Prognostic significance of the chemerin level in coronavirus disease 2019 patients.

Increased serum chemerin levels have been reported in several inflammatory diseases. Few studies have investigated the relationship between chemerin and clinical features of COVID-19. Thus, chemerin may modulate the development and progression of COVID-19. We compared the serum chemerin concentration between patients with and without SARS-CoV-2 infection and its association with the severity and prognosis of COVID-19 pneumonia. This is a prospective, single-center, cross-sectional study. We enrolled COVID-19 patients who presented to our tertiary hospital and healthy controls. The COVID-19 patients were conducted and the dates of symptom onset were recorded. After admission to the hospital and stabilization, blood samples were obtained for routine hemogram, biochemistry, and chemerin. The chemerin level was 37.93 ±â€…17.3 ng/mL in patients followed in the ICU, 29.41 ±â€…12.79 ng/mL in inpatients, 30.48 ±â€…10.86 ng/mL in outpatients, and 25.12 ±â€…9.82 ng/mL in healthy controls. The difference between patients treated in the ICU and healthy controls was significant (P < .001). The high-sensitivity C-reactive protein (hs-CRP), ferritin, procalcitonin (PCT), and D-dimer levels were significantly higher in the intensive care unit (ICU) group (P < .001). Moreover, the chemerin level of patients who died was significantly higher than that of those who survived (P < .001). The chemerin level was increased in COVID-19 patients and also increased with increasing disease severity. The chemerin level was higher in the COVID-19 patients than healthy controls and was significantly higher in patients who died compared to those who did not.

On-site detection of infectious disease based on CaCO3-based magnetic micromotor integrated with graphene field effect transistor.

A new detection platform based on CaCO3-based magnetic micromotor (CaCO3@Fe3O4) integrated with graphene field effect transistor (GFET) was construct and used for on-site SARS-CoV-2 coronavirus pathogen detection. The CaCO3@Fe3O4 micromotor, which was modified with anti-SARS-CoV-2 (labelled antibody, AntiE1), can self-moved in the solution containing hydrochloric acid (HCl) and effective to capture the SARS-CoV-2 coronavirus pathogens. After magnetic field separation, the capture micromotor was detected by GFET, exhibiting a good linear relationship within the range of 1 ag/mL to 100 ng/mL and low detection limit (0.39 ag/mL). Furthermore, the detection platform was also successfully applied to detection of SARS-CoV-2 coronavirus pathogens in soil solution, indicating the potential use in on-site application.

A generalizable and easy-to-use COVID-19 stratification model for the next pandemic via immune-phenotyping and machine learning.

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has affected billions of people worldwide, and the lessons learned need to be concluded to get better prepared for the next pandemic. Early identification of high-risk patients is important for appropriate treatment and distribution of medical resources. A generalizable and easy-to-use COVID-19 severity stratification model is vital and may provide references for clinicians. Methods: Three COVID-19 cohorts (one discovery cohort and two validation cohorts) were included. Longitudinal peripheral blood mononuclear cells were collected from the discovery cohort (n = 39, mild = 15, critical = 24). The immune characteristics of COVID-19 and critical COVID-19 were analyzed by comparison with those of healthy volunteers (n = 16) and patients with mild COVID-19 using mass cytometry by time of flight (CyTOF). Subsequently, machine learning models were developed based on immune signatures and the most valuable laboratory parameters that performed well in distinguishing mild from critical cases. Finally, single-cell RNA sequencing data from a published study (n = 43) and electronic health records from a prospective cohort study (n = 840) were used to verify the role of crucial clinical laboratory and immune signature parameters in the stratification of COVID-19 severity. Results: Patients with COVID-19 were determined with disturbed glucose and tryptophan metabolism in two major innate immune clusters. Critical patients were further characterized by significant depletion of classical dendritic cells (cDCs), regulatory T cells (Tregs), and CD4+ central memory T cells (Tcm), along with increased systemic interleukin-6 (IL-6), interleukin-12 (IL-12), and lactate dehydrogenase (LDH). The machine learning models based on the level of cDCs and LDH showed great potential for predicting critical cases. The model performances in severity stratification were validated in two cohorts (AUC = 0.77 and 0.88, respectively) infected with different strains in different periods. The reference limits of cDCs and LDH as biomarkers for predicting critical COVID-19 were 1.2% and 270.5 U/L, respectively. Conclusion: Overall, we developed and validated a generalizable and easy-to-use COVID-19 severity stratification model using machine learning algorithms. The level of cDCs and LDH will assist clinicians in making quick decisions during future pandemics.

