Suwarti Suwarti’s research while affiliated with Oxford University Clinical Research Unit and other places

Background Data on the dynamics and persistence of humoral immunity against SARS-CoV-2 after primary vaccination with two-dose inactivated vaccine (CoronaVac) are limited. This study evaluated the sequential effects of prior infection, heterologous boosting with mRNA-1273 (Moderna), and the occurrence of Omicron vaccine-breakthrough infection (VBI) thereafter. Methods We evaluated anti-spike IgG (Abbott) and neutralising (cPASS/GenScript) antibody (nAb) titers up to one year after mRNA-1273 boost in two-dose-CoronaVac-primed Indonesian healthcare workers (August 2021-August 2022). We used linear mixed modeling to estimate the rate of change in antibody levels, and logistic regression to examine associations between antibody levels and VBI. Results Of 138 participants, 52 (37.7%) had a prior infection and 78 (56.5%) received an mRNA-1273 booster. After two-dose CoronaVac, antibody titers had significantly declined within 180 days, irrespective of prior infection. After mRNA-1273 booster, anti-spike IgG (1.47% decline/day) and Omicron B.1.1.529/BA.2 nAbs declined between day 28–90, and IgG titers plateaued between day 90–360. During the BA.1/BA.2 wave (February–March 2022), 34.6% (27/78) of individuals experienced a VBI (median 181 days after mRNA-1273), although none developed severe illness. VBI was associated with low pre-VBI anti-spike IgG and B.1.1.529/BA.2 nAbs, which were restored post-VBI. Conclusions mRNA-1273 booster after two-dose CoronaVac did not prevent BA.1/BA.2 VBI. Periodic vaccine boosters may be warranted against emerging SARS-CoV-2 variants.

Background To reduce the high HIV incidence among key populations in Indonesia, we implemented a clinical pathway for screening, diagnosis and treatment of acute HIV infection (AHI) in sexual health clinics in Jakarta and Bali. This paper presents a cohort profile and analysis of baseline data on the study uptake, diagnostic yield, and estimated AHI prevalence and screening cascade outcomes. Methods We performed a baseline analysis of 1879 individuals who underwent AHI screening at three sexual health clinics in Jakarta and Bali between May and December 2023, comprising a risk-score assessment, fourth-generation antibody/p24 antigen-based rapid diagnostic test (RDT; Abbott Determine HIV Early Detect) and HIV-PCR (Xpert) testing. Results Median age was 27 years (IQR24-31), and 75.4% were male. Men who have sex with men (MSM) accounted for 50.4%, clients of sex workers 20.1%, and sex workers 5.2%. Of 1866 participants tested at study enrolment, 113 (6.1% [113/1866]) had chronic HIV (antibody-positive) and 6 (0.34% [6/1748]) had AEHI. HIV-PCR testing led to a 5.3% (95%CI1.9-11.2) increase in confirmed HIV diagnoses. The number needed to test to detect one AEHI case was 291 (1748/6) overall and 169 (842/5) among MSM. Overall HIV and AHI prevalence was 6.4% (95%CI 5.3-7.6; 119/1866) and 0.34% (95%CI0.12-0.74; 6/1748) overall; and 10.8% (95%CI8.9-13.0; 102/940) and 0.53% (95%CI 0.17-1.2; 5/940) among MSM. The Abbott Determine HIV Early Detect RDT only detected 2 (18.2%) of 11 AEHI cases. 113 (95.0%) newly diagnosed individuals were linked to care and started ART, of whom 75 (66.4%) on the same day and 104 (92.0%) within a week (median 0 days, range 0-93). Conclusion AHI screening, diagnosis and prompt treatment is feasible among high-risk urban MSM in Indonesia. Further evaluations are needed to estimate clinical impact and cost-effectiveness of AHI screening in this setting. The study continues accrual and follow-up, and provides a platform for future immuno-virological, social science, and intervention studies in Indonesia.

