Epileptic seizure and electroencephalographic characteristics of adult COVID-19 inpatients during the Omicron outbreak in China: a single center retrospective study (preprint)

Background This retrospective analysis assessed the characteristics of epileptic seizure and continuous electroencephalogram (CEEG) data in hospitalized patients diagnosed with COVID-19 during the Omicron outbreak.Methods CEEG was performed in 28 patients, with 17 showing unexplained altered mental status and 11 suspected of having seizures. Demographic and clinical variables, imaging results, outcomes, and comorbidities were collected.Results In total, 1,405 patients with COVID-19 infection were admitted during the study period. The proportion of patients who required intensive care unit (ICU) care and the in-hospital mortality was 16.3% and 7.8%, respectively. Among patients who underwent CEEG monitoring, 11 were in ICU, and 17 were in regular wards. Of these, 8 patients (28.5%) had severe COVID-19, whereas 6 had acute neuroimaging findings. EEG findings were not specific, with 7 patients (25%) having normal EEG results. Furthermore, 11 (39.3%) had benign EEG alterations, 6 (21.4%) had malignant, and 4 (14.3%) had highly malignant. Six patients exhibited epileptiform abnormalities, including 1 with a prior epilepsy history. Moreover, 4 patients experienced electrographic seizures, with 2 manifesting as epilepsia partialis continua and 2 as nonconvulsive status epilepticus. Periodic and rhythmic patterns were observed in 2 patients, spike-and-wave in 1 patient and generalized rhythmic delta activity in another patient. EEG attenuation without reactivity was seen in 4 patients.Conclusions Seizures can manifest as early symptoms in individuals infected with the Omicron variant of COVID-19. Despite the increased contagiousness associated with Omicron, we observed a higher prevalence of normal EEG results. This suggested that the Omicron variant may be associated with a lower likelihood of causing encephalitis or encephalopathy compared to other variants.

Evolving trend change during the COVID-19 pandemic

Coronavirus disease (COVID-19) has caused unimaginable damage to public health and socio-economic structures worldwide;thus, an epidemiological depiction of the global evolving trends of this disease is necessary. As of March 31, 2022, the number of cases increased gradually over the four waves of the COVID-19 pandemic, indicating the need for continuous countermeasures. The highest total cases per million and total deaths per million were observed in Europe (240,656.542) and South America (2,912.229), despite these developed countries having higher vaccination rates than other continents, such as Africa. In contrast, the lowest of the above two indices were found in undeveloped African countries, which had the lowest number of vaccinations. These data indicate that the COVID-19 pandemic is positively related to the socio-economic development level;meanwhile, the data suggest that the vaccine currently used in these continents cannot completely prevent the spread of COVID-19. Thus, rethinking the feasibility of a single vaccine to control the disease is needed. Although the number of cases in the fourth wave increased exponentially compared to those of the first wave, ~43.1% of deaths were observed during the first wave. This was not only closely linked to multiple factors, including the inadequate preparation for the initial response to the COVID-19 pandemic, the gradual reduction in the severity of additional variants, and the protection conferred by prior infection and/or vaccination, but this also indicated the change in the main driving dynamic in the fourth wave. Moreover, at least 12 variants were observed globally, showing a clear spatiotemporal profile, which provides the best explanation for the presence of the four waves of the pandemic. Furthermore, there was a clear shift in the trend from multiple variants driving the spread of disease in the early stage of the pandemic to a single Omicron lineage predominating in the fourth wave. These data suggest that the Omicron variant has an advantage in transmissibility over other contemporary co-circulating variants, demonstrating that monitoring new variants is key to reducing further spread. We recommend that public health measures, along with vaccination and testing, are continually implemented to stop the COVID-19 pandemic.

Forecasting of Automobile Sales Based on Support Vector Regression Optimized by the Grey Wolf Optimizer Algorithm

With the development of the Internet and big data, more and more consumer behavior data are used in different forecasting problems, which greatly improve the performance of prediction. As the main travel tool, the sales of automobiles will change with the variations of the market and the external environment. Accurate prediction of automobile sales can not only help the dealers adjust their marketing plans dynamically but can also help the economy and the transportation sector make policy decisions. The automobile is a product with high value and high involvement, and its purchase decision can be affected by its own attributes, economy, policy and other factors. Furthermore, the sample data have the characteristics of various sources, great complexity and large volatility. Therefore, this paper uses the Support Vector Regression (SVR) model, which has global optimization, a simple structure, and strong generalization abilities and is suitable for multi-dimensional, small sample data to predict the monthly sales of automobiles. In addition, the parameters are optimized by the Grey Wolf Optimizer (GWO) algorithm to improve the prediction accuracy. First, the grey correlation analysis method is used to analyze and determine the factors that affect automobile sales. Second, it is used to build the GWO-SVR automobile sales prediction model. Third, the experimental analysis is carried out by using the data from Suteng and Kaluola in the Chinese car segment, and the proposed model is compared with the other four commonly used methods. The results show that the GWO-SVR model has the best performance of mean absolute percentage error (MAPE) and root mean square error (RMSE). Finally, some management implications are put forward for reference.

