The Effects of CoronaVac and ChAdOx1 nCoV-19 in Reducing Severe Illness in Thailand: A Retrospective Cohort Study.

Two primary vaccines for coronavirus disease 2019 (COVID-19) have been rolled out in the mass vaccination campaign that started simultaneously with the spread of the delta variant. To explore the vaccines' effect on reducing viral load and disease severity, we conducted a retrospective cohort study in Thai patients aged ≥18 years who were confirmed COVID-19 positive by RT-PCR. Compared to unvaccinated patients, Ct values and the number of severe cases among vaccine regimens were analyzed. Ct values of vaccinated patients were not significantly different from unvaccinated patients, despite an increase of Ct values in a booster dose. The adjusted odd ratio for prevention of delta-related severe diseases was 0.47, 95% CI: 0.30-0.76 and 0.06, 95% CI: 0.01-0.45 after receiving one dose and two doses, respectively. No severe illness was found in booster-vaccinated individuals. Focusing on the vaccine types, one dose of ChAdOx1 nCoV-19 gave significant protection, whereas one dose of CoronaVac did not (0.49, 95% CI: 0.30-0.79, p = 0.003 vs. 0.28, 95% CI: 0.04-2.16, p = 0.223). Two-dose vaccination showed robust protective effects in all subpopulations regardless of vaccine type. Vaccinations with two primary vaccines could not reduce viral load in patients with COVID-19, but could prevent severe illness.

Performance of colorimetric reverse transcription loop-mediated isothermal amplification as a diagnostic tool for SARS-CoV-2 infection during the fourth wave of COVID-19 in Thailand.

BACKGROUND: COVID-19, which is caused by SARS-CoV-2 and its variants, poses an ongoing global threat, particularly in low-immunization coverage regions. Thus, rapid, accurate, and easy-to-perform diagnostic methods are in urgent demand to halt the spread of the virus. OBJECTIVES: We aimed to validate the clinical performance of the FastProof 30 min-TTR SARS-CoV-2 reverse transcription loop-mediated isothermal amplification (RT-LAMP) method using leftover RNA samples extracted from 315 nasopharyngeal swabs. The sensitivity and specificity of RT-LAMP were determined in comparison with reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: Of 315 nasopharyngeal swabs, viral RNA was detected in 154 samples (48.9%) by RT-PCR assay. Compared with RT-PCR, overall sensitivity and specificity of RT-LAMP were 81.82% (95% CI: 74.81-87.57) and 100% (95% CI: 97.73-100), respectively. A 100% positivity rate was achieved in samples with cycle threshold (Ct) <31 for RT-PCR targeting the ORF1ab gene. However, samples with Ct >31 accounted for false-negative results by RT-LAMP in 28 samples. CONCLUSIONS: RT-LAMP reliably detected viral RNA with high sensitivity and specificity and has potential application for mass screening of patients with acute COVID-19 infection when viral load is high.

BiP-bound and nonclustered mode of Ire1 evokes a weak but sustained unfolded protein response.

In eukaryotic cells under nonstressed conditions, the endoplasmic reticulum (ER)-located molecular chaperone BiP is associated with an ER-membrane protein Ire1 to inhibit its self-association. While ER stress leads Ire1 to form transiently BiP-unbound clusters, which strongly evoke the unfolded protein response (UPR), here we propose an alternative activation status of Ire1. When yeast cells are physiologically ER-stressed by inositol depletion for a prolonged time, the UPR is weakly activated in a sustained manner after a transient peak of activation. During persistent stress, Ire1 foci disappear, while Ire1 continues to be self-associated. Under these conditions, Ire1 may be activated as a homo-dimer, as it shows considerable activity even when carrying the W426A mutation, which allows Ire1 to form homo-dimers but not clusters. Unlike the Ire1 clusters, the nonclustered active form seems to be associated with BiP. An Ire1 mutant not carrying the BiP-association site continued to form clusters and to be activated strongly even after long-term stress. Similar observations were obtained when cells were ER-stressed by dithiothreitol. We thus propose that upon persistent ER stress, Ire1 is weakly and continuously activated in a nonclustered form through its (re)association with BiP, which disperses the Ire1 clusters.

Membrane aberrancy and unfolded proteins activate the endoplasmic reticulum stress sensor Ire1 in different ways.

Eukaryotic cells activate the unfolded-protein response (UPR) upon endoplasmic reticulum (ER) stress, where the stress is assumed to be the accumulation of unfolded proteins in the ER. Consistent with previous in vitro studies of the ER-luminal domain of the mutant UPR initiator Ire1, our study show its association with a model unfolded protein in yeast cells. An Ire1 luminal domain mutation that compromises Ire1's unfolded-protein-associating ability weakens its ability to respond to stress stimuli, likely resulting in the accumulation of unfolded proteins in the ER. In contrast, this mutant was activated like wild-type Ire1 by depletion of the membrane lipid component inositol or by deletion of genes involved in lipid homeostasis. Another Ire1 mutant lacking the authentic luminal domain was up-regulated by inositol depletion as strongly as wild-type Ire1. We therefore conclude that the cytosolic (or transmembrane) domain of Ire1 senses membrane aberrancy, while, as proposed previously, unfolded proteins accumulating in the ER interact with and activate Ire1.