Long-Term Outcomes of COVID-19 and Risk Factors for Prolonged or Persistent COVID-19 in Lymphoma Patients: A Multicenter, Retrospective Cohort Study.

BACKGROUND: Patients with hematologic malignancies exhibit persistent severe acute respiratory syndrome coronavirus 2 positivity over long periods after coronavirus disease 2019 (COVID-19) diagnosis. However, the frequency of, risk factors for, and prognosis of prolonged COVID-19 in immunocompromised patients remain unclear. Therefore, we investigated the long-term outcomes of COVID-19 in lymphoma patients and identified the associated factors and impact of prolonged COVID-19 on mortality. METHODS: A multicenter retrospective cohort study of 583 lymphoma patients was conducted in 3 tertiary hospitals in South Korea. Patients receiving lymphoma treatment who were quarantined after obtaining a diagnosis of COVID-19 by polymerase chain reaction (PCR) or antigen test from August 2021 to September 2022 were examined. RESULTS: Overall, 115 patients (19.7%) were diagnosed with COVID-19. Among 77 patients with clinical data, 24 had prolonged COVID-19. Patients in the prolonged COVID-19 group showed higher rates of receiving rituximab maintenance therapy following bendamustine and rituximab (BR) treatment for follicular lymphoma. This group did not show significant differences in clinical presentation within 30 days of COVID-19 diagnosis; however, it showed higher rates of re-admission due to COVID-19 pneumonia compared with the non-prolonged COVID-19 group. BR treatment followed by rituximab maintenance therapy is one of the risk factors for persistent PCR positivity, delayed or persistent pneumonia, and COVID-19 related admission after quarantine period. Prolonged COVID-19 was an independent risk factor for 1-year mortality. CONCLUSION: Prolonged COVID-19 was more frequent in lymphoma patients who received BR treatment followed by rituximab maintenance therapy and associated with unfavorable long-term outcomes and higher 1-year mortality.

Efficacy of CP-COV03 (a niclosamide-based inorganic nanohybrid product) against severe fever with thrombocytopenia syndrome virus in an in vitro model.

Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne infectious disease caused by the SFTS virus (SFTSV). CP-COV03 is a novel antiviral candidate that significantly enhanced the bioavailability of niclosamide through inorganic-based drug delivery technology. The active pharmaceutical ingredient of CP-COV03, niclosamide, has been previously shown to possess broad-spectrum antiviral activity against over 30 different viruses in the in vitro tests. The aim of this study is to confirm the antiviral activity of CP-COV03 against the SFTSV in an in vitro model. Vero cells and SFTS viral stock NCCP43270, a 2015 Gangwon Province isolate, were used to obtain the 50% tissue culture infective dose of the virus. Vero cells seeded in 96-well plates were infected with SFTSV for 1 h. SFTSV-infected cells were treated with CP-COV03 at various concentrations of 0.1-100 µM and incubated for 7 days. On the seventh day of the culture, the cytopathic effect (CPE) of SFTSV was checked by microscopy and the cell viability was checked by using Cell Counting Kit-8 assay. The CPE reduced as the CP-COV03 concentration increased. The 50% inhibitory concentration (IC50) range of CP-COV03 was below 0.125 µM, as determined from the viral titers of culture supernatants collected on the third day posttreatment of CP-COV03. The plaque reduction assay showed that the IC50 of CP-COV03 was 1.893 µM, as determined from the percentage reduction of plaque counts for each drug concentration on the second day posttreatment with CP-COV03. This study suggests that CP-COV03 could be used as a potential antiviral agent for SFTS.IMPORTANCEWe demonstrated a concentration-dependent response and identified low a IC50 of CP-COV03. This result is comparable to other antiviral drugs used against viruses like severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We believe that our study makes a significant contribution to the literature as our findings suggest that CP-COV03 may serve as a potential treatment for SFTS, highlighting its importance in the field of antiviral research.

Epidemiological and Clinical Characteristics of Women Living with HIV in Korea.