Structural and functional characterizations of altered infectivity and immune evasion of SARS-CoV-2 Omicron variant (preprint)

The SARS-CoV-2 Omicron with increased fitness is spreading rapidly worldwide. Analysis of cryo-EM structures of the Spike (S) from Omicron reveals amino acid substitutions forging new interactions that stably maintain an active conformation for receptor recognition. The relatively more compact domain organization confers improved stability and enhances attachment but compromises the efficiency of viral fusion step. Alterations in local conformation, charge and hydrophobic microenvironments underpin the modulation of the epitopes such that they are not recognized by most NTD- and RBD-antibodies, facilitating viral immune escape. Apart from already existing mutations, we have identified three new immune escape sites: 1) Q493R, 2) G446S and 3) S371L/S373P/S375F that confers greater resistance to five of the six classes of RBD-antibodies. Structure of the Omicron S bound with human ACE2, together with analysis of sequence conservation in ACE2 binding region of 25 sarbecovirus members as well as heatmaps of the immunogenic sites and their corresponding mutational frequencies sheds light on conserved and structurally restrained regions that can be used for the development of broad-spectrum vaccines and therapeutics.

A subset of Memory B-derived antibody repertoire from 3-dose vaccinees is ultrapotent against diverse and highly transmissible SARS-CoV-2 variants, including Omicron (preprint)

Omicron, the most heavily mutated SARS-CoV-2 variant so far, is highly resistant to neutralizing antibodies, raising unprecedented concerns about the effectiveness of antibody therapies and vaccines. We examined whether sera from individuals who received two or three doses of inactivated vaccine, could neutralize authentic Omicron. The seroconversion rates of neutralizing antibodies were 3.3% (2/60) and 95% (57/60) for 2- and 3-dose vaccinees, respectively. For three-dose recipients, the geometric mean neutralization antibody titer (GMT) of Omicron was 15, 16.5-fold lower than that of the ancestral virus (254). We isolated 323 human monoclonal antibodies derived from memory B cells in 3-dose vaccinees, half of which recognize the receptor binding domain (RBD) and show that a subset of them (24/163) neutralize all SARS-CoV-2 variants of concern (VOCs), including Omicron, potently. Therapeutic treatments with representative broadly neutralizing mAbs individually or antibody cocktails were highly protective against SARS-CoV-2 Beta infection in mice. Atomic structures of the Omicron S in complex with three types of all five VOC-reactive antibodies defined the binding and neutralizing determinants and revealed a key antibody escape site, G446S, that confers greater resistance to one major class of antibodies bound at the right shoulder of RBD through altering local conformation at the binding interface. Our results rationalize the use of 3-dose immunization regimens and suggest that the fundamental epitopes revealed by these broadly ultrapotent antibodies are a rational target for a universal sarbecovirus vaccine. One sentence summary A sub-set of antibodies derived from memory B cells of volunteers vaccinated with 3 doses of an inactivated SARS-CoV-2 vaccine work individually as well as synergistically to keep variants, including Omicron, at bay.

A third dose of inactivated vaccine augments the potency, breadth, and duration of anamnestic responses against SARS-CoV-2 (preprint)

Emergence of variants of concern (VOC) with altered antigenic structures and waning humoral immunity to SARS-CoV-2 are harbingers of a long pandemic. Administration of a third dose of an inactivated virus vaccine can boost the immune response. Here, we have dissected the immunogenic profiles of antibodies from 3-dose vaccinees, 2-dose vaccinees and convalescents. Better neutralization breadth to VOCs, expeditious recall and long-lasting humoral response bolster 3-dose vaccinees in warding off COVID-19. Analysis of 171 complex structures of SARS-CoV-2 neutralizing antibodies identified structure-activity correlates, revealing ultrapotent, VOCs-resistant and broad-spectrum antigenic patches. Construction of immunogenic and mutational heat maps revealed a direct relationship between "hot" immunogenic sites and areas with high mutation frequencies. Ongoing antibody somatic mutation, memory B cell clonal turnover and antibody composition changes in B cell repertoire driven by prolonged and repeated antigen stimulation confer development of monoclonal antibodies with enhanced neutralizing potency and breadth. Our findings rationalize the use of 3-dose immunization regimens for inactivated vaccines. One sentence summaryA third booster dose of inactivated vaccine produces a highly sifted humoral immune response via a sustained evolution of antibodies capable of effectively neutralizing SARS-CoV-2 variants of concern.

Exploration on the emergency support mode of hospital medical supplies under the epidemic of NCP / 中华医院管理杂志

Since the outbreak of Novel Coronavirus Pneumonia(NCP), hospitals have taken the fight against the virus as its own responsibility, and keep standing in the front line of epidemic prevention and control. The continuous input of anti-epidemic forces in hospitals also brings challenges to the medical supplies support, including the management of protective supplies and the maintenance of medical equipment. In the face of increasing security pressure, the medical materials support team broke the game on multiple fronts. Firstly, the team implements active material procurement strategy, sets material distribution priority according to risk level, releases materials uniformly based on stock and use, and implements traceability management of donated materials to ensure material supply. Secondly, centralized allocation management of equipment, emergency installation, advanced maintenance and emergency maintenance work is effectively completed. Thirdly, disinfection strategies for items and equipment are developed safely and effectively with the aid of disinfection equipment functions. At last, personnel management and training have been strengthened. These measures have provided strong support for the orderly prevention and control of the epidemic.