Influencing factors of negative conversion time of nucleic acid detection in 228 patients infected with Omicron variant of SARS-CoV-2 in Shanghai

Objective: To analyze and compare the effects of different clinical characteristics on the negative conversion time of nucleic acid detection after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant infection, and to provide a scientific basis for the isolation and treatment of coronavirus disease 2019 (COVID-19). Methods: The epidemiological and clinical data of 228 mild SARS-CoV-2 Omicron variant infected patients diagnosed in Shanghai were retrospectively collected from April 27, 2022 to June 8, 2022 in Wujiaochang designated Hospital, Yangpu District, Shanghai. The negative conversion time of nucleic acid detection was used as the outcome variable, and the patients were divided into A (18 days) and B (>18 days). Univariate and multivariate logistic regression analysis were used to analyze the influencing factors of the negative conversion time of nucleic acid detection. Results: The mean nucleic acid conversion time of 228 patients was (18.7+or-12.1) d, with the median time of 18 (2-46) d. Among them, 120 patients in group A had an average nucleic acid conversion time of (13.2+or-2.0) d, and 108 cases in group B had an average nucleic acid conversion time of (20.8+or-1.3) d. Univariate analysis showed that there were no statistically significant differences in the effects of hypertension, coronary heart disease, diabetes, hypokalemia, malignant tumors, neuropsychiatric diseases, chronic digestive diseases on the negative nucleic acid conversion time (P > 0.05);however, there were significant differences in the effects of combined cerebrovascular disease, leukopenia, chronic respiratory system diseases and vaccination on the negative nucleic acid conversion time (P < 0.05). Further multivariate logistic regression analysis revealed that the combination of chronic respiratory diseases and non-vaccination were significant risk factors for prolongation of negative nucleic acid conversion time (P < 0.05). Conclusions: The results of this study show that gender, age and whether hypertension, coronary heart disease, diabetes mellitus, hypokalemia, malignant tumor, neuropsychiatric disease and chronic digestive disease have no significant effect on the nucleic acid conversion time, whereas chronic respiratory disease and no vaccination are significantly correlated with the prolongation of nucleic acid conversion time in SARS-CoV-2 Omicron-infected patients.

A New Registry for Genetic Diagnosis of Inborn Errors of Immunity within the Military Health System

Genotypic definition of monogenic inborn errors of immunity (IEIs) continues to accelerate with broader access to next generation sequencing, underscoring this aggregated group of disorders as a major health burden impacting both civilian and military populations. At an estimated prevalence of 1 in 1200 individuals, IEIs affect ~8,000 patients within the Military Health System (MHS). Despite access to targeted gene/exome panels at military treatment facilities, most affected patients never receive a definitive genetic diagnosis that would significantly improve clinical care. To address this gap, we established the first registry of IEI patients within the MHS with the goal of identifying known and novel pathogenic genetic defects to increase diagnosis rates and enhance clinical care. Using the registry, a research protocol was opened in July 2022. Since July we have enrolled 75 IEI patients encompassing a breadth of phenotypes including severe and recurrent infections, bone marrow failure, autoimmunity/autoinflammation, atopic disease, and malignancy. Enrolled patients provide blood and bone marrow samples for whole genome, ultra-deep targeted panel and comprehensive transcriptome sequencing, plus cryopreservation of peripheral blood mononuclear cells for future functional studies. We are also implementing and developing analytical methods for identifying and interrogating non-coding and structural variants. Suspected pathogenic variants are adjudicated by a clinical molecular geneticist using state-of-the-art analysis pipelines. These analyses subsequently inform in vitro experiments to validate causative mutations using cell reporter systems and primary patient cells. Clinical variant validation and return of genetic results are planned with genetic counseling provided. As a proof of principle, this integrated genetic evaluation pipeline revealed a novel, candidate TLR7 nonsense variant in two adolescent brothers who both endured critical COVID-19 pneumonia, requiring mechanical ventilation and extracorporeal membrane oxygenation. Our protocol is therefore poised to greatly enrich clinical genetics resources available in the MHS for IEI patients, contributing to better diagnosis rates, informed family counseling, and targeted treatments that collectively improve the health and readiness of the military community. Moreover, our efforts should yield new mechanistic insights on immune pathogenesis for a broad variety of known and novel IEIs.Copyright © 2023 Elsevier Inc.

