Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a common cause of hospital admissions. Coronavirus disease 2019 (COVID-19) has large impact on patients with pulmonary diseases. The purpose of the study is to evaluate the impact of COVID-19 on patients with AECOPD.
UNASSIGNED: Retrospective study with two cohorts, the first period included patients with AECOPD before COVID-19 pandemic; the second period included patients with AECOPD since the beginning of COVID-19 pandemic. The length of stay (LOS), number of patients requiring mechanical ventilation, and allcause mortality were calculated.
UNASSIGNED: There was a total of 55 (44.72%) patients in the pre-COVID period compared to 68 (55.28%) patients in the COVID period. In the pre-COVID period: 14 (19.44%) had hypertension, 26(36.11%) had diabetes, 27(37.50%) had ischemic heart disease, 3(4.17%) had myocardial infarction; in the COVID period: 20 (29.41%) had hypertension, 24(35.29%) had diabetes, 27(39.71%) had ischemic heart disease, 1(1.47) had myocardial infarction. The LOS was shorter in pre-COVID period compared to COVID period, 6.51(SD 5.02) days vs 8.91(SD7.88) days with P-value of 0.042 respectively. The total number of patients needing mechanical ventilation in pre-COVID period was similar to the COVID period with P-value of 0.555. All-cause mortality number was 2 (3.64%) in the pre-COVID period compared to 6 (8.82%) in COVID period with P-value of 0.217.
UNASSIGNED: Study results revealed significant difference in length of stay for patients with AECOPD, patient in COVID period had increased LOS compared to pre-COVID period. There was no significant difference in the other parameters.

UNASSIGNED: Inflammatory bowel disease (IBD) patients use a wide variety of immunosuppressive drugs, including biologics, but their effect on SARS-CoV-2 vaccine antibody levels remains a mystery.
UNASSIGNED: We analysed whether the drugs used in the treatment of IBD patients could affect the concentration of SARS-CoV-2 antibodies.
UNASSIGNED: This is a prospective, single-centre evaluation of the persistence of SARS-CoV-2 antibodies after vaccination at various time points: every 2 months throughout the 6th month after the first dose.
UNASSIGNED: We included a total of 346 vaccinated IBD patients in the study. A negative correlation between antibody level and time from full vaccination was confirmed for the following types of therapy: infliximab (rho = -0.32, p < 0.001), adalimumab (rho = -0.35, p = 0.025), and vedolizumab (rho = -0.50, p < 0.001). In the case of other, long-term drug administration, a negative correlation between antibody level and time from full vaccination was confirmed for mesalazine (rho = -0.35, p < 0.001), budesonide (rho = -0.58, p = 0.004), systemic glucocorticoids (rho = -0.58, p < 0.001), and azathioprine (rho = -0.44, p < 0.001).
UNASSIGNED: Due to the immunosuppressive and biological treatment, IBD patients are exposed to a shorter persistence of SARS-CoV-2 antibodies and require booster doses. The role of gastroenterologists in educating patients about the need to continue SARS-CoV-2 vaccination remains crucial.

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.

(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.

