Persistent lymphocyte reduction and interleukin-6 levels are independently associated with death in patients with COVID-19.

To investigate the value of the peripheral blood lymphocyte count (LYM) combined with interleukin-6 (IL-6) in predicting disease severity and prognosis in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia. This was a prospective observational cohort study. A total of 109 patients with SARS-CoV-2 pneumonia who were admitted to Nanjing First Hospital from December 2022 to January 2023 were enrolled. The patients were divided into two groups based on disease severity: severe (46 patients) and critically ill (63 patients). The clinical data of all patients were collected. The clinical characteristics, sequential organ failure assessment (SOFA) score, peripheral blood lymphocyte count, IL-6 level and other laboratory test results were compared between the two groups. A receiver operating characteristic (ROC) curve was plotted to evaluate the predictive value of each index for SARS-CoV-2 pneumonia severity; patients were regrouped using the optimal cut-off value of the ROC curve, and the relationship between different LYM and IL-6 levels and the prognosis of patients was analysed. Kaplan‒Meier survival curve analysis was performed; in the different LYM and IL-6 groups, the patients were regrouped based on whether thymosin was used, and the effect of thymosin on patient prognosis was compared between the groups. Patients in the critically ill group were significantly older than patients in the severe group (age: 78 ± 8 vs. 71 ± 17, t = 2.982, P < 0.05), and the proportion of patients with hypertension, diabetes and cerebrovascular disease was significantly higher in the critically ill group than in the severe group (69.8% vs. 45.7%, 38.1% vs. 17.4%, 36.5% vs. 13.0%; χ2 values, 6.462, 5.495, 7.496, respectively, all P < 0.05). Compared with the severe group, the critically ill group had a higher SOFA score on admission (score: 5.4 ± 3.0 vs. 1.9 ± 1.5, t = 24.269, P < 0.05); IL-6 and procalcitonin (PCT) in the critically ill group were significantly higher than those in the severe group on the first day of admission [288.4 (191.4, 412.9) vs. 513.0 (288.2, 857.4), 0.4 (0.1, 3.2) vs. 0.1 (0.05, 0.2); Z values, 4.000, 4.456, both P < 0.05]. The lymphocyte count continued to decline, and the lymphocyte count on the 5th day (LYM-5d) was still low (0.6 ± 0.4 vs. 1.0 ± 0.4, t = 4.515, both P < 0.05), with statistically significant differences between the two groups. ROC curve analysis indicated that LYM-5d, IL-6 and LYM-5d + IL-6 all had value for predicting SARS-CoV-2 pneumonia severity; the areas under the curve (AUCs) were 0.766, 0.725, and 0.817, respectively, and the 95% confidence intervals (95% CI) were 0.676-0.856, 0.631-0.819, and 0.737-0.897, respectively. The optimal cut-off values for LYM-5d and IL-6 were 0.7 × 109/L and 416.4 pg/ml, respectively. LYM-5d + IL-6 had the greatest value in predicting disease severity, and LYM-5d had higher sensitivity and specificity in predicting SARS-CoV-2 pneumonia severity. Regrouping was performed based on the optimal cut-off values for LYM-5d and IL-6. Comparing the IL-6 ≥ 416.4 pg/ml and LYM-5d < 0.7 × 109/L group with the other group, i.e., patients in the non-low-LYM-5d and high-IL-6 group, patients in the low-LYM-5d and high-IL-6 group had a higher 28-day mortality rate (71.9% vs. 29.9%, χ2 value 16.352, P < 0.05) and a longer hospital stay, intensive care unit (ICU) stay and mechanical ventilation time (days: 13.7 ± 6.3 vs. 8.4 ± 4.3, 9.0 (7.0, 11.5) vs. 7.5 (4.0, 9.5), 8.0 (6.0, 10.0) vs. 6.0 (3.3, 8.5); t/Z values, 11.657, 2.113, 2.553, respectively, all P < 0.05), as well as a higher incidence of secondary bacterial infection during the disease course (75.0% vs. 41.6%, χ2 value 10.120, P < 0.05). Kaplan‒Meier survival analysis indicated that the median survival time of patients in the low LYM-5d and high-IL-6 group was significantly shorter than that of patients in the non-low LYM-5d and high-IL-6 group (14.5 ± 1.8 d vs. 22.2 ± 1.1 d, Z value 18.086, P < 0.05). There was no significant difference in the curative effect between the thymosin group and the nonthymosin group. LYM and IL-6 levels are closely related to SARS-CoV-2 pneumonia severity. The prognosis for patients with IL-6 ≥ 416.4 pg/ml at admission and a lymphocyte count < 0.7 × 10 9/L on the 5th day is poor.

