By Sandy Estrada, Pharm. D.
As COVID-19 cases continue to sweep the nation, an increase in demand for diagnostic tests that can confirm if patients have the virus continues to grow. However, since the onset of the pandemic there have been challenges with current diagnostic tools due to reports of false negative tests, which can have a harmful downstream impact on patients. For severely ill patients, a false negative result can exclude them from participating in investigational therapy or clinical trials, for which patients must have a positive result to be considered and enrolled, preventing them from accessing therapy that can potentially be life-saving. Meanwhile, mild to moderately ill patients who falsely test negative may go out into the community, increasing the risk of further exposure and spreading the virus to others. Additionally, lack of testing supplies and reagent availability has led to wait times of seven days or longer for test results, limiting the ability for timely treatment of positive patients and presenting additional challenges in the quarantine of suspected patients. These consequences call for the availability of more sensitive and rapid diagnostic tests, with many tests still being developed and brought to market as the pandemic continues. One such test, the T2SARS-CoV-2™ Panel from T2 Biosystems, has a 95 percent sensitivity and 100 percent specificity, is not on allocation, and runs on the FDA-cleared T2Dx® Instrument which can run seven samples simultaneously and return results in under two hours.
Further complicating matters, the SARS-CoV-2 virus, which is responsible for causing primary COVID-19 infections, is not necessarily an isolated condition. The virus is also associated with secondary and co-infections, potentially leading to severe consequences, such as sepsis, which can be fatal. As with COVID-19 virus testing, unfortunately, the current process for diagnosing secondary and co-infections has shortcomings that further demonstrate an urgent need for improved testing capabilities and sensitive rapid diagnostics.
Before examining the diagnostic process for secondary and co-infections, it’s important to understand the prevalence and how common it is for patients to contract an infection associated with COVID-19. Hospitalized patients, especially those who are critically ill and mechanically ventilated are already at high risk for infections, independent of the COVID-19 virus. Similarly, patients like those in oncology units who are immunocompromised due to cancer, those in long-term care facilities or nursing homes and beyond, are already at risk for infection; when adding the COVID-19 virus into the equation, this disease itself is associated with immune dysregulation, creating opportunity for bacterial or fungal growth. Additionally, the COVID-19 virus has also been associated with Cytokine release syndrome, immune exhaustion and lung damage, which may also pre-dispose patients to superinfections.
When clinicians suspect their patients have a bloodstream infection, specifically, they order a blood culture to confirm, among other protocoled steps. In the meantime, they begin treating patients with broad-spectrum antimicrobial therapy without truly knowing (1) if their patients actually have an infection and (2) what pathogen is causing the infection, which is a critical piece of information to determine exactly what therapy needs to be given. Blood culture results often take days to return, and subsequent time is then needed to complete susceptibility testing. As a result, patients can go a long period of time before clinicians have information that can guide targeted clinical treatment, which can potentially lead to a decline in health for patients as well as extensive costs for hospitals, between the length of stay and cost of therapies.
Fortunately, technology now exists that can bypass the wait for blood culture, confirming the presence of a bloodstream infection and what pathogen is causing it, within hours and directly from whole blood. For example, T2 Biosystems’ T2Bacteria® Panel is the only FDA-cleared test to identify sepsis-causing bacterial pathogens directly from whole blood without the need to wait for blood culture, and its counterpart for fungal bloodstream infections, the T2Candida® Panel, is the only FDA-cleared direct-from-whole blood diagnostic for detection of fungal pathogens that are associated with sepsis. Both panels provide results in three to five hours instead of days, which helps clinicians make targeted treatment decisions quickly, often before the second dose of antimicrobials is administered.
Rapid results not only help clinicians start patients on the right antimicrobial therapy, but they also help prevent or manage de-escalation of antimicrobial therapy that patients do not need, which is crucial for antimicrobial stewardship – an initiative that all major hospitals need in order to help manage costs, improve patient outcomes and combat antimicrobial resistance.
According to The Review On Antimicrobial Resistance’s “Tackling Drug-resistant Infections Globally: Final Report and Recommendations,” antimicrobial resistant infections are estimated to cause 700,000 deaths annually, and this number is projected to increase to 10 million per year by 2050. As a result, it’s important to help prevent the overuse of antimicrobial drugs, which can be done by eliminating “just in case” prescriptions. Rapid diagnostics can help accomplish this – a quick confirmation that a patient does not have a bloodstream infection can mean that clinicians can completely rule out starting patients on, or quickly stop, an antimicrobial therapy. Likewise, a quick detection of the presence of a bloodstream infection and what pathogen is causing it can help fast-track a tailored approach to treatment.
Bacterial and fungal infections may lead to sepsis; a critical illness that can clearly have dire consequences for patients and hospitals, and therefore they deserve significant attention when it comes to evaluating and ensuring their diagnostic process is of the highest possible standards. These infections have been here long before the COVID-19 virus, and will no doubt continue to thrive long after we tackle the pandemic; meanwhile we cannot diminish the importance of having an efficient, accurate COVID-19 virus diagnostic process for patients as well.
It’s not enough to just have an effective rapid diagnostic test for bacterial and fungal infections or an effective COVID-19 virus diagnostic test during this pandemic. The two are married to one another for optimal patient outcomes throughout this time in global and medical history.
If they haven’t already, health care professionals must begin to shift their perspective on the COVID-19 pandemic from one that is solely focused on the virus to a longer-term view that recognizes that the virus is one component of a broader stream of health care scenarios and outcomes. If professionals do not value the importance of improving the current infection diagnostic and management process as much as they do the COVID-19 virus diagnostic process, progress made in antimicrobial stewardship may be lost and they are at risk of committing a disservice to their patients.
Sandy Estrada, Pharm. D. is Vice President, Medical Affairs at T2 Biosystems.