BACKGROUND: Following the short-term outbreak of coronavirus disease 2019 (COVID-19) in December 2022 in China, clinical data on kidney transplant recipients (KTRs) with COVID-19 are lacking. METHODS: We conducted a single-center retrospective study to describe the clinical features, complications, and mortality rates of hospitalized KTRs infected with COVID-19 between Dec. 16, 2022 and Jan. 31, 2023. The patients were followed up until Mar. 31, 2023. RESULTS: A total of 324 KTRs with COVID-19 were included. The median age was 49 years. The median time between the onset of symptoms and admission was 13 d. Molnupiravir, azvudine, and nirmatrelvir/ritonavir were administered to 67 (20.7%), 11 (3.4%), and 148 (45.7%) patients, respectively. Twenty-nine (9.0%) patients were treated with more than one antiviral agent. Forty-eight (14.8%) patients were treated with tocilizumab and 53 (16.4%) patients received baricitinib therapy. The acute kidney injury (AKI) occurred in 81 (25.0%) patients and 39 (12.0%) patients were admitted to intensive care units. Fungal infections were observed in 55 (17.0%) patients. Fifty (15.4%) patients lost their graft. The 28-d mortality rate of patients was 9.0% and 42 (13.0%) patients died by the end of follow-up. Multivariate Cox regression analysis identified that cerebrovascular disease, AKI incidence, interleukin (IL)‍-6 level of >6.8 pg/mL, daily dose of corticosteroids of >50 mg, and fungal infection were all associated with an increased risk of death for hospitalized patients. CONCLUSIONS: Our findings demonstrate that hospitalized KTRs with COVID-19 are at high risk of mortality. The administration of immunomodulators or the late application of antiviral drugs does not improve patient survival, while higher doses of corticosteroids may increase the death risk.
2022年12月2019冠状病毒病（COVID-19）在中国出现短期的暴发流行，大量肾移植受者在感染COVID-19后需住院治疗。本研究回顾分析了在2022年12月16日至2023年1月31日期间感染COVID-19并在浙江大学医学院附属第一医院住院治疗的肾移植受者的临床特征和预后，随访截至2023年3月31日。本研究共纳入324名患者，其中位年龄为49岁，从出现症状到入院的中位时间为13天。分别有67例（20.7%）、11例（3.4%）和148例（45.7%）患者接受了莫那匹韦、阿兹夫定和奈玛特韦/利托那韦治疗，29例（9.0%）患者接受了多种抗病毒药物治疗，48例（14.8%）接受了托珠单抗治疗，53例（16.4%）接受了巴瑞替尼治疗。其中，81例（25.0%）发生急性肾损伤（AKI），39例（12.0%）转入ICU治疗，55例（17.0%）发生真菌感染，50例（15.4%）最终发生移植肾失功。患者的28天死亡率为9.0%，截至随访终点时共有42例（13.0%）患者死亡。多因素Cox回归分析显示合并脑血管疾病、AKI出现、白介素-6（IL-6）水平大于6.8 pg/mL、每日平均糖皮质激素剂量大于50 mg以及真菌感染等因素与住院患者死亡风险增加相关。结果表明，感染COVID-19后需住院治疗的肾移植受者死亡率很高。此外，服用免疫调节剂或过迟应用抗病毒药物，并不能提高患者生存率，而且大剂量的糖皮质激素使用则会增加死亡风险。.

UNASSIGNED: Coronavirus disease 2019 (COVID-19), a disease that affected tens of millions of people, upended the lives of countless individuals around the globe. The chloroquine (CQ) and its analogue hydroxychloroquine (HCQ) were the most frequently cited as potential treatments and preventatives against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The primary aim of this investigation was to scrutinize the effectiveness and safety of HCQ for COVID-19 prevention and to present powerful evidence and reference for clinical practice.
UNASSIGNED: PubMed, Ovid and the Cochrane COVID-19 Register of Controlled Trials (CENTRAL) were systematically searched from inception to January 31, 2022. Randomized controlled trials (RCTs) trials that included participants who were SARS-CoV-2 negative at the time of registration were enrolled in this meta-analysis. The intervention group took HCQ or CQ orally. The control group was not blinded by quinine or placebo. Pooled relative risk (RR) of SARS-CoV-2 infection, mortality, hospitalization, adverse events, and compliance were calculated. The software tools utilized for statistical analyses were Stata 14 and Review Manager 5.3.
UNASSIGNED: A total of 9 studies including 7,825 participants were enrolled. Bias of individual studies were assessed as low risk. The pooled RR for SARS-CoV-2 infection was 0.75 [95% confidence interval (CI): 0.68-0.83] (z=-4.01, P<0.0001; I2=11%). The pooled RR for hospitalization was 0.72 (95% CI: 0.35-1.50) (z=0.87, P=0.39; I2=0.0%). The pooled RR for mortality and adverse events were 3.26 (95% CI: 0.13-79.74) (z=0.72, P=0.47; I2=0.0%) and 1.90 (95% CI: 1.20-3.02) (z=2.73, P=0.0063; I2=94%).
UNASSIGNED: Results of this meta-analysis indicated significant impact of HCQ on SARS-CoV-2 infection with higher risk of adverse events. These findings must be considered with caution, and further research is necessary to delineate the specific circumstances where HCQ may be effective for COVID-19 prevention.

