|Year : 2023 | Volume
| Issue : 4 | Page : 194-200
Point of care tests: Changing paradigms in the diagnosis of SARS-CoV-2
Anuradha Sharma1, Ekta Chourasia2, Shubham Goswami1
1 Department of Microbiology, Faculty of Dentistry, Jamia Millia Islamia, New Delhi, India
2 Department of Microbiology, B. Y. L. Nair Charitable Hospital, Mumbai, Maharashtra, India
|Date of Submission||25-Mar-2023|
|Date of Acceptance||27-Aug-2023|
|Date of Web Publication||03-Nov-2023|
Dr. Anuradha Sharma
Department of Microbiology, Faculty of Dentistry, Jamia Millia Islamia, New Delhi - 110 025
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: Point of care tests provide rapid information about the patient's condition, with a turnaround time of 15 min. During the COVID-19 pandemic, many such point of care tests were developed, to aid in the rapid diagnosis of SARS-Cov-2 infection.
Aim: To describe and synthesize the available literature on point of care tests for diagnosis of SARS-CoV-2.
Methodology: This narrative review was done through online literature search,using Google Scholar and PubMed.
Result: There were 51 point of care tests for diagnosis of SARS-CoV-2 which were validated using different samples,such as such as nasopharyngeal swabs(42), oropharyngeal and naso-pharyngealswabs(2), oropharyngeal swab in VTM(1) nasal swabs(5) and throat swab(1).
Conclusion: There was global developement of point of care tests on a war footing. The Indian states of Delhi, Maharashtra, Gujarat, Uttar Pradesh, Tamil Nadu, Karnataka, Haryana, Rajasthan, Kerala, Himachal Pradesh, Goa and Uttarakhand, were in the forefront of these developments, as also the USA, Belgium, Taiwan, Korea and South Korea.
Keywords: Home health care, infection control, infectious disease, patient care, point-of-care diagnostics, SARS-CoV-2
|How to cite this article:|
Sharma A, Chourasia E, Goswami S. Point of care tests: Changing paradigms in the diagnosis of SARS-CoV-2. Heart Views 2023;24:194-200
| Introduction|| |
Any diagnostic testing at or near the site of patient care to provide immediate information, with a turnaround time of 15 min, to the clinician about the patient's condition whenever medical care is needed is known as point-of-care (POC) diagnostic testing. There has been an increase in these tests in recent years with the advances in technology to cater to the growing need for convenient diagnosis, monitoring, and screening tests. POC tests (POCT's) can be performed at various locations such as home, health-care community clinics, the emergency department, in an ambulance, and in infectious disease containment units. It is useful not only in the prevention, early detection, and management of chronic conditions but also in the differentiation of high-risk infections such as COVID-19 from other flu-like infections.
A cluster of pneumonia cases caused by a novel coronavirus, SARS-CoV-2 was reported in Wuhan, China, in December 2019. As of February 16th 2023, there have been 756.4 million confirmed cases of COVID-19, including 6.84 million deaths, reported to the WHO from all over the globe. The first case in India was reported on January 30, 2020, and by mid-March 2020, the number of cases had exploded. The morbidity due to this respiratory viral infection has been unimaginable and mortality, unaccountable, unfathomable.
To effectively address the COVID-19 pandemic and reopen civil society, rapid POC diagnostics capable of operating in any low-resource context, even at home, were required. The long turnaround time that was associated with centralized laboratory polymerase chain reaction testing (PCR), which took several days to provide conclusive results, made it difficult to manage suspected COVID-19 disease. These delays could cause poor patient flow across clinical departments with suspected patients being grouped into assessment sections until their results are ready. Furthermore, owing to a lack of single-occupancy rooms, COVID-19-negative individuals in these assessment regions were susceptible to contracting the disease from patients who did not have it before the results were made available.
In 1917, Dochez and Avery reported that pneumococcal polysaccharide can be detected by immunoassay of serum and urine from patients with lobar pneumonia. There have been “over-the-counter” and so-called “non-professional testing,” such as glucose monitoring and pregnancy testing as also the “professional testing” encompassing critical care, infectious disease, cardiac markers, diabetes, lipids, coagulation, and hematology.,
This narrative review was done with the aim of having an insight into the various point of care tests developed for the diagnosis of COVID-19 infection. Online literature search was done using the MeSh keywords,COVID-19, communicable diseases, immunoassay, pandemics, polymerase chain reaction, SARS-COV-2, World Health Organization. The search engines used were Google Scholar and PubMed, through the years 2018-2023.
