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The high variability observed in the clinical symptoms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections has been attributed to the presence, in a proportion of infection-naive subjects, of pre-existing cross-reactive immune responses. Here, we demonstrate that the bovine coronavirus spike protein (BoS) may represent a source of protective immunity to SARS-CoV-2. Indeed, vaccination of BALB/c mice with a Bovine herpesvirus 4 (BoHV-4)-based vector expressing BoS induced both cell-mediated and humoral immune responses that cross-react with SARS-CoV-2 spike protein. Although the spike-specific antibodies induced by BoS did not neutralize SARS-CoV-2, the T lymphocytes activated by BoS were able to induce cytotoxicity of cells expressing spike proteins derived from several SARS-CoV-2 variants. These results demonstrate that immunization with BoS may represent a source of cross-reactive immunity to SARS-CoV-2, and that these cross-reactive immune responses may exert protective functions. These results contribute to deciphering the mechanisms responsible for lack or mildness of symptoms observed in many individuals upon SARS-CoV-2 infection and may open new ways for the development of new vaccines for coronaviruses. [ABSTRACT FROM AUTHOR]

Nanotechnology is an emerging area of science that deals with making and designing of nanosized objects having widespread applications. Nanomaterials or nanosized objects have that have at least one dimension in the nanoscale range. Nanozymes are enzymes or nanomaterials showing enzyme-like properties. Nanozymes have similar advantages that are associated with other nanomaterials, too. Nanozymes have combined properties of nanomaterials as well as enzymes, they are capable of leading innovations in science and medicine, and their utility has been demonstrated by the emergence of large number of nanotechnology-based products in the modern scenario for disease prevention and diagnosis. Many of the products utilize enzyme-mimicking properties of the nanozymes besides their other properties. But they do have their limitations and disadvantages. The present review focuses on the diverse potential uses of this newly identified group of enzymes with specific reference to their applications in tackling various aspects of coronavirus disease 2019 (COVID-19). [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a highly heterogeneous malignancy with poor prognosis and a common cause of cancer-related death worldwide, and despite ongoing therapeutic breakthroughs, patient survival benefits are limited. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19) and poses a major threat to humanity worldwide. As the epidemic continues to develop, more and more people are infected with SARS-CoV-2, including patients with HCC. However, the relationship between COVID-19 and HCC has not yet been fully elucidated. Our study aimed to identify the shared genetic characteristics and molecular mechanisms between COVID-19 and HCC. The data involved in this study come from Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression(GTEx), and Cancer Cell Line Encyclopedia(CCLE) databases. We used differentially expressed genes to perform enrichment analysis to reveal the biological landscape of COVID-19 combined with HCC. In addition, weighted gene co-expression network analysis (WGCNA) was used to study the co-expression network related to COVID-19 and HCC. We then combined the validation datasets to screen out immunoglobulin superfamily member 1 (IGSF1) as the most important core gene. Finally, we extensively studied the functional expression of IGSF1 in tumor samples, normal tissues, and cancer cell lines. The molecular mechanisms related to COVID-19 and HCC are rarely studied. Our study identifies IGSF1 as a potential therapeutic target and immune-related biomarker for patients with COVID-19 and HCC. [ABSTRACT FROM AUTHOR]

Abstract Hepatocellular carcinoma (HCC) is a highly heterogeneous malignancy with poor prognosis and a common cause of cancer-related death worldwide, and despite ongoing therapeutic breakthroughs, patient survival benefits are limited. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19) and poses a major threat to humanity worldwide. As the epidemic continues to develop, more and more people are infected with SARS-CoV-2, including patients with HCC. However, the relationship between COVID-19 and HCC has not yet been fully elucidated. Our study aimed to identify the shared genetic characteristics and molecular mechanisms between COVID-19 and HCC. The data involved in this study come from Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression(GTEx), and Cancer Cell Line Encyclopedia(CCLE) databases. We used differentially expressed genes to perform enrichment analysis to reveal the biological landscape of COVID-19 combined with HCC. In addition, weighted gene co-expression network analysis (WGCNA) was used to study the co-expression network related to COVID-19 and HCC. We then combined the validation datasets to screen out immunoglobulin superfamily member 1 (IGSF1) as the most important core gene. Finally, we extensively studied the functional expression of IGSF1 in tumor samples, normal tissues, and cancer cell lines. The molecular mechanisms related to COVID-19 and HCC are rarely studied. Our study identifies IGSF1 as a potential therapeutic target and immune-related biomarker for patients with COVID-19 and HCC.

Despite the availability of vaccines and antiviral treatments, the continued emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and breakthrough infections underscores the need for new, potent antiviral therapies. In a previous study, we established a transcription and replication-competent SARS-CoV-2 virus-like particle (trVLP) system that recapitulates the complete viral life cycle. In this study, we combined high-content screening (HCS) with the SARS-CoV-2 trVLP cell culture system, providing a powerful phenotype-oriented approach to assess the antiviral potential of compounds on a large scale. We screened a library of 3,200 natural compounds and identified drupacine as a potential candidate against SARS-CoV-2 infection. Furthermore, we utilized a SARS-CoV-2 replicon system to demonstrate that drupacine could inhibit viral genome transcription and replication. However, in vitro, enzymatic assays revealed that the inhibition could not be attributed to conventional antiviral targets, such as the viral non-structural proteins nsp5 (MPro) or nsp12 (RdRp). In conclusion, our findings position drupacine as a promising antiviral candidate against SARS-CoV-2, providing a novel scaffold for developing anti-coronavirus disease 2019 therapeutics. Further investigation is required to pinpoint its precise target and mechanism of action.

Although epidemiological surveillance of COVID-19 has been gradually downgraded globally, the transmission of COVID-19 continues. It is critical to quantify the transmission dynamics of COVID-19 using multiple datasets including wastewater virus concentration data. Herein, we propose a comprehensive method for estimating the effective reproduction number using wastewater data. The wastewater virus concentration data, which were collected twice a week, were analyzed using daily COVID-19 incidence data obtained from Takamatsu, Japan between January 2022 and September 2022. We estimated the shedding load distribution (SLD) as a function of time since the date of infection, using a model employing the delay distribution, which is assumed to follow a gamma distribution, multiplied by a scaling factor. We also examined models that accounted for the temporal smoothness of viral load measurement data. The model that smoothed temporal patterns of viral load was the best fit model (WAIC = 2795.8), which yielded a mean estimated distribution of SLD of 3.46 days (95% CrI: 3.01–3.95 days). Using this SLD, we reconstructed the daily incidence, which enabled computation of the effective reproduction number. Using the best fit posterior draws of parameters directly, or as a prior distribution for subsequent analyses, we first used a model that assumed temporal smoothness of viral load concentrations in wastewater, as well as infection counts by date of infection. In the subsequent approach, we examined models that also incorporated weekly reported case counts as a proxy for weekly incidence reporting. Both approaches enabled estimations of the epidemic curve as well as the effective reproduction number from twice-weekly wastewater viral load data. Adding weekly case count data reduced the uncertainty of the effective reproduction number. We conclude that wastewater data are still a valuable source of information for inferring the transmission dynamics of COVID-19, and that inferential performance is enhanced when those data are combined with weekly incidence data.