A Lightweight AMResNet Architecture with an Attention Mechanism for Diagnosing COVID-19.

AIMS: COVID-19 has become a worldwide epidemic disease and a new challenge for all mankind. The potential advantages of chest X-ray images on COVID-19 were discovered. We proposed a lightweight and effective Convolution Neural Network framework based on chest X-ray images for the diagnosis of COVID-19, named AMResNet. BACKGROUND: COVID-19 has become a worldwide epidemic disease and a new challenge for all mankind. The potential advantages of chest X-ray images on COVID-19 were discovered. OBJECTIVE: A lightweight and effective Convolution Neural Network framework based on chest X-ray images for the diagnosis of COVID-19. METHOD: By introducing the channel attention mechanism and image spatial information attention mechanism, a better level can be achieved without increasing the number of model parameters. RESULT: In the collected data sets, we achieved an average accuracy rate of more than 92%, and the sensitivity and specificity of specific disease categories were also above 90%. CONCLUSION: The convolution neural network framework can be used as a novel method for artificial intelligence to diagnose COVID-19 or other diseases based on medical images.

Epidemiological Characteristics and Antimicrobial Resistance Changes of Carbapenem-Resistant Klebsiella pneumoniae and Acinetobacter baumannii under the COVID-19 Outbreak: An Interrupted Time Series Analysis in a Large Teaching Hospital.

BACKGROUND: To investigate the epidemiological characteristics and resistance changes of carbapenem-resistant organisms (CROs) under the COVID-19 outbreak to provide evidence for precise prevention and control measures against hospital-acquired infections during the pandemic. METHODS: The distribution characteristics of CROs (i.e., carbapenem-resistant Klebsiella pneumoniae and Acinetobacter baumannii) were analyzed by collecting the results of the antibiotic susceptibility tests of diagnostic isolates from all patients. Using interrupted time series analysis, we applied Poisson and linear segmented regression models to evaluate the effects of COVID-19 on the numbers and drug resistance of CROs. We also conducted a stratified analysis using the Cochran-Mantel-Haenszel test. RESULTS: The resistance rate of carbapenem-resistant Acinetobacter baumannii (CRAB) was 38.73% higher after the COVID-19 outbreak compared with before (p < 0.05). In addition, the long-term effect indicated that the prevalence of CRAB had a decreasing trend (p < 0.05). However, the overall resistance rate of Klebsiella pneumoniae did not significantly change after the COVID-19 outbreak. Stratified analysis revealed that the carbapenem-resistant Klebsiella pneumoniae (CRKP) rate increased in females (OR = 1.98, p < 0.05), those over 65 years old (OR = 1.49, p < 0.05), those with sputum samples (OR = 1.40, p < 0.05), and those in the neurology group (OR = 2.14, p < 0.05). CONCLUSION: The COVID-19 pandemic has affected the change in nosocomial infections and resistance rates in CROs, highlighting the need for hospitals to closely monitor CROs, especially in high-risk populations and clinical departments. It is possible that lower adherence to infection control in crowded wards and staffing shortages may have contributed to this trend during the COVID-19 pandemic, which warrants further research.

Safety of inactivated COVID-19 vaccines in autoimmune encephalitis: A real-world cross-sectional survey.