| Review Of Literature: 2018–2023|| |
- Kellner et al., in 2019, developed a sensitive and specific nucleic detection technology called SHERLOCK (Specific High-sensitivity Enzymatic Reporter UnLOCKing). It detected DNA or RNA virus signatures through two consecutive reactions, amplification of the viral RNA using an isothermal amplification reaction followed by the detection of the resulting amplicon using CRISPR-mediated collateral reporter unlocking. There were disadvantages due to complexity and sample cross-contamination prohibiting their use outside well-controlled laboratory environments
- Brendish et al., in October 2020, in Southampton, UK, conducted a nonrandomized trial to study the clinical impact of molecular POCT for COVID-19 in acute admissions. They demonstrated that the routine use of POCT may provide clinical and infection control teams with timely, accurate, and actionable data. The POCT group's median time to results during the study was 1.7 h, whereas the control group's median time to results with the laboratory PCR was 21.3 h (difference of 19.6 h). Seventy-three percent of the patients in the POCT group and 57% of the patients in the control group who were admitted to the hospital for at least 24 h each, were transferred from assessment areas to the appropriate definitive clinical area (i.e., a COVID-19-positive or COVID-19-negative ward)
- Li et al., in May 2021, China, developed the easy-readout and sensitive-enhanced (ERASE) lateral flow strips which detected 1 copy/L of extracted SARS-CoV-2 RNA, making it a sensitive and easy test to interpret. The presence or absence of a test band, T-band, indicates the findings of an ERASE assay. To reduce the false-positive rates, the interpretation mode of the ERASE test was changed, and the disappearance of the T-band was marked as the positive threshold
- Drevinek et al. in January 2020, Prague, Czech Republic, developed an immunochromatography assay for the antigen-based detection of SARS-CoV-2. They assessed the low-sensitivity issues of rapid antigen-based POCTs and compared this with the effectiveness of the gold standard reverse transcription-PCR (RT-PCR) test. It was found that false-negative antigen testing may have a substantial negative impact on the success of epidemic containment, as it is critical to detect any positive person as soon as possible, even those with a low viral load at first. Not to be overlooked, a single round of testing, as is likely the case when a population-wide screening is ordered, appears insufficient and ineffective. If the antigen test is employed as a frontline screening tool, a strategy based on repeated testing at a high enough frequency should be used instead
- Gerlier et al. in September 2021, France, in their study, compared patient cohorts from 2 to 7-week periods, observational pre-POC period versus interventional POC period. When the treatment outcomes of the two groups were compared, it was noted that employing POCT for SARS-CoV-2 diagnosis was also linked to improve COVID-19-specific treatment for thromboembolic disorders
- Krüger et al., in 2022, conducted a prospective, manufacturer-independent, multicenter clinical study, to assist global decision-makers and researchers, and evaluate the clinical performance and ease-of-use (EoU) of seven antigen-detecting rapid diagnostic tests (Ag-RDTs). At six sites, specifically in Germany and Brazil, unvaccinated volunteers suspected of having their first SARS-CoV-2 infection were recruited. The collection of paired swabs for routine RT-PCR testing and Ag-RDT testing was done in order. Overall and in subgroup studies, performance was compared to RT-PCR. A System Usability Scale questionnaire and EoU assessment were used to better understand usability. A total of 7471 informed participants were included in the study. Some Ag-RDTs were tested one after the other, although only one Ag-RDT was performed on each individual that arrived at the testing facilities.,,,
The conclusions of this study backed up WHO's EUL determinations where the WHO recommends sensitivity >80% and specificity >97% for three tests (Mologic, Bionote, and Standard Q). When comparing groups based on viral load, all assays had a high sensitivity (>88.6%) on samples with higher viral loads.
| Principle Of Point-Of-Care Tests|| |
Rackus, Shamsi, and Wheeler proposed through a Venn diagram, the interaction of biosensors, microfluidics, different technologies, and analytical methods, used for POC devices [Figure 1].
|Figure 1: Venn diagram proposed by Rackus, Shamsi, and Wheeler, showing the interaction of biosensors, microfluidics, and different technologies and analytical methods, used for point-of-care devices|
Click here to view
There are certain components in POCTs such as operator interface, bar code identification system, sample delivery devices, reagent storage and availability, reaction cell, and sensors, to detect the measurement reaction, control and communication systems, data management, storage, and manufacturing requirements.