ObjectiveTo investigate the levels of neutralizing antibodies against the novel coronavirus in the serum of elderly individuals aged 60 years and above in Shanghai’s Changning District, following natural infection and mixed immunity, in order to provide a basis for strengthening immunity in the elderly.MethodsElderly people who participated in free health check-ups at 10 community health service centers in Changning District from May to June 2023 were selected as the subjects. Information such as gender, age, COVID-19 infection history, COVID-19 vaccine immunization history, and chronic disease history were collected. Serum samples of the subjects were collected and quantitative detection of SARS-CoV-2 neutralizing antibodies was performed by magnetic particle chemiluminescence method. The antibody levels of different populations were analyzed.ResultsA total of 620 subjects were included, 586 of whom (241 males and 345 females) met the study conditions. There were 90 people in the full vaccination + infection group, 224 people in the intensive vaccination + infection group, and 272 people in the unvaccinated + infection group. The positive rates of COVID-19 antibody in the three groups were 94.44% (95%CI: 87.51%‒98.17%), 95.98% (95%CI:92.51%‒98.15%) and 22.06% (95%CI: 17.28%‒27.46%), respectively. The positive rates in full vaccination + infection group and intensive vaccination + infection group was significantly higher than that in unvaccinated + infection group (χ2=147.561,P

The effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection persist months and years after recovery. We conducted an online survey to assess the health condition of convalescents approximately 5 months following the primary infection of SARS-CoV-2. The study recruited 5,510 individuals who were primary infected, 626 participants who had experienced reinfection, and 521 participants who were without infective history. The most common disorders after the primary infection group were fatigue (15.18 %), memory issue (13.13 %), post-exertional malaise (PEM, 11.68 %), and brain fog (11.29 %) at the time of survey. In addition, SARS-CoV-2 infection had an impact on the reproductive systems. In stepwise logistic regression analysis, smoking currently, with background diseases, and outpatient visits in the acute phase could be associated with moderate / severe disorders. Further analysis of different background diseases showed that allergic rhinitis, hyperlipidemia, cardiovascular disease, autoimmune diseases, neurological diseases, and asthma likely increased the risk of moderate/severe disorders. The probability of developing disorders of individuals with SARS-CoV-2 reinfection was higher before the secondary infection than uninfected people. Fatigue, PEM, muscle pain/spasms, chills, joint pain, excessive sweating at rest, headache / dizziness, sore throat or foreign body sensation in the throat, cough, expectoration, dry / painful / watery eyes, loss of appetite and constipation were associated with an increased risk of reinfection. It was essential to undertake further research with enhanced randomization in a larger sample in the community, and to strengthen the validation of the research conclusions. The findings of this study contribute to a deeper understanding of the health recovery process among coronavirus disease 2019 (COVID-19) convalescents. Moreover, the findings help identify characteristic health risk factors associated with convalescents and highlight the risk of moderate / severe disorders and reinfection. Furthermore, the findings also provide valuable guidance and reference for SARS-CoV-2 rehabilitation strategies and the prevention of reinfection, offering insights for scientific recommendations.

During the continuing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the Omicron variant of concern emerged in the second half of 2021 and has been dominant since November of that year. Along with its sublineages, it has maintained a prominent role ever since. The Nsp5 main protease (Mpro) of the Omicron virus is characterized by a single dominant mutation, P132H. Here we determined the X-ray crystal structures of the P132H mutant (or O-Mpro) as a free enzyme and in complex with the Mpro inhibitor, the alpha-ketoamide 13b-K, and we conducted enzymological, biophysical, as well as theoretical studies to characterize the O-Mpro. We found that O-Mpro has a similar overall structure and binding with 13b-K; however, it displays lower enzymatic activity and lower thermal stability compared to the WT-Mpro (with “WT” referring to the prototype strain). Intriguingly, the imidazole ring of His132 and the carboxylate plane of Glu240 are in a stacked configuration in the X-ray structures determined here. Empirical folding free energy calculations suggest that the O-Mpro dimer is destabilized relative to the WT-Mpro due to less favorable van der Waals interactions and backbone conformations in the individual protomers. All-atom continuous constant-pH molecular dynamics (MD) simulations reveal that His132 and Glu240 display coupled titration. At pH 7, His132 is predominantly neutral and in a stacked configuration with respect to Glu240 which is charged. In order to examine whether the Omicron mutation eases the emergence of further Mpro mutations, we also analyzed the P132H+T169S double mutant, which is characteristic of the BA.1.1.2 lineage. However, we found little evidence of a correlation between the two mutation sites.

Thromboinflammation/immunothrombosis plays a role in several diseases including thrombotic thrombocytopenic purpura (TTP) and COVID-19. Unlike the extensive research that has been conducted on COVID-19 cytokine storms, the baseline and acute phase cytokine profiles of TTP are poorly characterized. Moreover, we compared the cytokine profiles of TTP and COVID-19 to identify the disease-specific/general characteristics of thromboinflammation/immunothrombosis. Plasma concentrations of 33 soluble mediators (SMs: cytokines, chemokines, soluble receptors, and growth factors) were measured by multiplex bead-based LEGENDplex™ immunoassay from 32 COVID-19 patients (32 non-vaccinated patients in three severity groups), 32 TTP patients (remission/acute phase pairs of 16 patients), and 15 control samples. Mainly, the levels of innate immunity-related SMs changed in both diseases. In TTP, ten SMs decreased in both remission and acute phases compared to the control, one decreased, and two increased only in the acute phase compared to remission, indicating mostly anti-inflammatory changes. In COVID-19, ten pro-inflammatory SMs increased, whereas one decreased with increasing severity compared to the control. In severe COVID-19, sixteen SMs exceeded acute TTP levels, with only one higher in TTP. PCA identified CXCL10, IL-1RA, and VEGF as the main discriminators among their cytokine profiles. The innate immune response is altered in both diseases. The cytokine profile of TTP suggests a distinct pathomechanism from COVID-19 and supports referring to TTP as thromboinflammatory rather than immunothrombotic, emphasizing thrombosis over inflammation as the driving force of the acute phase. [ABSTRACT FROM AUTHOR]

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A highly ultrafast and sensitive electrochemical sensor based on electrical potential-assisted hybridization was developed for the determination of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The electrode was modified with multi-walled carbon nanotubes (MWCNTs) and Au nanoparticles (AuNPs) for excellent electrochemical performance. The constant electric field was applied to rapidly and efficiently enrich the capture probes to the electrode surface in 60 s. Meanwhile, pyrene as the backfill reagent resulted in a significant reduction of nonspecific adsorption. The electrochemical properties of the modified electrode were investigated via electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). The analytical response was measured by differential pulse voltammetry (DPV). The sensor achieved the ultrafast hybridization of nucleic acids at the electrode interface within 90 s, substantially reducing the reaction time from hours to minutes. Under optimal conditions, the sensor exhibited a superior detection limit of 60 fM and showed satisfactory specificity toward single-base mismatch. Additionally, the proposed sensor realized sensitive determination of SARS-CoV-2 in throat swabs. The enzyme-free and non-amplification sensing strategy showed promising potential for application in point-of-care testing (POCT). [ABSTRACT FROM AUTHOR]

We conducted a cross-sectional study to evaluate cellular and humoral immunogenicity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination or infection and examine how lymphocyte subpopulations in peripheral blood correlate with cellular and humoral immunogenicity in adult allogeneic hematopoietic cell transplantation (HCT) recipients. The median period from SARS-CoV-2 vaccination or infection to sample collection was 110.5 days (range, 6–345 days). The median SARS-CoV-2 spike-specific antibody level was 1761 binding antibody units (BAU)/ml (range, 0 to > 11,360 BAU/ml). Enzyme-linked immunosorbent spot (ELISpot) assay of T cells stimulated with SARS-CoV-2 spike antigens showed that interferon-gamma (IFN-γ)-, interleukin-2 (IL-2)-, and IFN-γ + IL-2-producing T cells were present in 68.9%, 62.0%, and 56.8% of patients, respectively. The antibody level was significantly correlated with frequency of IL-2-producing T cells (P = 0.001) and IFN-γ + IL-2-producing T cells (P = 0.006) but not IFN-γ-producing T cells (P = 0.970). Absolute counts of CD8+ and CD4+ central memory T cells were higher in both IL-2- and IFN-γ + IL-2-producing cellular responders compared with non-responders. These data suggest that cellular and humoral immunogenicity against SARS-CoV-2 vaccination or infection is associated with the memory phenotype of T cells and B cells in adult allogeneic HCT recipients. [ABSTRACT FROM AUTHOR]

