N1 influenza suggest the effectiveness of transfusion of convalescent plasma. (1,2,3,4,5) A recent uncontrolled case series of 5 critically ill patients study published by Chenguang Shen et al in JAMA suggests that convalescent plasma transfusion may help in the treatment of critically-ill patients with COVID-19. While awaiting confirmation in randomized clinical trials, the approach continues to hold much promise. (6) 

Conclusion: 

Rapid POC antibody COVID-19 specific testing is the best means at our disposal to improve our epidemiologic understanding of the virus and to empower a robust public health response. The ability to determine immunity will enable us to safely restore our economy. This will further permit safe and cost-effective way to create a registry of immune individuals whereby enabling collection of convalescent plasma, a possible treatment for patients critically ill with COVID-19. 

Rashid A. Chotani, MD, MPH rashid@carelife.md | Office: 703-854-1298 | Mobile: 571-425-9730 

 

Boston Biopharma. March, 2020.

COVID-19 is spreading at a rapid pace throughout the United States and Western Europe. Fragmented strategies of banning travel, social distancing, and quarantine have provided little avail in slowing the steep upward trajectory of daily exponential growth rates. Waiting for a vaccine to become available or for the majority of the population to develop herd immunity, characterized by 70-80% infected and recovered, are the pivotal turning points we strive for in the fight against COVID-19. With positive cases dispersed geographically throughout the world, completely stopping the infection is highly improbable. Efforts to slow transmission in an attempt to prevent overwhelm of our healthcare systems is the primary plan of action for developed countries. 

 

Finding a balance between our current methodology of testing, performed in the laboratory and rapid tests capable of producing real time results in the field, will allow for a broad spectrum COVID-19 testing. Current testing takes a few hours to be completed per sample, but backlogs of tests has shifted time estimates for results to a few days following initial sample collection. Additionally, shortages in testing kits has resulted in a formalized symptom-driven guidance as to which patients can be tested. Test kits are being rationed for those presenting with acute respiratory distress, fever, and associated severe clinical sequeale. Testing only those exhibiting substantial symptoms not only negatively skews overall infection rates, but prevents classification of asymptomatic individuals capable of transmitting the virus to the surrounding population without detection. As a means of augmenting the bottleneck of testing required to support largescale population testing, BB has developed a rapid test kit available for use by clinicians and medical staff. 

 

Finding alternative testing options that allow for rapid and on the spot results can allow Physicians to implement broad spectrum testing to individuals both asymptomatic and those actively exhibiting symptoms associated with COVID-19. Rapid tests for SARS-CoV-2 specific IgM and IgG using immunohistochemistry via whole blood, plasma, or serum sample analysis are currently in development. This rapid testing platform can be implemented for screening at border crossings, and pop-up medical testing facilities in order to screen mass numbers of potentially infected individuals. 

 

BB COVID-19 test kits applied will assist in decreasing the total morbidity and mortality suffered by society in this global pandemic. Flattening the curve using rapid clinical testing side by side with the current standard laboratory test can help to shape a new reality of hope that we are all desperately searching for.