Rapid exchange of a percutaneous gastrostomy tube during an early episode of COVID-19

We retrospectively report a case of rapid exchange of a percutaneous radiologic gastrostomy tube (balloon-occluded type catheter) via off-label use of a pigtail catheter for nutrition supply during a very early episode of coronavirus disease 2019 (COVID-19) in an outpatient clinic. This case demonstrates that minimally invasive percutaneous procedures might be provided safely and effectively under appropriate precautions for preventing COVID-19 transmission during the pandemic.Copyright © 2023, Society of Gastrointestinal Intervention.

Whole genome sequencing of a German cohort to understand host genetics in COVID-19

Background/Objectives: The disease course upon SARS-CoV-2 infection is highly variable and comprises a range from asymptomatic infection to severe (and even lethal) COVID-19. Genetic factors substantially contribute to this variability, as evidenced by epidemiological studies and recent results from genome-wide association studies (GWAS) as well as sequencing-based approaches. The host genetics group of the German COVID-19 OMICs Initiative (DeCOI) has been founded with the aim to identify additional genetic variants that influence COVID-19 severity through whole genome sequencing (WGS) analyses. Method(s): Until January 2022, WGS has been performed on approximately 1200 individuals affected by COVID-19. Result(s): The most recent data freeze comprised 952 individuals. In this dataset, no carrier of a deleterious protein-altering variant has been detected in TLR7, which is the only conclusive risk gene for severe COVID-19. Applying a gene-based association test of rare variants to the subcohort of European individuals (n = 752, mean age: 56 years, females: 44%), including 199 severely affected individuals, we did not observe any significant association after correction for multiple testing. Exome-wide association analysis of common variants in this subcohort replicated the GWAS-locus on chromosome 3. Conclusion(s): With this ongoing work, we are contributing to international efforts to elucidate the host genetics of COVID-19, also by sharing our summary statistics for meta-analyses. Currently, we are sequencing additional severely affected individuals and we are refining analytical strategies, which will also include the joint analysis of common and rare variants at genomewide scale.

Function and interaction of coronavirus ion channel proteins

Objective: COVID-19 has emerged as a significant global health crisis causing devastating effects on world population accounting for over 6 million deaths worldwide. Although acute RTI is the prevalent cause of morbidity, kidney outcomes centered on a spectrum of AKI have evolved over the course of the pandemic. Especially the emerging variants have posed a daunting challenge to the scientific communities, prompting an urging requirement for global contributions in understanding the viral dynamics. In addition to canonical genes, several subgroup- specific accessory genes are located between the S and E genes of coronaviruses regarding which little is known. Previous studies have shown that accessory proteins (aps) in viruses function as viroporins that regulate viral infection, propagation and egress [1]. In this study we attempted to characterize the function of aps of coronavirus variants as ion channels. Furthermore, we also probed the interaction of ap4 with the host system. Method(s): Serial passaging (selection pressure), growth kinetics, confocal imaging, genome sequence analysis and proteomics were performed in Huh-7, MRC5 cells and/or human monocyte derived macrophages. Potassium uptake assay was performed in a Saccharo myces cerevisiae strain, which lacks the potassium transporters trk1 and trk2. Ion conductivity experiments were performed in Xenopus laevis oocytes using Two Electrode Voltage Clamp (TEVC) method. Result(s): Serial passaging demonstrated the acquisition of several frameshift mutations in ORF4 resulting in C-terminally truncated protein versions (ap4 and ap4a) and indicate a strong selection pressure against retaining a complete ORF4 in vitro. Growth kinetics in primary cells illustrated a reduction of viral titers when the full-length ap4 was expressed compared to the C-terminally truncated protein ap4a. Confocal imaging showed that ap4 and ap4a are not exclusively located in a single cellular compartment. Potassium uptake assay in yeast and TEVC analyses in Xenopus oocytes showed that ap4 and ap4a act as a weak K+ selective ion channel. In addition, accessory proteins of other virus variants also elicited microampere range of currents. Conclusion(s): Our study provides the first evidence that ap4 and other accessory proteins of coronavirus variants act as viroporins. Future studies are aimed at demonstrating the role of ap4 during the viral life cycle by modulating ion homeostasis of host cell in vivo (interacting proteins obtained from proteomic studies) and thereby serve as a tool for potential drug target.

