key: cord-0715790-db5zw4kd authors: PAVIA, Charles; Plummer, Maria title: The evolution of rapid antigen detection systems and their application for COVID-19 and other serious respiratory infectious diseases date: 2021-06-26 journal: J Microbiol Immunol Infect DOI: 10.1016/j.jmii.2021.06.003 sha: e49fed452cd8de12e2a1dd57ef6172dfdd153eef doc_id: 715790 cord_uid: db5zw4kd Making the correct diagnosis of a patient seeking medical attention is the ultimate goal of a practicing physician, irrespective of whether the cause of the patient's condition is infectious or non-infectious. Antigen detection tests can be used to aid in the diagnosis of various infectious-related disorders including COVID-19 where it has become especially important due to the serious nature of this disease and its worldwide prevalence. These tests closely mimic one of the earliest prototypes – the urine pregnancy test – and as a result they have gained wide acceptance based on their overall simplicity, low cost and relative accuracy. In some situations, especially as a screening test, they can be used instead of the more technically demanding and complex molecular and serologic assays that are still useful and helpful under many different circumstances. Antigen detection systems are based on finding a particular immunogenic component, typically a protein or polysaccharide molecule, that is both unique and an integral part of the pathogen or other biological entity. Because these tests generally provide only qualitative results, they often need to be supplemented with other and sometimes more sophisticated laboratory-based diagnostic procedures to corroborate the initial test result. In this review, we first describe general background information on antigen-detection methods, including any unique aspects of their overall design, and then follow with an extensive description on the merits and limitations of these tests for detecting COVID-19 and, to a lesser extent, for other serious respiratory diseases caused by three common bacterial pathogens – Streptococcus pyogenes, Streptococcus pneumoniae and Legionella pneumophila. 1. Introduction and historical background house for routine use. Antigen-detection tests are perhaps most helpful in point-of-care 126 settings where diagnosis and treatment can be done expeditiously. 10 This would be 127 especially desirable in underdeveloped parts of the world having weak health-care 128 systems and/or poor access to reliable laboratory facilities, where more sophisticated 129 detection methods may not be readily available to the local community. For many years, the lateral flow format has been the desired platform for use in many 133 antigen detection systems that are currently in use for diagnostic purposes. 1 They have 134 been available commercially for many years and were first developed to detect abused 135 drugs, 11 and for the aforementioned early pregnancy testing. 7 In their most simplistic 136 design, they are easy to use, require minimal training, and test results can be obtained 137 rapidly, usually within 15-30 minutes. In most cases, the manufacturer provides simple 138 instructions that include pictures of positive and negative results (Figures 1 and 2) . 139 Typically, all of the materials that are required to perform the test, including sample 140 collection materials and known controls, are provided in the commercial kit, with the 141 exception of a timer and, in most cases, a sophisticated mechanical reader instrument. 142 With shelf lives generally over 2 years, these "hand-held" assays (HHA) do not require 143 special storage conditions, however, high humidity and heat could affect performance 144 due to possible degrading of some of the reagents or component parts. The assays are 145 typically put together with the use of nitrocellulose or nylon membranes contained within 146 a plastic or cardboard housing usually referred to as a cassette or cartridge. Another 147 version involves the use of a dipstick. The method used for determining if an assay 148 result is positive depends on whether it is a competitive or an antigen-capture assay. Most systems adhere to the antigen-capture format, where a capture antibody is bound 150 to the membrane, and a second labeled antibody is placed on a sample application pad 151 that has been incorporated within the device. As the sample migrates down the 152 membrane by capillary action (as shown in Figures 1 and 2) , antigen present in the 153 sample binds to the labeled antibody and is captured as the complex passes through Since COVID-19 is a newly recognized disorder and key epidemiologic, microbiologic 176 and pathologic features about it were unavailable prior to its outbreak, we will initially 177 provide some of the more pertinent details in this area before describing the impact that 19 (see below). Initially, SARS-CoV-2 targets nasal and bronchial epithelial cells, and 220 pneumocytes via the S spike protein that binds to the ACE2 receptor. 15, 17 In later stages 221 of infection, as the virus replicates and the viral load becomes higher, the epithelial-222 endothelial barrier in the alveoli is compromised, and the inflammatory response is 223 accelerated which elicits an infiltration of numerous monocytes and neutrophils to the 224 target sites. 17 The viral infection is believed to cause an excessive immune response 225 which is known as a "cytokine storm"the likely key factor leading to critical illness and Current laboratory 605 methods for biological threat agent identification Immunological methods for detection and identification of 608 infectious disease and biological warfare agents Development of the home pregnancy test Aptamers: an emerging class of molecules that rival antibodies 615 in diagnostics Aptasensors-the future of biosensing Developments in immunological technologies leading to 621 improvements in point-of-care diagnostic testing Enzyme 624 immunochromatography-a quantitative immunoassay requiring no instrumentation Genomic characterization 628 and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor 629 binding WHO declares COVID-19 a pandemic Johns Hopkins University of Medicine coronaviruses 633 resources web site A comprehensive review of COVID-19 characteristics /COVID-19 and advances in developing potential therapeutics and vaccines to counter 641 this emerging pandemic Pathophysiology, 645 transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19): A 646 Review A review of postmortem findings in 649 patients with COVID-19 Centers for Disease Control and Prevention. 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