Trapping non-cognate nucleotide upon initial binding for replication fidelity control in SARS-CoV-2 RNA dependent RNA polymerase (preprint)

The RNA dependent RNA polymerase (RdRp) in SARS-CoV-2 is a highly conserved enzyme responsible for viral genome replication/transcription. Here we investigate computationally natural non-cognate vs cognate nucleotide addition cycle (NAC) and intrinsic nucleotide selectivity during the viral RdRp elongation, focusing prechemically from initial nucleotide substrate binding (enzyme active site open) to insertion (active site closed) of RdRp in contrast with one-step only substrate binding process. Current studies have been first carried out using microsecond ensemble equilibrium all-atom molecular dynamics (MD) simulations. Due to slow conformational changes (from the open to closed) accompanying nucleotide insertion and selection, enhanced or umbrella sampling methods have been further employed to calculate free energy profiles of the non-cognate NTP insertion. Our studies show notable stability of noncognate dATP and GTP upon initial binding in the active-site open state. The results indicate that while natural cognate ATP and Remdesivir drug analogue (RDV-TP) are biased to be stabilized in the closed or insertion state, the natural non-cognate dATP and GTP can be well trapped in off-path initial binding configurations. Current work thus presents an intrinsic nucleotide selectivity mechanism of SARS-CoV-2 RdRp for natural substrate fidelity control in viral genome replication.

Enantioselective Effect of Chiral Small Molecules in SARS-CoV-2 Vaccine-Induced Immune Response.

Although numerous chiral small molecules have been discovered and synthesized, the investigation on their enantioselective immunological effects remains limited. In this study, we designed and synthesized a pair of small molecule enantiomers (R/S-ResP) by covalently bonding two immunostimulators (resiquimod/Res) onto a planar chiral framework (paracyclophane/P). Notably, we found that S-ResP exhibits a 4.05-fold higher affinity for toll-like receptor 7 (TLR7) than R-ResP, thereby more effectively enhancing the functions of dendritic cells and macrophages in cytokine secretion and antigen internalization. Furthermore, we observed that S-ResP significantly enhances RBD antigen-induced cross-neutralization against various SARS-CoV-2 strains compared to R-ResP. These findings demonstrate the enantioselective effects of small molecules on regulating vaccine-induced immune responses and emphasize the significance of chirality in designing small molecular adjuvants.

Gut microbiome alterations in patients with COVID-19-related coagulopathy.

COVID-19 is characterized by a predominantly prothrombotic state, which underlies severe disease and poor outcomes. Imbalances of the gut microbiome have been linked with abnormal hemostatic processes. Understanding the relationship between the gut microbiome and abnormal coagulation parameters in COVID-19 could provide a novel framework for the diagnosis and management of COVID-related coagulopathies (CRC). This cross-sectional study used shotgun metagenomic sequencing to examine the gut microbiota of patients with CRC (n = 66) and compared it to COVID control (CCs) (n = 27) and non-COVID control (NCs) (n = 22) groups. Three, 1, and 3 taxa were found enriched in CRCs, CCs, and NCs. Next, random forest models using 7 microbial biomarkers and differential clinical characteristics were constructed and achieved strong diagnostic potential in distinguishing CRC. Specifically, the most promising biomarker species for CRC were Streptococcus thermophilus, Enterococcus faecium, and Citrobacter portucalensis. Conversely, Enterobacteriaceae family and Fusicatenibacter genus are potentially protective against CRC in COVID patients. We further identified 4 species contributing to 20 MetaCyc pathways that were differentially abundant among groups, with S. thermophilus as the main coding species in CRCs. Our findings suggest that the alterations of gut microbiota compositional and functional profiles may influence the pathogenesis of CRC and that microbiota-based diagnosis and treatment could potentially benefit COVID patients in preventing and alleviating thrombosis-related clinical outcomes.