Objective: Various types and combinations of vaccines have been utilized at different time intervals due to the variable availability of vaccines in many countries during the Coronavirus Disease 2019 (COVID-19) pandemic. Most current vaccine administrations involve a series of primary doses followed by a homologous booster dose. This study aimed to examine the antibody levels after the BNT162b2 or CoronaVac vaccine was administered as a booster dose to volunteers who received two doses of CoronaVac and to identify the ideal vaccination combination. Materials and Methods: This cross-sectional study included 254 participants. The groups consisted of volunteers who received two doses of CoronaVac, those who received two doses of BNT162b2, those who received two doses of CoronaVac plus one dose of BNT162b2, and finally, those who received three doses of CoronaVac. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) specific spike (S) Immunoglobulin G (IgG) levels were measured by electrochemiluminescence method on Roche COBAS 8000 series using Anti-SARS-CoV-2 S kit. Results: Antibody levels after three doses of CoronaVac were found to be lower compared to after two doses of CoronaVac + one dose BNT162b2 (p<0.001). IgG responses after three doses of the CoronaVac vaccine (two primary + one booster dose) were lower than those after two doses of BNT162b2 (p<0.001). Conclusion: The use of a heterogeneous booster dose due to problems in vaccine supply may be a good alternative to the homologous approaches applied so far. [ABSTRACT FROM AUTHOR]

Accurate medical image classification poses a significant challenge in designing expert computer-aided diagnosis systems. While deep learning approaches have shown remarkable advancements over traditional techniques, addressing inter-class similarity and intra-class dissimilarity across medical imaging modalities remains challenging. This work introduces the advanced gating transformer network (MedTransNet), a deep learning model tailored for precise medical image classification. MedTransNet utilizes channel and multi-gate attention mechanisms, coupled with residual interconnections, to learn category-specific attention representations from diverse medical imaging modalities. Additionally, the use of gradient centralization during training helps in preventing overfitting and improving generalization, which is especially important in medical imaging applications where the availability of labeled data is often limited. Evaluation on benchmark datasets, including APTOS-2019, Figshare, and SARS-CoV-2, demonstrates effectiveness of the proposed MedTransNet across tasks such as diabetic retinopathy severity grading, multi-class brain tumor classification, and COVID-19 detection. Experimental results showcase MedTransNet achieving 85.68% accuracy for retinopathy grading, 98.37% ( ± 0.44 ) for tumor classification, and 99.60% for COVID-19 detection, surpassing recent deep learning models. MedTransNet holds promise for significantly improving medical image classification accuracy. [ABSTRACT FROM AUTHOR]

Background and Aim: Currently, SARS‐CoV‐2 is still spreading rapidly and globally. A large proportion of patients with COVID‐19 developed liver injuries. The human‐induced pluripotent stem cell (iPSC)‐derived hepatocytes recapitulate primary human hepatocytes and have been widely used in studies of liver diseases. Methods: To explore the susceptibility of hepatocytes to SARS‐CoV‐2, we differentiated iPSCs to functional hepatocytes and tried infecting them with different MOI (1, 0.1, 0.01) of SARS‐CoV‐2. Results: The iPSC‐derived hepatocytes are highly susceptible to virus infection, even at 0.01 MOI. Other than the ancestral strain, iHeps also support the replication of SARS‐CoV‐2 variants including alpha, beta, theta, and delta. More interestingly, the ACE2 expression significantly upregulated after infection, suggesting a vicious cycle between virus infection and liver injury. Conclusions: The iPSC‐derived hepatocytes can support the replication of SARS‐CoV‐2, and this platform could be used to investigate the SARS‐CoV‐2 hepatotropism and hepatic pathogenic mechanisms. [ABSTRACT FROM AUTHOR]

This cohort study, conducted between July and August 2023, evaluated the adverse events (AEs) and immune response to a bivalent mRNA-1273.222 (containing sequences of the original Wuhan-H1 strain and the Omicron BA.4/5 variant) booster vaccine in 122 participants. The study included individuals with diverse vaccination histories, and their responses were assessed based on anti-receptor binding domain (RBD) IgG levels and neutralizing antibodies against the wild-type, Omicron BA.5, and XBB.1.16 variants. Following administration of the BA.4/5 bivalent vaccine, AEs were generally mild to moderate and well-tolerated within a few days. There were no reports of vomiting and no serious AEs or death. The findings demonstrated robust immune responses, with significant increases in anti-RBD IgG levels, particularly in groups that had received 3 –6 doses before the booster dose. The BA.4/5 bivalent booster effectively induced neutralizing antibodies against the vaccine strains, providing robust neutralization, including the XBB.1.16 strain. The study also highlighted that individuals with hybrid immunity, especially those assumed infected with the BA.5 strain or who had been infected twice, showed higher levels of robust neutralizing activity against Omicron XBB.1.16. Overall, these results indicate that the BA.4/5 bivalent booster vaccines can induce potent and good antibody responses in emerging Omicron subvariants, supporting its efficacy as a booster in individuals with diverse vaccination histories.

Microglia, the resident macrophage of the central nervous system, are increasingly recognized as contributing to diverse aspects of human development, health, and disease. In recent years, numerous studies in both mouse and human models have identified microglia as a double edged sword in the progression of neurotropic viral infections: protecting against viral replication and cell death in some contexts, while acting as viral reservoirs and promoting excess cellular stress and cytotoxicity in others. It is imperative to understand the diversity of human microglial responses in order to therapeutically modulate them; however, modeling human microglia has been historically challenging due to significant interspecies differences in innate immunity and rapid transformation upon in vitro culture. In this review, we discuss the contribution of microglia to the neuropathogenesis of key neurotropic viral infections: human immunodeficiency virus 1 (HIV-1), Zika virus (ZIKV), Japanese encephalitis virus (JEV), West Nile virus (WNV), Herpes simplex virus (HSV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We pay special attention to recent work with human stem cell-derived microglia and propose strategies to leverage these powerful models to further uncover species- and disease-specific microglial responses and novel therapeutic interventions for neurotropic viral infections.

Inactivated coronavirus disease 2019 (COVID-19) vaccines such as CoronaVac and BBIBP-CorV have been widely used in China. However, more investigation is still needed to understand antibodies' duration and effectiveness against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants in the real world. In this study, 575 participants who had been vaccinated with two or three doses of the inactivated vaccine were recruited. Serum samples were collected and tested for anti-spike IgG and neutralizing antibodies against SARS-CoV-2 (original strain, Dela, and Omicron). Unsurprisingly, a third dose of the vaccine significantly enhanced antibody responses against SARS-CoV-2 and its variants. However, despite a booster dose, the neutralizing antibody levels against Omicron, particularly the BA.5.2 subvariant, remained low. There was no sex bias, but an age bias was observed. Notably, the predominant IgG subclass antibodies were IgG1 and IgG2, with a much lower level of IgG4. After the booster shot, the ratio of IgG4 to IgG1 significantly increased. The observation of IgG1 to the IgG4 class switch after repeated inactivated vaccinations underscores the importance of continuous monitoring of subclass antibody responses. Further clinical investigations are required to understand the implications of this class switch for optimizing immunization strategies.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has severely impacted public health. In 2022, the Omicron variant of SARS-CoV-2 rapidly became the dominant circulating variant in the local COVID-19 outbreaks in Tianjin Municipality, China. To gain a deeper understanding of the genetic variations of the Omicron variant in Tianjin, specimens from individuals who tested positive for SARS-CoV-2 between December 2021 and November 2022 were used for virus whole genome sequencing and phylogenetic analysis. A total of 1,674 high-quality Omicron sequences were obtained, consisting of 1,339 sequences from local cases belonging to 20 Phylogenetic Assignment of Named Global Outbreak (PANGO) lineages and 335 sequences from imported cases belonging to 70 lineages. Tianjin experienced five waves of local outbreaks, accompanied by multiple substitutions among subvariants, ranging from the initial BA.1.1 lineage to the subsequent BA.2, BF.7, and BA.5.2 lineages. The evolutionary rate of local strains, estimated to be 28.999 substitutions per year, and the evolutionary rate of imported strains, estimated to be 24.946 substitutions per year, were lower than that of the strains circulating globally. The additional substitutions and deletions of local strains have been used to identify and disrupt the virus transmission chains. The subvariants such as BA.5.2.48, BA.5.2.49, BF.7.14, and XBB.1 circulating in the fifth epidemic wave presented criterial immune escape mutations including S: R346T, S: L452R and S: F486V. It is essential to implement genomic surveillance strategies to investigate further the development of genomic mutation characteristics in the SARS-CoV-2 variant. This ongoing monitoring will contribute to a better understanding of the virus's genetic changes and aid in effective control measures.