Bioinformatics and system biology approach to identify the influences among COVID-19, influenza, and HIV on the regulation of gene expression.

Background: Coronavirus disease (COVID-19), caused by SARS-CoV-2, has emerged as a infectious disease, coexisting with widespread seasonal and sporadic influenza epidemics globally. Individuals living with HIV, characterized by compromised immune systems, face an elevated risk of severe outcomes and increased mortality when affected by COVID-19. Despite this connection, the molecular intricacies linking COVID-19, influenza, and HIV remain unclear. Our research endeavors to elucidate the shared pathways and molecular markers in individuals with HIV concurrently infected with COVID-19 and influenza. Furthermore, we aim to identify potential medications that may prove beneficial in managing these three interconnected illnesses. Methods: Sequencing data for COVID-19 (GSE157103), influenza (GSE185576), and HIV (GSE195434) were retrieved from the GEO database. Commonly expressed differentially expressed genes (DEGs) were identified across the three datasets, followed by immune infiltration analysis and diagnostic ROC analysis on the DEGs. Functional enrichment analysis was performed using GO/KEGG and Gene Set Enrichment Analysis (GSEA). Hub genes were screened through a Protein-Protein Interaction networks (PPIs) analysis among DEGs. Analysis of miRNAs, transcription factors, drug chemicals, diseases, and RNA-binding proteins was conducted based on the identified hub genes. Finally, quantitative PCR (qPCR) expression verification was undertaken for selected hub genes. Results: The analysis of the three datasets revealed a total of 22 shared DEGs, with the majority exhibiting an area under the curve value exceeding 0.7. Functional enrichment analysis with GO/KEGG and GSEA primarily highlighted signaling pathways associated with ribosomes and tumors. The ten identified hub genes included IFI44L, IFI44, RSAD2, ISG15, IFIT3, OAS1, EIF2AK2, IFI27, OASL, and EPSTI1. Additionally, five crucial miRNAs (hsa-miR-8060, hsa-miR-6890-5p, hsa-miR-5003-3p, hsa-miR-6893-3p, and hsa-miR-6069), five essential transcription factors (CREB1, CEBPB, EGR1, EP300, and IRF1), and the top ten significant drug chemicals (estradiol, progesterone, tretinoin, calcitriol, fluorouracil, methotrexate, lipopolysaccharide, valproic acid, silicon dioxide, cyclosporine) were identified. Conclusion: This research provides valuable insights into shared molecular targets, signaling pathways, drug chemicals, and potential biomarkers for individuals facing the complex intersection of COVID-19, influenza, and HIV. These findings hold promise for enhancing the precision of diagnosis and treatment for individuals with HIV co-infected with COVID-19 and influenza.

Computational identification and experimental verification of a novel signature based on SARS-CoV-2-related genes for predicting prognosis, immune microenvironment and therapeutic strategies in lung adenocarcinoma patients.

