Characteristics and clinical outcomes of patients with pre-delta, delta and omicron SARS-CoV-2 infection in Indonesia (2020-2023): a multicentre prospective cohort study.

Background: Limited data exist from southeast Asia on the impact of SARS-CoV-2 variants and inactivated vaccines on disease severity and death among patients hospitalised with COVID-19. Methods: A multicentre hospital-based prospective cohort was enrolled from September 2020 through January 2023, spanning pre-delta, delta, and omicron periods. The participant hospitals were conveniently sampled based on existing collaborations, site willingness and available study resources, and included six urban and two rural general hospitals from East Nusa Tenggara, Jakarta, and North Sumatra provinces. Factors associated with severe disease and day-28 mortality were examined using logistic and Cox regression. Findings: Among 822 participants, the age-adjusted percentage of severe disease was 26.8% (95% CI 22.7-30.9) for pre-delta, 50.1% (44.0-56.2) for delta, and 15.2% (9.7-20.7) for omicron. The odds of severe disease were 64% (18-84%) lower for omicron than delta (p < 0.001). One or more vaccine doses reduced the odds of severe disease by 89% (65-97%) for delta and 98% (91-100%) for omicron. Age-adjusted mortality was 11.9% (8.8-15.0) for pre-delta, 24.4% (18.8-29.9) for delta and 9.6% (5.2-14.0) for omicron. The day-28 cumulative incidence of death was lower for omicron (9.2% [5.6-13.9%]) than delta (28.6% [22.0-35.5%]) (p < 0.001). Severe disease on admission was the predominant prognostic factor for death (aHR34.0 [16.6-69.9] vs mild-or-moderate; p < 0.001). After controlling for disease severity on admission as an intermediate, the risk of death was 48% (32-60%) lower for omicron than delta (p < 0.001); and 51% (38-61%; p < 0.001) lower for vaccinated participants than unvaccinated participants overall, and 56% (37-69%; p < 0.001) for omicron, 46% (-5 to 73%; p = 0.070) for pre-delta (not estimable for delta). Interpretation: Infections by omicron variant resulted in less severe and fatal outcomes than delta in hospitalised patients in Indonesia. However, older, and unvaccinated individuals remained at greater risk of adverse outcomes. Funding: University of Oxford and Wellcome Trust.

Development and validation of a pharmacogenomics reporting workflow based on the illumina global screening array chip.

Background: Microarrays are a well-established and widely adopted technology capable of interrogating hundreds of thousands of loci across the human genome. Combined with imputation to cover common variants not included in the chip design, they offer a cost-effective solution for large-scale genetic studies. Beyond research applications, this technology can be applied for testing pharmacogenomics, nutrigenetics, and complex disease risk prediction. However, establishing clinical reporting workflows requires a thorough evaluation of the assay's performance, which is achieved through validation studies. In this study, we performed pre-clinical validation of a genetic testing workflow based on the Illumina Global Screening Array for 25 pharmacogenomic-related genes. Methods: To evaluate the accuracy of our workflow, we conducted multiple pre-clinical validation studies. Here, we present the results of accuracy and precision assessments, involving a total of 73 cell lines. These assessments encompass reference materials from the Genome-In-A-Bottle (GIAB), the Genetic Testing Reference Material Coordination Program (GeT-RM) projects, as well as additional samples from the 1000 Genomes project (1KGP). We conducted an accuracy assessment of genotype calls for target loci in each indication against established truth sets. Results: In our per-sample analysis, we observed a mean analytical sensitivity of 99.39% and specificity 99.98%. We further assessed the accuracy of star-allele calls by relying on established diplotypes in the GeT-RM catalogue or calls made based on 1KGP genotyping. On average, we detected a diplotype concordance rate of 96.47% across 14 pharmacogenomic-related genes with star allele-calls. Lastly, we evaluated the reproducibility of our findings across replicates and observed 99.48% diplotype and 100% phenotype inter-run concordance. Conclusion: Our comprehensive validation study demonstrates the robustness and reliability of the developed workflow, supporting its readiness for further development for applied testing.

Clinical Epidemiology of Pediatric COVID-19 Delta Variant Cases From North Sumatra, Indonesia.

The Delta variant of SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) dominated the coronavirus disease 2019 (COVID-19) pandemic in 2021. Here we report the Delta variant among pediatric cases in North Sumatra, Indonesia, from June to July 2021. Whole-genome sequencing (WGS) from 18 new COVID-19 pediatric patients showed that six were B.1.459 and six were B.1.466.2, known variants in Indonesia in clade 20A. Six were the Delta variant B.1.617.2 of clade 21A, with five on one branch and one on a distant branch consistent with that patient's geographic separation, suggesting at least two introductions to the region. Variants tended to be spatially clustered, and four children with Delta variant had an adult infected household member, all of whom had lower real-time polymerase chain reaction cycle threshold (Ct) values compared with the child. No temporal trends were observed for Ct. These data support a paradigm shift with children being highly susceptible to the Delta variant and a priority for vaccination.

Accelerating Detection of Variants During COVID-19 Surges by Diverse Technological and Public Health Partnerships: A Case Study From Indonesia.

Early detection of Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) variants and use of data for public health action requires a coordinated, rapid, and high throughput approach to whole genome sequencing (WGS). Currently, WGS output from many low- and middle-income countries (LMIC) has lagged. By fostering diverse partnerships and multiple sequencing technologies, Indonesia accelerated SARS-CoV-2 WGS uploads to GISAID from 1,210 in April 2021 to 5,791 in August 2021, an increase from 11 submissions per day between January to May, to 43 per day between June to August. Turn-around-time from specimen collection to submission decreased from 77 to 5 days, allowing for timely public health decisions. These changes were enabled by establishment of the National Genomic Surveillance Consortium, coordination between public and private sector laboratories with WGS capability, and diversification of sequencing platform technologies. Here we present how diversification on multiple levels enabled a rapid and significant increase of national WGS performance, with potentially valuable lessons for other LMICs.

The COVID-19 surge in Indonesia: what we learned and what to expect.

Through the implementation of a test and trace system, disciplined public health measures, the acceleration of vaccinations, and a genome surveillance programme, LMICs such as Indonesia can prevent future outbreaks and survive the COVID-19 pandemic. https://bit.ly/3JBBSie.