(1) Background/Objectives: Dexmedetomidine is a sedative for patients receiving invasive mechanical ventilation (IMV) that previous single-site studies have found to be associated with improved survival in patients with COVID-19. The reported clinical benefits include dampened inflammatory response, reduced respiratory depression, reduced agitation and delirium, improved preservation of responsiveness and arousability, and improved hypoxic pulmonary vasoconstriction and ventilation-perfusion ratio. Whether improved mortality is evident in large, multi-site COVID-19 data is understudied. (2) Methods: The association between dexmedetomidine use and mortality in patients with COVID-19 receiving IMV was assessed. This retrospective multi-center cohort study utilized patient data in the United States from health systems participating in the National COVID Cohort Collaborative (N3C) from 1 January 2020 to 3 November 2022. The primary outcome was 28-day mortality rate from the initiation of IMV. Propensity score matching adjusted for differences between the group with and without dexmedetomidine use. Adjusted hazard ratios (aHRs) for 28-day mortality were calculated using multivariable Cox proportional hazards models with dexmedetomidine use as a time-varying covariate. (3) Results: Among the 16,357,749 patients screened, 3806 patients across 17 health systems met the study criteria. Mortality was lower with dexmedetomidine use (aHR, 0.81; 95% CI, 0.73–0.90; p < 0.001). On subgroup analysis, mortality was lower with earlier dexmedetomidine use—initiated within the median of 3.5 days from the start of IMV—(aHR, 0.67; 95% CI, 0.60–0.76; p < 0.001) as well as use prior to standard, widespread use of dexamethasone for patients on respiratory support (prior to 30 July 2020) (aHR, 0.54; 95% CI, 0.42–0.69; p < 0.001). In a secondary model that was restricted to 576 patients across six health system sites with available PaO2/FiO2 data, mortality was not lower with dexmedetomidine use (aHR 0.95, 95% CI, 0.72–1.25; p = 0.73); however, on subgroup analysis, mortality was lower with dexmedetomidine use initiated earlier than the median dexmedetomidine start time after IMV (aHR, 0.72; 95% CI, 0.53–0.98; p = 0.04) and use prior to 30 July 2020 (aHR, 0.22; 95% CI, 0.06–0.78; p = 0.02). (4) Conclusions: Dexmedetomidine use was associated with reduced mortality in patients with COVID-19 receiving IMV, particularly when initiated earlier, rather than later, during the course of IMV as well as use prior to the standard, widespread usage of dexamethasone during respiratory support. These particular findings might suggest that the associated mortality benefit with dexmedetomidine use is tied to immunomodulation. However, further research including a large randomized controlled trial is warranted to evaluate the potential mortality benefit of DEX use in COVID-19 and evaluate the physiologic changes influenced by DEX that may enhance survival. [ABSTRACT FROM AUTHOR]

In April 2020, the Aboriginal and Torres Strait Islander COVID-19 Point-of-Care (POC) Testing Program was initiated to improve access to rapid molecular-based SARS-CoV-2 detection in First Nations communities. At capacity, the program reached 105 health services across Australia. An external review estimated the program contributed to averting between 23,000 and 122,000 COVID-19 infections within 40 days of the first infection in a remote community, equating to cost savings of between AU$337 million and AU$1.8 billion. Essential to the quality management of this program, a customised External Quality Assessment (EQA) program was developed with the Royal College of Pathologists of Australasia Quality Assurance Programs (RCPAQAP). From July 2020 to May 2022, SARS-CoV-2 EQA participation ranged from 93 to 100%. Overall concordance of valid EQA results was high (98%), with improved performance following the first survey. These results are consistent with those reported by 12 Australian and 4 New Zealand laboratories for three SARS-CoV-2 RNA EQA surveys in March 2020, demonstrating that SARS-CoV-2 RNA POC testing in primary care settings can be performed to an equivalent laboratory analytical standard. More broadly, this study highlights the value of quality management practices in real-world testing environments and the benefits of ongoing EQA program participation. [ABSTRACT FROM AUTHOR]

Many emerging and re-emerging infectious diseases are prevalent, and the number of patients with allergies is increasing. Therefore, the importance of purifying the living environment is increasing. Photocatalysts undergo extreme redox reactions and decompose organic matter upon exposure to the excitation light. In contrast to ultraviolet light and disinfectants, which are standard methods for inactivating viruses and eliminating microorganisms, photocatalysts can decompose toxic substances, such as endotoxins and allergens, rendering them harmless to the human body. Photocatalysts have attracted significant attention as potential antiviral and antimicrobial agents. This review outlines the antiviral, antimicrobial, and anti-allergenic effects of photocatalysts. Especially, we have discussed the inactivation of SARS-CoV-2 in liquids and aerosols, elimination of Legionella pneumophila in liquids, decomposition of its endotoxin, decomposition of cat and dog allergens, and elimination of their allergenicity using photocatalysts. Furthermore, we discuss future perspectives on how photocatalysts can purify living environments, and how photocatalytic technology can be applied to companion animals and the livestock industry. [ABSTRACT FROM AUTHOR]

Background: Routine use of immunosuppressive agents in systemic lupus erythematosus (SLE) patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) potentially increases the risk of adverse outcomes. belimumab, a monoclonal antibody for the treatment of SLE, remains untested for its specific impact on coronavirus disease 2019 (COVID-19) symptoms in these patients. Here, this research investigated the effect of belimumab on COVID-19 symptoms in SLE patients infected with SARS-CoV-2. Methods: This study enrolled SLE patients who underwent treatment with belimumab. After thorough screening based on the inclusion and exclusion criteria, data pertaining to COVID-19 for both the participants and their cohabitants were obtained through telephone follow-up. The potential impact of belimumab on COVID-19 was evaluated by comparing COVID-19 symptoms and medication use across various groups to investigate the association between belimumab treatment and COVID-19 in SLE. Results: This study involved 123 SLE patients, of whom 89.4% tested positive for SARS-CoV-2. Among cohabitants of SLE patients, the SARS-CoV-2 positive rate was 87.2% (p = 0.543). Patients treated with belimumab exhibited a lower incidence of multiple COVID-19 symptoms than their cohabitating counterparts (p < 0.001). This protective effect was found to be partially related to the time of last belimumab administration. Among those with COVID-19, 30 patients opted to discontinue their anti-SLE drugs, and among them, 53% chose to discontinue belimumab. Discontinuing drugs did not increase the risk of hospitalization due to SARS-CoV-2 infection. Conclusion: This study concluded that treatment with belimumab did not increase susceptibility to COVID-19 and beneficially alleviated the symptoms of COVID-19. [ABSTRACT FROM AUTHOR]

At times of pandemics, such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the situation demands rapid development and production timelines of safe and effective vaccines for delivering life-saving medications quickly to patients. Typical biologics production relies on using the lengthy and arduous approach of stable single-cell clones. Here, we used an alternative approach, a stable cell pool that takes only weeks to generate compared to a stable single-cell clone that needs several months to complete. We employed the membrane, envelope, and highly immunogenic spike proteins of SARS-CoV-2 to produce virus-like particles (VLPs) using the HEK293-F cell line as a host system with an economical transfection reagent. The cell pool showed the stability of protein expression for more than one month. We demonstrated that the production of SARS-CoV-2 VLPs using this cell pool was scalable up to a stirred-tank 2 L bioreactor in fed-batch mode. The purified VLPs were properly assembled, and their size was consistent with the authentic virus. Our particles were functional as they specifically entered the cell that naturally expresses ACE-2. Notably, this work reports a practical and cost-effective manufacturing platform for scalable SARS-CoV-2 VLPs production and chromatographic purification. [ABSTRACT FROM AUTHOR]