Background: Early research indicates that cancer patients are more vulnerable to adverse outcomes and mortality when infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Nonetheless, the specific attributes of SARS-CoV-2 in lung Adenocarcinoma (LUAD) have not been extensively and methodically examined. Methods: We acquired 322 SARS-CoV-2 infection-related genes (CRGs) from the Human Protein Atlas database. Using an integrative machine learning approach with 10 algorithms, we developed a SARS-CoV-2 score (Cov-2S) signature across The Cancer Genome Atlas and datasets GSE72094, GSE68465, and GSE31210. Comprehensive multi-omics analysis, including assessments of genetic mutations and copy number variations, was conducted to deepen our understanding of the prognosis signature. We also analyzed the response of different Cov-2S subgroups to immunotherapy and identified targeted drugs for these subgroups, advancing personalized medicine strategies. The expression of Cov-2S genes was confirmed through qRT-PCR, with GGH emerging as a critical gene for further functional studies to elucidate its role in LUAD. Results: Out of 34 differentially expressed CRGs identified, 16 correlated with overall survival. We utilized 10 machine learning algorithms, creating 101 combinations, and selected the RFS as the optimal algorithm for constructing a Cov-2S based on the average C-index across four cohorts. This was achieved after integrating several essential clinicopathological features and 58 established signatures. We observed significant differences in biological functions and immune cell statuses within the tumor microenvironments of high and low Cov-2S groups. Notably, patients with a lower Cov-2S showed enhanced sensitivity to immunotherapy. We also identified five potential drugs targeting Cov-2S. In vitro experiments revealed a significant upregulation of GGH in LUAD, and its knockdown markedly inhibited tumor cell proliferation, migration, and invasion. Conclusion: Our research has pioneered the development of a consensus Cov-2S signature by employing an innovative approach with 10 machine learning algorithms for LUAD. Cov-2S reliably forecasts the prognosis, mirrors the tumor's local immune condition, and supports clinical decision-making in tumor therapies.

Community health worker outreach to farmworkers in rural North Carolina: Learning from adaptations to the SARS-CoV-2 pandemic.

BACKGROUND: Community health workers represent a critical part of the health outreach and services for migrant and seasonal farmworkers ('farmworkers') in rural areas of the United States. PURPOSE: We sought to identify adaptations to farmworker patient engagement and health outreach made by community health workers during the first 18 months of the COVID-19 pandemic. METHODS: In this qualitative study, we used semi-structured interviews with community health workers from August 2020 to February 2022 (n = 21). Two coders used thematic analysis to identify three themes related to the experiences of community health workers in conducting health education and outreach to farmworkers prior to and following the onset of the pandemic. FINDINGS: We found themes related to pre-pandemic outreach efforts to provide health education resource sharing with farmworkers and pandemic-related outreach efforts that included adoption of porch drops and distanced delivery of health education, adaptation of modes of health education and communication through technology and the internet, and taking on new roles related to COVID-19. Finally, we identified changes that reverted after the pandemic or will continue as adaptations. CONCLUSIONS: Community health workers created practice-based innovations in outreach in response to the COVID-19 pandemic. These innovations included new COVID-19 related roles and new modes of health education and outreach, including the use of digital resources. The changes developed for emergency use in COVID-19, particularly related to internet and technology, have likely altered how community health workers conduct outreach in North Carolina going forward. Funders, community health worker training programs, and researchers should take note of these innovations. PATIENT OR PUBLIC CONTRIBUTION: Community health workers who typically come from patient populations and provide critical navigation and connection with the health care system advised on the design and creation of this research project, including serving on an advisory board. Two authors have experience working as community health workers.

[Singularities of COVID-19 in immunosuppressed persons]. / Singularités du Covid-19 chez les personnes immunosupprimées.

Immunosuppressed persons are a heterogeneous population that represents approximately 3 % of the adult population. They are more vulnerable to infectious agents, such as SARS-CoV-2. This is reflected by a reduced response to vaccination, a higher rate of progression towards a severe form of the disease, and recurrent or persistent infections associated with intra-host viral evolution. This review summarizes the evidence regarding vaccine efficacy, clinical and virological singularities, and the management in immunosuppressed patients.

Les personnes immunosupprimées (PI) constituent une population hétérogène représentant environ 3 % de la population adulte et sont plus vulnérables aux infections, telles que le Covid-19, face auquel elles présentent une réponse vaccinale diminuée, un taux plus élevé d'évolution vers une forme sévère de la maladie, et des infections persistantes associées à une excrétion virale prolongée et à une possible évolution virale intrahôte. Cet article résume l'évidence concernant l'efficacité vaccinale, les particularités clinico-virologiques et la prise en charge spécifique, dans la population des PI.