OBJECTIVE: To assess safety data of the inactivated COVID-19 vaccines in a real-world sample of people with autoimmune encephalitis (pwAE). METHODS: A cross-sectional study was performed between 1 March and 30 April 2022. We invited pwAE from our previous ONE-WC (Outcome of Autoimmune Encephalitis Study in Western China) registration study database, to attend neurological clinics, at West China Hospital to participate in a face-to-face survey using a custom-designed questionnaire for this study. The ONE-WC study began in October 2011 and prospectively enrolled pwAE from four large comprehensive neurological centers in Sichuan province, China. RESULTS: Of the 387 pwAE, 240 (62.0%) completed the questionnaire. Half the 240 participants (121, 50.4%) reported receiving at least one dose of COVID-19 vaccine, which in all but two patients received inactivated COVID-19 vaccine. Among vaccinated pwAE, the median age was 35 years (range 15-69) and 57.8% of them were women. The most frequent reasons that unvaccinated individuals reported for not receiving the COVID-19 vaccine were concern about vaccine-induced relapse of AE (50.4%) and advice from a physician to delay vaccination (21.0%). Small proportions of vaccinated individuals reported adverse events after the first dose (11.5%) or the second dose (10.2%), and none of the adverse events was serious. Across the entire sample, one individual reported relapsing within 30 days after the first dose and three individuals reported relapsing more than 120 days after the first dose. CONCLUSIONS: This real-world survey indicates an overall favorable safety profile of the inactivated COVID-19 vaccine for pwAE.

Caregiver Perceptions of Children's and Adolescents' Psychosocial Functioning During the Stringent COVID-19 Lockdown Restrictions in Shanghai: Cross-sectional Study.

BACKGROUND: The COVID-19 pandemic represents a global health crisis. The Shanghai municipal government in China implemented strict and comprehensive pandemic control strategies in the first half of 2022 to eliminate a wave of COVID-19 infection. The pandemic and the resulting government responses have led to abrupt changes to families' daily lives, including the mental health of children and adolescents. OBJECTIVE: The aim of this paper is to examine the impact of COVID-19 exposure and the stringent lockdown measures on the daily life and mental health of children and adolescents and to provide suggestions on maintaining their mental health when similar public health emergencies occur in the future. METHODS: In this cross-sectional study, an anonymous survey was distributed online in May 1-15, 2022, in Shanghai. Individuals were eligible to participate if they were currently the caregiver of a child or adolescent (aged 4-17 years). Outcomes were psychosocial functioning of children and adolescents, as reported by parents, using the Pediatric Symptom Checklist-17. COVID-19 exposure and life changes were also reported. Multivariate logistic regression was used to analyze risk factors for poor psychosocial functioning. RESULTS: In total, 2493 valid questionnaires were analyzed. The rate of positive scores on the global Pediatric Symptom Checklist-17 scale was 16.5% (n=411). Internalizing, attention, and externalizing problem subscale positivity rates were 17.3% (n=431), 10.9% (n=272), and 8.9% (n=221), respectively. Caregivers reported that 64.2% (n=1601) and 20.7% (n=516) of the children's interactions with friends or peers and parents deteriorated, respectively. Compared with male caregivers, female caregivers were less likely to report psychosocial problems in children and adolescents (adjusted odds ratio [aOR] 0.68; 95% CI 0.53-0.88). Older children and those with lower COVID-19 Exposure and Family Impact Scales scores were less likely to have psychological problems (aOR 1.15; 95% CI 1.10-1.21). Compared with children with screen times <1 hour per day for recreation, those using screens for >3 hours had higher odds of psychological distress (aOR 2.09; 95% CI 1.47-1.97). Children who spent 1-2 hours exercising and had better interactions with friends or peers and parents showed a trend toward lower odds of psychological problems. Children and adolescents with worse sleep compared with preclosure were more likely to have psychological problems. CONCLUSIONS: The prevalence of psychosocial problems among children and adolescents is relatively high. Being young, having more COVID-19 exposure, and having more screen times (>3 h/day), less exercise time (<30 min), worse sleep, and deteriorated interactions with friends or peers and parents were risk factors for poor psychosocial functioning. It is necessary for governments, communities, schools, and families to take appropriate countermeasures to reduce the negative impact of the stringent control measures on caregivers' parenting and psychosocial functioning of children and adolescents.

