In December of 2019, there was an outbreak of pneumonia of unknown etiology linked to a seafood market in Wuhan, Hubei Province, China. The viral cause of the outbreak was later determined to be a novel coronavirus disease classified as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), also known as COVID-19. Since the original report in December, the epidemic escalated quickly, and a pandemic was declared by the World Health Organization in March of 2020. At the time of this writing, there are over 43 million cumulative cases of COVID-19 and greater than one million deaths reported to the World Health Organization (WHO). The pandemic has spread to 214 countries globally.
Symptoms of the viral infection may be mild, including a dry cough, sore throat and fever. The majority of affected individuals recover from their symptoms after one to two weeks. However, some patients, particularly those who are older or who have co-morbidities have more severe manifestations and can require intensive care including ventilator support to breathe. Other manifestations of severe disease may impact the cardiovascular, cerebrovascular, endocrine, and digestive systems. Regardless of the symptoms, patients are contagious and may spread the virus to other people with whom they come in contact.
Governments, the global medical community, and laboratory testing infrastructure were largely unprepared for the magnitude of what was required to adequately manage and extinguish the COVID-19 pandemic. Although there have been viral outbreaks in the 21st century, (Ebola, SARS, and H1N1, among others), there has not been a global pandemic of this enormity since the Spanish flu pandemic of 1918. Even with over one hundred years of additional technological, scientific and medical progress, the world was still not ready to appropriately respond to COVID-19.
As the virus can be transmitted prior to the onset of symptoms, it is best to diagnose patients with COVID-19 prior to symptomatic onset to reduce the spread of the virus. Laboratory testing is crucial in this process, so that effective containment protocols may be followed. The purpose of this article is to review the different testing strategies available for COVID-19, in order to provide the best patient outcome.
Nucleic acid amplification testing (NAAT), which uses real-time reverse transcriptase-polymerase chain reaction (rRT-PCR, also known as RT-PCR) technology, is considered the “gold standard” for COVID-19 diagnostic testing by the Centers for Disease Control and Prevention (CDC). It has the highest sensitivity in patients who are early in their infection and symptom progression, which allows for quicker isolation and treatment of the patient. NAAT may be performed on a variety of specimen types, including Bronchoalveolar lavage ﬂuid, ﬁber bronchoscope brush biopsies, sputum, nasal swabs, nasopharyngeal swabs, or saliva. Nucleic acid testing has a turn-around time (TAT) of about 2-3 hours after the sample has been transported to the laboratory and, the instrumentation can be conducive with a scalable, high throughput set up. However, the increased demand of NAAT has made materials and equipment in short supply, and high degree of technical expertise is required for the testing process. It is also laborious, compared to other testing methodologies.
Another testing technique for COVID-19 is a serological test. Typically, immunoglobulin M (IgM) antibodies may be detected within a week of a viral infection, which is followed by IgG antibodies. Evidence suggests COVID-19 may show abnormal kinetics with IgG and IgM arising at essentially the same time. One study reported antibody positivity rate was 29.4% after 5 days and increased to 81% after day 10. A molecular test therefore would show a patient is infected (i.e. a positive test) before they produce antibodies against COVID-19. Therefore, a serological test performed too early is at risk of a false negative result. Serological testing may have utility as a wide screening tool, rather than a point of care diagnostic testing for an individual. Serology may also identify those who have had a previous exposure to COVID-19 but are not currently infected. Some laboratories may have the facilities to scale up serological testing to be high-throughput, testing hundreds of specimens per hour. Compared to NAAT, serology tests are easier to perform and require less technical expertise.
A specific method of serological testing is the Lateral Flow Immunoassay (LFIA). There are LFIA kits for the detection of COVID-19 antibodies that are commercially available. Additionally, there have been published studies on the sensitivity, specificity, and accuracy of LFIA for COVID-19, compared to other testing methodologies. An advantage of the LFIA kit is the ability to perform field testing and obtain results external to the clinical laboratory space, thus reducing the logistical burden in the lab. However, field testing has its own set of challenges, including the ability to properly interpret the result, and document accordingly.
The mechanism of testing (in collaboration with the methodology of testing) is crucial for containing a global pandemic such as COVID-19. The traditional logistics of triaging patients, physical exam, determining who meets criteria for testing, obtaining a specimen, and sending said specimen to a lab for analysis is not scalable to meet the widespread demand seen with the COVID-19 pandemic. The traditional model also exposes healthcare workers to an unnecessary increased risk of infection from patient to clinician because of the amount of time spent in consultation in close quarters. Several medical centers shifted to a car drive-through model, which increased efficiency and lowered exposure risk to medical workers. This was facilitated by changing nasopharyngeal to nasal swabs and allowing patients to self-collect in the presence of a healthcare worker. The entire service can take as little as 10 minutes. One medical center in Korea reported an increased efficiency to over 100 tests per day with this methodology. Having patients in their cars also reduces COVID-19 exposure among patients and mitigates the risk to medical workers who staff the drive-through. Specific logistical set ups may be modified for the patient population being screened in a drive-through setting. For example, a pediatric site in the United States had a “fast lane” for older children and a “slow lane” for younger children or multiple children who may take longer to provide a specimen for testing.
One more mechanism of testing is the at-home testing model. Given the national and local social distancing mandates and ordinances, at-home testing provides the greatest protection against the spread of the virus if someone is truly infected. Some would say the Direct to Consumer (DTC) testing model may be translated to wide-spread population screening that is needed for a global pandemic. DTC genetic testing has been available for over two decades. Testing may be ordered by the consumer without a physician’s orders. DNA is obtained via a collection swab or saliva cup from the customer in the comfort and privacy of the consumer’s own residence. The sample is then sent to the lab for analysis. While those being tested for COVID-19 should be under the care of a physician or other healthcare provider, the ability for patients to take advantage of the at-home testing model already in place with DTC companies, allows for patient privacy, and mitigates against spreading the virus. One study reviewed at-home specimen collection methods under the observation of a clinician via telehealth. More than 84% of the 153 study participants reported the logistics of collecting saliva, oropharyngeal swab, or dried blood spot samples were acceptable. Additionally, 87% of patients enrolled in this study reported being confident or very confident that their self-collected specimens would be adequate for laboratory analysis. Although this study population is small, it demonstrates that, an at-home testing method may be scalable to meet the needs of population screening.
Indeed, the world is in the midst of a global pandemic that has impacted millions of people. Governments, the medical community, and laboratory infrastructure have had to re-think how to support affected patients while trying to slow the spread of infection. DNA and serological testing may be used differently, but all have the same goal of virus containment and patient care. At the time this article is written, it is unclear how soon the pandemic will end. Fortunately, there is a monumental effort by the scientific and medical communities to devise new testing technologies, and to change the logistical paradigm of how specimens are collected for testing. It is likely that the COVID-19 pandemic of the early twenty first century has changed how medicine is practiced for the foreseeable future.
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Insights / August 31, 2020 / by beaconlbs
We are proud to introduce Dr. Dorothy Adcock, an important member of the BeaconLBS Clinical Advisory Team. Dr. Adcock is an eminent specialist in the field of pathology who collaborates with our clinical team in the development of clinical policies.