Predictors of severity in COVID-19

Background: In the context of home monitoring of severe acute respiratory syndrome coronavirus-2 disease (COVID-19) patients, it is imperative to evaluate the accuracy of finger pulse oximetry oxygen saturation (SpO2) in the assessment of hypoxia. Methods: Retrospective data analysis was performed on (n = 132) hospitalised COVID-19 patients with various levels of severity, in whom SpO2, haematological, biochemical and arterial blood gas (ABG) parameters were measured within 48 h after admission. Discrepancy between SpO2 and arterial blood oxygen saturation SaO2 was compared between mild, moderate and severe COVID-19 to assess the accuracy of finger pulse oximetry. Results: We found that total white blood cell count, neutrophil %, neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, ferritin, C-reactive protein and lactate dehydrogenase (LDH) were significantly increased in severe COVID-19, while lymphocyte % was significantly less when compared to mild and moderate cases. Multivariable analysis suggested that red cell distribution width (RDW) and LDH together account for significant variance in the severity of disease. The SpO2 and SaO2 were significantly less in the severe group. The difference between SpO2 and SaO2 has a clinically meaningful albeit statistically nonsignificant trend with the discrepancy greater in severe COVID-19 cases when compared to mild and moderate cases. Conclusions: Finger pulse oximetry has the potential to underestimate the severity of hypoxia in severe COVID-19 and this has implications in the decision to start oxygen therapy. RDW and LDH constitute the best parsimonious set of variables to predict severity.

Effectiveness of ivermectin and atazanavir on time to resolution from COVID-19 symptoms: a prospective cohort

Objective: to evaluate the effectiveness of Ivermectin and Atazanavir compared to placebo in the time to resolution of symptoms and duration of illness due to COVID-19. Method: observational, prospective, longitudinal, descriptive and analytical cohort study with symptomatic outpatients, followed for 06 months in two Basic Health Units for COVID-19 care in Teresina-Piaui, Brazil, from November to April 2021 identified by 1:1:1 random sampling. Reverse transcription polymerase chain reaction (RT-PCR) tests were performed for laboratory confirmation of suspected infection with the new coronavirus and sociodemographic and clinical evaluation. Results: of the 87 randomized patients, 62.1% (n=54) were male, with a mean age of 35.1 years, had a partner (53.9%), low income (50.6%), eutrophic (40.7%) and without health comorbidities (78.2%). There was no difference between the median time to resolution of symptoms, which was 21 days (IQR, 8-30) in the atazanavir group, 30 days (IQR, 5-90) in the ivermectin group compared with 14 days (IQR, 9-21) in the control group. At day 180, there was resolution of symptoms in 100% in the placebo group, 93.9% in the atazanavir group, and 95% in the ivermectin group. The median duration of illness was 8 days in all study arms. Conclusion: Treatment with atazanavir (6 days) and ivermectin (3 days) did not reduce the time to symptom resolution or the duration of illness among outpatients with mild COVID-19 compared to the placebo group. The results do not support the use of ivermectin and atazanavir for the treatment of mild to moderate COVID-19.

Factors for prolonged hospital length of stay in discharged patients with COVID-19

Hospitals were overburdened during peak periods of Coronavirus disease 2019 (COVID-19) pandemic, and bed occupancy was full. The ability to predict and plan patients' hospital length of stay allows predictability in terms of the free capacity of hospital facilities. The purpose of this article is to evaluate the factors that influence the hospital length of stay among discharged (recovered) from COVID-19 patients. This will allow the prediction of the likely number of bed days in the conditions of intensive workload of medical facilities for hospital care. A total of 441 discharged after hospital treatment for COVID-19 patients are followed up. Factors for prolonged hospital length of stay are searched among the indicators recorded at admission. Median hospital length of stay of the patients discharged from COVID-19 ward is 9 days (IQR 6-12) and in the COVID-19 intensive care unit 12 days (IQR 9.75-18.75). The median length of stay assessed by a survival analysis is 35 days in the COVID-19 unit and only 8 days in intensive care, due to the high mortality in the intensive care unit. The longer hospital length of stay of patients discharged from the COVID-19 wards is associated with the presence of hypertension (median 10 vs. 8 days for patients without the disease, p=0.006), ischemic heart disease (10 vs. 8 days, p<0.001), cerebrovascular disease (10 vs. 8 days, p=0.061 - did not reach significance), peripheral arterial disease (12 vs. 8 days, p=0.024), chronic renal failure or chroniodialysis (14 vs. 8 days, p<0.001), oncological illness (11 vs. 8 days, p=0.024), presence of at least one comorbidity (9 vs. 8 days, p=0.006), arrival at the hospital by ambulance vs. the patient's own transport (11 vs. 8 days, p=0.003), severe lung involvement shown on X-ray (10 vs. 8 days, p=0.030) or CT (18 vs. 10 days, p=0.045). Prolonged hospital length of stay is associated with older age (Spearman's rho=0.185, p<0.001), greater number of comorbidities (Spearman's rho=0.200, p<0.001), lower oxygen saturation on admission (Spearman's rho=- 0.294, p<0.001) and lower lymphocytes count (Spearman's rho=-0.209, p<0.001), as well as higher CRP (Spearman's rho=0.168, p<0.001), LDH (Spearman's rho=0.140, p=0.004), ferritin (Spearman's rho=0.143, p=0.004) and d-dimer (Spearman's rho=0.207, p<0.001). The multiple linear regression model found that the increase in the number of bed days of discharged from COVID-19 unit patients depends on the way the patient arrived at the Emergency Department (by ambulance instead of on their own transportation) and the presence of an accompanying oncological disease (R2=0.628, p<0.001). The hospital length of stay of patients discharged from COVID-19 intensive care unit is associated with the presence of hypertension (median 14 vs. 9 days for patients without the disease, p=0.067 - significance not reached) and at least one comorbidity (14 vs. 9 days, p=0.067 - significance not reached). The number of bed days is higher when recorded more comorbidities (Spearman's rho=0.818, p=0.004), lower oxygen saturation (Spearman's rho=-0.605, p=0.067 - significance not reached) and higher leukocytes count (Spearman's rho=0.546, p=0.102 - significance not reached). A multiple linear regression model demonstrated the hospital length of stay of patients in the COVID-19 intensive care unit as an outcome of the number of comorbidities only (R2=0.826, p=0.003). The ability to estimate and forecast quickly the number of bed-days based on a small number of variables would help reduce the burden on the healthcare system during a pandemic.