Proton pump inhibitors and risk of severe COVID-19 in older people.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 is a viral respiratory infection that can cause systemic disorders and lead to death, particularly in older people. Proton pump inhibitors (PPIs) increase the risk of enteric and lung infections. Considering the broad use of PPIs in older people, the potential role of PPIs in COVID-19 could be of dramatic significance. The objective of our study was to evaluate the link between PPIs and severe COVID-19 in older people. METHOD: We performed a retrospective cohort study, including all patients aged ≥65, hospitalised for a diagnosis of COVID-19. Epidemiological, clinical and biological data were extracted and we performed an Inverse Probability of Treatment Weighing method based on a propensity score. RESULTS: From March 2020 to February 2021, a total of 834 patients were included, with a median age of 83 and 52.8% were male. A total of 410 patients had a PPIs prescription, 358 (87.3%) were long-term PPIs-users and 52 (12.7%) were recent PPIs-users. Among PPIs-users, 163 (39.8%) patients developed severe COVID-19 versus 113 (26.7%) in PPIs-non users (odds ratio (OR) = 1.59 [1.18-2.14]; P < 0.05). Moreover, the double dose PPI-users had a higher risk of developing severe COVID-19 (OR = 3.36 [1.17-9.66]; P < 0.05) than the full dose PPI-users (OR = 2.15 [1.22-3.76]; P < 0.05) and the half dose PPI-users (OR = 1.64 [1.13-2.37]; P < 0.05). CONCLUSION: Our study reports evidence that the use of PPIs was associated with an increased risk of severe COVID-19 in older people.

Perinatal outcomes after admission with COVID-19 in pregnancy: a UK national cohort study.

There are few population-based studies of sufficient size and follow-up duration to have reliably assessed perinatal outcomes for pregnant women hospitalised with SARS-CoV-2 infection. The United Kingdom Obstetric Surveillance System (UKOSS) covers all 194 consultant-led UK maternity units and included all pregnant women admitted to hospital with an ongoing SARS-CoV-2 infection. Here we show that in this large national cohort comprising two years' active surveillance over four SARS-CoV-2 variant periods and with near complete follow-up of pregnancy outcomes for 16,627 included women, severe perinatal outcomes were more common in women with moderate to severe COVID-19, during the delta dominant period and among unvaccinated women. We provide strong evidence to recommend continuous surveillance of pregnancy outcomes in future pandemics and to continue to recommend SARS-CoV-2 vaccination in pregnancy to protect both mothers and babies.

Correlation of pre-existing comorbidities with disease severity in individuals infected with SARS-COV-2 virus.

Shortly after the first publication on the new disease called Coronavirus Disease 2019 (Covid-19), studies on the causal consequences of this disease began to emerge, initially focusing only on transmission methods, and later on its consequences analyzed in terms of gender, age, and the presence of comorbidities. The aim of our research is to determine which comorbidities have the greatest negative impact on the worsening of the disease, namely which comorbidities indicate a predisposition to severe Covid-19, and to understand the gender and age representation of participants and comorbidities. The results of our study show that the dominant gender is male at 54.4% and the age of 65 and older. The most common comorbidities are arterial hypertension, diabetes mellitus, and cardiovascular diseases. The dominant group is recovered participants aged 65 and older, with comorbidities most frequently present in this group. The highest correlation between patients with different severity of the disease was found with cardiovascular diseases, while the coefficient is slightly lower for the relationship between patients with different disease severity and urinary system diseases and hypertension. According to the regression analysis results, we showed that urinary system diseases have the greatest negative impact on the worsening of Covid-19, with the tested coefficient b being statistically significant as it is 0.030 < 0.05. An increase in cardiovascular diseases affects the worsening of Covid-19, with the tested coefficient b being statistically significant as it is 0.030 < 0.05. When it comes to arterial hypertension, it has a small impact on the worsening of Covid-19, but its tested coefficient b is not statistically significant as it is 0.169 > 0.05. The same applies to diabetes mellitus, which also has a small impact on the worsening of Covid-19, but its tested coefficient b is not statistically significant as it is 0.336 > 0.05. Our study has shown that comorbidities such as urinary system diseases and cardiovascular diseases tend to have a negative impact on Covid-19, leading to a poor outcome resulting in death, while diabetes mellitus and hypertension have an impact but without statistical significance.