The primary targets of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the lungs are type I pneumocytes, macrophages, and endothelial cells. We aimed to identify lung cells targeted by SARS-CoV-2 using viral nucleocapsid protein staining and morphometric features on patients with fatal COVID-19. We conducted a retrospective analysis of fifty-one autopsy cases of individuals who tested positive for SARS-CoV-2. Demographic and clinical information were collected from forensic reports, and lung tissue was examined for microscopic lesions and the presence of specific cell types. Half of the evaluated cohort were older than 71 years, and the majority were male (74.5%). In total, 24 patients presented diffuse alveolar damage (DAD), and 50.9% had comorbidities (56.9% obesity, 33.3% hypertension, 15.7% diabetes mellitus). Immunohistochemical analysis showed a similar pattern of infected macrophages, infected type I pneumocytes, and endothelial cells, regardless of the presence of DAD (p > 0.5). The immunohistochemical reactivity score (IRS) was predominantly moderate but without significant differences between patients with and without DAD (p = 0.633 IRS for type I pneumocytes, p = 0.773 IRS for macrophage, and p = 0.737 for IRS endothelium). The nucleus/cytoplasm ratio shows lower values in patients with DAD (median: 0.29 vs. 0.35), but the difference only reaches a tendency for statistical significance (p = 0.083). Our study confirms the presence of infected macrophages, type I pneumocytes, and endothelial cells with a similar pattern in patients with and without diffuse alveolar damage. [ABSTRACT FROM AUTHOR]

The coronavirus disease (COVID-19) pandemic has resulted in an increasing population that is experiencing a wide range of long-lasting symptoms after recovery from the acute infection. Long COVID refers to this specific condition and is associated with diverse symptoms, such as fatigue, myalgias, dyspnea, headache, cognitive impairment, neurodegenerative symptoms, anxiety, depression, and a sense of despair. The potential of hyperbaric oxygen therapy (HBOT) to improve chronic fatigue, cognitive impairments, and neurological disorders has been established; therefore, the use of HBOT to treat long COVID has also been studied. We conducted a literature search between 1 January 2019 and 30 October 2023, focusing on the clinical efficacy and utility of HBOT for treating long COVID and found ten clinical studies that fit the review topic, including one case report, five one-group pretest-posttest design studies, one safety report from a randomized controlled trial (RCT), and three complete reports of RCTs. Most studies found that HBOT can improve quality of life, fatigue, cognition, neuropsychiatric symptoms, and cardiopulmonary function. Although HBOT has shown some benefits for long COVID symptoms, further rigorous large-scale RCTs are required to establish precise indications, protocols, and post-treatment evaluations. [ABSTRACT FROM AUTHOR]

Objective: To study the mechanism of Artemisia in the treatment of respiratory tract infection (RTI) by network pharmacology and molecular docking. Methods: The active constituents and targets of Artemisia were screened by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Gene Cards database to obtain disease targets associated with RTI. The key targets of intersection were used to construct the protein–protein interaction (PPI) network, and the hub gene was obtained through topological analysis to construct the pharmacology regulation network of traditional Chinese medicine. The key targets were analyzed by R language enrichment, and the regulatory network diagram of the key target function/pathway was constructed. Molecular docking verifies the binding of the drug to the target predicted by network pharmacology. Results: 144 active components of Artemisia regulated 133 target proteins related to RTI, the core components were β-sitosterol, quercetin, isorhamnetin, artemisinin, etc. Gene ontology enrichment analysis showed that Artemisia regulates receptor ligand activity, cytokine activity, and other molecular functions by acting on membrane region, membrane raft and other cellular structures in the treatment of RTI, thus affecting biological processes such as the response to drugs and bacteria-derived molecules. Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt), tumor necrosis factor, interleukin-17 (IL-17) signaling pathway was the main pathway for RTI treatment. The molecular docking method confirmed the high affinity between the active ingredient and the RTI target. Conclusions: Artemisia species, a multitarget medication, has been shown to be a viable therapy option for RTI by network pharmacology techniques based on data mining and molecular docking approaches. [ABSTRACT FROM AUTHOR]

Background: According to the Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients (EPIC-HR) study, compared with a placebo, nirmatrelvir/ritonavir significantly reduced the risk of coronavirus disease 2019 (COVID-19)-related hospitalization or mortality in unvaccinated patients. The Delta variant was the most prevalent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant among all treatment recipients in the EPIC-HR study. The Omicron variant is less pathogenic than the Delta variant. The efficacy of nirmatrelvir/ritonavir in partially or fully immunized patients with Omicron variant-related infections must be further evaluated. Objectives: The current meta-analysis aimed to evaluate the therapeutic efficacy of nirmatrelvir/ritonavir based on factors including hospitalization, all-cause mortality, and COVID-19 rebound in patients who were partially or fully immunized against COVID-19. Methods: This meta-analysis aimed to evaluate the therapeutic efficacy of nirmatrelvir/ritonavir based on factors including hospitalization, all-cause mortality, and COVID-19 rebound in patients who were partially or fully immunized against COVID-19. It included 26 studies that directly examined the clinical efficacy of nirmatrelvir/ritonavir versus placebo in adult patients with SARS-CoV-2 infection caused by the Omicron variant. The search criteria comprised keywords such as hospitalization, all-cause mortality, and COVID-19 rebound. Results: The all-cause mortality risk was reduced by 59% in patients aged ≥65 years. However, their hospitalization risk decreased by only 36%. The reduction in all-cause mortality and hospitalization risk was similar between patients with low and high COVID-19 vaccination coverage. Patients receiving nirmatrelvir/ritonavir had a higher incidence of COVID-19 rebound than those receiving a placebo. However, the hospitalization risk and all-cause mortality of adult patients with COVID-19 treated with nirmatrelvir/ritonavir reduced by 53% and 57%, respectively. Conclusion: The current meta-analysis of 26 studies indicates that adult patients with COVID-19 treated with nirmatrelvir/ritonavir reduced the risk of hospitalization by 53% and all-cause mortality by 57% compared to a placebo.

Abstract Background and Aim Currently, SARS‐CoV‐2 is still spreading rapidly and globally. A large proportion of patients with COVID‐19 developed liver injuries. The human‐induced pluripotent stem cell (iPSC)‐derived hepatocytes recapitulate primary human hepatocytes and have been widely used in studies of liver diseases. Methods To explore the susceptibility of hepatocytes to SARS‐CoV‐2, we differentiated iPSCs to functional hepatocytes and tried infecting them with different MOI (1, 0.1, 0.01) of SARS‐CoV‐2. Results The iPSC‐derived hepatocytes are highly susceptible to virus infection, even at 0.01 MOI. Other than the ancestral strain, iHeps also support the replication of SARS‐CoV‐2 variants including alpha, beta, theta, and delta. More interestingly, the ACE2 expression significantly upregulated after infection, suggesting a vicious cycle between virus infection and liver injury. Conclusions The iPSC‐derived hepatocytes can support the replication of SARS‐CoV‐2, and this platform could be used to investigate the SARS‐CoV‐2 hepatotropism and hepatic pathogenic mechanisms.

Cardiovascular involvements are one of the most important and threatening problems of SARS-CoV-2 infection and can cause a wide range of clinical manifestations in children. Therefore, a review of previous studies is necessary to prevent the occurrence of cardiovascular complications and reduce the risk of mortality in this age group of patients. To investigate the cardiovascular complications in children with COVID-19, international authoritative databases including PubMed, Scopus, Embase, Web of Science, Google Scholar, and Persian databases were searched using the main concepts, all articles were published between January 2020 and November 2022. According to the results of the present study, no deaths due to cardiovascular involvement were reported in the studied healthy children with COVID-19. In addition, in electrocardiogram (ECG) findings, supraventricular arrhythmias (SVA) and ventricular arrhythmias (VA) and in echo findings, left ventricular dysfunction (LVD) have had the most consequences.

