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.

Car-borne survey and dose assessment from external radiation exposure in Bangka Island.

With a history of more than 200 years of tin mining, Bangka Island has brought along a byproduct of heavy minerals containing radionuclide elements. There are some concerns about this byproduct material contributing to natural radiation in the environment. In this study, a car-borne survey was conducted to accurately assess natural background radiation in Bangka Island. Indoor and outdoor ambient dose rates in 146 houses were also measured to assess the radiation dose from external exposure received by the public. Soil samples were collected and measured using a gamma spectroscopy system to evaluate the contributions of specific radionuclides to external terrestrial exposure. From 3790 measurement points during the car-borne survey, the highest ambient dose equivalent rate was 596 nSv h-1 measured in Muntok area, with a mean value of 101 nSv h-1 and a median value of 95 nSv h-1. The ambient dose equivalent rate distribution map showed a relatively higher value in the northern coastal area of the island, where the Pemali tin deposit is located. The annual effective dose received from external radiation in the 146 houses in Bangka Island ranged from 0.44 to 1.30 mSv year-1, with a median value of 0.66 mSv year-1. The soil contained a relatively high amount of thorium (232Th), which contributed 69% to external radiation exposure in Bangka Island.

Antibody Responses and Reactogenicity of a Heterologous, Full-Dose Messenger RNA-1273 Booster in Heavily SARS-CoV-2-Exposed CoronaVac-Vaccinated Health-Care Workers in Indonesia: A Real-World Observational Study.

Real-world data on heterologous boosting with messenger RNA (mRNA)-1273 (Moderna) after inactivated COVID-19 vaccination are limited. We report mRNA-1273 boosting in heavily SARS-CoV-2-exposed Indonesian health-care workers who received a two-dose CoronaVac 6 months prior. Between August and November 2021, we measured SARS-CoV-2 spike-specific IgG binding antibody (Bab) titers in all 304 participants, and neutralizing antibody titers in a random subset of 71 participants, on stored paired serum samples taken before and 28 days after a full-dose (100-µg) mRNA-1273 booster. At the time of the mRNA-1273 boost, 107 participants (35.2%) were not previously infected (naive vaccinated), 42 (13.8%) were infected before CoronaVac (infected vaccinated), and 155 (51.0%) were infected after CoronaVac (mostly during the Delta wave; vaccinated infected). At time of the mRNA-1273 boost, neutralizing antibodies could still be detected in 83% of participants (59 of 71) overall, 60% of naive-vaccinated participants (15 of 25), 95.7% of vaccinated-infected participants (22 of 23), and 95.7% of infected vaccinated participants (22 of 23). After the mRNA-1273 boost, 100% of participants (71 of 71) had neutralizing antibody activity, with increases in median Bab and neutralizing antibody serum titers of 9.3- and 27.0-fold overall, 89.1- and 2,803.4-fold in naive-vaccinated participants, 15.9- and 19.9-fold in infected-vaccinated participants, and 2.2- and 18.4-fold in vaccinated-infected participants. In the multivariable analysis, Bab titers after the mRNA-1273 boost were greatest in individuals who had a previous virus breakthrough post-CoronaVac, and when a longer time period (> 4 months) had elapsed since the most recent prior "spike antigen exposure" (either second CoronaVac or virus breakthrough). Overall, adverse reactions were mild and short-lived. In conclusion, a full-dose mRNA-1273 booster after CoronaVac was well tolerated and immunogenic after 28 days, including in those with very low antibody levels.

Evaluating Saliva Sampling with Reverse Transcription Loop-mediated Isothermal Amplification to Improve Access to SARS-CoV-2 Diagnosis in Low-Resource Settings.

Standard diagnosis of SARS-CoV-2 by nasopharyngeal swab (NPS) and real-time reverse transcriptase-polymerase chain reaction (PCR) requires a sophisticated laboratory, skilled staff, and expensive reagents that are difficult to establish and maintain in isolated, low-resource settings. In the remote setting of tropical Sumba Island, eastern Indonesia, we evaluated alternative sampling with fresh saliva (FS) and testing with colorimetric loop-medicated isothermal amplification (LAMP). Between August 2020 and May 2021, we enrolled 159 patients with suspected SARS-CoV-2 infection, of whom 75 (47%) had a positive PCR on NPS (median cycle threshold [Ct] value: 27.6, interquartile range: 12.5-37.6). PCR on FS had a sensitivity of 72.5% (50/69, 95% confidence interval [CI]: 60.4-82.5) and a specificity of 85.7% (66/77, 95% CI: 75.9-92.6), and positive (PPV) and negative (NPV) predictive values of 82.0% (95% CI: 0.0-90.6) and 77.6% (95% CI: 67.3-86.0), respectively. LAMP on NPS had a sensitivity of 68.0% (51/75, 95% CI: 56.2-78.3) and a specificity of 70.8% (63/84, 95% CI: 58.9-81.0), with PPV 70.8% (95% CI: 58.9-81.0) and NPV 72.4% (95% CI: 61.8-81.5%). LAMP on FS had a sensitivity of 62.3% (43/69, 95% CI: 49.8-73.7%) and a specificity of 72.7% (56/77, 95% CI: 61.4-82.3%), with PPV 67.2% (95% CI: 54.3-78.4) and NPV 68.3% (95% CI: 57.1-78.1%). LAMP sensitivity was higher for NPS and FS specimens with high viral loads (87.1% and 75.0% for Ct value < 26, respectively). Dried saliva on filter paper was stable for 4 days at room temperature. LAMP on either NPS or FS could offer an accessible alternative for SARS-CoV-2 diagnosis in low-resource settings, with potential for optimizing sample collection and processing, and selection of gene targets.