Convalescent plasma transfusion in severe or critically ill COVID 19 patients: a rapid systematic review

Currently, there is no availability of any proven specific treatment or prevention strategy to fight against COVID-19. Convalescent plasma (CP) therapy is expected to increase survival rates in COVID-19 as in the case of emerging viral infection (SARS-CoV and MERS-CoV). To collect all the studies relevant to CP therapy in critically ill or severe COVID-19 patients and summarize the findings. The systematic review was conducted according to the PRISMA consensus statement. A systematic search was performed in PubMed, Scopus, Web of Science, and Cochrane databases on April 25, 2020. A total of six studies (28 patients) relevant to CP therapy in severe or critical COVID-19 are considered for inclusion. Two authors extracted the data about study characteristics, demographics, symptoms, co-morbidities, clinical classification of COVID-19, drug therapies, oxygen therapy, laboratory results, chest CT, neutralizing antibody titer, SARS-CoV-2 RNA load, aal outcome. The review findings revealed that CP therapy increases lymphocyte count, reduced s serum inflammatory markers (CRP, IL-6, Procalcitonin) and liver enzyme levels (AST or ALT). There was a rise in serum neutralizing antibody titers in 10 of 14 patients after CP transfusion. In 4 of 14 patients, the titer levels remain unchanged after CP transfusion. All 28 cases (100%) achieved negative to the SARS-CoV-2 RNA after CP transfusion. The convalescent plasma transfusion can improve neutralizing antibody titers and reduces the viral load in severe/critical COVID-19 patients. The review recommends a well-controlled trial design is required to give a definite statement on the safety and efficacy of convalescent plasma therapy in severe/critical COVID-19.

A comprehensive review and meta-analysis of the relationships between interleukin-7 levels and COVID-19 severity

Introduction: As the major mechanism for coronavirus disease 2019, cytokine storm-mediated organ harm continues to dominate current understanding. Despite the first hyper-inflammatory phase, emerging data show that virus-induced poor host immunity may be the true cause of mortality in many individuals. Interleukin 7 (IL-7) is an interleukin that participates in the COVID-19 cytokine storm and regulates the immune system. Its role in COVID-19 cytokine storms is thought to be related to its ability to stimulate the formation and activation of immune cells such as T cells and B cells. This meta-analysis aims to determine the relationship, if any, between interleukin-7 and COVID-19 severity. Methods: This study was planned as a systematic review and meta-analysis and followed the PRISMA guidelines. Four main electronic databases (Web of Science, PubMed, Scopus, and the Cochrane Central Register of Controlled Trials) were searched from January 1st, 2020 to September 2nd, 2022, to find papers investigating the prognostic significance of interleukin-7 in COVID-19-hospitalized adults. Google Scholar was used in addition to the online database search. A random effects model was used to calculate mean differences and 95% confidence interval (CIs) as well as the I2 statistics for heterogeneity analysis. Results: Seven papers were chosen for meta-analysis findings synthesis. All six trials reported interleukin-7 levels among severe and non-severe COVID-19 patients. Pooled analysis showed that IL-7 levels in the severe group were 62.79±81.03 pg/mL, compared to 33.39±56.54 pg/mL for the non-severe group (SMD =-0.17;95%CI:-0.93 to 0.60;p=0.67). Discussion: Available evidence suggests that elevated levels of IL-7 were not associated with the disease severity of COVID-19. While IL-7 levels alone may not have a substantial impact on COVID-19 severity, the interaction between IL-7 and other cytokines, immune cells, and variables such as viral load and genetics should be investigated further. Take-home message: This meta-analysis found that there was no strong link between levels of interleukin-7 and the severity of COVID-19. However, further research is needed to explore the interaction between IL-7 and other factors such as cytokines, immune cells, viral load, and genetics in order to better understand the role of IL-7 in COVID-19 pathogenesis. © 2023 by the authors.