Coronavirus disease 2019 (COVID-19) is an infectious viral disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that emerged at the end of 2019. SARS-CoV-2 can be transmitted through droplets, aerosols, and fomites. Disinfectants such as alcohol, quaternary ammonium salts, and chlorine-releasing agents, including hypochlorous acid, are used to prevent the spread of SARS-CoV-2 infection. In the present study, we investigated the efficacy of ionless hypochlorous acid water (HOCl) in suspension and by spraying to inactivate SARSCoV-2. The virucidal efficacy of HOCl solution in tests against SARS-CoV-2 was evaluated as 50% tissue culture infectious dose. Although the presence of organic compounds influenced the virucidal efficacy, HOCl treatment for 20 s was significantly effective to inactivate Wuhan and Delta strains in the suspension test. HOCl atomization for several hours significantly reduced the SARS-CoV-2 attached to plastic plates. These results indicate that HOCl solution with elimination containing NaCl and other ions may have high virucidal efficacy against SARS-CoV-2. This study provides important information about the virucidal efficacy and use of HOCl solution. [ABSTRACT FROM AUTHOR]

To characterize Coronavirus Disease 2019 (COVID-19) transmission dynamics in each of the metropolitan statistical areas (MSAs) surrounding Dallas, Houston, New York City, and Phoenix in 2020 and 2021, we extended a previously reported compartmental model accounting for effects of multiple distinct periods of non-pharmaceutical interventions by adding consideration of vaccination and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants Alpha (lineage B.1.1.7) and Delta (lineage B.1.617.2). For each MSA, we found region-specific parameterizations of the model using daily reports of new COVID-19 cases available from January 21, 2020 to October 31, 2021. In the process, we obtained estimates of the relative infectiousness of Alpha and Delta as well as their takeoff times in each MSA (the times at which sustained transmission began). The estimated infectiousness of Alpha ranged from 1.1x to 1.4x that of viral strains circulating in 2020 and early 2021. The estimated relative infectiousness of Delta was higher in all cases, ranging from 1.6x to 2.1x. The estimated Alpha takeoff times ranged from February 1 to February 28, 2021. The estimated Delta takeoff times ranged from June 2 to June 26, 2021. Estimated takeoff times are consistent with genomic surveillance data. [ABSTRACT FROM AUTHOR]

Background: The association between proteinuria, which is also an indicator of chronic kidney disease (CKD), and coronavirus disease 2019 (COVID-19) severity is unclear. Methods: We selected 342 hospitalized patients with COVID-19 diagnosed via polymerase chain reaction testing between February 2020 and October 2022 and who had at least one urinalysis 14–365 days before admission. Results: Proteinuria before admission was associated neither with oxygen administration nor developing pneumonia in multivariate analysis (odds ratio [OR] 1.03; 95% confidence interval (CI) 0.44–2.40, p = 0.95 and OR 1.01; 95% CI 0.47–2.17, p = 0.98, respectively). Proteinuria on admission was associated both with oxygen administration and developing pneumonia in multivariate analysis (OR 3.29; 95% CI 1.37–7.88, p < 0.01 and OR 3.81; 95% CI 1.68–8.62, p < 0.01, respectively). The percentage of patients with proteinuria on admission was significantly higher than those before admission (37.4% vs. 17.8%; p < 0.01). In the subgroup analysis, proteinuria on admission among patients with eGFR ≥ 60 mL/min/1.73 m2 was associated with both oxygen administration and developing pneumonia (OR 4.86; 95% CI 1.22–19.38, p = 0.03, OR 3.65; 95% CI 1.06–12.58, p = 0.04, respectively). In contrast, proteinuria on admission among patients with eGFR < 60 mL/min/1.73 m2 was associated with developing pneumonia (OR 6.45; 95%CI 1.78–23.35, p = 0.01), not with oxygen administration (OR 3.28; 95% CI 0.92–11.72, p = 0.07). Conclusions: Although underlying proteinuria before admission was not associated with COVID-19 severity, proteinuria on admission was associated with oxygen demand and developing pneumonia. [ABSTRACT FROM AUTHOR]

Intranasal drug delivery is as a noninvasive and efficient approach extensively utilized for treating the local, central nervous system, and systemic diseases. Despite numerous reviews delving into the application of intranasal drug delivery across biomedical fields, a comprehensive analysis of advancements and future perspectives remains elusive. This review elucidates the research progress of intranasal drug delivery through a scientometric analysis. It scrutinizes several challenges to bolster research in this domain, encompassing a thorough exploration of entry and elimination mechanisms specific to intranasal delivery, the identification of drugs compatible with the nasal cavity, the selection of dosage forms to surmount limited drug-loading capacity and poor solubility, and the identification of diseases amenable to the intranasal delivery strategy. Overall, this review furnishes a perspective aimed at galvanizing future research and development concerning intranasal drug delivery. [Display omitted] [ABSTRACT FROM AUTHOR]

Angiotensin-converting enzyme 2 (ACE2), one of the key enzymes of the renin-angiotensin system (RAS), plays an important role in SARS-CoV-2 infection by functioning as a virus receptor. Angiotensin peptides Ang I and Ang II, the substrates of ACE2, can modulate the binding of SARS-CoV-2 Spike protein to the ACE2 receptor. In the present work, we found that co-incubation of HEK-ACE2 and Vero E6 cells with the SARS-CoV-2 Spike pseudovirus (PVP) resulted in stimulation of the virus entry at low and high micromolar concentrations of Ang I and Ang II, respectively. The potency of Ang I and Ang II stimulation of virus entry corresponds to their binding affinity to ACE2 catalytic pocket with 10 times higher efficiency of Ang II. The Ang II induced mild increase of PVP infectivity at 20 µM; while at 100 µM the increase (129.74±3.99 %) was highly significant (p<0.001). Since the angiotensin peptides act in HEK-ACE2 cells without the involvement of angiotensin type I receptors, we hypothesize that there is a steric interaction between the catalytic pocket of the ACE2 enzyme and the SARSCoV-2 S1 binding domain. Oversaturation of the ACE2 with their angiotensin substrate might result in increased binding and entry of the SARS-CoV-2. In addition, the analysis of angiotensin peptides metabolism showed decreased ACE2 and increased ACE activity upon SARS-CoV-2 action. These effects should be taken into consideration in COVID-19 patients suffering from comorbidities such as the over-activated renin-angiotensin system as a mechanism potentially influencing the SARS-CoV-2 invasion into recipient cells. [ABSTRACT FROM AUTHOR]