Clan loyalty and COVID-19 diffusion: Evidence from China.

This paper addresses the substantial role of clan loyalty in promoting COVID-19 diffusion in China. Using a city-date panel dataset of observations from 183 cities (prefecture-level and above) in the period of the special long holiday of Chinese New Year in 2020 (January 24-March 1), we find that regions with higher clan loyalty have more COVID-19 cases than regions with lower clan loyalty. A one standard deviation increase in clan loyalty is associated with an 8.1% increase in COVID-19 cases. We further document that clan loyalty drives COVID-19 cases by promoting mass gatherings, exploiting a staggered difference-in-differences (DID) regression based on city community-management policy shocks. Our paper provides novel evidence of one negative public health consequence of clan loyalty, namely, its aggravation of COVID-19 cases.

Nesting the SIRV model with NAR, LSTM and statistical methods to fit and predict COVID-19 epidemic trend in Africa.

OBJECTIVE: Compared with other regions in the world, the transmission characteristics of the COVID-19 epidemic in Africa are more obvious, has a unique transmission mode in this region; At the same time, the data related to the COVID-19 epidemic in Africa is characterized by low data quality and incomplete data coverage, which makes the prediction method of COVID-19 epidemic suitable for other regions unable to achieve good results in Africa. In order to solve the above problems, this paper proposes a prediction method that nests the in-depth learning method in the mechanism model. From the experimental results, it can better solve the above problems and better adapt to the transmission characteristics of the COVID-19 epidemic in African countries. METHODS: Based on the SIRV model, the COVID-19 transmission rate and trend from September 2021 to January 2022 of the top 15 African countries (South Africa, Morocco, Tunisia, Libya, Egypt, Ethiopia, Kenya, Zambia, Algeria, Botswana, Nigeria, Zimbabwe, Mozambique, Uganda, and Ghana) in the accumulative number of COVID-19 confirmed cases was fitted by using the data from Worldometer. Non-autoregressive (NAR), Long-short term memory (LSTM), Autoregressive integrated moving average (ARIMA) models, Gaussian and polynomial functions were used to predict the transmission rate ß in the next 7, 14, and 21 days. Then, the predicted transmission rate ßs were substituted into the SIRV model to predict the number of the COVID-19 active cases. The error analysis was conducted using root-mean-square error (RMSE) and mean absolute percentage error (MAPE). RESULTS: The fitting curves of the 7, 14, and 21 days were consistent with and higher than the original curves of daily active cases (DAC). The MAPE between the fitted and original 7-day DAC was only 1.15% and increased with the longer of predict days. Both the predicted ß and DAC of the next 7, 14, and 21 days by NAR and LSTM nested models were closer to the real ones than other three ones. The minimum RMSEs for the predicted number of COVID-19 active cases in the next 7, 14, and 21 days were 12,974, 14,152, and 12,211 people, respectively when the order of magnitude for was 106, with the minimum MAPE being 1.79%, 1.97%, and 1.64%, respectively. CONCLUSION: Nesting the SIRV model with NAR, LSTM, ARIMA methods etc. through functionalizing ß respectively could obtain more accurate fitting and predicting results than these models/methods alone for the number of confirmed COVID-19 cases in Africa in which nesting with NAR had the highest accuracy for the 14-day and 21-day predictions. The nested model was of high significance for early understanding of the COVID-19 disease burden and preparedness for the response.