POCTs are broadly of three categories: the first is a small handheld devices, providing qualitative or quantitative determination, the second is a larger bench-top device, reduced in both size and complexity, and the third, a small new emerging device utilizing molecular techniques such as PCR. Analytes, microbial antigens, nucleic acids of microbes, or antibodies toward the microbes present in or extracted from clinical samples are detected in POCTs.
Biosensors, fluorescent biosensors, biological microelectromechanical systems, microfluidics/paper-based technology, electric field-induced release and measurement, and smartphone-based biosensor are some of the technologies used in POCTs.
| The Pros and Cons of Point-Of-Care Testing|| |
Every coin has two sides, so also the POCT. On the pro side, delivery of rapid results through POCTs enables the clinician to start empirical therapy, promote antibiotic stewardship, and curtail outbreaks of infectious diseases. These are low-cost health-care technologies that can be used for various purposes in health-care setup such as, for the early detection of disease, for prognosis of disease outcome and possible patient stratification for those at elevated risk of disease recurrence, for prediction of treatment outcome, and surrogate endpoints.
On the other hand, POCTs may lack sensitivity and the complexity, and sample cross-contamination in some tests limits their use outside well-controlled laboratory environments. Where whole blood samples are used, hemolysis and lipemia can lead to inaccurate test results.
The COVID-19 pandemic saw the development of many POCTs in India as well as abroad. These were antigen detection kits for the qualitative detection of nucleocapsid (N) protein antigen from SARS-CoV-2 in individuals with or without symptoms. In India, these were mostly from the states of Maharashtra, Haryana, Gujarat, Himachal Pradesh, and Goa. South Korea, the USA, Belgium, and Taiwan were the countries outside India. Samples used for validation were nasopharyngeal swabs (42), oropharyngeal swabs (01), nasal swabs (05), and throat swabs (1). Five tests that were validated using nasal swabs found their way into residences as home-based kits. Of these, two were from India, two from the USA, and one from Korea. [Table 1]
|Table 1: Point-of-care testings developed for the diagnosis of severe acute respiratory syndrome coronavirus 2|
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| Discussion|| |
Economic upheavals and the COVID-19 pandemic led to a worldwide recognition of the need for less fragmented and more patient-centered care, thereby making a judicious health-care budget. To do so, there has been a shift from the secondary and tertiary hospitals to primary care or community care. Accordingly, the central laboratory concept has to gradually accommodate an alternative model utilizing POCT, for both marginalized people in remote areas as also in densely populated areas along with tele-health applications. As the need grows for economically friendly health care, closer to the patient with minimalized turnaround time, the volume of POCT is growing steadily. There is an increased availability of easy-to-use devices, thus making it possible to cater to the growing needs of patients and clinicians alike.
The COVID-19 pandemic furthermore brought to the fore the relevance of POCTs, especially in the diagnosis and home care of COVID-19-infected patients. COVID-19 suspects needed to know whether they were infected, as early as possible, for further timely isolation and notification of their close contacts. The gold standard for the diagnosis of SARS-CoV-2, RT-PCR test, is a time-consuming test with turn around time (TAT) of up to 24 h. rapid POCTs made testing more accessible to a wider range of people, both with and without symptoms, and in places other than hospitals. Rapid diagnosis allowed many people to take appropriate action in time, thereby reducing the spread of SARS-CoV-2. Some patients who underwent POCT received their results while remaining in the emergency room itself and were transported directly to definitive clinical areas, skipping the assessment cohort wards entirely. If findings could be returned even faster, it is possible that all patients' results might have been received while they were still in the emergency room, eliminating the need for assessment cohort areas.
In comparison to laboratory PCR, POCT brought about a significant reduction in the turnaround time, which was linked to improvements in infection control and patient flow. Patients spent around 1 day less in assessment areas and had fewer bed moves before arriving in the definitive COVID-19-positive or COVID-19-negative clinical areas. Noninfected patients spent less time in the assessment areas and were thus less exposed to infected patients and had lesser chances to contract nosocomial infection. Also, a quicker moveover of COVID-19-positive patients to COVID-19-positive areas, prevented exposure of health-care personnel to the infection.
There was an improvement in the preventive and curative therapy of thromboembolic disorders in COVID-19 patients because clinical decisions were made faster with quick and readily available POC technology.
