Accurate covid-19 diagnosis is critical to the covid-19 response strategy. Early diagnosis improves care outcomes and reduces potential complications that may arise as a result of delayed diagnosis, which opens the door for disease progression into severity. However, accurate diagnosis is dependent on the accuracy of the available tests. The RT-PCR test was used as the reference standard by the various studies included in this review to determine the diagnostic accuracy of the index tests. RT-PCR is a Nucleic acid amplification test (NAAT) that is recommended as the gold standard for the confirmation of acute SARS-CoV-2 infections (3). The use of RT-PCR for COVID-19 diagnosis is limited in many settings due to its complexity, high cost compared to other assays, and longer sample-to-result turnaround time (31).
The other nucleic acid amplification tests whose diagnostic accuracy was determined in studies included in this review was the reverse transcriptase loop mediated isothermal amplification (RT-LAMP). In comparison to RT-PCR, RT-LAMP has higher sensitivity and specificity, is much faster, and does not require expensive reagents or instruments (32). In addition, studies in this review demonstrated the diagnostic accuracy of serological tests such as colloidal-gold lateral flow immunoassay (CLFIA), chemiluminescence immunoassay, enzyme linked immunosorbent assay (ELISA), and Quantum dot immunofluorescent assay. These tests detect antibodies produced by the human body in response to SARS-CoV-2 infection (3). For SARS-CoV-2, these tests rely on IgG/IgM affinity to recombinant spike (S) and nucleocapsid (N) proteins (31). They are particularly useful during the investigation of an ongoing outbreak and to support the retrospective assessment of an outbreak's attack rate or size (3). These tests, however, should not be used in isolation to identify acute cases in clinical care or for contact tracing (3).
Antigen tests, such as lateral flow immunoassays that detect the presence of SARS-CoV-2 viral proteins (antigens) in respiratory tract specimens, are also used in COVID diagnosis (3, 13). Due to the limitations of PCR, such as infrastructure, human resources, equipment, and reagents, WHO strongly encourages countries to begin using Antigen Rapid Diagnostic Tests (Ag-RDT) to detect infection as quickly as possible using the recommended testing algorithm (13) Currently, four WHO-approved Ag-RDTs are available for emergency use: SD Biosensor STANDARD Q, Sure Status COVID-19 Antigen Card Test, Abbott PanBio COVID-19 Ag Rapid Test Device (nasal), and Abbott PanBio COVID-19 Ag Rapid Test Device (nasopharyngeal swab) (13). The sensitivity and specificity of these antigen tests, however, were not determined in any of the studies included in this review.
It's surprising that none of the articles mentioned the costs of the tests. The fact that the majority of test kits in developing countries were donated or obtained through subsidized grants from international organizations/countries and collaborations (33) could explain why the costs were not stated. The cost of diagnostic tests is determined by several factors. For example, saliva collected samples have been found to be less expensive than nasopharyngeal collected samples (34). Costs are also affected by the type of test, as PCR tests are generally more expensive than rapid antigen tests (35). According to reports, PCR tests (which require an expensive laboratory to set up) have sometimes cost more than USD 100 in Sub-Saharan Africa (36). However, regardless of severity, testing people for COVID-19 is cost-effective and would reduce the overall risk of infections, hospitalization, and deaths (37). Importantly, there are ongoing efforts in Africa to make Covid-19 testing accessible and affordable. For example, the Access to COVID-19 Tools Accelerator (ACT-A) collaboration between UNICEF, COVID-19 test manufacturers, and other partners resulted in the procurement of some of the most affordable test kits for Africa. Each of these new kits costs $2.55, which is less than the $4.00 and $4.20 per test price of other COVID-19 rapid diagnostic tests currently available (38). Furthermore, the collaboration between Africa CDC and the Foundation for Innovative New Diagnostics is intended to strengthen the continent's capacity for developing COVID-19 diagnostic kits. Currently, nations such as Kenya, Morocco, Senegal and South Africa are manufacturing test kits (39).
The sensitivities of the diagnostic assays (the proportion of people with COVID-19 who were identified as positive) for RT-LAMP, real time RT-PCR, serological tests, and overall (all diagnostic tests combined) were 94.07%, 84.82%, 83.04%, and 87.55%, respectively. The specificities (proportion of people without COVID-19 who were identified as negative) for RT-LAMP, real time RT-PCR, serological tests, and overall (all diagnostic tests combined) was 99.60%, 96.79%, 96.97%, and 98.10%, respectively. In general, the diagnostic tests were better at identifying those without COVID-19 as negative than those with COVID-19 as positive, regardless of the population of interest tested. Our findings on serological test specificity are consistent with those of two systematic reviews of studies from both high-income and low- and middle-income countries which reported pooled sensitivities ranging from 66.0% (95%CI: 49.3–79.3%) for LFIAs measuring IgM and IgG to 84.3% (95%CI: 75.6–90.9%) for ELISAs measuring
IgM or IgG and pooled specificities ranging from 96.6% (95%CI: 94.3–98.2%) for LFIAs measuring IgM and IgG to 97.6% (95% CI: 93.2–99.4% ) for ELISAs measuring IgM or IgG (14, 40), the presence of articles from high income countries in the above studies may cause a slight discrepancy in results since we exclusively assessed studies from low- and middle-income countries. Bronchial lavage samples demonstrated the highest specificity and sensitivity (26) compared serum specimens (25), this means that respiratory specimens are more appropriate in regard to accuracy of test results. These findings are consistent with those of a systematic review of studies from both high-income and low- and middle-income countries, which found that rectal stools/swabs, urine, and plasma were less sensitive than sputum for detecting COVID-19 (40).
We noticed a dearth of evidence on accuracy, costs of tests and cost effectiveness of tests. We set out to evaluate the predictive value of tests, but we also noticed that studies did not report positive and negative predictive values, which are important when evaluating test accuracy. Because the costs of tests were not mentioned in any of the included studies, the cost effectiveness could not be determined. Furthermore, none of the studies included were from Africa, indicating a significant gap in evidence on the availability and utility of laboratory tests in Africa. Given the slow pace of vaccine access in Africa (41), COVID-19 will continue to pose a significant global health security risk in the region. Member states should prioritize both increasing access to vaccines to vaccinate the population and generating evidence on cost-effective laboratory testing options, given the central role testing plays in the COVID-19 response. Patients must be correctly diagnosed before receiving appropriate treatment. Furthermore, despite a plethora of evidence on COVID-19, there is a scarcity of studies conducted on the African continent, particularly on COVID-19 testing, and thus there is room for research in terms of primary studies in this particular area that has yet to be adequately explored.
Strengths & Limitations
The study will help to strengthen the evidence base on the effectiveness of COVID-19 laboratory testing strategies in hospitals and community populations in low- and middle-income countries (LMICs). The protocol was written in accordance with the guidelines for Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Some of the articles did not report on key information required to make a comprehensive assessment of diagnostic test accuracy, for example, only 64.3% and 57.1% of the articles reported sensitivity and specificity, respectively, and the majority lacked information on negative predictive value (NPV) and positive predictive value (PPV), so we are unable to highlight a diagnostic test's ability to make a diagnosis in terms of the discriminatory value of the test. Our efforts to synthesize evidence on the cost effectiveness of COVID-19 strategies were also hampered by a lack of studies reporting on the subject. We excluded studies not published in English hence this may introduce bias.