• Assessing vaccine effectiveness (VE) became challenging due to incidental infection. • A case-control study in 24 hospitals during Delta and Omicron with various outcomes. • Multiple outcomes with high protection of 2 doses for Delta and 3 doses for Omicron. • There was a trend towards higher VE for more severe and specific disease outcomes. • Importance of severe/specific outcomes to accurately show VE against severe disease. Since the SARS-CoV-2 Omicron variant became dominant, assessing COVID-19 vaccine effectiveness (VE) against severe disease using hospitalization as an outcome became more challenging due to incidental infections via admission screening and variable admission criteria, resulting in a wide range of estimates. To address this, the World Health Organization (WHO) guidance recommends the use of outcomes that are more specific to severe pneumonia such as oxygen use and mechanical ventilation. A case-control study was conducted in 24 hospitals in Japan for the Delta-dominant period (August-November 2021; "Delta") and early Omicron (BA.1/BA.2)-dominant period (January-June 2022; "Omicron"). Detailed chart review/interviews were conducted in January-May 2023. VE was measured using various outcomes including disease requiring oxygen therapy, disease requiring invasive mechanical ventilation (IMV), death, outcome restricting to "true" severe COVID-19 (where oxygen requirement is due to COVID-19 rather than another condition(s)), and progression from oxygen use to IMV or death among COVID-19 patients. The analysis included 2125 individuals with respiratory failure (1608 cases [75.7%]; 99.2% of vaccinees received mRNA vaccines). During Delta, 2 doses provided high protection for up to 6 months (oxygen requirement: 95.2% [95% CI:88.7–98.0%] [restricted to "true" severe COVID-19: 95.5% {89.3–98.1%}]; IMV: 99.6% [97.3–99.9%]; fatal: 98.6% [92.3–99.7%]). During Omicron, 3 doses provided high protection for up to 6 months (oxygen requirement: 85.5% [68.8–93.3%] ["true" severe COVID-19: 88.1% {73.6–94.7%}]; IMV: 97.9% [85.9–99.7%]; fatal: 99.6% [95.2–99.97]). There was a trend towards higher VE for more severe and specific outcomes. Multiple outcomes pointed towards high protection of 2 doses during Delta and 3 doses during Omicron. These results demonstrate the importance of using severe and specific outcomes to accurately measure VE against severe COVID-19, as recommended in WHO guidance in settings of intense transmission as seen during Omicron. [ABSTRACT FROM AUTHOR]

Wastewater surveillance has been widely implemented to monitor COVID-19 incidences in communities worldwide. One notable application of wastewater surveillance is for providing early warnings of disease outbreaks. Many studies have reported time lags between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) wastewater concentrations and confirmed clinical COVID-19 cases. To our best knowledge, only a few studies to date have explored time lags between SARS-CoV-2 wastewater concentrations and other clinical metrics. In this study, we investigated time lags between SARS-CoV-2 wastewater concentrations and three COVID-19 clinical metrics: confirmed clinical cases, hospitalizations, and intensive care unit (ICU) admissions, in the Tricounty Detroit Area, Michigan, US. The COVID-19 clinical metrics were dated between September 1, 2020, and October 31, 2022, and were collected from public data sources. SARS-CoV-2 N1 and N2 gene concentrations between September 1, 2020, and May 31, 2022, were generated using two sampling and concentration methods: virus adsorption-elution (VIRADEL) and polyethylene glycol precipitation (PEG). The data were collected from our recently published study. Time-lagged cross correlation was implemented to estimate time lags between gene concentrations and the three clinical metrics. Original gene concentrations were normalized by wastewater flow parameters through nine approaches to estimate the impact of wastewater flow on time lags. Vector autoregression models were established to analyze the relationship between gene concentrations and clinical metrics. The results indicate that VIRADEL gene concentrations in wastewater preceded all clinical metrics prior to the COVID-19 Omicron surge, for instance, 32, 47, and 51 days preceding confirmed cases, hospitalizations, and ICU admissions, respectively (gene concentrations unit: gc/day). When translated to a public health context, these time lags become critical lead times for officials to prepare and react. During the Omicron surge, there were significant reductions in time lags, with VIRADEL measurements trailing total ICU admissions. PEG measurements lagged behind the three clinical metrics and did not provide early warnings of disease surges. [ABSTRACT FROM AUTHOR]

Background: There are limited and partially contradictory data on the effects of airway pressure release ventilation (APRV) in COVID-19-associated acute respiratory distress syndrome (CARDS). Therefore, we analyzed the clinical outcome, complications, and longitudinal course of ventilation parameters and laboratory values in patients with CARDS, who were mechanically ventilated using APRV. Methods: Respective data from 4 intensive care units (ICUs) were collected and compared to a matched cohort of patients receiving conventional low tidal volume ventilation (LTV). Propensity score matching was performed based on age, sex, blood gas analysis, and APACHE II score at admission, as well as the implementation of prone positioning. Findings: Forty patients with CARDS, who were mechanically ventilated using APRV, and 40 patients receiving LTV were matched. No significant differences were detected for tidal volumes per predicted body weight, peak pressure values, and blood gas analyses on admission, 6 h post admission as well as on day 3 and day 7. Regarding ICU survival, no significant difference was identified between APRV patients (40%) and LTV patients (42%). Median duration of mechanical ventilation and duration of ICU treatment were comparable in both groups. Similar complication rates with respect to ventilator-associated pneumonia, septic shock, thromboembolic events, barotrauma, as well as the necessity for hemodialysis were detected for both groups. Clinical characteristics that were associated with increased mortality in a Cox proportional hazards regression analysis included age (hazard ratio [HR] 1.08, 95% confidence interval [CI] 1.04-1.1; P <.001), severe acute respiratory distress syndrome (HR 2.62, 95% CI 1.02-6.7; P =.046) and the occurrence of septic shock (HR 17.18, 95% CI 2.06-143.2; P =.009), but not the ventilation mode. Interpretation: Intensive care unit survival, duration of mechanical ventilation, and ICU treatment as well as ventilation-associated complication rates were equivalent using APRV compared to conventional LTV in patients with CARDS. [ABSTRACT FROM AUTHOR]

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on postoperative recovery of non-small cell lung cancer (NSCLC) is need to be understood, thereby informing the optimal timing of surgical decision-making during the COVID-19 pandemic for NSCLC patients. This study reports the postoperative outcomes of surgical NSCLC patients with preoperative SARS-CoV-2 infection. Method: This single-center retrospective cohort study included 241 NSCLC patients who underwent lobectomy or sub-lobectomy between December 1, 2022 and February 14, 2023. Surgical outcomes of patients with preoperative SARSCoV-2 infection (stratified by the time from diagnosis of SARS-CoV-2 infection to surgery) were compared with those without preoperative SARS-CoV-2 infection. The primary outcomes were total postoperative complications and postoperative pulmonary complications (PPCs), the secondary outcomes included operation time, total postoperative drainage and time, length of hospital stay (LOS), 30-day and 90-day postoperative symptoms. Results: This study included 153 (63.5%) patients with preoperative SARS-CoV-2 infection and 88 (36.5%) patients without previous SARS-CoV-2 infection. In patients with a preoperative SARS-CoV-2 diagnosis, the incidence of total postoperative complications (OR, 3.00; 95% CI, 1.12–8.01; p=0.028) and PPCs (OR, 4.20; 95% CI, 1.11–15.91; p=0.035) both increased in patients infected having surgery within 2weeks compared with non-infection before surgery. However, patients who underwent lung resection more than 2weeks after SARS-CoV-2 diagnosis had a similar risk of postoperative complications and surgical outcomes with those non-infection before surgery. Conclusion: This is the first study to provide evidence regarding the optimum timing of lung resection surgery and assessing early outcomes after surgery in NSCLC patients with SARS-CoV-2 infection. Our study documents that the SARS-CoV-2 infection did not complicate surgical procedures for lung cancer, and suggest that lung surgery should be postponed at least 2weeks after SARSCoV-2 infection for NSCLC patients. [ABSTRACT FROM AUTHOR]

Background: In early 2021, the Ministry of Public Health of Thailand announced heterologous regimens for COVID-19 vaccines using CoronaVac as the first dose followed by ChAdOx1 nCoV-19 at 3 weeks apart. Priority was given to individuals above 60 years old and those who had seven underlying conditions, including obesity. The vaccine regimen was evaluated for safety and immunogenicity in overweight populations in Chiang Mai, Thailand. Methods: Participants who had a COVID-19 vaccination appointment for the heterologous prime-boost regimen were enrolled. Before each immunization and on day 28 following the second dosage, blood samples were taken, and were examined for anti-spike and neutralizing antibodies by using an indirect ELISA and virus neutralization assays. Safety profile of the vaccine regimen was assessed via a self-recorded diary of adverse events after each vaccination. Results: No serious adverse events related to vaccination were reported during study period and the majority of adverse reactions were fatigue and pain at the injection site. The levels of anti-spike IgG were 26.3, 56.4 and 1752.1 BAU/mL at baseline, 21 days after first dose and 28 days after second dose, respectively. At 4 weeks after complete vaccination, the median inhibition rates of neutralizing antibody determined by surrogate neutralization assay against wild type, Delta and Omicron variants were 95.2, 85.0 and 3.8, respectively. Moreover, the NT50 level against wild type and Delta variants determined by pseudotyped virus neutralization assay were 133.3 and 41.7, respectively. The neutralizing activity against Omicron variant was almost lower than cutoff level for detection. Conclusions: The heterologous CoronaVac-ChAdOx1vaccination was safe, well-tolerated and able to induce humoral immunity against wild-type and Delta variants but not against the Omicron variant in overweight population.