Safety of inactivated COVID-19 vaccines in autoimmune encephalitis: a real-world cross-sectional survey

Objective To assess safety data of the inactivated COVID-19 vaccines in a real-world sample of people with autoimmune encephalitis (pwAE). Methods A cross-sectional study was performed between 1 March and 30 April 2022. We invited pwAE from our previous ONE-WC (Outcome of Autoimmune Encephalitis Study in Western China) registration study database, to attend neurological clinics, at West China Hospital to participate in a face-to-face survey using a custom-designed questionnaire for this study. The ONE-WC study began in October 2011 and prospectively enrolled pwAE from four large comprehensive neurological centers in Sichuan province, China. Results Of the 387 pwAE, 240 (62.0%) completed the questionnaire. Half the 240 participants (121, 50.4%) reported receiving at least one dose of COVID-19 vaccine, which in all but two patients received inactivated COVID-19 vaccine. Among vaccinated pwAE, the median age was 35 years (range 15-69) and 57.8% of them were women. The most frequent reasons that unvaccinated individuals reported for not receiving the COVID-19 vaccine were concern about vaccine-induced relapse of AE (50.4%) and advice from a physician to delay vaccination (21.0%). Small proportions of vaccinated individuals reported adverse events after the first dose (11.5%) or the second dose (10.2%), and none of the adverse events was serious. Across the entire sample, one individual reported relapsing within 30 days after the first dose and three individuals reported relapsing more than 120 days after the first dose. Conclusions This real-world survey indicates an overall favorable safety profile of the inactivated COVID-19 vaccine for pwAE.

Attention and Emotion Recovery Effects of Urban Parks during COVID-19-Psychological Symptoms as Moderators

Previous research that compared the restorative effects of natural settings with poor-quality urban settings may have exaggerated the restorative benefits of greenspace. Few studies have been conducted to examine the restorative benefits of green streets and other types of park landscapes on attention and emotion. In addition, it is not clear how negative psychological symptoms (e.g., stress, depression) affect natural's restorative benefits, especially as the current COVID-19 pandemic has added to people's psychological burden. In this study, 125 participants were randomly assigned to view one of five videos (green street, lawn, plaza, forest, waterside) for a break after completing an emotion and attention fatigue induction task. Attention function and emotion were measured using the backward digit span test and the Self-Assessment Manikin scale. Stress and depressive symptoms experienced over the last month were measured using the Perceived Stress Scale(PSS-10) and the Patient Health Questionnaire(PHQ-9). Our results indicate that the four park settings showed significant attention function recovery and valence improvement compared to the green streets, while subjects' arousal changed only over time. Hardscapes (plazas) could provide the same attentional and emotional restorative benefits as natural landscapes (forests, watersides, lawns). In addition, we also found that the mood-improving benefits of natural environments may decrease with increasing depressive symptoms, although chronic stress symptoms did not show the same trend.

Efficacy and safety of glycyrrhizic acid preparation treating comorbid liver injury in COVID-19: A systematic review.

Background: No specific drug for COVID-19 has been found, and many studies have found that different degrees of liver injury often occurred after infection with COVID-19. Glycyrrhizic acid preparation (GAP) has been frequently used clinically, often combined with conventional treatments such as antiviral therapy, to improve the prognosis of COVID-19 and patients' liver function. Aims: To critically review and analyze clinical evidence on the efficacy and safety of GAP in the treatment of COVID-19 alone and COVID-19 with comorbid liver injury. Methods: A systematic literature review was performed following a sensitive searching strategy that examines all articles published in "WHO COVID-19 Research Database," "Cochrane Library," "VIP," "CNKI," "Wanfang," and "CBM" from 2020 to July 2022. Articles were evaluated by peer reviewers and used Joanna Briggs Institute (JBI) critical appraisal tools to complete the assessment of the risk of bias. Results: Ten clinical studies were finally included, involving 598 patients with COVID-19, of whom 189 were confirmed to be with comorbid liver injury. The main GAPs used are diammonium glycyrrhizinate and magnesium isoglycyrrhizinate, which have shown efficacy in improving liver function, inhibiting inflammation, and enhancing immunity. We are still seeking more related research. Conclusion: Glycyrrhizic acid preparations (mainly diammonium glycyrrhizinate and magnesium isoglycyrrhizinate) have a considerable clinical effect on improving liver function in patients with COVID-19 alone or with comorbid liver injury. Further studies on the use of GAP in the treatment of COVID-19 with comorbid liver injury and its mechanism are still needed. Systematic Review Registration: [www.crd.york.ac.uk/prospero], identifier [CRD42021234647].