Thrombosis and bleeding in COVID-19 patients requiring extracorporeal membrane oxygenation: A systematic review and meta-analysis

Background Extracorporeal membrane oxygenation (ECMO) and COVID-19 significantly impact on coagulation system. A systematic review and meta-analysis were performed to explore the prevalence of thrombotic and bleeding events in COVID-19 patients supported with ECMO, summarize anticoagulation regimens, and guide future research. Methods Cochrane, EMBASE, Scopus, and PubMed were searched for studies examining thrombosis and bleeding in COVID-19 patients requiring ECMO. The primary outcomes were prevalence of different types of hemorrhage and thrombosis. The pooled estimated rates and relative risk (RR) were calculated to summarize the outcomes. Results Twenty-three peer-reviewed studies involving 6,878 subjects were included. For thrombotic events, the prevalence of circuit thrombosis was 21.5% (95% CI: 15.5%–27.6%;1,532 patients);ischemic stroke was 2.6% (95% CI: 1.5%–3.7%;5,926 patients);and pulmonary embolism (PE) was 11.8% (95% CI: 6.8%–16.8%;5,853 patients). For bleeding events, 37.4% of patients experienced major hemorrhage (95% CI: 28.1%–46.8%;1,558 patients) and 9.9% experienced intracranial hemorrhage (ICH) (95% CI: 7.8%–12.1%;6,348 patients). COVID-19 cases on ECMO complicated with more ICH than non-COVID-19 patients on respiratory ECMO [RR=2.23 (95% CI: 1.32–3.75)]. Anticoagulation strategies varied among centers. Conclusions Circuit thrombosis and major bleeding were the most common thrombotic and bleeding events. The incidence of ICH was significantly higher when ECMO was indicated for COVID-19 than for other respiratory diseases. There is no evidence for stronger anticoagulation practice and remains no consistent anticoagulation strategy to reduce the occurrence of thrombosis and bleeding under the double "hit” of COVID-19 and ECMO.

Thrombosis and bleeding in patients with COVID-19 requiring extracorporeal membrane oxygenation: a systematic review and meta-analysis.

Background: Extracorporeal membrane oxygenation (ECMO) and COVID-19 significantly impact the coagulation system. A systematic review and meta-analysis were performed to explore the prevalence of thrombotic and bleeding events in patients with COVID-19 supported with ECMO, summarize anticoagulation regimens, and guide future research. Methods: Cochrane, EMBASE, Scopus, and PubMed were searched for studies examining thrombosis and bleeding in patients with COVID-19 requiring ECMO. The primary outcomes were the prevalences of different types of hemorrhage and thrombosis. The pooled estimated rates and relative risk (RR) were calculated to summarize the outcomes. Results: Twenty-three peer-reviewed studies involving 6878 subjects were included. For thrombotic events, the prevalence of circuit thrombosis was 21.5% (95% CI: 15.5%-27.6%; 1532 patients), that of ischemic stroke was 2.6% (95% CI: 1.5%-3.7%; 5926 patients), and that of pulmonary embolism (PE) was 11.8% (95% CI: 6.8%-16.8%; 5853 patients). For bleeding events, 37.4% of the patients experienced major hemorrhage (95% CI: 28.1%-46.8%; 1558 patients) and 9.9% experienced intracranial hemorrhage (ICH; 95% CI: 7.8%-12.1%; 6348 patients). COVID-19 cases on ECMO were complicated with more ICH than patients without COVID-19 on respiratory ECMO [RR = 2.23 (95% CI: 1.32-3.75)]. Anticoagulation strategies varied among centers. Conclusions: Circuit thrombosis and major bleeding were the most common thrombotic and bleeding events. The incidence of ICH was significantly higher when ECMO was indicated for COVID-19 than for other respiratory diseases. There is no evidence for stronger anticoagulation practice, and remains no consistent anticoagulation strategy to reduce the occurrence of thrombosis and bleeding under the double "hit" of COVID-19 and ECMO.

A new polysaccharide platform constructs self-adjuvant nanovaccines to enhance immune responses.