Persistent Work Limitations in Long COVID: A Cross-Sectional Analysis of Employed US Respondents to the 2022 National Health and Wellness Survey

Objectives: Many Americans experience continued symptoms after SARS-CoV-2 infection. In addition to people who leave the workforce after experiencing COVID, those who remain employed may experience loss of productivity from short-term absences (absenteeism) and reduced productivity while working (presenteeism). We examined reported losses of work productivity among adults who reported physician-identified Long COVID. Method(s): We conducted a retrospective, cross-sectional analysis of data from National Health and Wellness Survey (May-Aug 2022) respondents. We included employed adults who reported having experienced COVID in the past (no date specified), said their physician identified them as having Long COVID or COVID syndrome, and reported symptoms at the time of survey. Respondents were stratified by their magnitude of activity limitations reported on the Work Productivity and Activity Impairment questionnaire;we describe responses for the lowest (LT) and highest tertiles (HT). Work productivity (absenteeism, presenteeism, overall work limitations from either absenteeism or presenteeism), and mental health (anxiety via General Anxiety Disorder-7 questionnaire, depression via Patient Health Questionnaire-9), were compared across tertiles. Result(s): Among 1036 Long COVID respondents meeting inclusion criteria, presenteeism ranged from 24.2% of LT respondents (n=291) to 92.8% of HT respondents (n=304), and absenteeism ranged from 12.7% (LT respondents) to 47.3% (HT respondents). Almost all (99.7%) HT respondents reported their overall work productivity was reduced by 50% or more while 26.7% of LT respondents reported the same. The prevalence of moderate-to-severe depression (92.4% vs. 37.8%) and moderate-to-severe anxiety (84.2% vs. 26.1%) was higher among HT relative to LT (all p<.001). Conclusion(s): Adults with Long COVID exhibit substantial heterogeneity in activity limitations;however, work limitations were substantial in all groups. Our results suggest significant economic impacts of Long COVID through lower productivity among those who remain employed. Further work with a comparison group is important to understand Long COVID-related work impairments, limitations, and disability.Copyright © 2023

Association Between COVID-19 Pandemic and Serious Mental Illness: Systematic Review within Salutogenesis Model for Public Health Management

Background: The outbreak of the COVID-19 pandemic, the constant transformation of the SARS-COV-2 virus form, exposure to substantial psychosocial stress, environmental change, and isolation have led to the inference that the overall population's mental health could be affected, resulting in an increase in cases of psychosis. Objective(s): We initiated a systematic review to determine the impact of the SARS-COV-2 virus and its long-term effects-in both symptomatic and asymptomatic cases-on people with or without psychosis. We envisioned that this would give us an insight into effective clinical intervention methods for patients with psychosis during and after the pandemic. Method(s): We selected fifteen papers that met our inclusion criteria, i.e., those that considered participants with or without psychiatric illness and exposed to SARS-COV-2 infection, for this review and were retrieved via Google, Google Scholar, MEDLINE, PubMed, and PsychINFO Database. Key Gap: There is a dearth of research in understanding how COVID-19 affects people with or without a prior personal history of psychosis. Result(s): The systematic review summary provides insight into the state of knowledge. Insights from the systematic review have also been reviewed from the salutogenesis model's perspec-tive. There is moderate evidence of new-onset psychosis during the COVID-19 pandemic in which some antipsychotics treated the psychotic symptoms of patients while treating for COVID-19. Suggestions and recommendations are made for preventive and promotive public health strategies. Conclusion(s): The Salutogenesis model and Positive Psychology Interventions (PPI) provide another preventive and promotive public health management approach.Copyright © 2023 Bentham Science Publishers.

