Clinical Symptoms and Types of Samples Are Critical Factors for the Molecular Diagnosis of Symptomatic COVID-19 Patients: A Systematic Literature Review

Abstract

Background. Currently, a novel coronavirus found in 2019 known as SARS-CoV-2 is the etiological agent of the COVID-19 pandemic. Various parameters including clinical manifestations and molecular evaluation can affect the accuracy of diagnosis. This review aims to discuss the various clinical symptoms and molecular evaluation results in COVID-19 patients, to point out the importance of onset symptoms, type, and timing of the sampling, besides the methods that are used for detection of SARS-CoV-2. Methods. A systematic literature review of current articles in the Web of Science, PubMed, Scopus, and EMBASE was conducted according to the PRISMA guideline. Results. Of the 12946 patients evaluated in this investigation, 7643 were confirmed to be COVID-19 positive by molecular techniques, particularly the RT-PCR/qPCR combined technique (qRT-PCR). In most of the studies, all of the enrolled cases had 100% positive results for molecular evaluation. Among the COVID-19 patients who were identified as such by positive PCR results, most of them showed fever or cough as the primary clinical signs. Less common symptoms observed in clinically confirmed cases were hemoptysis, bloody sputum, mental disorders, and nasal congestion. The most common clinical samples for PCR-confirmed COVID-19 patients were obtained from throat, oropharyngeal, and nasopharyngeal swabs, while tears and conjunctival secretions seem to be the least common clinical samples for COVID-19 diagnosis among studies. Also, different conserved SARS-CoV-2 gene sequences could be targeted for qRT-PCR detection. The suggested molecular assay being used by most laboratories for the detection of SARS-CoV-2 is qRT-PCR. Conclusion. There is a worldwide concern on the COVID-19 pandemic and a lack of well-managed global control. Hence, it is crucial to update the molecular diagnostics protocols for handling the situation. This is possible by understanding the available advances in assays for the detection of the SARS-CoV-2 infection. Good sampling procedure and using samples with enough viral loads, also considering the onset symptoms, may reduce the qRT-PCR false-negative results in symptomatic COVID-19 patients. Selection of the most efficient primer-probe for target genes and samples containing enough viral loads to search for the existence of SARS-CoV-2 helps detecting the virus on time using qRT-PCR.

Clinical Accuracy of Instrument-Read SARS-CoV-2 Antigen Rapid Diagnostic Tests (Ag-IRRDTs)

“…As the research on specific problems [ 63 – 65 ] related to COVID-19 is exponentially growing, use of reliable, cost effective and fast means of diagnosing the disease become very valuable. In order to meet this need, numerous non-molecular tests such as SARS-CoV-2 Ag-RDTs and SARS-CoV-2 Ag-IRRDTs have been introduced by different manufacturers in the worldwide market.…”

Performance evaluation of STANDARD Q COVID‐19 Ag home test for the diagnosis of COVID‐19 during early symptom onset

“…A molecular diagnostic, that is, real‐time polymerase chain reaction (RT‐PCR) that has been widely used as a gold standard of detection depends on the sampling locations, probes of SARS‐CoV‐2 gene sequence that is used as a target for detection and days of symptom onset. 5 Therefore, considering that RT‐PCR is complex, expensive, and slow to deliver, 6 an alternative diagnostic method that is more user‐friendly and cost‐effective, which permits new cases to be isolated immediately, is in high demand.…”

Seroprevalence of COVID-19 in Blood Donors: A Systematic Review and Meta-Analysis

“…The researchers concluded that despite the fact that the spread of the epidemic has been somewhat prevented and that it has progressed globally to vaccination and treatment, the adequacy of vaccines and treatments has not yet been determined. Therefore, early detection of infected people remains the key to limiting the epidemic [ 17 ]. Determining the prevalence of SARS-CoV-2 in blood donors enables the control of virus circulation in healthy individuals and helps implement strategies to reduce transmission, especially in the absence of seroprevalence surveys.…”