Anti-synthase syndrome associated with SARS-Cov-2 infection.

BACKGROUND: Anti-synthetase syndrome (AS) is a rare autoimmune idiopathic inflammatory myopathy (IIM) with diverse manifestations, including arthritis, interstitial lung disease (ILD), Raynaud's phenomenon, unexplained persistent fever, and mechanic's hands. CASE PRESENTATION: We present the case of a 72-year-old woman, previously healthy, who was admitted to our hospital for treatment of cough and rapid breathing. The patient had elevated white blood cells and C-reactive protein, and tested negative for severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2). She was initially diagnosed with community-acquired pneumonia and received tamoxifen for anti-infection treatment, but her dystonia worsened. She eventually required non-invasive ventilator support, tested positive for SARS-Cov-2 again, and started antiviral therapy, corticosteroids to reduce alveolar effusion, anticoagulation, and other treatments. However, her condition continued to deteriorate, with the lowest oxygenation index reaching only 80mmHg. Ultimately, she underwent tracheal intubation and mechanical ventilation. Chest CT revealed rapid progressive interstitial changes in her lungs, and her hands showed noticeable fraternization changes. At this point, we suspected that the novel coronavirus infection might be associated with autoimmune diseases. The patient's autoimmune antibody spectrum showed positive results for anti-recombinant RO-52 antibody and myositis-specific antibody anti-alanyl tRNA synthetase (anti-PL-12). The patient was treated with dexamethasone sodium phosphate for anti-inflammatory and anti-fibrotic effects. After successful extubation, the patient was discharged with only oral prednisone tablets at a dose of 30 mg. CONCLUSIONS: This case presents an early diagnosis and successful treatment of anti-synthetase syndrome combined with SARS-Cov-2 infection, emphasizing the importance of comprehensive physical examination. Additionally, it highlights the rapid progression of interstitial lung disease under SARS-Cov-2 infection, which is often difficult to distinguish on imaging. In cases where treatment for SARS-Cov-2 infection is ineffective, early screening for autoimmune diseases is recommended. As there is currently no standardized method for treating AS-ILD, the successful treatment of this case provides a reference for clinical research on anti-synthetase syndrome in the later stage.

Trajectories of Inflammatory Markers and Post-COVID-19 Cognitive Symptoms: A Secondary Analysis of the CONTAIN COVID-19 Randomized Trial.

BACKGROUND AND OBJECTIVES: Chronic systemic inflammation has been hypothesized to be a mechanistic factor leading to post-acute cognitive dysfunction after COVID-19. However, little data exist evaluating longitudinal inflammatory markers. METHODS: We conducted a secondary analysis of data collected from the CONTAIN randomized trial of convalescent plasma in patients hospitalized for COVID-19, including patients who completed an 18-month assessment of cognitive symptoms and PROMIS Global Health questionnaires. Patients with pre-COVID-19 dementia/cognitive abnormalities were excluded. Trajectories of serum cytokine panels, D-dimer, fibrinogen, C-reactive peptide (CRP), ferritin, lactate dehydrogenase (LDH), and absolute neutrophil counts (ANCs) were evaluated over 18 months using repeated measures and Friedman nonparametric tests. The relationships between the area under the curve (AUC) for each inflammatory marker and 18-month cognitive and global health outcomes were assessed. RESULTS: A total of 279 patients (N = 140 received plasma, N = 139 received placebo) were included. At 18 months, 76/279 (27%) reported cognitive abnormalities and 78/279 (28%) reported fair or poor overall health. PROMIS Global Mental and Physical Health T-scores were 0.5 standard deviations below normal in 24% and 51% of patients, respectively. Inflammatory marker levels declined significantly from hospitalization to 18 months for all markers (IL-2, IL-2R, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, INFγ, TNFα, D-dimer, fibrinogen, ferritin, LDH, CRP, neutrophils; all p < 0.05), with the exception of IL-1ß, which remained stable over time. There were no significant associations between the AUC for any inflammatory marker and 18-month cognitive symptoms, any neurologic symptom, or PROMIS Global Physical or Mental health T-scores. Receipt of convalescent plasma was not associated with any outcome measure. DISCUSSION: At 18 months posthospitalization for COVID-19, cognitive abnormalities were reported in 27% of patients, and below average PROMIS Global Mental and Physical Health scores occurred in 24% and 51%, respectively. However, there were no associations with measured inflammatory markers, which decreased over time.

