Predictive factors of COVID-19 in patients with negative RT-qPCR

Abstract

Objective: To evaluate the factors associated with false negatives in RT-qPCR in patients with mild-moderate symptoms of COVID-19. Materials and methods: This was a cross-sectional study that used a random sample of nonhospitalized patients from the primary care management division of the Healthcare Area of Leon (58 RT-qPCR-positive cases and 52 RT-qPCR-negative cases). Information regarding symptoms was collected and all patients were simultaneously tested using two rapid diagnostic tests ---RDTs (Combined ---cRDT and Differentiated ---dRDT). The association between symptoms and SARS-CoV-2 infection was evaluated by non-conditional logistic regression, with estimation of Odds Ratio. Results: A total of 110 subjects were studied, 52% of whom were women (mean age: 48.2 ± 11.0 years). There were 42.3% of negative RT-qPCRs that were positive in some RDTs. Fever over 38 • C (present in 35.5% of cases) and anosmia (present in 41.8%) were the symptoms most associated with SARS-CoV-2 infection, a relationship that remained statistically significant in patients with negative RT-qPCR and some positive RDT (aOR = 6.64; 95%CI = 1.33---33.13 and aOR = 19.38; 95% CI = 3.69---101.89, respectively). Conclusions: RT-qPCR is the technique of choice in the diagnosis of SARS-CoV-2 infection, but it is not exempt from false negatives. Our results show that patients who present mild or moderate

Characteristics and outcomes of clinically diagnosed RT-PCR swab negative COVID-19: a retrospective cohort study

“…Our results provide evidence to validate swab-negative COVID-19 as a real clinical entity commonly encountered in hospital settings, findings which have important implications for current clinical practice and public health guidance 15 . This is supported by reported cohorts in the literature of patients with clinical features of COVID-19 with negative RT-PCR swab testing and positive serological testing 16 – 18 .…”

Sample Adequacy Control (SAC) Lowers False Negatives and Increases the Quality of Screening: Introduction of “Non-Competitive” SAC for qPCR Assays

“…This has led to the introduction of the term "indeterminate, or weak positive result", as a clinical disclaimer for uncertainty in such cases. Strikingly, this new category of resulting (weak positives), during the current COVID-19 pandemic, approaches almost 40% of our day-to-day positive results (see also [12,13,[16][17][18][26][27][28]36,37]). Test resulting via relative normalization: Current qPCR assays, including COVID-19 screening tests, are typically qualitative (positive/negative, i.e., binary resulting).…”

“…Pitfalls in qPCR-based diagnosis can reduce the effectiveness of public infection control efforts [16,17,19,[26][27][28][29][30]. For example, even though emergency uses of different COVID-19 tests are authorized, recommendations made by CDC (https://www.cdc.gov/ coronavirus/2019-ncov/index.html or https://www.cdc.gov/coronavirus/2019-ncov/ lab/virus-requests.html, accessed on 6 June 2021) and WHO (https://www.who.int/ diagnostics_laboratory/eual/eul_0515_202_00_covid19_coronavirus_real_time_pcr_kit_ifu.…”

“…Pitfalls in qPCR-based diagnosis can reduce the effectiveness of public infection control efforts [ 16 , 17 , 19 , 26 , 27 , 28 , 29 , 30 ]. For example, even though emergency uses of different COVID-19 tests are authorized, recommendations made by CDC ( or , accessed on 6 June 2021) and WHO ( , accessed on 6 June 2021) which assure quality of testing must include: (a) control of sampling, (b) control of reaction inhibition, (c) control of the chemical integrity of biomarker (RNA, or DNA, or protein…) and (d) the control of sample processing/extraction.…”

Real-world assessment of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) nasopharyngeal swab testing in a region with a high burden of coronavirus disease 2019 (COVID-19)

“…Prior work has shown potential false negative results in nearly 20% of respiratory swab samples, however these were smaller studies, pooled analyses or studies conducted that varied substantially in test used, timing of testing, and comparator methods. [1][2][3][4] Thus, these findings may not be generalizable to U.S. hospital-based testing performed with FDAauthorized tests in CLIA-regulated laboratories. Reporting a true false negative rate for RT-PCR testing is infeasible given the lack of an established gold standard, the need to use limited testing supplies sparingly for clinical purposes, and the variability in access to different testing platforms.…”