FALSE-NEGATIVE RESULTS OF INITIAL RT-PCR ASSAYS FOR COVID-19: A SYSTEMATIC REVIEW

Ingrid Arevalo-Rodriguez; Diana Buitrago-Garcia; Daniel Simancas-Racines; Paula Zambrano-Achig; Rosa del Campo; Agustin Ciapponi; Omar Sued; Laura Martinez-Garcia; Anne Rutjes; Nicola Low; Jose A Perez-Molina; Javier Zamora

We applied the QUADAS-II tool to all included studies to reflect critical limitations in the validity of 220 the findings (Figure 3 and S3 Appendix). The reference standard domain was the most affected by 221 the potential risk of bias due to the lack of independence between the index test and the 222 confirmation of cases (repeated RT-PCR testing). Details about the criteria for positivity were not 223 provided by all included studies, and this domain was judged as under unclear risk and unclear 224 applicability concerns. In addition, the applicability of patient selection was judged as with great 225 concerns due to most of the studies selected patients who underwent both RT-PCR and Chest CT, 226 excluding patients who can be candidates to receive the index test in the current clinical practice. The pooled estimation of false-negative proportion was 0.085 (95% CI 0.034 to 0.196) estimated by 236 a mixed-effects logistic regression model. However, pooled data is affected by a considerable 237 between-study heterogeneity (tau-squared = 1.08; 95% CI= 0.27 to 8.28; p<0.001), since we are not 238 able to warrant that the average estimation provided by the meta-analysis is a valid and 239 representative estimation of the true value of the false-negative proportion in the current practice, 240