BACKGROUND: Nanovaccines have shown the promising potential in controlling and eradicating the threat of infectious diseases worldwide. There has been a great need in developing a versatile strategy to conveniently construct diverse types of nanovaccines and induce potent immune responses. To that end, it is critical for obtaining a potent self-adjuvant platform to assemble with different types of antigens into nanovaccines. RESULTS: In this study, we identified a new natural polysaccharide from the rhizomes of Bletilla striata (PRBS), and used this polysaccharide as a platform to construct diverse types of nanovaccines with potent self-adjuvant property. In the construction process of SARS-CoV-2 nanovaccine, PRBS molecules and RBD protein antigens were assembled into ~ 300 nm nanoparticles by hydrogen bond. For HIV nanovaccine, hydrophobic effect dominantly drove the co-assembly between PRBS molecules and Env expression plasmid into ~ 350 nm nanospheres. Importantly, PRBS can potently activate the behaviors and functions of multiple immune cells such as macrophages, B cells and dendritic cells. Depending on PRBS-mediated immune activation, these self-adjuvant nanovaccines can elicit significantly stronger antigen-specific antibody and cellular responses in vivo, in comparison with their corresponding traditional vaccine forms. Moreover, we also revealed the construction models of PRBS-based nanovaccines by analyzing multiple assembly parameters such as bond energy, bond length and interaction sites. CONCLUSIONS: PRBS, a newly-identified natural polysaccharide which can co-assemble with different types of antigens and activate multiple critical immune cells, has presented a great potential as a versatile platform to develop potent self-adjuvant nanovaccines.

Safety and immunogenicity of a mosaic vaccine booster against Omicron and other SARS-CoV-2 variants: a randomized phase 2 trial.

An ongoing randomized, double-blind, controlled phase 2 trial was conducted to evaluate the safety and immunogenicity of a mosaic-type recombinant vaccine candidate, named NVSI-06-09, as a booster dose in subjects aged 18 years and older from the United Arab Emirates (UAE), who had administered two or three doses of inactivated vaccine BBIBP-CorV at least 6 months prior to enrollment. The participants were randomly assigned with 1:1 to receive a booster dose of NVSI-06-09 or BBIBP-CorV. The primary outcomes were immunogenicity and safety against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant, and the exploratory outcome was cross-immunogenicity against other circulating strains. Between May 25 and 30, 2022, 516 adults received booster vaccination with 260 in NVSI-06-09 group and 256 in BBIBP-CorV group. Interim results showed a similar safety profile between two booster groups, with low incidence of adverse reactions of grade 1 or 2. For immunogenicity, by day 14 post-booster, the fold rises in neutralizing antibody geometric mean titers (GMTs) from baseline elicited by NVSI-06-09 were remarkably higher than those by BBIBP-CorV against the prototype strain (19.67 vs 4.47-fold), Omicron BA.1.1 (42.35 vs 3.78-fold), BA.2 (25.09 vs 2.91-fold), BA.4 (22.42 vs 2.69-fold), and BA.5 variants (27.06 vs 4.73-fold). Similarly, the neutralizing GMTs boosted by NVSI-06-09 against Beta and Delta variants were also 6.60-fold and 7.17-fold higher than those by BBIBP-CorV. Our findings indicated that a booster dose of NVSI-06-09 was well-tolerated and elicited broad-spectrum neutralizing responses against divergent SARS-CoV-2 variants, including Omicron and its sub-lineages.

Risk Factors for Radiological Progression Within Admissive One Week in the Hospitalized COVID-19 Omicron Variant-Infected Patients.

