The administration of COVID-19 vaccines is the primary strategy used to prevent further infections by COVID-19, especially in people living with HIV (PLWH), who are at increased risk for severe symptoms and mortality. However, the vaccine hesitancy, safety, and immunogenicity of COVID-19 vaccines among PLWH have not been fully characterized. We estimated vaccine hesitancy and status of COVID-19 vaccination in Chinese PLWH, explored the safety and impact on antiviral therapy (ART) efficacy and compared the immunogenicity of an inactivated vaccine between PLWH and healthy controls (HC). In total, 27.5% (104/378) of PLWH hesitated to take the vaccine. The barriers included concerns about safety and efficacy, and physician counselling might help patients overcome this vaccine hesitancy. A COVID-19 vaccination did not cause severe side effects and had no negative impact on CD4+ T cell counts and HIV RNA viral load. Comparable spike receptor binding domain IgG titer were elicited in PLWH and HC after a second dose of the CoronaVac vaccine, but antibody responses were lower in poor immunological responders (CD4+ T cell counts < 350 cells/µL) compared with immunological responders (CD4+ T cell counts ≥ 350 cells/µL). These data showed that PLWH have comparable safety and immune response following inactivated COVID-19 vaccination compared with HC, but the poor immunological response in PLWH is associated with impaired humoral response.
Purpose: Vaccination reduces the incidence of severe COVID-19 and death and effectively limits viral spread. Concerns have been raised about COVID-19 vaccine responses in the large population of HIV-infected patients. This study aims to explore the safety and immunogenicity of the inactivated COVID-19 vaccine in people living with HIV (PLWH). Patients and Methods: All participants in this study already had their second dose of an inactivated COVID-19 vaccine at least 14 days earlier, without a history of SARS-CoV-2 infection. The primary safety outcomes were the incidence of adverse reactions and changes in CD4+ T-cell counts. SARS-CoV-2 IgG and neutralizing antibody responses to the D614G variant and delta variant were measured for immune response assessment. Results: Forty-seven HIV-infected patients and 18 healthy donors (HDs) were enrolled in this study. Adverse reactions were mild or self-limiting and were reported in 19.1% of HIV-infected patients. Most PLWH developed antibody responses against the inactivated COVID-19 vaccine. The longitudinal analysis of antibody responses in PLWH (median interval between detection and complete vaccination, 59 days) showed that antibodies were maintained for at least three months, though their titers were reduced. However, the antibody-positive rates in PLWH were significantly lower than those in HDs. Additionally, compared to HDs (Geomean titers (GMT) of 165 for D614G and GMT of 72 for delta), the neutralizing antibody titers against the two variants in PLWH (GMT of 43 for D614G and GMT 13 for delta) were decreased significantly (p = 0.018 and p < 0.001, respectively). HIV-infected patients with CD4+T-cell counts ≤ 350 cells/μL appeared to exhibit a poor antibody response to inactivated vaccination. Conclusion: Inactivated COVID-19 vaccines appear to be efficacious in PLWH. However, antibody responses in HIV-infected patients are inferior to those in healthy individuals, especially PLWH with lower CD4+T-cell counts.
3 May 2023 in Frontiers in Cellular and Infection Microbiology
Objective: Ursodeoxycholic acid (UDCA) may reduce susceptibility to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection by downregulating angiotensin-converting enzyme 2 (ACE2), based on recent experimental investigation. This study aimed to determine the potential protective effect of UDCA against SARS-CoV-2 infection in patients with chronic liver disease.Methods: Patients with chronic liver disease receiving UDCA (taking UDCA ≥1 month) at Beijing Ditan Hospital between January 2022 and December 2022 were consecutively enrolled. These patients were matched in a 1:1 ratio to those with liver disease not receiving UDCA during the same period by using a propensity score matching analysis with nearest neighbor matching algorithm. We conducted a phone survey of coronavirus disease 2019 (COVID-19) infection during the early phase of the pandemic liberation (from 15 December 2022 to 15 January 2023). The risk of COVID-19 was compared in two matched cohorts of 225 UDCA users and 225 non-UDCA users based on patient self-report.Results: In the adjusted analysis, the control group was superior to the UDCA group in COVID-19 vaccination rates and liver function indicators, including γ-glutamyl transpeptidase and alkaline phosphatase (p < 0.05). UDCA was associated with a lower incidence of SARS-CoV-2 infection (UDCA 85.3% vs. control 94.2%, p = 0.002), more mild cases (80.0% vs. 72.0%, p = 0.047), and shorter median time from infection to recovery (5 vs. 7 days, p < 0.001). Logistic regression analysis showed that UDCA was a significant protective factor against COVID-19 infection (OR: 0.32, 95%CI: 0.16–0.64, p = 0.001). Furthermore, diabetes mellitus (OR: 2.48, 95%CI: 1.11–5.54, p = 0.027) and moderate/severe infection (OR: 8.94, 95%CI: 1.07–74.61, p = 0.043) were more likely to prolong the time from infection to recovery.Conclusion: UDCA therapy may be beneficial in reducing COVID-19 infection risk, alleviating symptoms, and shortening the recovery time in patients with chronic liver disease. However, it should be emphasized that the conclusions were based on patient self-report rather than classical COVID-19 detection by experimental investigations. Further large clinical and experimental studies are needed to validate these findings.