Hydrogenated Boron Phosphide THz-Metamaterial-Based Biosensor for Diagnosing COVID-19: A DFT Coupled FEM Study.

Recent reports focus on the hydrogenation engineering of monolayer boron phosphide and simultaneously explore its promising applications in nanoelectronics. Coupling density functional theory and finite element method, we investigate the bowtie triangle ring microstructure composed of boron phosphide with hydrogenation based on structural and performance analysis. We determine the carrier mobility of hydrogenated boron phosphide, reveal the effect of structural and material parameters on resonance frequencies, and discuss the variation of the electric field at the two tips. The results suggest that the mobilities of electrons for hydrogenated BP monolayer in the armchair and zigzag directions are 0.51 and 94.4 cm2·V-1·s-1, whereas for holes, the values are 136.8 and 175.15 cm2·V-1·s-1. Meanwhile, the transmission spectra of the bowtie triangle ring microstructure can be controlled by adjusting the length of the bowtie triangle ring microstructure and carrier density of hydrogenated BP. With the increasing length, the transmission spectrum has a red-shift and the electric field at the tips of equilateral triangle rings is significantly weakened. Furthermore, the theoretical sensitivity of the BTR structure reaches 100 GHz/RIU, which is sufficient to determine healthy and COVID-19-infected individuals. Our findings may open up new avenues for promising applications in the rapid diagnosis of COVID-19.

Cluster head selection method of multiple UAVs under COVID-19 situation.

As COVID-19 continues to spread, people are unable to move freely when their residence region is temporarily lockdown, supplies cannot normally enter into such zones, leading to the shortage of supplies in these areas. Thus to ensure the delivery of supplies while reducing contact, the unmanned aerial vehicle (UAV) deliveries have become a common way. In order to efficiently use UAV resources and reduce energy loss in data transmission while performing the tasks, clustering is often used for achieving the above objectives, where the selected cluster heads centrally plan tasks so that reduce the communication times. However, problems such as unreasonable clustering, high energy consumption of cluster heads, and high mortality of cluster heads, directly lead the low cooperation efficiency and short life cycle of UAVs. Considering the nodes often died earlier through the k-means algorithm and ant colony algorithm, and highly dependent on the base station, these factors affect the working cycle and coordination efficiency of the UAVs. Facing the issues above, the cluster head selection algorithm of UAV based on game (CHSA) is proposed, where the mixed game model is adopted to select cluster heads for each region after regional division, and selecting the representative node to perform the cluster head selection algorithm, which help to reduce the energy consumption of each round of communication between nodes. Moreover, the key properties of the CHSA algorithm are proved, and the comparison experiment are conducted to prove the CHSA algorithm can effectively reduce energy consumption and prolong the network life cycle.

Deep mutational scanning identifies SARS-CoV-2 Nucleocapsid escape mutations of currently available rapid antigen tests.

The effects of mutations in continuously emerging variants of SARS-CoV-2 are a major concern for the performance of rapid antigen tests. To evaluate the impact of mutations on 17 antibodies used in 11 commercially available antigen tests with emergency use authorization, we measured antibody binding for all possible Nucleocapsid point mutations using a mammalian surface-display platform and deep mutational scanning. The results provide a complete map of the antibodies' epitopes and their susceptibility to mutational escape. Our data predict no vulnerabilities for detection of mutations found in variants of concern. We confirm this using the commercial tests and sequence-confirmed COVID-19 patient samples. The antibody escape mutational profiles generated here serve as a valuable resource for predicting the performance of rapid antigen tests against past, current, as well as any possible future variants of SARS-CoV-2, establishing the direct clinical and public health utility of our system.