Purpose: Recently, the SARS-CoV-2 Omicron variant was identified as responsible for a novel wave of COVID-19 worldwide. We perform a retrospective study to identify potential risk factors contributing to radiological progression in the COVID-19 patients due to the Omicron variant infection. These findings would provide guiding information for making clinical decisions that could improve the Omicron infection prognosis and reduce disease-related death. Methods: This is a retrospective cohort study from a single center in China. According to the radiological change within admissive one week, enrolled cases were divided into two groups: the progressive (1w-PD) and the stable or improved disease (1w-non-PD). Separate analyses were performed on patients stratified into subgroups using the Mann-Whitney U-test, the Fisher exact test, or the Chi-squared test and a multivariable logistic regression analysis. Results: Both the 1w-non-PD and 1w-PD cohorts displayed comparable asymptomatic infection, have similar underlying disease, impairment in respiratory function, coagulation dysfunction, tissue injury, SARS-CoV-2 viral load, and disease severity. However, the 1w-PD cohort was more inclined to cluster in populations presented with age between 41 and 65, higher CURB-65 scores, undetectable SARS-CoV-2 IgG, and lung affection. Based on the multiple logistic regression analysis, complicated bilateral and ground-glass opacities (GGOs) like pneumonia at admission were independent risk factors to radiological progression within admissive one week. Conclusion: This study provided preliminary data regarding disease progression in Omicron-infected patients that indicated the development of pneumonia in the context of Omicron infection was worthy of potential risk factors.

The requirements of nucleic acid test for COVID-19 during public health emergency: Current regulatory in Taiwan, Singapore, and the United States.

In mid-2022, the COVID-19 cases have reached close to 562 million, but its overall infection rate is hard to confirm. Even with effective vaccines, break-through infections with new variants occur, and safe and reliable testing still plays a critical role in isolation of infected individuals and in control of an outbreak of a COVID-19 pandemic. In response to this urgent need, the diagnostic tests for COVID-19 are rapidly evolving and improving these days. The health authorities of many countries issued requirements for detecting SARS-CoV-2 diagnosis tests during the pandemic and have timely access to these tests to ensure safety and effectiveness. In this study, we compared the requirements of EUA in Taiwan, Singapore, and the United States. For the performance evaluations of nucleic acid extraction, inclusivity, limit of detection (LoD), cross-reactivity, interference, cutoff, and stability, the requirements are similar in the three countries. The use of natural clinical specimens is needed for clinical evaluation in Taiwan and the United States. However, carry-over and cross-contamination studies can be exempted in Taiwan and the United States but are required in Singapore. This review outlines requirements and insight to guide the test developers on the development of IVDs. Considering the rapidly evolving viruses and severe pandemic of COVID-19, timely and accurate diagnostic testing is imperative to the management of diseases. As noted above, the performance requirements for SARS-CoV-2 nucleic acid tests are similar between Taiwan, Singapore and the United States. The differences are mainly in two points: the recommended microorganisms for cross-reactivity study, and the specimen requirement for clinical evaluation. This study provides an overview of current requirements of SARS-CoV-2 nucleic acid tests in Taiwan, Singapore, and the United States.

Ischemic stroke and intracranial hemorrhage in extracorporeal membrane oxygenation for COVID-19: A systematic review and meta-analysis.

PURPOSE: Extracorporeal membrane oxygenation (ECMO) is employed to support critically ill COVD-19 patients. The occurrence of ischemic stroke and intracranial hemorrhage (ICH), as well as the implementation of anticoagulation strategies under the dual influence of ECMO and COVID-19 remain unclear. We conducted a systematic review and meta-analysis to describe the ischemic stroke, ICH and overall in-hospital mortality in COVID-19 patients receiving ECMO and summarize the anticoagulation regimens. METHODS: EMBASE, PubMed, Cochrane, and Scopus were searched for studies examining ischemic stroke, ICH, and mortality in COVID-19 patients supported with ECMO. The outcomes were incidences of ischemic stroke, ICH, overall in-hospital mortality and anticoagulation regimens. We calculated the pooled proportions and 95% confidence intervals (CIs) to summarize the results. RESULTS: We analyzed 12 peer-reviewed studies involving 6039 COVID-19 patients. The incidence of ischemic stroke had a pooled estimate of 2.2% (95% CI: 1.2%-3.2%). The pooled prevalence of ICH was 8.0% (95% CI: 6.3%-9.6%). The pooled estimate of overall in-hospital mortality was 40.3% (95% CI: 33.1%-47.5%). The occurrence of ICH was significantly higher in COVID-19 patients supported with ECMO than in other respiratory ECMO [relative risk=1.75 (95% CI: 1.00-3.07)]. Unfractionated heparin was the most commonly used anticoagulant, and anticoagulation monitoring practice varied among centers. CONCLUSIONS: Ischemic stroke and ICH were common under the double "hit" of COVID-19 and ECMO. The prevalence of ICH was significantly higher in COVID-19 patients supported with ECMO than non-COVID-19 patients requiring ECMO. Individualized anticoagulation regimens may be a good choice to balance thrombosis and bleeding. More detailed research and further exploration are needed to clarify the underlying mechanism and clinical management decisions.

