Time series analysis revealed prognostic value of continuous nasopharyngeal SARS-CoV-2 nucleic acid quantification for COVID-19: A retrospective study of >3000 COVID-19 patients from 2 centers.

BACKGROUND: Early stratification of disease progression remains one of the major challenges towards the post-coronavirus disease 2019 (COVID-19) era. The clinical relevance of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid load is debated due to the heterogeneity in patients' underlying health conditions. We determined the prognostic value of nasopharyngeal viral load dynamic conversion for COVID-19. METHODS: The cycling threshold (Ct) values of 28,937 nasopharyngeal SARS-CoV-2 RT-PCRs were retrospectively collected from 3,364 COVID-19 patients during hospitalization and coordinated to the onset of disease progression. The ROC curve was utilized to determine the predictive performance of the rate of Ct value alteration between two consecutive RT-PCR runs within 48 h (ΔCt%) for disease transformation across patients with different COVID-19 severity and immune backgrounds, and further validated with 1,860 SARS-CoV-2 RT-PCR results from an independent validation cohort of 262 patients. For the 67 patients with severe COVID-19, Kaplan-Meier analysis was performed to evaluate the difference in survival between patients stratified by the magnitude of Ct value alteration between the late and early stages of hospitalization. RESULTS: The kinetics of viral nucleic acid conversion diversified across COVID-19 patients with different clinical characteristics and disease severities. The ΔCt% is a clinical characteristic- and host immune status-independent indicator for COVID-19 progression prediction (AUC = 0.79, 95 % CI = 0.76 to 0.81), which outperformed the canonical blood test markers, including c-reactive protein (AUC = 0.57, 95 % CI = 0.53 to 0.61), serum amyloid A (AUC = 0.61, 95 % CI = 0.54 to 0.68), lactate dehydrogenase (AUC = 0.61, 95 % CI = 0.56 to 0.67), d-dimer (AUC = 0.56, 95 % CI = 0.46 to 0.66), and lymphocyte count (AUC = 0.62, 95 % CI = 0.58 to 0.66). Patients with persistent high SARS-CoV-2 viral load (an increase of mean Ct value < 50 %) during the first 3 days of hospitalization demonstrated a significantly unfavorable survival (HR = 0.16, 95 % CI = 0.04 to 0.65, P = 2.41 × 10-3). CONCLUSIONS: Viral nucleic acid dynamics of SARS-CoV-2 eliminates the inter-patient variance of basic health conditions and therefore, can serve as a prognostic marker for COVID-19.

Application of ultrasensitive assay for SARS-CoV-2 antigen in nasopharynx in the management of COVID-19 patients with comorbidities during the peak of 2022 Shanghai epidemics in a tertiary hospital.

OBJECTIVES: Various comorbidities associated with COVID-19 add up in severity of the disease and obviously prolonged the time for viral clearance. This study investigated a novel ultrasensitive MAGLUMI® SARS-CoV-2 Ag chemiluminescent immunoassay assay (MAG-CLIA) for diagnosis and monitoring the infectivity of COVID-19 patients with comorbid conditions during the pandemic of 2022 Shanghai. METHODS: Analytical performances of the MAG-CLIA were evaluated, including precision, limit of quantitation, linearity and specificity. Nasopharyngeal specimens from 232 hospitalized patients who were SARS-CoV-2 RT-qPCR positive and from 477 healthy donors were included. The longitudinal studies were performed by monitoring antigen concentrations alongside with RT-qPCR results in 14 COVID-19 comorbid participants for up to 22 days. The critical antigen concentration in determining virus infectivity was evaluated at the reference cycle threshold (Ct) of 35. RESULTS: COVID-19 patients were well-identified using an optimal threshold of 0.64 ng/L antigen concentration, with sensitivity and specificity of 95.7% (95% CI: 92.2-97.9%) and 98.3% (95% CI: 96.7-99.3%), respectively, while the Wondfo LFT exhibited those of 34.9% (95% CI: 28.8-41.4%) and 100% (95% CI: 99.23-100%), respectively. The sensitivity of MAG-CLIA remained 91.46% (95% CI: 83.14-95.8%) for the samples with Ct values between 35 and 40. Close dynamic consistence was observed between MAG-CLIA and viral load time series in the longitudinal studies. The critical value of 8.82 ng/L antigen showed adequate sensitivity and specificity in evaluating the infectivity of hospitalized convalescent patients with comorbidities. CONCLUSIONS: The MAG-CLIA SARS-CoV-2 Ag detection is an effective and alternative approach for rapid diagnosis and enables us to evaluate the infectivity of hospitalized convalescent patients with comorbidities.

Neural correlates of a load-dependent decline in visual working memory.

Previous studies have shown that a rate of temporal decline in visual working memory (vWM) highly depends on a number of memory items. When people retain the information of many (≥ 4) stimuli simultaneously, their memory representations are fragile and rapidly degrade within 2-3 s after an offset (called the "competition" among memory items). When a memory load is low (1 or 2 items), in contrast, the fidelity of vWM is preserved for a longer time because focused attention to the small number of items prevents the temporal degradation. In the present study, we explored neural correlates of this load-dependent decline of vWM in the human brain. Using electroencephalography and a classical change-detection task, we recorded neural measures of vWM that have been reported previously, such as the contralateral delay activity (CDA) and a suppression of alpha power (8-12 Hz). Results indicated that the load-dependent decline of vWM was more clearly reflected in the change in power and speed of alpha/beta rhythm than CDA, suggesting a close relationship of those signals to an attention-based preservation of WM fidelity.