Clinical characteristics of nucleic acid negative neonates delivered by pregnant women infected with SARS-CoV-2 in Sanya, Hainan

Objective: To explore the clinical characteristics of nucleic acid negative newborns delivered by pregnant women infected with SARS-CoV-2 (Omicron variant BA. 5.1.3) in Sanya area, and to provide evidence for understanding its clinical characteristics. Methods: A retrospective analysis was performed on 14 neonates with negative nucleic acid delivered by pregnant women who tested positive for SARS-CoV-2 (Omicron variant BA.5.1.3) in Sanya Central Hospital (the Third People's Hospital of Hainan Province) from June 2022 to September 2022 (observation group, n=14). The corresponding nucleic acid-negative newborns delivered by pregnant women detected negative with SARS-CoV-2 (Omicronon variant strain BA.5.1.3) were set as the control group (n=56), and the general data and clinical characteristics of neonates in the two groups were compared. Results: There was no significant difference between the observation group and the control group in pregnancy diabetes, pregnancy induced hypertension, gestational pre-eclampsia, fetal intrauterine distress, premature rupture of membranes (P > 0.05);there was no significant difference between the observation group and the control group in terms of sex, gestational age, birth weight, age, mode of delivery, birth Apgar score, heart screening, pulmonary disease, glucose 6-phosphate dehydrogenase (G6PD) deficiency, thalassemia, breast milk jaundice, hemolytic jaundice (P > 0.05). The bilirubin level, blue light irradiation cases and the duration of blue light irradiation of the newborns in the observation group at 7 days after birth were higher than those in the control group (P < 0.05);the ratio of blood oxygen saturation 90% in the observation group was lower than that in the control group (21.43% vs 89.29%, P < 0.05), and the ratio of blood oxygen saturation occasionally<90% was higher than that in the control group (57.14% vs 10.71%, P < 0.05). The ratio of blood oxygen saturation<90% had no significant difference compared with that in the control group (7.14% vs 0, P > 0.05), and the ratio of blood oxygen saturation reduced to the required oxygen uptake was higher than that in the control group (14.29% vs 0, P < 0.05). Conclusions: The jaundice manifestation of the nucleic acid-negative newborns delivered by pregnant women infected with SARS-CoV-2 (Omicronon variant strain BA.5.1.3) in Sanya area is relatively obvious, with blood oxygen saturation easily lower than 90% and even requiring oxygen inhalation in severe cases.

"Actionable" host genetic markers for repurposing "add-on therapy" in COVID-19

Background/Objectives: COVID-19 still represents a lifethreatening disease in individuals with a specific genetic background. We successfully applied a new Machine Learning method on WES data to extract a set of coding variants relevant for COVID- 19 severity. We aim to identify personalized add-on therapy. Method(s): A subset of identified variants, "actionable" by repurposed drugs, were functionally tested by in vitro and in vivo experiments. Result(s): Males with either rare loss of function variants in the TLR7 gene or L412F polymorphism in the TLR3 gene benefit from IFN-gamma, which is specifically defective in activated PBMCs, restoring innate immunity. Females heterozygous for rare variants in the ADAMTS13 gene and males with D603N homozygous polymorphism in the SELP gene benefit from Caplacizumab, which reduces vWF aggregation and thrombus formation. Males with either the low-frequency gain of function variant T201M in CYP19A1 gene or with poly-Q repeats >=23 in the AR gene benefit from Letrozole, an aromatase inhibitor, which restores normal testosterone levels, reducing inflammation and which rescues male golden hamsters from severe COVID-19. Conclusion(s): By adding these commonly used drugs to standard of care of selected patients, the rate of intubation is expected to decrease consistently, especially in patients with high penetrance rare genetic markers, mitigating the effect of the pandemic with a significant impact on the healthcare system.

YOLOv7 for Face Mask Identification Based on Deep Learning

The World Health Organization (WHO) has publicized a global public health emergency due to the COVID-19 coronavirus pandemic. Wearing a mask in public can provide protection against the spread of disease. Tremendous progress has been made in object detection in recent times, thanks in large part to deep learning models, which have shown encouraging results when it comes to recognizing objects in images. Recent technological developments have made this progress possible. Wearing a mask in public is one way to prevent the transmission of COVID-19 from others. Our study employs You Only Look Once (YOLO) v7 to determine whether a subject is wearing a mask, and then divides them into three groups depending on the degree to which they are wearing a mask correctly (none, bad, and good). In this study, we merged two datasets, the Face Mask Dataset (FMD) and the Medical Mask Dataset (MMD), to conduct our experiment. These models' evaluations and ratings include crucial criteria. According to our data, YOLOv7 achieves the highest mAP (98.5%) in the "Good"class. © 2023 IEEE.

