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Cross-sectional cycle threshold values reflect epidemic dynamics of COVID-19 in Madagascar.

ABSTRACT: As the national reference laboratory for febrile illness in Madagascar, we processed samples from the first epidemic wave of COVID-19, between March and September 2020. We fit generalized additive models to cycle threshold (Ct) value data from our RT-qPCR platform, demonstrating a peak in high viral load, low-Ct value infections temporally coincident with peak epidemic growth rates estimated in real time from publicly-reported incidence data and retrospectively from our own laboratory testing data across three administrative regions. We additionally demonstrate a statistically significant effect of duration of time since infection onset on Ct value, suggesting that Ct value can be used as a biomarker of the stage at which an individual is sampled in the course of an infection trajectory. As an extension, the population-level Ct distribution at a given timepoint can be used to estimate population-level epidemiological dynamics. We illustrate this concept by adopting a recently-developed, nested modeling approach, embedding a within-host viral kinetics model within a population-level Susceptible-Exposed-Infectious-Recovered (SEIR) framework, to mechanistically estimate epidemic growth rates from cross-sectional Ct distributions across three regions in Madagascar. We find that Ct-derived epidemic growth estimates slightly precede those derived from incidence data across the first epidemic wave, suggesting delays in surveillance and case reporting. Our findings indicate that public reporting of Ct values could offer an important resource for epidemiological inference in low surveillance settings, enabling forecasts of impending incidence peaks in regions with limited case reporting.

SUBMITTER: Andriamandimby SF

PROVIDER: S-EPMC8628610 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe ability to predict likely prognosis and infectiousness for patients with COVID-19 would aid patient management decisions. Diagnosis is usually via real-time PCR, and it is unclear whether the semi-quantitative capability of this method, determining viral load through cycle threshold (Ct) values, can be leveraged.ObjectivesWe aim to review available knowledge on correlations between SARS-COV-2 Ct values and patient- or healthcare-related outcomes to determine whether Ct values provide useful clinical information.SourcesA PubMed search was conducted on 1 June 2020 based on a search strategy of (Ct value OR viral load) AND SARS-CoV-2. Data were extracted from studies reporting on the presence or absence of an association between Ct values, or viral loads determined via Ct value, and clinical outcomes.ContentData from 18 studies were relevant for inclusion. One study reported on the correlation between Ct values and mortality and one study reported on the correlation between Ct values and progression to severe disease; both reported a significant association (p < 0.001 and p = 0.008, respectively). Fourteen studies reported on the correlation between Ct value or viral loads determined via Ct value and disease severity, and an association was observed in eight (57%) studies. Studies reporting on the correlation of viral load with biochemical and haematological markers showed an association with at least one marker, including increased lactate dehydrogenase (n = 4), decreased lymphocytes (n = 3) and increased high-sensitivity troponin I (n = 2). Two studies reporting on the correlation with infectivity showed that lower Ct values were associated with higher viral culture positivity.ImplicationsData suggest that lower Ct values may be associated with worse outcomes and that Ct values may be useful in predicting the clinical course and prognosis of patients with COVID-19; however, further studies are warranted to confirm clinical value.

Project description:BackgroundThe distribution of population-level real-time reverse transcription-polymerase chain reaction (RT-PCR) cycle threshold (Ct) values as a proxy of viral load may be a useful indicator for predicting COVID-19 dynamics.ObjectiveThe aim of this study was to determine the relationship between the daily trend of average Ct values and COVID-19 dynamics, calculated as the daily number of hospitalized patients with COVID-19, daily number of new positive tests, daily number of COVID-19 deaths, and number of hospitalized patients with COVID-19 by age. We further sought to determine the lag between these data series.MethodsThe samples included in this study were collected from March 21, 2021, to December 1, 2021. Daily Ct values of all patients who were referred to the Molecular Diagnostic Laboratory of Iran University of Medical Sciences in Tehran, Iran, for RT-PCR tests were recorded. The daily number of positive tests and the number of hospitalized patients by age group were extracted from the COVID-19 patient information registration system in Tehran province, Iran. An autoregressive integrated moving average (ARIMA) model was constructed for the time series of variables. Cross-correlation analysis was then performed to determine the best lag and correlations between the average daily Ct value and other COVID-19 dynamics-related variables. Finally, the best-selected lag of Ct identified through cross-correlation was incorporated as a covariate into the autoregressive integrated moving average with exogenous variables (ARIMAX) model to calculate the coefficients.ResultsDaily average Ct values showed a significant negative correlation (23-day time delay) with the daily number of newly hospitalized patients (P=.02), 30-day time delay with the daily number of new positive tests (P=.02), and daily number of COVID-19 deaths (P=.02). The daily average Ct value with a 30-day delay could impact the daily number of positive tests for COVID-19 (β=-16.87, P<.001) and the daily number of deaths from COVID-19 (β=-1.52, P=.03). There was a significant association between Ct lag (23 days) and the number of COVID-19 hospitalizations (β=-24.12, P=.005). Cross-correlation analysis showed significant time delays in the average Ct values and daily hospitalized patients between 18-59 years (23-day time delay, P=.02) and in patients over 60 years old (23-day time delay, P<.001). No statistically significant relation was detected in the number of daily hospitalized patients under 5 years old (9-day time delay, P=.27) and aged 5-17 years (13-day time delay, P=.39).ConclusionsIt is important for surveillance of COVID-19 to find a good indicator that can predict epidemic surges in the community. Our results suggest that the average daily Ct value with a 30-day delay can predict increases in the number of positive confirmed COVID-19 cases, which may be a useful indicator for the health system.

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Cross-sectional cycle threshold values reflect epidemic dynamics of COVID-19 in Madagascar.

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