[Characteristics of stable isotopes in precipitation over Northeast China and its water vapor sources].

Based on the data of the hydrogen and oxygen stable isotopes in precipitation over Northeast China provided by the Global Network of Isotopes in Precipitation (GNIP) and the meteorological statistics, the spatial and temporal variations of stable isotopes in precipitation and their influencing factors were analyzed and the Local Meteoric Water Line (LMWL) was established. The results were as follows: delta18O value was low in winter and high in summer; the spatial distribution showed that the weighted delta18O value decreased from the south to the north; the linear relationship between delta18O in precipitation and temperature was significant, but no linear relationship was found for the precipitation amount; delta18O in precipitation can be evaluated quantitatively based on a multiple linear regression equation with delta18O and related parameters (temperature, precipitation amount, elevation, longitude and latitude). The water vapor source of the sampling sites was tracked by HYSPLIT 4. 9 model, and the modeled trajectory of vapor source indicated that there were two main paths, including the cold wet water vapor from the Atlantic Ocean and the Arctic Ocean via Westerlies, and the warm one from the Pacific Ocean.

[Characteristics of delta18O in precipitation and moisture transports over the arid region in Northwest China].

Based on the observed data of stable isotopes in precipitation and meteorological statistics at Urümqi (1986-2003), Zhangye (1986-2003), and Hotan (1988-1992) from IAEA/WMO, the precipitation equation of arid region in Northwest China was calculated through the regression analysis, and the characteristics of stable isotopic in precipitation, as well as the correlation between stable isotopic and meteorological records, were analyzed. The water vapor source of the three sites was tracked by the HYSPLIT4. 9 model, and water vapour transmission regime of arid region in Northwest China was established, while the record of delta18O in cryosphere was discussed. Results showed that the precipitation equation of deltaD = 7.24 delta18O + 1.96 per thousand indicates intense evaporation; delta18O values at Urümqi, Zhangye and Hotan fluctuates at -20.58 per thousand- -5.4 per thousand, -18.58 per thousand- -2.46 per thousand and -20.33 per thousand- -0.01 per thousand, respectively. The delta18O value is low in winter and high in summer, but the values of d-excess is on the contrary; The spatial distribution shows that delta18O value at Zhangye is highest, followed by Hotan, and the lowest is at Urümqi; The highest of d-excess value is at Urümqi, followed by Hotan, the lowest is at Zhangye; The temperature effect of delta18O in precipitation is significant with the correlation coefficients of 0.85, 0.81 and 0.86, respectively, and the rainfall effect does not exist; The modeled trajectory of vapor source showed there are two main paths all the year, which are from the Atlantic Ocean via Westerlies and the Arctic region, respectively, influence by different vapor sources, the seasonality of delta18O values lower in winter, higher in summer; In addition, according to the cryospheric environment, the correlation between delta18O in snow pack or ice core and the corresponding meteorological station record was significant, which reflects the variation of temperature efficiently.

Pterisolic acids A-F, new ent-kaurane diterpenoids from the fern Pteris semipinnata.

Six new ent-15-oxokauran-19-oic acid derivatives, named pterisolic acids A-F (1-6), were isolated from the ethanol extract of the fern Pteris semipinnata (Pteridaceae), and the structures of these new ent-kauranoids were elucidated on the basis of extensive spectroscopic studies and single crystal X-ray diffraction analysis.

Scutebarbatines W-Z, new neo-clerodane diterpenoids from Scutellaria barbata and structure revision of a series of 13-spiro neo-clerodanes.

Four new neo-clerodane diterpenoids, scutebarbatines W-Z (1-4), were isolated from the ethanol extract of Scutellaria barbata (Labiatae), and their structures were elucidated on the basis of extensive spectroscopic studies. In addition, the proposed structures of at least seven 13-spiro subtype neo-clerodanes: scutehenanine B (5), scutebarbatine G (6), 6-O-nicotinoylscutebarbatine G (7), barbatin A (8), 6,7-di-O-nicotinoylscutebarbatine G (9), 6-O-nicotinoyl-7-O-acetylscutebarbatine G (10), and scutebarbatine F (11), reported by Dai and co-workers from the same species, were incorrectly assigned and have been revised by reanalysis of the published NMR data.

ent-Pimarane diterpenoids from Siegesbeckia orientalis and structure revision of a related compound.

Six new ent-pimarane diterpenoids, namely, ent-14beta,16-epoxy-8-pimarene-3beta,15alpha-diol (1), 7beta-hydroxydarutigenol (2), 9beta-hydroxydarutigenol (3), 16-O-acetyldarutigenol (4), 15,16-di-O-acetyldarutoside (5), and 16-O-acetyldarutoside (6), were isolated from the ethanol extract of Siegesbeckia orientalis. Their structures were elucidated on the basis of spectroscopic studies, and the absolute configuration of 1 was established by the modified Mosher's method. Furthermore, the structure of ent-12beta,16-epoxy-8-pimarene-2alpha,15beta,19-triol, recently isolated from the same plant, should be revised as ent-14beta,16-epoxy-8-pimarene-2alpha,15alpha,19-triol (10).