Oral Ursodeoxycholic Acid Therapy Failed to Mitigate SARS-CoV-2 Omicron Variants BA.5.2 Infection (preprint)

Background Ursodeoxycholic acid (UDCA) was reported to reduce susceptibility to SARS-CoV-2 infection by downregulating farnesoid X receptor (FXR) -ACE2 signaling. However, we found a different story in real-world clinical studies.Objectives We attempted to verify whether UDCA can effectively prevent SARS-CoV-2 transmission or have positive therapeutic effects in a real-world clinical study.Methods We performed a retrospective study, collected and assessed clinical presentation and laboratory data on patients with liver diseases infected with SARS-CoV-2 Omicron sub-variant BA.5.2 who had been treated with or without UDCA.Results Treatment with UDCA did not prevent infection with the Omicron sub-variant BA.5.2, failed in reducing the duration of infection and hardly mitigated the severity of COVID-19. Meanwhile, the severity of liver diseases, especially TBil, ALP, γ-GT, liver cirrhosis and Child-Pugh classification, should be considered as risk factors for severe COVID-19 in chronic hepatic patients.Conclusion UDCA failed to show inhibitory effects against SARS-CoV-2 infection in complex clinical settings. The regulatory mechanism of the novel UDCA-FXR-ACE2 pathway needs to be further investigated in real-world clinical studies.

An automated nucleic acid detection platform using digital microfluidics with an optimized Cas12a system.

Outbreaks of both influenza virus and the novel coronavirus SARS-CoV-2 are serious threats to human health and life. It is very important to establish a rapid, accurate test with large-scale detection potential to prevent the further spread of the epidemic. An optimized RPA-Cas12a-based platform combined with digital microfluidics (DMF), the RCD platform, was established to achieve the automated, rapid detection of influenza viruses and SARS-CoV-2. The probe in the RPA-Cas12a system was optimized to produce maximal fluorescence to increase the amplification signal. The reaction droplets in the platform were all at the microliter level and the detection could be accomplished within 30 min due to the effective mixing of droplets by digital microfluidic technology. The whole process from amplification to recognition is completed in the chip, which reduces the risk of aerosol contamination. One chip can contain multiple detection reaction areas, offering the potential for customized detection. The RCD platform demonstrated a high level of sensitivity, specificity (no false positives or negatives), speed (≤30 min), automation and multiplexing. We also used the RCD platform to detect nucleic acids from influenza patients and COVID-19 patients. The results were consistent with the findings of qPCR. The RCD platform is a one-step, rapid, highly sensitive and specific method with the advantages of digital microfluidic technology, which circumvents the shortcomings of manual operation. The development of the RCD platform provides potential for the isothermal automatic detection of nucleic acids during epidemics. Electronic Supplementary Material: Supplementary material is available in the online version of this article at 10.1007/s11426-021-1169-1.

Monitoring Multi-respiratory Indices via a Smart Nanofibrous Mask Filter Based on a Triboelectric Nanogenerator

Respiratory parameters, such as respiratory rate (RR), inhalation time (tin), exhalation time (tex), and their ratio (IER=tin/tex), are of great importance to indicate clinical differences between healthy people and those with respiratory diseases. Herein, we report a respiration monitoring triboelectric nanogenerator (RM-TENG) with nanofibrous membranes, which can be used as a smart, changeable, self-powered mask filter with high filtration efficiency for monitoring multiple respiratory indices (e.g., RR, tin, tex, IER). We created a mathematical model to quantitatively analyze the effects of gap distance between two triboelectric layers on the contact area by recording the nanofibers layer's deformation profile with digital image correlation (DIC) tests. The RM-TENG is more sensitive to smaller gap distances between 1mm - 5mm because the high specific area of nanofibers can provide a more effective contact area. An RM-TENG built with optimized structure parameters can accurately and consistently detect the above-mentioned respiratory indices with excellent sensing stability for 40hours. The monitored RR and IER have 100% and 93.53% agreement with the real-time RR and IER set on the ventilator, respectively. Furthermore, it has a filtration efficiency of 99wt% for particle sizes between 0.3µm and 5µm. This study introduces a mask filter fabricated with a simple structure with both filtering and sensing capability, which has excellent potential for self-powered health diagnostics.