UNASSIGNED: The coronavirus disease 2019 (COVID-19) is a condition caused by the novel severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). Although several papers have reported the presence bradycardia in patients with COVID-19, the pathophysiology behind this remains unclear. Therefore, we investigated the presence of bradycardia in patients with COVID-19.
UNASSIGNED: We conducted a retrospective cohort study in a total of 153 patients with COVID-19 and 90 patients with influenza who were hospitalized in our hospital from January 1, 2020 to December 31, 2021 and from January 1, 2014 to December 31, 2021, respectively. Data were collected from patient medical records, which included sex, age, duration of hospitalization, pneumonia complications, supplemental oxygen therapy, antiviral treatment, past history, and vital signs.
UNASSIGNED: After adjustment, the incidence of bradycardia and steroid use in patients with COVID-19 were significantly higher than those in patients with influenza (P=0.007 and P<0.001, respectively). We then compared the detailed characteristics of patients with COVID-19 to evaluate risk factors for bradycardia. Multivariate logistic regression analysis revealed that steroid use was significantly related to bradycardia [P=0.031; odds ratio (OR): 3.67; 95% confidence interval (CI): 1.12-11.96]. Overall, results showed a higher incidence of bradycardia in patients with COVID-19 who received steroid treatment.
UNASSIGNED: Our results showed that steroid treatment in patients with COVID-19 may be associated with the incidence of bradycardia.

Epidemiological studies link COVID-19 to increased cardiac arrest (CA) risk, but causality remains unclear due to potential confounding factors in observational studies . We conducted a Mendelian randomization (MR) analysis using genome-wide association study (GWAS) data, employing COVID-19-associated single nucleotide polymorphisms (SNPs) with significance values smaller than 5 × 10⁻⁸. We calculated inverse-variance weighted (IVW) MR estimates and performed sensitivity analyses using MR methods robust to horizontal pleiotropy. Additionally, a reverse MR analysis was conducted using CA-associated SNPs with significance values smaller than 1 × 10⁻⁵. Results indicated that infected COVID-19 (OR = 1.12, 95% CI = 0.47-2.67, p = 0.79), hospitalized COVID-19 (OR = 1.02, 95% CI = 0.70-1.49, p = 0.920), and severe respiratory COVID-19 (OR = 0.99, 95% CI = 0.81-1.21, p = 0.945) did not causally influence CA risk. Reverse MR analysis also did not support a causal effect of CA on COVID-19. Thus, associations in observational studies may stem from shared biological factors or environmental confounding.

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.

Background The associations and risk factors for venous thromboembolism (VTE) among hospitalized COVID-19 patients remain ambiguous in the literature, with some conflicting findings, especially in Saudi Arabia. In this study, we aim to elaborate on these data by examining regional patient populations and exploring the incidence, lab findings, and outcomes of VTE among hospitalized COVID-19 patients known to have diabetes mellitus (DM). Methodology This cross-sectional study was conducted at King Abdulaziz Medical City in Riyadh. The BestCare system was used to collect patients\' data between September 2020 and February 2022. JMP15 was used for data analysis. Frequencies and percentages were used for categorical data, and median and interquartile ranges were used for quantitative data. The chi-square and Kruskal-Wallis rank-sum tests were used to assess the difference between categorical and quantitative variables, respectively. Nominal logistical regression was used to assess diabetes as a risk factor for developing VTE among COVID-19 patients. Results Data from 153 admitted patients were collected after they satisfied the inclusion criteria. Of these patients, 39 (25.49%) developed VTE. The demographic data included age group, gender, and DM status presented as frequencies and percentages. Through bivariate analysis, patients with longer hospital stays had at least one episode of VTE (p = 0.0072). Using nominal logistic regression analysis, diabetes as a risk factor (odds ratio = 4.11, confidence interval = 0.955-5.05, p = 0.0287) was significantly associated with the development of VTE in COVID-19 patients. Conclusions Based on our study, diabetes proved significant when evaluating the possible factors regarding VTE development in COVID-19 patients. In addition, the length of stay also played a critical role in the severity of VTE in COVID-19 patients. Similar studies should be conducted on a national scale in Saudi Arabia to accomplish two goals: first, to gain further understanding of the impact of the variables investigated in our population, and second, to publish data that are more generalizable to the larger population of Saudi Arabia.