Hematopoietic Stem/Progenitor Cells and Engineering: HEMATOPOIETIC STEM/PROGENITOR CELLS (HPC-A) CRYOPRESERVATION PROCESS VALIDATION USING CRYOSTOR CS10 FREEZE MEDIA

Background & Aim: During the COVID-19 pandemic, we performed HPC-A cryopreservation process validation using the CryoStor CS10 freeze media to replace the current 10% DMSO cryoprotectant (Control), which encountered severe backorder. Methods, Results & Conclusion(s): This process validation included phase I, phase II, and follow-up studies. Ten HPC-A collection cell product samples were cryopreserved in the phase I study using CS10 and Control (1:1) post-plasma depletion. Post-thaw viability tests using the 7-AAD method were performed on the cryopreserved samples for parallel comparison. In phase II, each of three patient HPC-A cell products was split evenly into CS10 and Control cryopreservation. The CS10 cryopreserved HPC-A cell products only were used for infusion. The recipients' engraftment outcomes of white blood cells (WBC), granulocytes (ANC), and platelets (Plts) were monitored. Post-thaw viability test was performed on the quality control samples from both groups. In the follow-up study, engraftment outcomes of WBC, ANC, and Plts were evaluated from ten recipients who received the CS10 cryopreserved HPC-A. In the phase I study, the post-thaw viability of the CS10 group was significantly higher than the Control group (p=0.002). All post-thaw viability results were above 60%, the current lab release criteria. In the phase II study, all cryopreserved cell products met cell product release criteria (> 60%). All engraftment results were within our center-established ranges except for the Pt b's platelet engraftment. Three recipients had not had any cell product infusion-related adverse events post infusion. Both CD34 and CD45 post-thaw viability results in the CS10 group were remarkably higher than the Control group, except for the patient c's CD34 viability. In the follow-up study, the total infused cell product volume ranged from 60 ml to 118 ml, and the WBC concentration in the cryopreserved cell products ranged from 134 to 440 (x10

Inflammatory biomarkers: Breast cancer survival and possible role in COVID-19 associated comorbidity

It is known that inflammatory cytokines exacerbate the persistence and severity of various disease states. Breast cancer is the most frequently detected cancer among women worldwide and our recent studies suggest that the inflammatory state of breast (BrCa) cancer, a byproduct of elevated cytokine expression, induces epigenetic modifications leading to increased recurrence. Ongoing NCI clinical trial data (ClinicalTrials.gov, CCC19, NCT04354701) indicates that among patients with cancer and COVID-19, the mortality is high, and the most prevalent malignancies are of breast [21%] and prostate [16%] origin. Due to the risk of cytokine storm during SARS-CoV-2 infection, it is crucial to identify potential mechanisms of hyperinflammation in BrCa patients. In this study, we have evaluated the level of copy number alteration (CNA) of different inflammatory cytokines including IL-8, IL-1b, IL6, IL-8, GM-CSF, TNF-alpha and many others using cBioportal platform which includes over sixty-nine thousand tumor samples (n>69,000 from 213 different studies) from over 33 different cancers. We found that IL-8 has the highest level of amplification in different breast cancers subtypes. Besides, we also analyzed serum samples from BrCa patients, both recurrent and non-recurrent, by different proteomics methods to identify serum cytokines involved in prognosis and recurrence. Comparative data analysis between non-recurrent BrCa against recurrent BrCa patients identified several proteins with very high significance, mostly proteins associated with epigenetic pathways including HDAC9 (P = 0.0035), HDAC5 (P = 0.013), and HDAC7 (P = 0.020). Besides, we identified differential expression of several pro-inflammatory cytokines and immune regulators (IL-8, IL-4, IL-18, IL-12p70) that were present only in recurrent BrCa patient serum. Our data indicate that inflammatory processes contribute to epigenetic modifications that ultimately play a critical role in breast cancer recurrence. In terms of COVID-19 associated co-morbidity, the already dysregulated inflammatory state of BrCa patients may increase their susceptibility to cytokine-storm, leading to increased severity of COVID-related complications and increased mortality rate. Specifically, we hypothesize that the identified elevated level of IL-8 in BrCa patients may lead to a higher basal level of inflammation and contribute to the risk of attaining cytokine-storm during SARS-CoV-2 infection, making it a valuable target for future studies.