[Facilitating and Hindering Factors in the Implementation of Medical Rehabilitation of Adolescents with Scoliosis before and during the SARS-CoV-2 Pandemic: A Qualitative Study]. / Förderliche und hinderliche Faktoren für die Durchführung der medizinischen Rehabilitation bei Jugendlichen mit Skoliose vor und während der SARS-CoV-2-Pandemie: Eine qualitative Studie.

PURPOSE: Based on the experience during the SARS-CoV-2 pandemic, the study aimed to derive facilitating and hindering factors in the implementation of medical rehabilitation during future pandemics in adolescents with scoliosis. METHODS: A qualitative study design with guided expert interviews was chosen. Twelve interviews with adolescents and seven interviews with physiotherapists were conducted. The evaluation was carried out using qualitative content analysis according to Mayring and inductive categorization. RESULTS: For 83.3% of the adolescents a therapy considering individual patient needs was a facilitator. Good information management (91.7%), continued availability of leisure activities (66.7%), and a high perception of safety (100%) were facilitating. 71.4% favoured outdoor therapy. The increased exertion caused by wearing a mask (91.7%) and the shortened therapy times (66.7%) were seen as barriers. For 75.0% of the adolescents, social contacts were more difficult. All therapists stated that communication between patients and therapists was more difficult. CONCLUSION: For successful rehabilitation during the SARS-CoV-2 pandemic, depending on weather conditions, therapy should be outside, as there is no need to wear mouth-nose protection outdoors. In addition, the physiotherapeutic treatment (Schroth therapy) should be carried out without mask due to the intensity of the exercise. Social contacts among all adolescents should be supported as much as possible. The leisure activities should provide a wide choice and enough free places. Continuation of certain hygienic measures could help to reduce the incidence of illnesses (e. g., gastrointestinal infections) in the future. These were barely noticed in rehabilitation facilities during the pandemic.

A novel approach to designing viral precision vaccines applied to SARS-CoV-2.

Efficient precision vaccines against several highly pathogenic zoonotic viruses are currently lacking. Proteolytic activation is instrumental for a number of these viruses to gain host-cell entry and develop infectivity. For SARS-CoV-2, this process is enhanced by the insertion of a furin cleavage site at the junction of the spike protein S1/S2 subunits upstream of the metalloprotease TMPRSS2 common proteolytic site. Here, we describe a new approach based on specific epitopes selection from the region involved in proteolytic activation and infectivity for the engineering of precision candidate vaccinating antigens. This approach was developed through its application to the design of SARS-CoV-2 cross-variant candidates vaccinating antigens. It includes an in silico structural analysis of the viral region involved in infectivity, the identification of conserved immunogenic epitopes and the selection of those eliciting specific immune responses in infected people. The following step consists of engineering vaccinating antigens that carry the selected epitopes and mimic their 3D native structure. Using this approach, we demonstrated through a Covid-19 patient-centered study of a 500 patients' cohort, that the epitopes selected from SARS-CoV-2 protein S1/S2 junction elicited a neutralizing antibody response significantly associated with mild and asymptomatic COVID-19 (p<0.001), which strongly suggests protective immunity. Engineered antigens containing the SARS-CoV-2 selected epitopes and mimicking the native epitopes 3D structure generated neutralizing antibody response in mice. Our data show the potential of this combined computational and experimental approach for designing precision vaccines against viruses whose pathogenicity is contingent upon proteolytic activation.