A mosaic-type trimeric RBD-based COVID-19 vaccine candidate induces potent neutralization against Omicron and other SARS-CoV-2 variants.

Large-scale populations in the world have been vaccinated with COVID-19 vaccines, however, breakthrough infections of SARS-CoV-2 are still growing rapidly due to the emergence of immune-evasive variants, especially Omicron. It is urgent to develop effective broad-spectrum vaccines to better control the pandemic of these variants. Here, we present a mosaic-type trimeric form of spike receptor-binding domain (mos-tri-RBD) as a broad-spectrum vaccine candidate, which carries the key mutations from Omicron and other circulating variants. Tests in rats showed that the designed mos-tri-RBD, whether used alone or as a booster shot, elicited potent cross-neutralizing antibodies against not only Omicron but also other immune-evasive variants. Neutralizing antibody ID50 titers induced by mos-tri-RBD were substantially higher than those elicited by homo-tri-RBD (containing homologous RBDs from prototype strain) or the BIBP inactivated COVID-19 vaccine (BBIBP-CorV). Our study indicates that mos-tri-RBD is highly immunogenic, which may serve as a broad-spectrum vaccine candidate in combating SARS-CoV-2 variants including Omicron.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic continues to pose a serious threat to public health and has so far resulted in over six million deaths worldwide. Mass vaccination programs have reduced the risk of serious illness and death in many people, but the virus continues to persist and circulate in communities across the globe. Furthermore, the current vaccines may be less effective against the new variants of the virus, such as Omicron and Delta, which are continually emerging and evolving. Therefore, it is urgent to develop effective vaccines that can provide broad protection against existing and future forms of SARS-CoV-2. There are several different types of SARS-CoV-2 vaccine, but they all work in a similar way. They contain molecules that induce immune responses in individuals to help the body recognize and more effectively fight SARS-CoV-2 if they happen to encounter it in the future. These immune responses may be so specific that new variants of a virus may not be recognized by them. Therefore, a commonly used strategy for producing vaccines with broad protection is to make multiple vaccines that each targets different variants and then mix them together before administering to patients. Here, Zhang et al. took a different approach by designing a new vaccine candidate against SARS-CoV2 that contained three different versions of part of a SARS-CoV2 protein ­ the so-called spike protein ­ all linked together as one molecule. The different versions of the spike protein fragment were designed to include key features of the fragments found in Omicron and several other SARS-CoV-2 variants. The experiments found that this candidate vaccine elicited a much higher immune response against Omicron and other SARS-CoV-2 variants in rats than an existing SARS-CoV-2 vaccine. It was also effective as a booster shot after a first vaccination with the existing SARS-CoV-2 vaccine. These findings demonstrate that the molecule developed by Zhang et al. induces potent and broad immune responses against different variants of SARS-CoV-2 including Omicron in rats. The next steps following on from this work are to evaluate the safety and immunogenicity of this vaccine candidate in clinical trials. In the future, it may be possible to use a similar approach to develop new broad-spectrum vaccines against other viruses.

The Identification With All Humanity (IWAH) scale: its psychometric properties and associations with help-seeking during COVID-19.