The Views of Middle School Students on Distance and Face-to-Face Education on Mathematics Education during the COVID-19 Pandemic

The spread of the COVID-19 all over the world have negatively affected many areas, leading to a number changes throughout the world. Being one of these areas, education had to undergone some changes and shifted to distance education during the COVID-19 pandemic. However, distance education has also brought some discussions and problems. This study was carried out to investigate the thoughts of middle school students on distance education and face-to-face education. Based on quantitative research design, this study adopted a phenomenological design Data were collected from a participant group consisting of 240 secondary school students (60 5th grade, 60 6th grade, 60 7th grade and 60 8th grade) through a scale prepared by the researchers. The data were analyzed using SPSS package program with descriptive statistics such as frequency and percentage. As a result of the study It was found that middle school students' views on distance education and face-to-face education differed significantly with regard to parents' education level, gender, grade level and average monthly family income.

Mental health status of military healthcare workers in shelter hospitals in Shanghai during the epidemic caused by severe acute respiratory syndrome coronavirus 2 omicron variant and its influencing factors.

Objective To investigate the mental health status of military healthcare workers in shelter hospitals in Shanghai during the epidemic caused by severe acute respiratory syndrome coronavirus 2 omicron variant and its influencing factors. Methods A total of 540 military healthcare workers in shelter hospitals in Shanghai were investigated with patient health questionnaire-9 (PHQ-9), generalized anxiety disorder-7 (GAD-7) and Athens insomnia scale (AIS) to explore their mental health status, and logistic regression was used to analyze the influencing factors. Results A total of 536 valid questionnaires were collected, with an effective rate of 99.3% (536/540). The incidence of depression, anxiety and insomnia among military healthcare workers in shelter hospitals in Shanghai was 45.5% (244/536), 26.1% (140/536) and 59.5% (319/536), respectively. Logistic regression analysis showed that whether people resided in Shanghai, the proportion of negative information in daily browsing information and diet status in shelter hospitals were the influencing factors of depression, anxiety and insomnia (all P<0.05);age and confidence in the future of Shanghai were the influencing factors of depression and insomnia (all P<0.05);and the time spent daily on epidemic-related information was an influencing factor of insomnia (P=0.021). Conclusion The incidence of depressive, anxiety and insomnia among military healthcare workers in shelter hospitals in Shanghai is high during the epidemic caused by severe acute respiratory syndrome coronavirus 2 omicron variant. Psychological consequences of the epidemic should be monitored regularly and continuously to promote the mental health of military healthcare workers.Copyright © 2022, Second Military Medical University Press. All rights reserved.

Clinical characteristics and host immunity responses of SARS-CoV-2 Omicron variant BA.2 with deletion of ORF7a, ORF7b and ORF8.

BACKGROUND: The pathogenicity and virulence of the Omicron strain have weakened significantly pathogenesis of Omicron variants. Accumulating data indicated accessory proteins play crucial roles in host immune evasion and virus pathogenesis of SARS-CoV-2. Therefore, the impact of simultaneous deletion of accessory protein ORF7a, ORF7b and ORF8 on the clinical characteristics and specific immunity in Omicron breakthrough infected patients (BIPs) need to be verified. METHODS: Herein, plasma cytokines were identified using a commercial Multi-cytokine detection kit. Enzyme-linked immunosorbent assay and pseudovirus neutralization assays were utilized to determine the titers of SARS-CoV-2 specific binding antibodies and neutralizing antibodies, respectively. In addition, an enzyme-linked immunospot assay was used to quantify SARS-CoV-2 specific T cells and memory B cells. RESULTS: A local COVID-19 outbreak was caused by the Omicron BA.2 variant, which featured a deletion of 871 base pairs (∆871 BA.2), resulting in the removal of ORF7a, ORF7b, and ORF8. We found that hospitalized patients with ∆871 BA.2 had significantly shorter hospital stays than those with wild-type (WT) BA.2. Plasma cytokine levels in both ∆871 BA.2 and WT BA.2 patients were within the normal range of reference, and there was no notable difference in the titers of SARS-CoV-2 ancestor or Omicron-specific binding IgG antibodies, neutralizing antibody titers, effector T cells, and memory B cells frequencies between ∆871 BA.2 and WT BA.2 infected adult patients. However, antibody titers in ∆871 BA.2 infected adolescents were higher than in adults. CONCLUSIONS: The simultaneous deletion of ORF7a, ORF7b, and ORF8 facilitates the rapid clearance of the BA.2 variant, without impacting cytokine levels or affecting SARS-CoV-2 specific humoral and cellular immunity in Omicron-infected individuals.