Prevalence and associated factors of insomnia symptoms after ending China's dynamic zero-COVID policy: a cross-sectional survey of frontline nursing staff in Chinese hospitals.

Background: After the Chinese government announced the end of the dynamic zero-COVID policy on January 8, 2023, the COVID-19 pandemic peaked. Frontline nursing staff are at high risk of infection transmission due to their frequent contact with COVID-19 patients. In addition, due to the ending of China's dynamic zero-COVID policy, frontline nursing staff have grappled with increased workload, fatigue, and more. This study aimed to explore the prevalence of insomnia symptoms in frontline nursing staff and its influencing factors following the end of the policy. Methods: Between January and February 2023, this study was conducted by the Wenjuanxing platform to survey frontline nursing staff in a hospital in Wuhu City, Anhui Province. All the nursing staff included in this study had a COVID-19 infection. The questionnaires included the Athens Insomnia Scale (AIS), PC-PTSD-5 Chinese Version Scale, the Fear of COVID-19 Scale, The 2-item Connor-Davidson Resilience Scale (CD-RISC-2) Scale, and the burden of COVID-19 Scale. Binary logistic regression methods were used to identify variables associated with insomnia symptoms. Results: Among the 694 frontline nursing staff, 74.5% (517/694) exhibited insomnia symptoms. Fear of COVID-19 (p < 0.001), the burden of COVID-19 (p < 0.05), PTSD (p < 0.001), and higher technical titles (p < 0.008) were highly correlated with insomnia symptoms in frontline nursing staff. Psychological resilience (p < 0.001) was a protective factor for insomnia symptoms among frontline nursing staff. Conclusion: After ending China's dynamic zero-COVID policy, the prevalence of insomnia symptoms among frontline nursing staff is generally higher. This study highlights the association between insomnia symptoms and PTSD, fear of COVID-19, COVID-19 burden, and resilience. Psychological assistance is needed for frontline nursing staff to prevent insomnia symptoms and protect the mental health of frontline nursing staff after the end of China's dynamic zero-COVID policy.

Clonal structure and the specificity of vaccine-induced T cell response to SARS-CoV-2 Spike protein.

Adenovirus vaccines, particularly the COVID-19 Ad5-nCoV adenovirus vaccine, have emerged as promising tools in the fight against infectious diseases. In this study, we investigated the structure of the T cell response to the Spike protein of the SARS-CoV-2 virus used in the COVID-19 Ad5-nCoV adenoviral vaccine in a phase 3 clinical trial (NCT04540419). In 69 participants, we collected peripheral blood samples at four time points after vaccination or placebo injection. Sequencing of T cell receptor repertoires from Spike-stimulated T cell cultures at day 14 from 17 vaccinated revealed a more diverse CD4+ T cell repertoire compared to CD8+. Nevertheless, CD8+ clonotypes accounted for more than half of the Spike-specific repertoire. Our longitudinal analysis showed a peak T cell response at day 14, followed by a decline until month 6. Remarkably, multiple T cell clonotypes persisted for at least 6 months after vaccination, as demonstrated by ex vivo stimulation. Examination of CDR3 regions revealed homologous sequences in both CD4+ and CD8+ clonotypes, with major CD8+ clonotypes sharing high similarity with annotated sequences specific for the NYNYLYRLF peptide, suggesting potential immunodominance. In conclusion, our study demonstrates the immunogenicity of the Ad5-nCoV adenoviral vaccine and highlights its ability to induce robust and durable T cell responses. These findings provide valuable insight into the efficacy of the vaccine against COVID-19 and provide critical information for ongoing efforts to control infectious diseases.

Interpretations of Studies on SARS-CoV-2 Vaccination and Post-acute COVID-19 Sequelae.