The Identification With All Humanity (IWAH) scale was designed to measure the extent to which an individual identifies oneself with all human beings. The current research aimed to conduct the validation of IWAH in a Chinese population and its convergent validity, as well as test the implications of IWAH in associations with help-seeking behaviour during COVID-19. A serial of three studies was conducted from September 1st 2020 to the end of October 2020. The series of studies included Study 1- Exploring the dimensions of the IWAH scale with a sample of 2,881 participants, Study 2- Confirmatory Factor Analysis for the Chinese IWAH dimensions with a separate sample of 6,667 participants, and Study 3- Role of the IWAH in the COVID-19 pandemic with a sample of 9,046 participants. Study 1 found the Chinese version of the IWAH scale to be a two-dimensional construct, with factor 1 - Bond with Humanity and factor 2 - Human Kinship. Study 2 confirmed the two-factor construct as found in Study 1. It also showed positive relations between IWAH and moral judgement, collectivism, nature connectedness, and negative relations with callousness, and having anxiety and depressive symptoms. Study 3 found that IWAH was negatively related to fear of COVID-19 and positively related to the likeliness of help-seeking. This is the first research to test the factorial structure of the IWAH scale in a Chinese population, with the adaptation showing good psychometric properties. The implication of IWAH on fear of COVID-19 and help-seeking provided further understanding of the possible practical value of IWAH during times of global stressful life events. Furthermore, study 3 is the first to explore how IWAH relates to anxiety, depression, and callousness.

Clinical and epidemiological investigation of a child with asymptomatic COVID-19 infection following reoccurrence.

Objective: To investigate the case of a child infected with coronavirus disease 2019 (COVID-19) who had subsequent viral reactivation. Methods: We retrospectively analyzed the clinical manifestations, epidemiological data, laboratory and imaging examinations, treatment, and follow-up of the child. And then, we searched related literature using PubMed. Results: The 9-year-old boy was exposed to COVID-19 in Malawi and tested positive for NAT in Haikou, China. He was asymptomatic and admitted to our hospital. After six negative NATs, he was discharged from the hospital and quarantined in a hotel. His infection was reactivated again after 22 days (interval between first and last positive NATs). The cycle threshold (Ct) values of positive tests were 25 and 31, and the gene sequencing viral loads were very low. The viral strain Kenya/P2601/2020, a variant of the hCoV-19/Wuhan/IVDC-HB-01/2019 genome (GISAID accession IL: EPI_ISL_402119), was found when polymerase chain reaction enrichment was used to sequence the virus. However, people around him tested negative for COVID-19. Conclusion: First, we confirmed the reactivation of COVID-19 in a child. The risk of recurrent infection with SARS-CoV-2 was low, and the policy of strictly isolating patients carrying long-term viral ribonucleic acid should be reconsidered. The interval positivity was most likely due to incorrect sampling and/or testing methods. SGS and aB testing are recommended for children with viral reactivation. Second, SARS-CoV-2 viral reactivation cannot be ruled out. The possible mechanisms, such as prolonged infection and viral latent reactivation, need further investigation.

Network analysis of comorbid depression and anxiety and their associations with quality of life among clinicians in public hospitals during the late stage of the COVID-19 pandemic in China.

BACKGROUND: Mental health problems are common among clinicians working in public hospitals even in the late stage of the COVID-19 pandemic. Network analysis is a novel approach to explore interactions between mental health problems at the symptom level. This study examined the network structure of comorbid depression and anxiety and their associations with quality of life (QOL) among hospital clinicians in China during the late stage of the COVID-19 pandemic. METHODS: A total of 4931 participants were recruited from October 13 to 22, 2020. The nine-item Patient Health Questionnaire (PHQ-9), seven-item Generalized Anxiety Disorder Scale (GAD-7), and the World Health Organization Quality of Life Questionnaire-Brief Version (WHOQOL-BREF) were used to measure depressive and anxiety symptoms, and QOL, respectively. Central and bridge symptoms were identified with centrality and bridge centrality indices, respectively. Network stability was examined using the case-dropping procedure. RESULTS: The prevalence of depression (defined as PHQ-9 total score ≥ 5) was 35.1 % [95 % confidence interval (CI) = 33.73-36.41 %)], the prevalence of anxiety (GAD-7 total score ≥ 5) was 32.5 % (95 % CI = 31.20-33.84 %), while the prevalence of comorbid depression and anxiety was 26.9 % (95 % CI = 25.7-28.2 %). "Impaired motor skills", "Trouble relaxing" and "Uncontrollable worry" were the central symptoms in the whole depression-anxiety network. "Irritability", "Feeling afraid" and "Sad mood" were the most key bridge symptoms linking depression and anxiety. Three symptoms ("Fatigue", "Trouble relaxing" and "Nervousness") were the most strongly and negatively associated with QOL. Neither gender nor the experiences of caring for COVID-19 patients was associated with network global strength, distribution of edge weights or individual edge weights. LIMITATIONS: The causality between variables could not be established. Depressive and anxiety symptoms were assessed by self-report measures, which may result in recall bias and limitations in capturing clinical phenomena. CONCLUSIONS: Both the central (i.e., "Impaired motor skills", "Trouble relaxing" and "Uncontrollable worry") and bridge symptoms (i.e., "Irritability", "Feeling afraid" and "Sad mood") identified in this network analysis should be targeted in specific treatment and preventive measures for comorbid depressive and anxiety symptoms among clinicians in the late stage of the pandemic. Furthermore, "Fatigue", "Trouble relaxing" and "Nervousness" are key symptoms to address to improve clinicians' QOL.