Impact of Headache Frequency and Sleep on Migraine Patients During the COVID-19 Pandemic.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has spread worldwide and poses a great threat to global health. COVID-19 has also an unneglected effect on migraine patients. Migraine attack frequency is one of the migraine characteristics, and its impact during COVID-19 needs further research. We aimed to evaluate whether migraine attack frequency during the COVID-19 pandemic differed from pre-COVID-19 attack frequency and explore possible influencing factors during the pandemic. METHODS: This prospective cohort study enrolled 187 migraine patients from the Department of Neurology of West China Hospital from October 2019 to December 2019. After the inclusion and exclusion criteria, a total of 157 patients were included. We collected demographic data, clinical characteristics, and epidemiological contact information and followed up on March 2020. Then, paired-samples T-tests, logistic regression and interaction tests were used to analyze the data. RESULTS: We found that the migraine attack frequency was 2.47 ± 1.12 before and 3.54 ± 1.79 during COVID-19 (P<0.0001). Then, we divided patients into two groups based on the difference in migraine attack frequency between the COVID-19 and pre-COVID-19 periods and employed logistic regression analysis. In the logistic regression analysis, divorced status (OR = 6.53, P = 0.0453), good sleep pre-COVID-19 and poor sleep during COVID-19 (OR = 3.11, P = 0.0432) had independent effects on migraine attack frequency during the COVID-19 pandemic. We found no interaction in poor sleep during COVID-19 between various subgroups. CONCLUSION: We found that migraineurs' headache attacks were more frequent during COVID-19 than pre-COVID-19 and that increased migraine attack frequency was independently related to divorced status and poor sleep during COVID-19.

New onset neurologic events in people with COVID-19 in 3 regions in China.

OBJECTIVE: To investigate new-onset neurologic impairments associated with coronavirus disease 2019 (COVID-19). METHODS: A retrospective multicenter cohort study was conducted between January 18 and March 20, 2020, including people with confirmed COVID-19 from 56 hospitals officially designated in 3 Chinese regions; data were extracted from medical records. New-onset neurologic events as assessed by neurology consultants based on manifestations, clinical examination, and investigations were noted, in which critical events included disorders of consciousness, stroke, CNS infection, seizures, and status epilepticus. RESULTS: We enrolled 917 people with average age 48.7 years and 55% were male. The frequency of new-onset critical neurologic events was 3.5% (32/917) overall and 9.4% (30/319) among those with severe or critical COVID-19. These were impaired consciousness (n = 25) or stroke (n = 10). The risk of critical neurologic events was highly associated with age above 60 years and previous history of neurologic conditions. Noncritical events were seen in fewer than 1% (7/917), including muscle cramp, unexplained headache, occipital neuralgia, tic, and tremor. Brain CT in 28 people led to new findings in 9. Findings from lumbar puncture in 3 with suspected CNS infection, unexplained headache, or severe occipital neuralgia were unremarkable. CONCLUSIONS: People with COVID-19 aged over 60 and with neurologic comorbidities were at higher risk of developing critical neurologic impairment, mainly impaired consciousness and cerebrovascular accidents. Brain CT should be considered when new-onset brain injury is suspected, especially in people under sedation or showing an unexplained decline in consciousness. Evidence of direct acute insult of severe acute respiratory syndrome coronavirus 2 to the CNS is lacking.

Mitigating the impact of coronavirus disease 2019 on emergency stroke care: an original study and meta-analysis.

The coronavirus disease 2019 is still continuing and may affect stroke emergency care. We aim to investigate the impact of pandemic on stroke treatment in tertiary stroke centers in western China, and to quantitatively evaluate the worldwide influence with a meta-analysis. The original part was conducted in three tertiary stroke centers in Sichuan province. We compared emergency visits and efficiency of stroke treatment pre-, early, peak and late pandemic. Single-center analysis was further conducted in the largest local hospital and one hospital located close to the epicenter respectively. Relevant studies were searched in PubMed, Ovid Embase and Cochrane Library for English publications from December 2019 to July 2020 for systematic review. Fixed-and random-effect meta-analysis was performed to calculate the overall rates. Totally current original study showed fewer time of hospital admission and significantly higher rates of mechanical thrombectomy during the early and peak epidemic periods, compared with pre-epidemic time. The largest local hospital had significantly higher mechanical thrombectomy rates during the whole crisis and less daily admission during early and peak epidemic periods. The hospital located close to the epicenter presented higher proportions of intravenous thrombolysis since outbreak, and more favorable outcomes after reperfusion therapies than later (all P values <0.05). In meta-analysis, studies reported differences in reperfusion therapies and stroke severity but pooled results were non-significant. Overall, comprehensive measures should be implemented to keep hospital's capacity to deliver high-quality stroke emergency care during the global pandemic. Some key messages were provided for medical practice in the crisis.

The status and high risk factors of severe psychological distress in migraine patients during nCOV-2019 outbreak in Southwest China: a cross-sectional study.

