Vaccines alone are no silver bullets: a modeling study on the impact of efficient contact tracing on COVID-19 infection and transmission (preprint)

BackgroundThe computer simulation presented in this study aimed to investigate the effect of contact tracing on COVID-19 transmission and infection in the context of rising vaccination rates. MethodsThis study proposed a deterministic SEIRV model with contact tracing and vaccination components. We initialized some parameters using the Malaysian COVID-19 data to inform the model. We defined contact tracing effectiveness as the proportion of contacts of a positive case that was successfully traced and vaccination rate as the proportion of daily doses administered per population in Malaysia. Sensitivity analyses on the untraced and infectious populations were conducted. The study presented in silico findings on multiple scenarios by varying the contact tracing effectiveness and daily vaccination rates. ResultsAt a vaccination rate of 1.4%, a contact tracing with the effectiveness of 70% could delay the peak of untraced asymptomatic cases by 17 days and reduce the highest number of daily cases by 70% compared with a 30% contact tracing effectiveness. A similar trend was observed for symptomatic cases when a similar experiment setting was used. We also performed sensitivity analyses by using different combinations of contact tracing effectiveness and vaccination rates. In all scenarios, the effect of contact tracing on COVID-19 incidence persisted for both asymptomatic and symptomatic cases. ConclusionDespite testing only on two public health and social measures (PHSMs), we observed the scenario with low contact tracing and increasing vaccination rates successfully mimicked the current transmission trend in Malaysia. Hence, while vaccines are progressively rolled out, efficient contact tracing must be rapidly implemented concurrently to reach, find, test, isolate, and support the affected populations to bring the pandemic under control.

A Viral Fragmentation Signature for SARS-CoV-2 in Clinical Samples Correlating with Contagiousness (preprint)

The viral load of SARS-CoV-2 in clinical samples as measured by the primary diagnostic tool of RT-PCR is an imperfect readout for infection potential as most targeted assays designed for sensitivity, indiscriminately detect short and long RNA fragments, although infectivity is embodied only in the whole virus and its intact genome. Here, we used next-generation sequencing (NGS) to characterize 155 clinical samples and show sensitive and quantitative detection of viral RNA which confirmed subgenomic RNA in 57.6% of samples and provided a novel method to determine relative integrity of viral RNA in samples. The relative abundance of long fragments quantified as a viral fragmentation score was positively associated with viral load and inversely related to time from disease onset. An empirically determined score cut-off for presence of substantially fragmented RNA was able to identify 100% of samples collected after 8 days of illness with poor infection potential in line with current clinical understanding of infectiousness of SARS-CoV-2. The quantification of longer fragments in addition to existing short targets in an NGS or RT-PCR-based assay could provide a valuable readout of infection potential simultaneous to the detection of any fragments of SARS-CoV-2 RNA in test samples.

MassMark: A Highly Scalable Multiplex NGS-based Method for High-Throughput, Accurate and Sensitive Detection of SARS-CoV-2 for Mass Testing (preprint)

Mass testing has been proposed as a strategy to address and contain the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. We have developed MassMark, a novel and highly scalable multiplex method that employs next generation sequencing for high-throughput, accurate and sensitive detection of SARS-CoV-2, while minimizing handling complexity and resources by utilizing a serial pooling strategy to accommodate over 9,000 samples per workflow. Analytical validation showed that MassMark was able to detect SARS-CoV-2 RNA down to a level of 100 copies per reaction. We evaluated the clinical performance of MassMark in a simulated screening testing with 22 characterized samples from three different sources (nasopharyngeal swabs, nasal swabs and saliva), comprising of 12 SARS-CoV-2 positive samples with mid to late Ct values (range: 22.98-32.72) and 10 negative samples. There was one false negative and no false positives, giving an overall sensitivity and specificity of 91.67% and 100% respectively, when compared against an optimized RT-PCR test with a target size within 70 bp (CDC 2019-nCoV Real-Time RT-PCR Diagnostic Panel).

A Latent Class Analysis of COVID-19 Testing Response, Globalisation, and Democracy with National COVID-19 Outcomes: A Global Ecological Study (preprint)

Background: The Coronavirus Disease 2019 (COVID-19) pandemic impacts each country and region differently as countries and regions vary in terms of socioeconomic capacity, healthcare systems capacity, and pre-existing population characteristics. In this study, we analysed the associations of country and region-level attributes with four COVID-19-related outcomes after controlling for testing response by delineated classes of countries and regions. Methods: Country and region-level data of the exposures and COVID-19-related outcomes were obtained from several sources. Two hundred eighteen countries and regions were delineated into three classes using latent class analysis (LCA) based on the following variables: total tests performed per million of the population, current health expenditure per capita, and International Health Regulations (IHR) core capacity index. Bivariate analysis and multivariable linear regression were conducted to detect the associations of country and region-level attributes with COVID-19-related outcomes after controlling for testing response by class. Findings: LCA revealed three classes of countries which we labelled post-hoc as low testing, moderate testing, and high testing. Multivariable linear regression revealed that measures of globalisation, such as the international migrant stock and the number of air travel passengers reported, were positively associated with both total COVID-19 cases and deaths. We also found that democracy, measured through the Freedom in the World index, was negatively associated with total COVID-19 cases per million of the population and positively associated with total COVID-19 deaths. Interpretation: Our findings show that countries and regions with a large migrant stock and air travel, as well as democratic governance structures, may have poorer COVID-19 outcomes, and there is a need for the re-evaluation of their pandemic response. Funding: No funding to declare.Declaration of Interests: None.

Validation of Saliva and Self-Administered Nasal Swabs for COVID-19 Testing (preprint)

Background Active cases of COVID-19 has primarily been diagnosed via RT-PCR of nasopharyngeal (NP) swabs. Saliva and self-administered nasal (SN) swabs can be collected safely without trained staff. We aimed to test the sensitivity of naso-oropharyngeal saliva and SN swabs compared to NP swabs in a large cohort of migrant workers in Singapore. Methods We recruited 200 male adult subjects: 45 with acute respiratory infection, 104 asymptomatic close contacts, and 51 confirmed COVID-19 cases. Each subject underwent NP swab, SN swab and saliva collection for RT-PCR testing at 1 to 3 timepoints. We additionally used a direct-from-sample amplicon-based next-generation sequencing (NGS) workflow to establish phylogeny. Results Of 200 subjects, 91 and 46 completed second and third rounds of testing, respectively. Of 337 sets of tests, there were 150 (44.5%) positive NP swabs, 127 (37.7%) positive SN swabs, and 209 (62.0%) positive saliva. Test concordance between different sample sites was good, with a kappa statistic of 0.616 for NP and SN swabs, and 0.537 for NP and saliva. In confirmed symptomatic COVID-19 subjects, the likelihood of a positive test from any sample fell beyond 14 days of symptom onset. NGS was conducted on 18 SN and saliva samples, with phylogenetic analyses demonstrating lineages for all samples tested were Clade O (GISAID nomenclature) and lineage B.6 (PANGOLIN nomenclature). Conclusion This study supports saliva as a sensitive and less intrusive sample for COVID-19 diagnosis and further delineates the role of oropharyngeal secretions in increasing the sensitivity of testing. However, SN swabs were inferior as an alternate sample type. Our study also provides evidence that a straightforward next-generation sequencing workflow can provide direct-from-sample phylogenetic analysis for public health decision-making.