Blood purification in sepsis and systemic inflammation.

PURPOSE OF REVIEW: Sepsis and septic shock are life-threatening diseases with high mortality. Although efforts have made to improve the survivals, the outcomes are still frustrating. Blood purification was thought to be a promising adjunctive therapy to regulate the excessive cytokine storm or to reduce the endotoxin activity caused by sepsis. Critically ill COVID-19 characterized with the similar disease to sepsis may also benefit from blood purification. RECENT FINDINGS: The recent studies mainly focused on hemadsorption materials. The results of the clinical trials showed a tendency in decrease of cytokine levels and endotoxin activity and improvement in haemodynamics. However, the results were controversial. More evidence about blood purification in sepsis and COVID-19 are needed from currently ongoing trials and future well designed trials. SUMMARY: The blood purification therapy demonstrated the tendency in decrease of cytokines and endotoxin activity in different degree according to the current studies. However, the effect on mortality and haemodynamics is still in controversy. Further well designed, large sample sized studies should focus on the timing of initiating blood purification, the appropriate indications and the optimal type of blood purification membrane or cartridge to provide more evidence for clinical practice.

Comparison of initial clinic characteristics of hospitalized patients in Suzhou City during the COVID-19 Omicron wave with ancestral variant wave.

BACKGROUND: Recently, the SARS-CoV-2 variant of concern, Omicron (B.1.1.529), was identified as responsible for a novel wave of COVID-19 worldwide. Here, we compared initial clinical features of hospitalized COVID-19 patients during recent wave (Omicron Variant) with those in ancestral variant wave (2020). METHODS: This is a cohort study of electronic health record (EHR) data from a signal center in the China. The clinical data of 116 cases of Omicron hospitalized in 2022 and 87 cases hospitalized in 2020 were collected. The comparisons were performed with the Mann-Whitney U test, Fisher exact test or the chi-square test, and multivariable logistic regression analysis. RESULTS: Clinically, compared with 2020-cohort, Omicron-cohort was more inclined to cluster in younger population and had more nonsymptomatic (25.0%) and nonsevere cases, as well as suffered from comparable extrapulmonary complication. Radiologically, although the major computed tomography (CT) findings of both cohorts were ground-glass opacities (GGOs), crazy-paving pattern was relatively less seen in the Omicron-cohort. Based on multiple logistic regression analysis, Omicron-cohort was associated with a lower risk of complaining with fever, the presence of lung opacity, and increased Sequential Organ Failure Assessment (SOFA) score. CONCLUSION: This study provided the data of different patterns of clinic characteristics and reduced severity from infections that occurred in Omicron variant as compared with the outbreak of the epidemic in 2020 wave (ancestral variant).

Depressive symptoms and gender differences in older adults in Hong Kong during the COVID-19 pandemic: a network analysis approach.