This article discusses causal interpretations of epidemiologic studies of the effects of vaccination on sequelae after acute severe acute respiratory syndrome coronavirus 2 infection. To date, researchers have tried to answer several different research questions on this topic. While some studies assessed the impact of postinfection vaccination on the presence of or recovery from post-acute coronavirus disease 2019 syndrome, others quantified the association between preinfection vaccination and postacute sequelae conditional on becoming infected. However, the latter analysis does not have a causal interpretation, except under the principal stratification framework-that is, this comparison can only be interpreted as causal for a nondiscernible stratum of the population. As the epidemiology of coronavirus disease 2019 is now nearly entirely dominated by reinfections, including in vaccinated individuals, and possibly caused by different Omicron subvariants, it has become even more important to design studies on the effects of vaccination on postacute sequelae that address precise causal questions and quantify effects corresponding to implementable interventions.

Evidence of antigenic drift in the fusion machinery core of SARS-CoV-2 spike.

Antigenic drift of SARS-CoV-2 is typically defined by mutations in the N-terminal domain and receptor binding domain of spike protein. In contrast, whether antigenic drift occurs in the S2 domain remains largely elusive. Here, we perform a deep mutational scanning experiment to identify S2 mutations that affect binding of SARS-CoV-2 spike to three S2 apex public antibodies. Our results indicate that spatially diverse mutations, including D950N and Q954H, which are observed in Delta and Omicron variants, respectively, weaken the binding of spike to these antibodies. Although S2 apex antibodies are known to be nonneutralizing, we show that they confer protection in vivo through Fc-mediated effector functions. Overall, this study indicates that the S2 domain of SARS-CoV-2 spike can undergo antigenic drift, which represents a potential challenge for the development of more universal coronavirus vaccines.

COVID-19-induced acute loss of consciousness in Marchiafava-Bignami disease: a case report.

Among the various manifestations of COVID-19, the neurological implications of SARS-CoV-2 infection are of significant concern. Marchiafava-Bignami disease (MBD), a neurodegenerative disorder, exhibits a clinical spectrum ranging from mild progressive dementia in its chronic form to states of acute coma and varied mortality rates. Acute MBD primarily occurs in chronic alcoholics and malnourished individuals and is characterized by sudden loss of consciousness, seizures, confusion, and psychosis. We herein report a case of MBD presenting as acute loss of consciousness after the development of COVID-19. The patient presented with a history of fever and upper respiratory infection and was diagnosed with SARS-CoV-2 infection. He developed a neurological syndrome characterized by altered consciousness and convulsions, and brain magnetic resonance imaging revealed abnormal signals in the corpus callosum and frontoparietal lobes. Considering his alcohol intake history and the absence of other differential diagnoses, we diagnosed him with acute MBD triggered by COVID-19. After high-dose vitamin B1 and corticosteroid therapy, his clinical symptoms improved. In this case, we observed a temporal sequence between the development of COVID-19 and acute exacerbation of MBD. This case adds to the mounting evidence suggesting the potential effect of SARS-CoV-2 on the neurological system.

Interstitial macrophages are a focus of viral takeover and inflammation in COVID-19 initiation in human lung.

Early stages of deadly respiratory diseases including COVID-19 are challenging to elucidate in humans. Here, we define cellular tropism and transcriptomic effects of SARS-CoV-2 virus by productively infecting healthy human lung tissue and using scRNA-seq to reconstruct the transcriptional program in "infection pseudotime" for individual lung cell types. SARS-CoV-2 predominantly infected activated interstitial macrophages (IMs), which can accumulate thousands of viral RNA molecules, taking over 60% of the cell transcriptome and forming dense viral RNA bodies while inducing host profibrotic (TGFB1, SPP1) and inflammatory (early interferon response, CCL2/7/8/13, CXCL10, and IL6/10) programs and destroying host cell architecture. Infected alveolar macrophages (AMs) showed none of these extreme responses. Spike-dependent viral entry into AMs used ACE2 and Sialoadhesin/CD169, whereas IM entry used DC-SIGN/CD209. These results identify activated IMs as a prominent site of viral takeover, the focus of inflammation and fibrosis, and suggest targeting CD209 to prevent early pathology in COVID-19 pneumonia. This approach can be generalized to any human lung infection and to evaluate therapeutics.