Diagnostic performance and clinical implications of rapid SARS-CoV-2 antigen testing in Mexico using real-world nationwide COVID-19 registry data

Abstract

Background SARS-CoV-2 testing capacity is important to monitor epidemic dynamics and as a mitigation strategy. Given difficulties of large-scale quantitative reverse transcription polymerase chain reaction (qRT-PCR) implementation, rapid antigen tests (Rapid Ag-T) have been proposed as alternatives in settings like Mexico. Here, we evaluated diagnostic performance of Rapid Ag-T for SARS-CoV-2 infection and its associated clinical implications compared to qRT-PCR testing in Mexico. Methods We analyzed data from the COVID-19 registry of the Mexican General Directorate of Epidemiology up to April 30th, 2021 (n = 6,632,938) and cases with both qRT-PCR and Rapid Ag-T (n = 216,388). We evaluated diagnostic performance using accuracy measures and assessed time-dependent changes in the Area Under the Receiver Operating Characteristic curve (AUROC). We also explored test discordances as predictors of hospitalization, intubation, severe COVID-19 and mortality. Results Rapid Ag-T is primarily used in Mexico City. Rapid Ag-T have low sensitivity 37.6% (95%CI 36.6–38.7), high specificity 95.5% (95%CI 95.1–95.8) and acceptable positive 86.1% (95%CI 85.0–86.6) and negative predictive values 67.2% (95%CI 66.2–69.2). Rapid Ag-T has optimal diagnostic performance up to days 3 after symptom onset, and its performance is modified by testing location, comorbidity, and age. qRT-PCR (-) / Rapid Ag-T (+) cases had higher risk of adverse COVID-19 outcomes (HR 1.54 95% CI 1.41–1.68) and were older, qRT-PCR (+)/ Rapid Ag-T(-) cases had slightly higher risk or adverse outcomes and ≥7 days from symptom onset (HR 1.53 95% CI 1.48–1.59). Cases detected with rapid Ag-T were younger, without comorbidities, and milder COVID-19 course. Conclusions Rapid Ag-T could be used as an alternative to qRT-PCR for large scale SARS-CoV-2 testing in Mexico. Interpretation of Rapid Ag-T results should be done with caution to minimize the risk associated with false negative results.

Diabetes-Related Excess Mortality in Mexico: A Comparative Analysis of National Death Registries Between 2017–2019 and 2020

“…State-wide incidence, hospitalization, and deaths attributable to COVID-19 in Mexico were evaluated using data from the General Directorate of Epidemiology of the Mexican Ministry of Health, which is an open-source dataset that provides daily updated information of suspected COVID-19 cases 9 . COVID-19 cases are confirmed with a positive RT-PCR or rapid antigen test for SARS-CoV-2 9 , 13 , 21 . Estimates were obtained by COVID-19 cases with comorbid diabetes.…”

“…Second, by using state-level variables, we were unable to perform inferences for all identified associations at individual or even local levels; this is particularly relevant for socio-demographic inequalities, indicators of glycemic control (HbA1c), and COVID-19 seroprevalence, which may have significant heterogeneity within Mexican states at the municipal, local, and individual levels. Finally, since ascertainment of COVID-19 cases in Mexico has been insufficient 21 , many SARS-CoV-2 infections could have been undetected and some of these may have led to diabetes-related complications and deaths such as diabetic ketoacidosis or HHS 38 , 10 . Therefore, we cannot rule out that a portion of excess mortality formally ascribed to diabetes could have been in fact attributable to COVID-19, despite the fact that ascertainment by INEGI is generally robust 39 .…”

Diabetes-related excess mortality in Mexico: a comparative analysis of national death registries between 2017-2019 and 2020

“…By using state-level variables, we were unable to perform inferences for all identified associations at individual or even local levels; this is particularly relevant for socio-demographic inequalities, indicators of glycemic control, and COVID-19 seroprevalence which may have significant heterogeneity within Mexican states at both the municipal, local, and individual level. Finally, since ascertainment of COVID-19 cases in Mexico has been insufficient 17 , many SARS-CoV-2 infections could have been undetected and some of these may have led to diabetes-related complications such as diabetic ketoacidosis or HHS 29,9 . Therefore, we cannot rule out that a portion of excess mortality formally ascribed to diabetes could have been in fact in part attributable to COVID-19, despite the fact that ascertainment by INEGI is generally robust 30 .…”

“…Namely, COVID-19 seroprevalence, COVID-19 hospitalization rates, incidence of COVID-19, and COVID-19 deaths in people with diabetes. These estimates were derived from the General Directorate of Epidemiology of the Mexican Ministry of Health dataset and ENSANUT COVID 2020 for COVID-19 seroprevalence data 17 .…”

COVID-19 patients with increasing age experience differential time to initial medical care and severity of symptoms

“…Importantly, patients in different age categories have had important differences in SARS-CoV-2 testing rates in Mexico City, with the highest testing rates being in young adults and middle-aged adults; the lowest testing rates occurred in the <20 and ≥80 year categories. Although an important increase in testing capacity occurred with the introduction of antigen tests in Mexico City after 28 October 2020 [ 18 ], this pattern of testing rates by age category did not change, which suggests that low availability of testing may not determine whether younger people and older adults seek testing or not. Rather, lower testing rates in older adults, children and adolescents could be explained by the tendency to stay at home during the pandemic [ 19 ], as well as lower contacts with other people, and lower mobility indexes than young adults and middle-aged adults [ 20 ].…”