BACKGROUND: Psychological distress is highly prevalent among migraineurs during public health emergencies. The coronavirus disease 2019 (nCOV-2019) has created mass panic in China due to its highly contagious by contact and aerosols and lack of effective treatment. However, the emotion status of migraineurs stayed unclear during the nCOV-2019 outbreak. OBJECTIVE: To understand psychological distress of migraineurs by comparing with common population and identify potential high-risk factors of severe psychological distress among migraine patients. METHOD: We enrolled the migraineurs treated at the department of Neurology of West China Hospital and healthy controls with age- and sex-matched to migraineurs. Data on clinicodemographics and psychological distress in the month of February 2020 (during in the nCOV-2019 outbreak in China) were collected. We used the Kessler 6-item (K-6) scale to assess psychological distress. Potential risk factors of severe psychological distress were identified using univariate and multivariate logistic regression. RESULTS: The 144 migraineurs and 150 controls were included in the study. Migraineurs showed significantly higher K-6 scores than controls (P < 0.001). Migraine attack frequency in previous 30 days and time spent paying attention to outbreak showed significant in multivariate logistic regression with respective odds ratios of 2.225 (95%CI 1.361-3.628, P = 0.001) and 1.589 (95% 1.117-2.26, P = 0.01). CONCLUSION: During public health outbreaks, healthcare professionals should focus not only on controlling and reducing migraine attack but also on mental health of migraineurs, especially those with high frequency migraine attack.

Meteorological conditions and nonpharmaceutical interventions jointly determined local transmissibility of COVID-19 in 41 Chinese cities: A retrospective observational study.

BACKGROUND: Before effective vaccines become widely available, sufficient understanding of the impacts of climate, human movement and non-pharmaceutical interventions on the transmissibility of COVID-19 is needed but still lacking. METHODS: We collected by crowdsourcing a database of 11 003 COVID-19 cases from 305 cities outside Hubei Province from December 31, 2019 to April 27, 2020. We estimated the daily effective reproduction numbers (Rt ) of COVID-19 in 41 cities where the crowdsourced case data are comparable to the official surveillance data. The impacts of meteorological variables, human movement indices and nonpharmaceutical emergency responses on Rt were evaluated with generalized estimation equation models. FINDINGS: The median Rt was 0•46 (IQR: 0•37-0•87) in the northern cities, higher than 0•20 (IQR: 0•09-0•52) in the southern cities (p=0•004). A higher local transmissibility of COVID-19 was associated with a low temperature, a relative humidity near 70-75%, and higher intracity and intercity human movement. An increase in temperature from 0℃ to 20℃ would reduce Rt by 30% (95 CI 10-46%). A further increase to 30℃ would result in another 17% (95% CI 5-27%) reduction. An increase in relative humidity from 40% to 75% would raise the transmissibility by 47% (95% CI 9-97%), but a further increase to 90% would reduce the transmissibility by 12% (95% CI 4-19%). The decrease in intracity human movement as a part of the highest-level emergency response in China reduced the transmissibility by 36% (95% CI 27-44%), compared to 5% (95% CI 1-9%) for restricting intercity transport. Other nonpharmaceutical interventions further reduced Rt by 39% (95% CI 31-47%). INTERPRETATION: Climate can affect the transmission of COVID-19 where effective interventions are implemented. Restrictions on intracity human movement may be needed in places where other nonpharmaceutical interventions are unable to mitigate local transmission. FUNDING: China Mega-Project on Infectious Disease Prevention; U.S. National Institutes of Health and National Science Foundation.

New onset acute symptomatic seizure and risk factors in coronavirus disease 2019: A retrospective multicenter study.

Our aim was to clarify the incidence and risk of acute symptomatic seizures in people with coronavirus disease 2019 (COVID-19). This multicenter retrospective study enrolled people with COVID-19 from January 18 to February 18, 2020 at 42 government-designated hospitals in Hubei province, the epicenter of the epidemic in China; Sichuan province; and Chongqing municipality. Data were collected from medical records by 11 neurologists using a standard case report form. A total of 304 people were enrolled, of whom 108 had a severe condition. None in this cohort had a known history of epilepsy. Neither acute symptomatic seizures nor status epilepticus was observed. Two people had seizurelike symptoms during hospitalization due to acute stress reaction and hypocalcemia, and 84 (27%) had brain insults or metabolic imbalances during the disease course known to increase the risk of seizures. There was no evidence suggesting an additional risk of acute symptomatic seizures in people with COVID-19. Neither the virus nor potential risk factors for seizures seem to be significant risks for the occurrence of acute symptomatic seizures in COVID-19.