Background: The 2019 novel coronavirus disease (COVID-19) outbreak had a detrimental impact on the mental health of older adults. This study evaluated the central symptoms and their associations in the network of depressive symptoms and compared the network structure differences between male and female older adults in Hong Kong. Methods: Altogether, 3,946 older adults participated in this study. We evaluated the centrality indicators for network robustness using stability and accuracy tests, and examined the potential differences between the structure and connectivity of depression networks in male and female older adults. Results: The overall prevalence of depressive symptoms was 43.7% (95% CI=40.6-46.7%) in males, and 54.8% (95% CI=53.1-56.5%) in females (P<0.05). Sad Mood, Guilt, Motor problems and Lack of Energy were influential symptoms in the network model. Gender differences were found in the network global strength, especially in the following edges: Sad Mood--Guilt, Concentration--Guilt, Anhedonia--Motor, Lack of Energy--Suicide, Appetite--Suicide and Concentration--Suicide. Conclusions: Central symptoms in the depressive symptom network among male and female older adults may be prioritized in the treatment and prevention of depression during the pandemic.

Exploring the Perspective of Diabetes, Diabetes Self-Management, and Quality of Life Among Older Adults With Type 2 Diabetes: A Qualitative Study Before and During the COVID-19 Pandemic.

PURPOSE: The purpose of the study was to explore the perspective and impact of diabetes, diabetes self-management, and quality of life (QoL) among older adults with Type 2 diabetes (T2DM) before and during the COVID-19 pandemic to better inform T2DM self-management interventions. METHODS: A qualitative descriptive approach with focus group discussions (n = 5 sessions with 5-6 older adults per session) and in-depth interviews (n = 15) was conducted with community-dwelling older adults with T2DM. RESULTS: Five themes emerged. The definition of diabetes carries negative connotations, QoL is defined in terms of biopsychosocial health, diabetes self-management refers to the ability to adhere to medical advice and lifestyle changes, the QoL of older adults is differentially affected by COVID-19 measures, and important aspects of diabetes self-management activities are impacted by COVID-19 measures. CONCLUSIONS: Understanding older adults' perspectives on diabetes, diabetes self-management, and QoL provided insights into the facilitators and barriers to diabetes self-management practices before and during the COVID-19 pandemic. Findings inform the need for greater bottom-up initiatives and the need for a multipronged approach that considers the intra- and interpersonal and current policy factors to encourage diabetes self-management behaviors, especially during the COVID-19 era.

A new polysaccharide platform constructs self-adjuvant nanovaccines to enhance immune responses (preprint)

BackgroundNanovaccines have shown the promising potential in controlling and eradicating the threat of infectious diseases worldwide. There has been a great need in developing a versatile strategy to conveniently construct diverse types of nanovaccines and induce potent immune responses. To that end, it is critical for obtaining a potent self-adjuvant platform to assemble with different types of antigens into nanovaccines. ResultsIn this study, we identified a new natural polysaccharide from the rhizomes of Bletilla striata (PRBS), and used this polysaccharide as a platform to construct diverse types of nanovaccines with potent self-adjuvant property. In the construction process of SARS-CoV-2 nanovaccine, PRBS molecules and RBD protein antigens were assembled into ~300 nm nanoparticles by hydrogen bond. For HIV nanovaccine, hydrophobic effect dominantly drove the co-assembly between PRBS molecules and Env expression plasmid into ~350 nm nanospheres. Importantly, PRBS can potently activate the behaviors and functions of multiple immune cells such as macrophages, B cells and dendritic cells. Depending on PRBS-mediated immune activation, these self-adjuvant nanovaccines can elicit significantly stronger antigen-specific antibody and cellular responses in vivo, in comparison with their corresponding traditional vaccine forms. Moreover, we also revealed the construction models of PRBS-based nanovaccines by analyzing multiple assembly parameters such as bond energy, bond length and interaction sites.  ConclusionsPRBS, a newly-identified natural polysaccharide which can co-assemble with different types of antigens and activate multiple critical immune cells, has presented a great potential as a versatile platform to develop potent self-adjuvant nanovaccines.