Geno Leser MT(ASCP), MLS Specialist (SBB, SC, SH, SM, SCT, SLS)
As laboratorians we find ourselves in an unparalleled and historic situation in the laboratory. Never before had the modern world experienced a pandemic of this particularly insidious nature and magnitude, nor had the world's research and clinical labs had such powerful and effective tools to diagnose, prognose, and aid in treatment.
At a recent conference at a Central Indiana Diagnostics facility (Burnham et al), national experts discussed the basics of lifecycle measurement of the virus and their impact on vaccines. We ended up with some very satisfactory answers on one hand and some big question marks on the other for our profession including our interaction with other health care professions and our ability to serve the public.
Once the severity of the pandemic became obvious, the best-equipped research and development companies all over the world began the process of developing direct viral testing, rapid PCR testing, and immunoassay testing. The results of this response are familiar in clinical laboratories throughout the United States and around the world. The laboratory community has been key in discovering and communicating the fact that current testing is able to detect, with ≥82 - 95% sensitivity, current strains of the virus.
Vaccines directed at the most common strains known appear to be stabilizing new infections rates as of this date. This combined with face coverings, social distancing, and frequent sanitization have caused a plateau and decline in numbers of the new seven-day rolling case averages.
Multiple diagnostics companies have created immunoassays directed at physical components of the coronavirus, such as the spike protein. Different from the nucleocapsid-directed immunoassays that detects the presence of the antigen, this detects whether the patient has been exposed to the pathogen or the vaccine before. It is effective in showing the amount of protection against the virus.
Given the context of early 2020, all of this has brought us into better understanding to develop better tools quickly and effectively. There are still limitations to clinical effectiveness, though.
There is a concern that the tests, while demonstrating presence or absence of a response to the product for which it is testing, are subject to the ability of an elderly or immunocompromised patient’s ability to create a robust immune response versus that of a person with a healthy immune system.
Another complication is that diagnostic testing can't tell us the whole story about a virus. Mutations of the virus, such as B.1.1.7, P1, P.1.526, P.1.351 and P.1.617, have been reported globally and new variants are still being identified.
Once the changes to the virus start circulating into the general populations, will the current vaccines still be effective? Will the immunoassays we've developed be able to track them given the fact that they were not manufactured to identify the new variants? What happens when these new variants arrive on our shoreline? With the accessibility and ease of global travel the spread of new variants is inevitable and only a matter of time.
Conversely, what if new variants within the United States (such as one recently emerged from Washington Heights, NY) migrate to countries outside the US? The herd immunity that's been established between natural infection and vaccines has been largely directed toward the state of the virus early in the pandemic.
There is also the possibility of another breakout infection. This situation occurs which the vaccine has been given but does not confer immunity in the patient. This prevents the body from mounting an immune response to the vaccine so if the patient is infected naturally, the patient is not protected and contracts COVID-19. The data is only now being collected as the populace is immunized, so the prevalence of this situation is unknown but important to overall immunity in the human population.
Using the model of the respiratory influenza virus that most of the population is familiar with, the severity of the influenza virus is lessened when the body's immune system has previously been exposed to a similar variation either by vaccination or natural exposure. However, if a pathogen is different enough in morphology then it may cause a full-blown infection with severe heath complications. This occurs because the natural or vaccine immunity is unable to assist because it does not recognize this strain of virus. When coupled with concomitant illnesses and infections from a weakened immune response, the results were catastrophic and could be again.
The best-case scenario is that the genetic sequences represented by the mRNA and S protein already exposed to the body will be enough to mount an immune response that does not create an overwhelming inflammatory response that has proven fatal to so many people. We will only know the answer to this from the laboratory work being done to detect it and the tracing that models the spread of the variants and how effective the clinical and public health counter measures are.
The worst-case scenario is that not only would the vaccine fail to create immunity but the monoclonal antibody testing also fails to detect a new infection or detects a titer of antibody that is ineffective against the new antigen. The result would be a temporary return to square one, with rising infection rates and little ability to combat it until multivalent vaccines and polyclonal immunoassay tests are developed. The analogy is a very good catcher's mitt with a few holes in it used to catch golf balls instead of baseballs. This is certainly not where we hoped we would be a year from now.
As other variants become dominant in other parts of the world and as the variant here in the United States travels abroad, we are faced with continued COVID-19 spread and the continued need for in vitro monitoring. However, at this time we are no longer alone without resources. The research community has continually acquired data on the nature of emerging variants and is creating multivalent PCR and immunoassay tests.
The question remains will volume and type of testing go up or down over the long-term? The answer is obviously situational. Immunizations and infections from which patients have recovered are leading to greater herd immunity, lowered incidence and prevalence. This has, in turn, meant some shift back to conventional, non-COVID-19 focused laboratory medicine.
The factors countering this will be the uncertainty factors of viral mutation, incorporation of those mutations into multivalent vaccines, and time lag leading to community spread. One only needs to look to world hotspots of infection to see this in action and it can happen here, as well.
Though there has been a shift from PCR toward antigen and antibody testing, particularly monitoring antibody response and reduced immune response over time, it will be resource-intensive either way. It is part of the pound of prevention that is necessitated when the pound of cure is ignored or circumvented.
So, what can we, as laboratorians, do to help? We must be prepared for the next waves of this pandemic through properly targeted research and clinical funding, continued adequate staffing resources through education and retention, preservation of the laboratory supply chain, and increased public education about the laboratory’s role in combating the pandemic.
We must continue to support expert plans while retaining a critical approach to ensure their integrity. As an example, vaccine information must be made available all the time, particularly with multivalent vaccines in the near future. Our best resources remain reputable national and international sources to counter questionable social media outputs, which well-intended or not, lack intellectual rigor.
We must support hospitals, health systems, and laboratories other than our own to address current shortcomings. Finding the gaps in laboratory service provision ought to be the shared responsibility of every level of service provision. Those that are currently doing this in a collaborative manner are to be applauded and reinforced.
Finally, we must address equal access to care. Doing what is economically possible to support underserved urban and rural vaccinations and healthcare provisions (including self-isolation and quarantine in the public sector) minimizes viral mutation, incubation and outbreak. Together, the laboratory industry can continue to be the bellwether of patient care during this COVID-19 pandemic, supporting future efforts leading to eventual eradication.
Burnham, Carey-Ann Ph.D., Farnsworth, Christopher Ph.D., O’Halloran, Jane PhD, Parness, Laura, MD, McMullin, Allison. “COVID-19 in the Vaccine Era Diagnostic Topics Roundtable” Roche Diagnostics Corporation teleconference, 02/02/2021.
“COVID-19 Antibody Testing”, Versiti Beacon Club Newsletter, 10/15/2020.
“COVID-19 Survivor Meets Lifesaving Plasma Donor”, Versiti Beacon Club Newsletter, 11/04/2020.