The impact of COVID-19 pandemic on individuals at clinical high-risk for psychosis: Evidence from eye-tracking measures.

Emerging evidence suggested that people with severe mental disorders were more vulnerable to the negative effects of the COVID-19 pandemic. However, few researches investigated the influence of global pandemics on people at clinical high risk (CHR) for psychosis. This study aimed to investigate the impact of the COVID-19 pandemic on clinical symptoms, psychological distress, and eye-tracking characteristics in CHR individuals and healthy participants. Forty-nine CHR individuals and 50 healthy controls (HC) were assessed by PTSD Checklist for DSM-5 (PCL-5), Perceived Stress Scale, 10-item version (PSS-10), and Coronavirus Impact Scale (CIS). Eye movement performances were measured by the tests of fixation stability, free-viewing, and anti-saccade. According to the mean score of CIS, participants were stratified into high-impact (n = 35) and low-impact (n = 64) subgroups. Compared with the HC group, CHR participants reported significantly higher levels of post-traumatic symptoms caused by the COVID-19 pandemic and showed abnormalities in most of the eye movement indexes. Among the altered indexes, the saccade amplitude of fixation stability test (far distractor), the scan path length of free-viewing test, and the accuracy of anti-saccade test were negatively affected by the severity of impact level in the CHR group. Moreover, the altered eye movement indexes were significantly associated with the total scores of CIS, PCL-5, and subscales of the Scale of Prodromal Syndromes (SOPS) among CHR individuals. Overall, our findings suggested the negative impact of the COVID-19 pandemic on the eye movement characteristics of CHR individuals. The present study provides valuable information on physiological distress related to the COVID-19 pandemic and sensitive neuropsychological biomarkers that interacted with social and environment stress in the CHR population.

Correction: Breadth and function of antibody response to acute SARS-CoV-2 infection in humans.

[This corrects the article DOI: 10.1371/journal.ppat.1009352.].

The predictive role of lymphocyte subsets and laboratory measurements in COVID-19 disease: a retrospective study.

AIM: The aim of this study was to investigate the predictive role of lymphocyte subsets and other laboratory measurements in patients with COVID-19. METHODS: Electronic medical records of adult patients with confirmed diagnosis of COVID-19 from the Shanghai Public Health Clinical Center were reviewed retrospectively to obtain relevant data. RESULTS: The mean age of patients was 40.98 ± 15.95 years, with 58% of the patients being males. The cutoff values at the intensive care unit (ICU) admission, mechanical ventilation, and mortality were CD4+ cells (267, 198, and 405), CD8+ cells (263, 203, and 182), and CD4+ /CD8+ cells (1.4, 1.8, and 1.4). The cutoffs below these values indicate the higher chances of disease progression. Higher CD4+ cell count led to lesser chances for ICU admission [odds ratio (OR) (95% confidence interval (CI): 0.994 (0.991, 0.997); p = 0.0002] and mortality [OR (95% CI): 0.988 (0.979, 0.99); p = 0.001], higher CD8+ count was an independent risk factor for ICU admission. T-cell count positively correlated with total lymphocyte count and platelets, while negatively correlated with D-dimer and lactate dehydrogenase (LDH). Among patients with non-severe COVID-19, median CD8+ T cell, CD4+ T cell, total lymphocyte count, and platelets were 570, 362, 1.45, and 211, respectively, while median values decreased to 149, 106, 0.64, and 172, respectively, in patients with severe COVID-19. CONCLUSION: Lower T lymphocyte subsets were significantly associated with higher admission to ICU, mechanical ventilation, and mortality among patients with COVID-19. A cutoff value of ICU admission, mechanical ventilation, and mortality below CD4+ cells (267, 198, and 405), CD8+ cells (263, 203, 182), and CD4+/CD8+ cells (1.4, 1.8, 1.4) may help identify patients at high risk of disease progression. The continuous evaluation of laboratory indices may help with dismal prognosis and prompt intervention to improve outcomes.