Numerous diagnostic kits came to the fore in various states of India, such as Delhi, Maharashtra (Pune, Mumbai, IIT Mumbai), Gujarat (Ahmedabad, Vapi, and Valsad), Uttar Pradesh (NOIDA), Tamil Nadu (Chennai), Karnataka (Bengaluru), Haryana (Gurugram and Faridabad), Rajasthan (Alwar), Kerala (Kochi), Himachal Pradesh (Solano and Parwanoo), Goa, and Uttarakhand (Haridwar) as well as in the USA (Chicago), Belgium, Taiwan, Korea, and South Korea. The eastern states of India although rich in human and natural resources, such as the Steel Authority of India Limited (SAIL), seemingly to have lagged behind in developing such kits. There is a need in these areas to strengthen their research and development projects to contribute more toward POCT diagnostics. These will help the population of these areas which are industrial areas as well as educational hubs.
The research and development sectors, globally, ensured the availability of POCT's for the diagnosis of COVID-19 infection. This has helped in the timely homecare based diagnosis and therapeutic interventions, of a disease which had brought health care sector to a halt.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Broughton JP, Deng X, Yu G, Fasching CL, Servellita V, Singh J, et al.
CRISPR-Cas12-based detection of SARS-CoV-2. Nat Biotechnol 2020;38:870-4.
Shetti NP, Srivastava RK, Sharma S, Basu S, Aminabhavi TM. Invasion of novel corona virus (COVID-19) in Indian territory. Sens Int 2020;1:100012.
Brendish NJ, Poole S, Naidu VV, Mansbridge CT, Norton NJ, Wheeler H, et al.
Clinical impact of molecular point-of-care testing for suspected COVID-19 in hospital (COV-19POC): A prospective, interventional, non-randomised, controlled study. Lancet Respir Med 2020;8:1192-200.
Dochez AR, Avery OT. Soluble substance of pneumococcus origin in the blood and urine during lobar pneumonia. Proceedings of the Society for Experimental Biology and Medicine 1917;14:126-7.
Briggs C, Kimber S, Green L. Where are we at with point-of-care testing in Haematology? Epub 2012;158:679-90.
St John A, Price CP. Existing and emerging technologies for point-of-care testing. Clin Biochem Rev 2014;35:155-67.
Kellner MJ, Koob JG, Gootenberg JS, Abudayyeh OO, Zhang F. SHERLOCK: Nucleic acid detection with CRISPR nucleases. Nat Protoc 2019;14:2986-3012.
Li H, Dong X, Wang Y, Yang L, Cai K, Zhang X, et al.
Sensitive and easy-read CRISPR Strip for COVID-19 rapid point-of-care testing. CRISPR J 2021;4:392-9.
Drevinek P, Hurych J, Kepka Z, Briksi A, Kulich M, Zajac M et al
. The sensitivity of SARS-CoV-2 antigen tests in the view of large-scale testing. medRxiv 2020. [doi: 10.1101/2020.11.23.20237198].
Gerlier C, Pilmis B, Ganansia O, Le Monnier A, Nguyen Van JC. Clinical and operational impact of rapid point-of-care SARS-CoV-2 detection in an emergency department. Am J Emerg Med 2021;50:713-8.
Krüger LJ, Tanuri A, Lindner AK, Gaeddert M, Köppel L, Tobian F, et al.
Accuracy and ease-of-use of seven point-of-care SARS-CoV-2 antigen-detecting tests: A multi-Centre clinical evaluation. EBioMedicine 2022;75:103774.
Rackus DG, Shamsi MH, Wheeler AR. Electrochemistry, biosensors and microfluidics: A convergence of fields. Chem Soc Rev 2015;44:5320-40.
Kozel TR, Burnham-Marusich AR. Point-of-care testing for infectious diseases: Past, present, and future. J Clin Microbiol 2017;55:2313-20.
Gootenberg JS, Abudayyeh OO, Kellner MJ, Joung J, Collins JJ, Zhang F. Multiplexed and portable nucleic acid detection platform with Cas13, Cas12a, and Csm6. Science 2018;360:439-44.
Price C, St John A. Point-of-Care Testing Making Innovation Work for Patient-Centred Care. Washington, USA: AACC Press; 2012.
Tideman PA, Tirimacco R, Senior DP, Setchell JJ, Huynh LT, Tavella R, et al.
Impact of a regionalised clinical cardiac support network on mortality among rural patients with myocardial infarction. Med J Aust 2014;200:157-60.
Dave VP, Ngo TA, Pernestig AK, Tilevik D, Kant K, Nguyen T, et al.
MicroRNA amplification and detection technologies: Opportunities and challenges for point of care diagnostics. Lab Invest 2019;99:452-69.