Introduction: Acute kidney injury (AKI) has been identified as one of the most common and significant problems in hospitalized patients with COVID-19. However, studies examining the relationship between COVID-19 and AKI in low- and low-middle income countries (LLMIC) are lacking. Given that AKI is known to carry a higher mortality rate in these countries, it is important to understand differences in this population. Methods: This prospective, observational study examines the AKI incidence and characteristics of 32,210 patients with COVID-19 from 49 countries across all income levels who were admitted to an intensive care unit during their hospital stay. Results: Among patients with COVID-19 admitted to the intensive care unit, AKI incidence was highest in patients in LLMIC, followed by patients in upper-middle income countries (UMIC) and high-income countries (HIC) (53%, 38%, and 30%, respectively), whereas dialysis rates were lowest among patients with AKI from LLMIC and highest among those from HIC (27% vs. 45%). Patients with AKI in LLMIC had the largest proportion of community-acquired AKI (CA-AKI) and highest rate of in-hospital death (79% vs. 54% in HIC and 66% in UMIC). The association between AKI, being from LLMIC and in-hospital death persisted even after adjusting for disease severity. Conclusions: AKI is a particularly devastating complication of COVID-19 among patients from poorer nations where the gaps in accessibility and quality of healthcare delivery have a major impact on patient outcomes.

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.

The International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) COVID-19 dataset is one of the largest international databases of prospectively collected clinical data on people hospitalized with COVID-19. This dataset was compiled during the COVID-19 pandemic by a network of hospitals that collect data using the ISARIC-World Health Organization Clinical Characterization Protocol and data tools. The database includes data from more than 705,000 patients, collected in more than 60 countries and 1,500 centres worldwide. Patient data are available from acute hospital admissions with COVID-19 and outpatient follow-ups. The data include signs and symptoms, pre-existing comorbidities, vital signs, chronic and acute treatments, complications, dates of hospitalization and discharge, mortality, viral strains, vaccination status, and other data. Here, we present the dataset characteristics, explain its architecture and how to gain access, and provide tools to facilitate its use.

Background: The inactivated whole-virus vaccine CoronaVac (SinoVac) is the COVID-19 vaccine most administered worldwide. However, data on its immunogenicity and reactogenicity to heterologous boosting with mRNA vaccines are lacking. Methods: In a cohort of hospital staff in Jakarta, Indonesia, who received two-dose CoronaVac six months prior (median 190 days, IQR165-232), we measured anti-Spike IgG titers on paired serum samples taken before and 28 days after a 100μg mRNA-1273 (Moderna) booster. We performed correlations and multivariable ordinal regressions. Findings: Among 304 participants, the median age was 31 years (range 21-59), 235 (77.3%) were women, 197 (64.8%) had one or more previous SARS-CoV-2 infections (including 155 [51.0%] who had a post-CoronaVac breakthrough infection. Pre-boost IgG titers correlated negatively with the time since the latest documented virus exposure (either by the second CoronaVac or SARS-CoV-2-infection whichever most recent). Previous SARS-CoV-2 infection and a longer time interval between second vaccine and mRNA-1273 boost were associated with a higher pre-boost IgG titer. Post-booster, the median IgG titer increased 9.3-fold, from 250 (IQR32-1389) to 2313 (IQR1226-4324) binding antibody units (BAU/mL) (p<0.001). All participants, including seven whose pre-boost IgG was below assay detection limits, became seropositive and all reached a substantial post-boost titer (≥364 BAU/mL). Post-boost IgG was not associated with pre-boost titer or previous SARS-CoV-2 infection. Booster reactogenicity was acceptable, with 7.9% of participants experiencing short-lived impairment of activities of daily living (ADL). Interpretation: A heterologous, high-dose mRNA-1273 booster after two-dose CoronaVac was highly immunogenic and safe, including in those most in need of improved immunity. Funding: Wellcome Trust, UK Keywords SARS-CoV-2; COVID-19; inactivated vaccine; CoronaVac; mRNA-1273; antibodies

PIIS14733099210056 5X.pdf