Post-infection cognitive impairments in a cohort of elderly patients with COVID-19.

BACKGROUND: Understanding the long-term effects of coronavirus disease 2019 (COVID-19) on cognitive function is essential for monitoring the cognitive decline in the elderly population. This study aims to assess the current cognitive status and the longitudinal cognitive decline in elderly patients recovered from COVID-19. METHODS: This cross-sectional study recruited 1539 COVID-19 inpatients aged over 60 years who were discharged from three COVID-19-designated hospitals in Wuhan, China, from February 10 to April 10, 2020. In total, 466 uninfected spouses of COVID-19 patients were selected as controls. The current cognitive status was assessed using a Chinese version of the Telephone Interview of Cognitive Status-40 (TICS-40) and the longitudinal cognitive decline was assessed using an Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Cognitive assessments were performed 6 months after patient discharge. RESULTS: Compared with controls, COVID-19 patients had lower TICS-40 scores and higher IQCODE scores [TICS-40 median (IQR): 29 (25 to 32) vs. 30 (26 to 33), p < 0.001; IQCODE median (IQR): 3.19 (3.00 to 3.63) vs. 3.06 (3.00 to 3.38), p < 0.001]. Severe COVID-19 patients had lower TICS-40 scores and higher IQCODE scores than non-severe COVID-19 patients [TICS-40 median (IQR): 24 (18 to 28) vs. 30 (26 to 33), p < 0.001; IQCODE median (IQR): 3.63 (3.13 to 4.31) vs. 3.13 (3.00 to 3.56), p < 0.001] and controls [TICS-40 median (IQR): 24 (18 to 28) vs. 30 (26 to 33), p < 0.001; IQCODE median (IQR) 3.63 (3.13 to 4.31) vs. 3.06 (3.00 to 3.38), p < 0.001]. Severe COVID-19 patients had a higher proportion of cases with current cognitive impairment and longitudinal cognitive decline than non-severe COVID-19 patients [dementia: 25 (10.50 %) vs. 9 (0.69 %), p < 0.001; Mild cognitive impairment (MCI): 60 (25.21 %) vs. 63 (4.84 %), p < 0.001] and controls [dementia: 25 (10.50 %) vs. 0 (0 %), p < 0.001; MCI: 60 (25.21 %) vs. 20 (4.29 %), p < 0.001)]. COVID-19 severity, delirium and COPD were risk factors of current cognitive impairment. Low education level, severe COVID-19, delirium, hypertension and COPD were risk factors of longitudinal cognitive decline. CONCLUSIONS: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with an increased risk of long-term cognitive decline in elderly population. COVID-19 patients, especially severe patients, should be intensively monitored for post-infection cognitive decline.

Inclusion of cGAMP within virus-like particle vaccines enhances their immunogenicity.

Cyclic GMP-AMP (cGAMP) is an immunostimulatory molecule produced by cGAS that activates STING. cGAMP is an adjuvant when administered alongside antigens. cGAMP is also incorporated into enveloped virus particles during budding. Here, we investigate whether inclusion of cGAMP within viral vaccine vectors enhances their immunogenicity. We immunise mice with virus-like particles (VLPs) containing HIV-1 Gag and the vesicular stomatitis virus envelope glycoprotein G (VSV-G). cGAMP loading of VLPs augments CD4 and CD8 T-cell responses. It also increases VLP- and VSV-G-specific antibody titres in a STING-dependent manner and enhances virus neutralisation, accompanied by increased numbers of T follicular helper cells. Vaccination with cGAMP-loaded VLPs containing haemagglutinin induces high titres of influenza A virus neutralising antibodies and confers protection upon virus challenge. This requires cGAMP inclusion within VLPs and is achieved at markedly reduced cGAMP doses. Similarly, cGAMP loading of VLPs containing the SARS-CoV-2 Spike protein enhances Spike-specific antibody titres. cGAMP-loaded VLPs are thus an attractive platform for vaccination.