Background: Hemodialysis (HD) patients are particularly vulnerable to severe coronavirus disease 2019 (COVID-19) due to their immunocompromised state and comorbid conditions. Timely vaccination could be the most effective strategy to reduce morbidity and mortality. However, data on the survival benefit of the COVID-19 vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and death among HD patients are limited, especially during the Omicron-dominant period. Methods: In this prospective hospital-based cohort study, we identified HD patients from July 1, 2021, to April 29, 2022. The patients were divided into fully vaccinated and partially vaccinated groups. We compared the humoral response, risk of developing SARS-CoV-2 infection, and all-cause mortality between the two groups. Results: Among the 440 HD patients included, 152 patients were fully vaccinated, and 288 patients were partially vaccinated. Patients in the fully vaccinated group exhibited higher anti-spike protein receptor-binding domain (S protein RBD) antibody levels and lower risks of all-cause mortality (adjusted hazard ratio, 0.35; 95% confidence interval, 0.17–0.73; p = 0.005) than the partially vaccinated group. However, the risk for SARS-CoV-2 infection did not significantly differ between the two groups. Irrespective of the number of vaccinations, the risk of all-cause mortality was lower in patients with anti-S protein RBD antibody levels in the higher tertile. Conclusion: A third dose of the COVID-19 vaccine was associated with a decreased risk of all-cause mortality among HD patients during the Omicron-dominant period. A higher post-vaccination anti-S protein RBD antibody level was also associated with a lower risk of mortality.

Abstract Background Although the primary target of severe acute respiratory syndrome coronavirus 2 is the respiratory tract, the expression of the angiotensin-converting enzyme 2 receptor in other tissues facilitates viral entry in others parts of the body, including ocular structures. Ocular manifestations may occur before, during, or after systemic infection. Case presentation We report the case of a 60-year-old male who presented with bilateral interstitial keratitis after the onset of COVID-19, with ocular symptoms starting within 7 days after systemic symptoms. Laboratory investigation did not identify any alternative etiology for his disease, although the possibility of Epstein-Barr virus or herpes simpex virus could not be definitively ruled out. The patient had already developed significant corneal scarring and visual debilitation by the time topical steroids were initiated, and his final corrected visual acuity with rigid gas permeable contact lenses was 20/50 and 20/80 in the right and left eye, respectively. Conclusions The involvement of ocular tissue by the virus can lead to permanent sequelae such as severe visual loss, and clinicians should be aware of and recognize ophthalmic manifestations of this disease to prompt early intervention.

Abstract Background To report a case of simultaneous occurrence of acute exacerbation of ocular graft-versus-host disease (GVHD) and anterior uveitis following coronavirus disease 2019 (COVID-19) vaccination. Case presentation A 60-year-old man with primary myelofibrosis and GVHD after receiving allogeneic hematopoietic stem cell transplantation (HSCT), developed acute exacerbation of ocular GVHD and anterior uveitis after receiving first dose of COVID-19 vaccine. The patient developed erythema of the eyelids, conjunctival hyperemia, superficial punctate keratopathy, and prominent anterior chamber inflammation in both eyes. The ocular GVHD and anterior uveitis were managed with mainly topical corticosteroids, antibiotics, lubricants, and systemic corticosteroids, but were difficult to control. Intravitreal injection of dexamethasone was administered, and the inflammation gradually subsided 6 months after the onset of initial symptoms. Conclusions Clinicians should be aware of rare refractory anterior uveitis and acute exacerbation of ocular GVHD after COVID-19 vaccination in patients undergoing HSCT. Early diagnosis and aggressive treatment should be considered to reduce the likelihood of severe complications.

Abstract Background The COVID-19 pandemic continues to pose a significant worldwide threat to human health, as emerging SARS-CoV-2 Omicron variants exhibit resistance to therapeutic antibodies and the ability to evade vaccination-induced antibodies. Here, we aimed to identify human antibodies (hAbs) from convalescent patients that are potent and broadly neutralizing toward Omicron sublineages. Methods Using a single B-cell cloning approach, we isolated BA.5 specific human antibodies. We further examined the neutralizing activities of the most promising neutralizing hAbs toward different variants of concern (VOCs) with pseudotyped virus. Results Sixteen hAbs showed strong neutralizing activities against Omicron BA.5 with low IC50 values (IC50

Abstract Background The entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into the host cell is mediated through the binding of the SARS-CoV-2 Spike protein via the receptor binding domain (RBD) to human angiotensin-converting enzyme 2 (hACE2). Identifying compounds that inhibit Spike-ACE2 binding would be a promising and safe antiviral approach against COVID-19. Methods In this study, we used a BSL-2 compatible replication-competent vesicular stomatitis virus (VSV) expressing Spike protein of SARS-CoV-2 with eGFP reporter system (VSV-eGFP-SARS-CoV-2) in a recombinant permissive cell system for high-throughput screening of viral entry blockers. The SARS-CoV-2 permissive reporter system encompasses cells that stably express hACE2-tagged cerulean and H2B tagged with mCherry, as a marker of nuclear condensation, which also enables imaging of fused cells among infected EGFP positive cells and could provide real-time information on syncytia formation. Results A limited high-throughput screening identified six natural products that markedly inhibited VSV-eGFP-SARS-CoV-2 with minimum toxicity. Further studies of Spike-S1 binding using the permissive cells showed Scillaren A and 17-Aminodemethoxygeldanamycin could inhibit S1 binding to ACE2 among the six leads. A real-time imaging revealed delayed inhibition of syncytia by Scillaren A, Proscillaridin, Acetoxycycloheximide and complete inhibition by Didemnin B indicating that the assay is a reliable platform for any image-based drug screening. Conclusion A BSL-2 compatible assay system that is equivalent to the infectious SARS-CoV-2 is a promising tool for high-throughput screening of large compound libraries for viral entry inhibitors against SARS-CoV-2 along with toxicity and effects on syncytia. Studies using clinical isolates of SARS-CoV-2 are warranted to confirm the antiviral potency of the leads and the utility of the screening system.

This study investigates the clinical features and therapeutic outcomes of otitis media with effusion (OME) in adults following infection with the Omicron variant of coronavirus disease 2019 (COVID-19), in the context of China ending its "Zero-COVID-19" policy. Conducted as a multicenter, retrospective analysis at two medical institutions in Eastern China from December 2022 to February 2023, the study included patients with confirmed Omicron infection who were diagnosed with OME within two months, adhering to guidelines from the American Academy of Otolaryngology-Head and Neck Surgery Foundation (AAO-HNSF). Data on demographics, time from infection to OME manifestation, associated symptoms, and treatment outcomes were collected. Among 68 patients (73 affected ears) with OME post-Omicron infection, common symptoms included cough and nasal obstruction (69.1%). All reported ear fullness, with 86.8% experiencing hearing loss. Tympanic bullae were observed in 72.6% during otoscopy, and most tympanometry results showed a B-type tympanogram (80.0%). An integrated treatment strategy led to an 83.6% cure rate, although 8.2% experienced relapse within 2-3 months. Our findings highlight OME as a prevalent ear complication associated with COVID-19 during the Omicron pandemic, underscoring the necessity for further investigation into its complexities. While the integrated treatment approach proved effective, the 8.2% post-treatment recurrence rate underscores the importance of ongoing monitoring and signals an urgent need for more comprehensive research.