Background: Non-alcoholic fatty liver disease (NAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD) is closely associated with chronic inflammation and lipid metabolism disorders. The neutrophil-to-high-density lipoprotein cholesterol ratio (NHR) is an integrative marker reflecting inflammatory responses and lipid metabolism disorders and is associated with various diseases. This cross-sectional study aimed to determine the association between NHR and NAFLD, MASLD, and liver fibrosis.Methods: Data for this study were obtained from the 2017–2020 National Health and Nutrition Examination Survey (NHANES), we employed weighted multiple regression and restricted cubic spline (RCS) analysis to assess the relationship between NHR and NAFLD, MASLD, and liver fibrosis. Additionally, we performed stratified analyses based on gender, age, body mass index, diabetes, hypertension, smoking status, and history of cardiovascular disease to evaluate the consistency of these associations across different subgroups.Results: A total of 6,526 participants were included in the study. 2,839 (weighted 44.1%) participants were diagnosed with NAFLD and 2,813 (weighted 43.7%) participants were diagnosed with MASLD. After adjusting for confounders, NHR was positively associated with the risk of NAFLD/MASLD, and the correlation was particularly significant in the subgroups of females, those without hypertension, and those without diabetes (p < 0.05). By the NHR quartile, the risk of NAFLD/MASLD increased progressively with higher NHR levels (P for trend <0.001). In addition, RCS analysis showed a nonlinear association between NHR and NAFLD/MASLD and liver fibrosis (P-non-linear <0.05).Conclusion: NHR may serve as a potential marker for NAFLD/MASLD and liver fibrosis, and lowering NHR levels could help reduce the incidence of these conditions.
Background: Cryptococcal meningitis (CM) associated immune reconstitution inflammatory syndrome (CM-IRIS) is the second most common complication in HIV-infected individuals with cryptococcal meningitis, with a reported mortality rate ranging from 8 to 30%. Given the devastating consequences of CM-IRIS related intracranial neuroinflammation and its challenging in diagnosis, we conducted a study to explore the risk factors and the occurrence of paradoxical CM-IRIS in HIV-infected patients, which is of great value for prevention and clinical management. Methods: We conducted a retrospective cohort study to identify the indicators associated with paradoxical CM-IRIS among 86 HIV-infected patients with CM using univariate and multivariate cox analysis. A nomogram was constructed using selected variables to evaluate the occurrence of paradoxical CM-IRIS at 6 months and 12 months after ART initiation. The discrimination and calibration of the nomogram were assessed by concordance index (C-index) and calibration plots. Decision curves analysis (DCA) were used to evaluate clinical effectiveness of the nomogram. Subsequently, to help clinicians recognize patients at high risk faster, patients were divided into high-risk and low-risk groups according to the best cutoff point identified by X-tile. Results: Of 86 AIDS patients with CM, 22.1% experienced paradoxical CM-IRIS at a median of 32 days after antiretroviral therapy (ART) initiation. The occurrence of paradoxical CM-IRIS was associated with age, ART initiation within 4 weeks of antifungal treatment, a four-fold increase in CD4 T cell counts, C-reactive protein levels, and hemoglobin levels independently. These five variables were further used to construct a predictive nomogram. The C-index (0.876) showed the favorable discriminative ability of the nomogram. The calibration plot revealed a high consistency between the predicted and actual observations. DCA showed that the nomogram was clinically useful. Risk stratification based on the total score of the nomogram showed well-differentiated in the high-risk and low-risk groups. Clinicians should pay attention to patients with total points high than 273. Conclusions: We identified the predictive factors of paradoxical CM-IRIS and constructed a nomogram to evaluate the occurrence of paradoxical CM-IRIS in 6 months and 12 months. The nomogram represents satisfactory performance and might be applied clinically to the screening and management of high-risk patients.
Some patients with viral encephalitis in China seek treatment with Chinese patent medicine (CPM) to improve their symptoms, but few studies have focused on the impact of CPM on the prognosis of viral encephalitis (VE). The aim of this multicenter retrospective study was to assess the benefit of adjunctive CPM therapy on the outcome of children with VE in China. This study retrospectively included 834 children with viral encephalitis who were hospitalized at five medical institutions from 2018 to 2021. Univariate and multivariate logistic regression was used to assess the effect of CPM on sequelae in patients with VE. 1:1 propensity score matching was used to exclude the effect of confounding factors. Forest plots were used to observe the effect of CPM on the prognosis of VE in different subgroups. There were fewer patients with sequelae in the group of patients using CPM regardless of whether they were matched or not. The results of multivariate logistic regression analysis showed that the use of CPM was an independent protective factor for the development of sequelae in VE patients (OR = 0.063, 95 % CI: 0.011-0.350, p = 0.002). Subgroup analyses showed that CPM was a protective factor for the development of sequelae regardless of the presence or absence of coma and comorbidities. In addition, we evaluated other outcome indicators and found shorter duration of illness, fever and headache in children with EV in the CPM group. Adjunctive CPM therapy may significantly reduce sequelae in children with VE, as well as effectively alleviate patients' clinical symptoms. However, more prospective studies and clinical trials are needed to further evaluate its efficacy and safety.