Role and Utility of COVID-19 Laboratory Testing in Low-and Middle-Income Countries: A Systematic Review of Diagnostic Test Accuracy Studies (original) (raw)

2023, Research Square (Research Square)

Background Accurate and affordable laboratory testing is key for timely diagnosis and appropriate management of COVID-19 patients. As such, robust evidence regarding diagnostic accuracy and costs of available tests would inform policy and practice especially in resource-limited settings. We aimed to determine the diagnostic test accuracy, costs and utility of laboratory test strategies for COVID-19 in LMICs. Methods This was a multi-staged protocol-driven systematic review conducted in line with PRISMA guidelines for diagnostic test accuracy studies (PRISMA-DTA). We searched for relevant literature in six databases including: PubMed, Google Scholar, MEDLINE, SCOPUS, Web of Science, and the WHO Global Index Medicus. Studies were screened and coded in pairs. We conducted a structured narrative and quantitative synthesis of the results guided by Fryback and Thornbury framework. The primary outcome was COVID-19 diagnostic test accuracy. The results were reported following the PRISMA-DTA. Results Thirteen articles were from studies in China and one from Turkey. All studies included used the Real-time polymerase chain reaction test (RT-PCR) as their reference test. 21.4% (n = 3) of articles were determining the diagnostic accuracy of the PCR test. The remaining studies (n = 11) used other COVID-19 tests as the index tests. It is generally observed that the tests were more speci c than sensitive pooled sensitivity and speci city was 87.6%, (95% CI: 82.2% − 93%), 98.1% (95% CI: 96.4%-100%) respectively. The Reverse-transcription loop-mediated isothermal ampli cation (RT-LAMP) tests had the highest sensitivity as compared to RT-PCR, serological and chemiluminescent immunoassays (CLIA). The speci city and sensitivity of the tests were highest when bronchial lavage samples were used and lowest with the use of serum specimens/sample. No study documented cost of the diagnostic test used. Conclusion The evidence on COVID-19 testing in LMICs is summarized in this systematic review. The RT-PCR was used as the reference test in all studies. The diagnostic assays' combined sensitivity and speci city were 87.55% and 98.10%, respectively. In the reviewed literature, no study reported on the cost and cost effectiveness of diagnostic tests. Finally, no studies were carried out on the African continent. Registration: This review was registered in PROSPERO No. CRD42020209528. And the protocol published here https://bmjopen.bmj.com/content/11/10/e050296 Background The coronavirus disease (COVID-19) is a pandemic that resulted into serious and signi cant morbidity and mortality globally. In order to prevent the spread of the disease, early and accurate diagnosis is critical (1). Therefore, proper clinical management and control of this pandemic necessitates prioritizing rapid laboratory testing of appropriate specimens from patients meeting the suspected case de nition for COVID-19 and diagnosis (2). Currently, the gold standard for the diagnosis of SARS-CoV-2 infection involves detection of viral nucleic acid using nucleic acid ampli cation tests (NAATs) such as the reverse transcription polymerase chain reaction (RT-PCR)(3). Nucleic acid ampli cation assays target regions on the SARS-CoV-2 genome particularly the E, RdRP, N and S genes (3). The RT-PCR assay is characterized by rapid detection, high sensitivity, and speci city hence recommended for diagnosis of early COVID-19 infections (4). However, the RT-PCR assay is complex, time-consuming (long turnaround time) and associated with risk of eliciting false-negative and false-positive results because it is easily affected by factors such as collection time, sample type, and nature of sample preservation (1, 5, 6). Each PCR test may cost hundreds of dollars and requires the use of sophisticated equipment, expensive reagents and highly skilled labor (1, 7) all of which constitute a potential barrier to majority of the population. Furthermore, this method is unable to meet the principles of early detection, early isolation, and early treatment hence inauspicious to the prevention and control of the epidemic (5). Besides the NAATs, immunoassays have been developed as supplemental tools for rapid detection of antibodies (IgM and IgG) against COVID-19 or SARS-CoV-2 antigens (using rapid antigen tests) in biological samples like nasopharyngeal secretions (1, 8-11). The serological immunoassays detect antibodies to SARS-CoV-2 and these may include the enzyme-linked immunosorbent assays (ELISAs), chemiluminescent immunoassays (CLIAs) and lateral ow immunoassays (LFIAs) (2, 12). Serological tests are indirect measures of the infection and have proven to be useful in con rming past COVID-19 infections (2, 8). They therefore aid in investigating an ongoing outbreak, retrospective assessment of the attack rate or extent of an outbreak (2). Rapid antigen tests such as lateral ow immunoassays that detect the presence of SARS-CoV-2 viral proteins (antigens) in respiratory tract specimens are also currently used in diagnosis of COVID (3, 13). They are based on immunochromatography, which employs antibodies spotted onto nitrocellulose membranes that interact with speci c antigens from the patient sample (1). Immunoassays are less costly, more accessible to patients and have a short turnaround time compared to the RT-PCR assays (1, 2). Therefore, they are very important for real-time patient management and infection control decisions. However, they are likely to suffer from poor sensitivity in early infection mostly due to the low infectious burden or sampling variability (8). Existing evidence also highlights inconsistencies in the diagnostic accuracy of these assays. More so, most of the evidence on diagnostic accuracy is largely from developed countries, where the Covid-19 curves Data Sources We performed article search was in the following databases; PubMed, Google Scholar, MEDLINE, SCOPUS, Web of Science and the WHO Global Index Medicus. Additional targeted searches were conducted in websites of organizations championing COVID-19 management for grey literature including but not limited to manufacturers of COVID-19 laboratory tests, centers for disease control and prevention (CDC) in Africa, China, Europe and the USA; World Health Organization (WHO); specialized research institutions in Africa such as the