US Pharm. 2022;47(2):10-12.
Coronavirus (COVID-19), which currently classifies as a respiratory infection, spreads among human vectors that come into contact with contaminated respiratory droplets.1 While coronavirus itself is common, the 2019 strain as well as various mutations, including those such as alpha, beta, gamma, delta, and omicron, have plagued humanity on a national scale.2 Physical manifestations of COVID-19 may vary, as individuals may present either asymptomatically or with symptoms ranging from mild to severe.3 Additionally, physical manifestations are similar to those of influenza, including presentation of general malaise, nausea and vomiting, tussis, rhinorrhea, fever, etc.4 Individuals potentiate their risk for infection when they are exposed to people who are positive for COVID-19 and introduce contaminated respiratory droplets into their system, typically through orofacial contact.1 Respiratory droplets possess the ability to spread through a plethora of mechanisms, including tussis, sternutation, or directly via conversation. Further possible vectors include physical surfaces that individuals come in frequent contact with, encompassing items such as doorknobs, furniture, and clothing.5 Furthermore, the viral life span of COVID-19 depends on both environmental and hygienic factors and may therefore thrive anywhere from a few hours up to several days.1,5
Epidemiology
Epidemiologists have traced the origin of COVID-19 to Wuhan, China.6 The offending agent developed as a result of chiroptera fecal material introduced within a marketplace primarily focused on sea fare. We currently surmise that COVID-19 ultimately began with human consumption of contaminated food, allowing for the viral strain to proliferate within its host, and progressed to spread through several million hosts on a global scale.2 Additionally, due to the fact COVID-19 is similar to SARS-CoV, it gained the classification of SARS-CoV-2.2
Etiology
SARS-CoV-2 binds to angiotensin-converting enzyme 2 (ACE2) through the receptor-binding gene region of the enzyme’s spike protein. A study that monitored amino acid changes in the spike protein of SARS-CoV-2 isolates included in a large sequence database identified a D614G (glycine for aspartic acid) substitution that became the dominant polymorphism globally over time. The host receptor for SARS-CoV-2 cell entry is the same as for SARS-CoV—ACE2.7
Device: Guardant-19
The Guardant-19 is an automated method that utilizes reverse transcriptase PCR followed by next-generation sequencing to detect SARS-CoV-2 viral RNA in upper respiratory specimens.8 The Guardant-19 operates using a variety of different collection methods, including nasopharyngeal swabs (NP), oropharyngeal swabs, anterior nasal swabs, midturbinate nasal swabs, nasopharyngeal wash, aspirates, nasal aspirates, and nasal washes.7,8 Diagnostic results are typically delayed up to 24 hours after collection. Guardant-19 typically yields a limited detection of 125 copies per mL and can provide up to 10,000 tests daily.8 After testing has been completed, the Guardant-19 Bioinformatics Pipeline Software recognizes an individual sample to produce a test result. Replicate levels that were gathered following inspection come up with a ratio between SARS-CoV-2 reads and compared them to those observed within that replication.7 The Guardant-19 employs a numerical scoring method known as the Guardant-19 score as well as the G-19 score; the reported score represents the median value of roughly two or three per replicate scores.7 A sample demonstrating a G-19 score of 0.01 or higher indicates that the tested individual is positive for SARS-CoV-2, whereas any value below 0.01 indicates a negative SARS-CoV-2 diagnosis.7
Efficacy
Guardant-19 efficacy was evaluated with a limit-of-detection testing, which is the lowest concentration at which 95% of all positive replicates are positively detected. This was determined by creating 10 concentrations (1,500, 1,250, 1,000, 750, 500, 375, 250, 125, 50, and 25 copies/mL) of inactivated SARS-CoV-2 diluted with negative NP swab specimens. Of 408 tested samples, 360 (88.2%), passed quality control (QC). Analysis of the QC samples yielded results consistent with a limit of detection of 125 copies/mL.7 The FDA’s Emergency Use Authorization (EUA) summary for Guardant-19 examined the Guardant-19 test against the results obtained from a comparator EUA assay. Both tests have been authorized under EUA to detect and diagnose COVID-19 patients.
From March to April of 2020, 127 remnant nasopharyngeal samples were taken by healthcare providers from patients who were COVID-19–tested.7 These samples were divided into two cohorts identified as Cohort A and Cohort B, respectively. Cohort A comprised 67 nasopharyngeal swabs obtained by healthcare professionals from an unknown county. Cohort B consisted of 60 nasopharyngeal swabs obtained by healthcare professionals from patients who were on cruise ships and from patients from the same unknown county.7 In total, there was a 95.52% match in positive results with the Guardant-19 and the comparative EUA assay, and a 98.33% match in negative test results with Guardant-19 and the comparative EUA assay.7
Conclusion
The EUA of Guardant-19 demonstrates both high sensitivity (95.52%) and high specificity (98.33%) when utilized for the detection of SARS-CoV-2 in patients who present with COVID-19. Additional information about Guardant-19 may be found using the following link: www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/vitro-diagnostics-euas.REFERENCES
1. CDC. About COVID-19. www.cdc.gov/coronavirus/2019-ncov/cdcresponse/about-COVID-19.html. Accessed November 18, 2020.
2. WebMD. Pathak N. Coronavirus and COVID-19: what you should know. www.webmd.com/lung/coronavirus. Accessed November 18, 2020.
3. Heneghan C, Brassey J, Jefferson T. The Centre for Evidence-Based Medicine. COVID-19: what proportion are asymptomatic? The Centre for Evidence-Based Medicine. www.cebm.net/covid-19/covid-19-what-proportion-are-asymptomatic/. Accessed November 18, 2020.
4. CDC. Symptoms of coronavirus. www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html. Accessed November 18, 2020.
5. Wessler K, The truth about coronavirus on surfaces. OSF HealthCare Blog. www.osfhealthcare.org/blog/the-truth-about-coronavirus-on-surfaces/. Accessed November 18, 2020.
6. McIntosh, K. Coronavirus disease 2019 (COVID-19): epidemiology, virology, and prevention In: Post T, ed. UpToDate. Hirsch, MS. UpToDate: 2016. www.uptodate.com. Accessed November 18, 2020.
7. FDA. Emergency Use Authorization (EUA) Summary Guardant-19 [PDF]. Silver Spring, MD: FDA. August 21, 2020.
8. Guardant Health receives FDA EUA for its Guardant-19 next generation sequencing–based COVID-19 test. Medical Device News Magazine. https://infomeddnews.com/guardant-health-receives-fda-eua-for-its-guardant-19-next-generation-sequencing-based-covid-19-test/. Accessed November 18, 2020.
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