One important factor that influences the sensitivity of RDTs is a type of sample. Studies that evaluated different types of samples revealed that nasal examination swabs and saliva specimens for RDTs are associated with lower sensitivity (30). Our results showed the most collected samples were nasopharyngeal swabs; in this line, it was shown examine nasopharyngeal swab, the sensitivity of RDTs results increases (10, 41). After evaluating various specimens, Yamayoshi et al. found that soaking specimen directly to the lysing buffer can improve RDTs sensitivity (41).
Our analysis has shown the higher sensitivity observes in infected patients with lower Ct value by RT-PCR. In fact, in asymptomatic patients or patients with lower viral load, the sensitivity of RDTs decreases (7, 9, 42). In the subsequent analysis, Cerutti et al. examine the STANDARD Q COVID-19 Ags (R-Ag) among infected patients; they demonstrated that patients who were positive for R-Ag have higher viral load and lower Ct value are symptomatic, and this can be an explanation for higher RDTs sensitivity in symptomatic subjects (29). In contrast, Pilarowski et al. reported that asymptomatic subjects should not rule out because regardless of symptoms, it can be possible that asymptomatic patients have a high viral load (43). In this regard, to the assessment of RDTs sensitivity, Eshghifar et al. used various concentration of heat-inactivated COVID-19 virus to assess a cut-off detection for RDTs; their findings showed, they could not determine a cut-off and reported RDTs to be positive just in patients with high viral load (31); whereas CK Mak et al. by using cell culture, the limiting threshold of detection for RDTs reported 18.57 (28).
Additional to the RDTs, some writers compared the sensitivity of cell culture with RT-PCR for detecting COVID-19. Like the RDTs, the result showed that in cell culture with lower viral load, the sensitivity reduces (9). This can be explained by the fact that specimens with low viral load or Ct value > 30 do not cultured, suggesting low infectivity of virus (44).
Conducting RDTs with various assays is a serious discussion that can cause emerging different sensitivity. A study that set out to determine sensitivity of various assay for RDTs found different results for positive controls in different assays; which could offer the current methods detect different Ags and subsequently influence test accuracy (39).
The possible interference of time of testing cannot be ruled out. Some researchers revealed that testing less than 5 days from the onset of symptoms increases sensitivity (9, 10, 23, 31). It is inconsistent with previous reports that a load of infectious virus decreases after 7–10 days (10, 45). In one recent well-known recent experiment, Albert et al. with considering the age of participants found the sensitivity of RDTs is lower in pediatrics than adults (9).
Some recent attention has focused on the benefits of rapid Abs COVID-19 detection as one of the point-of-care tests. Our findings demonstrated that the rapid Ab detection has lower sensitivity than RDTs; it is accompanied by high false positives. Pere et al., in their investigation, showed a history of recent infection with cold Abs increase the false positive Ab rapid test, especially for IgM, which reduce the validation of the test (11). Fabre et al. performed a similar survey, but in pregnancy, surprisingly, their findings showed, the false positive is higher in pregnant women (32). One reason for the low accuracy of the rapid Ab test can be pointed out to the short-term immunity in such patients (46).
Much of the current systematic and meta-analysis literature focused on the accuracy of serological tests, and as the expected, their findings have shown lower accuracy of serological tests (12, 47, 48). Despite of aboard vaccination, still there is a remarkable new case of infection, especial in low to middle income countries. Hence, the progression in rapid diagnostic with lower costs still is a major challenging. The findings of this meta-analysis have important implication for developing RDTs in diagnosis of COVID-19 infection with the possible highest sensitivity and specificity.