BACKGROUND: While Korea maintains a low prevalence of human immunodeficiency virus (HIV), the number of newly diagnosed cases has been steadily rising, reaching approximately 1,000 annually in recent years. The 2022 annual report from the Korea Disease Control and Prevention Agency revealed that women living with HIV (WLWH) constitute 6.4% of the total confirmed people living with the HIV population, totaling 1,219 individuals. Despite this, only a few studies have focused on WLWH in Korea. This study aims to analyze the epidemiological and clinical characteristics of WLWH in Korea. MATERIALS AND METHODS: We retrospectively collected data by reviewing the medical records of all WLWH who visited 10 urban referral hospitals across Korea between January 2005 and May 2023. RESULTS: A total of 443 WLWH were enrolled in this study. The predominant risk exposure was heterosexual contact, with 235 (53%) participants either married or cohabiting with a male partner at their initial clinic visit. Among the participants, 334 (77.7%) were Korean, 27 (6.1%) were Southeast Asian, and 19 (4.3%) were African. Antiretroviral therapy was initiated by 404 WLWH (91.2%). We observed 118 pregnancies in WLWH following their HIV diagnosis, resulting in 78 live births (66.1%), 18 induced abortions (15.2%), 10 pre-viable fetal losses (8.5%), and four stillbirths (3.4%). Over a cumulative follow-up duration of 3,202.1 years, the incidence rates of breast and cervical cancers were both 2.18 per 1,000 person-years. Additionally, the incidence rates of pelvic inflammatory disease, cervical intraepithelial neoplasm (above grade II), and osteoporosis were 4.67, 11.21, and 13.39 per 1,000 patient-years, respectively. CONCLUSION: This is the first multicenter study to investigate the clinical and epidemiological characteristics of WLWH in Korea. The incidence and prevalence of diseases in women, including breast cancer, cervical cancer, and chronic comorbidities, are high in WLWH in Korea; therefore, further research and efforts are needed to manage these diseases.

Antiretroviral Therapy during Long-term Surgical Care: 'Exploring Difficult Cases in HIV Clinics' of the Korean Society for AIDS Conference in 2023.

With advancements in antiretroviral therapy (ART), the average lifespan of people with human immunodeficiency virus (HIV) is increasing, as is the number of older adults with HIV. Accordingly, the number of patients with HIV who undergo surgery or require critical care for various reasons is increasing. Since the prognosis of people with HIV depends on the continuous and effective maintenance of ART, there is a need to consider effectively maintaining ART in people with HIV in these conditions. This case involved a 55-year-old patient with well-controlled HIV who received ART and presented to the emergency room with acute abdominal pain. He was diagnosed with extensive bowel infarction and panperitonitis and received critical care in the intensive care unit, including mechanical ventilation and continuous renal replacement therapy. The patient was administered enteral nutrition via a nasogastric tube. The patient subsequently underwent extensive small bowel resection and developed short bowel syndrome. The patient maintained ART during that period. A literature review related to the use of ART under these conditions is included in this study. This case was discussed at the [Exploring Difficult Cases in HIV Clinics] of the Korean Society for AIDS Conference held in 2023.

Effect of physical activity on risk reduction of infective endocarditis among patients with diabetes: a nationwide cohort study.

Patients with diabetes mellitus (DM) are at a higher risk of infectious diseases, and exercise is an important treatment modality for DM. Despite their susceptibility to infection in diabetic patients, the association between the amount of physical activity and the incidence of infective endocarditis (IE) is unclear. We attempted to demonstrate risk reduction by physical activity in diabetic patients with IE. From the National Health Insurance database, patients with DM were verified, and the incidence of IE was investigated. The level of physical activity was categorized into < 500, 500-999, 1,000-1,499, and ≥ 1,500 metabolic equivalent task (METs) minutes/week. Cox proportional hazard models were used to analyze the relationship between incident IE and physical activity. A total of 2,603,012 patients were included in this study. The incidence rate of IE was 10.06, 9.45, 7.78, and 8.84 in < 500, 500-999, 1,000-1,499, and ≥ 1,500 METs-minutes/week groups, respectively (100,000 person/year). A significant risk reduction of incident IE was observed in the 1,000-1499 and ≥ 1,500 METs-min/week groups compared to the < 500 METs-min/week group (Hazard ratio = 0.82, 95% confidence interval [0.690-0.976], HR = 0.831, 95% CI [0.704-0.981]). An analysis of a large national cohort database demonstrated that physical exercise reduced the risk of IE in patients with DM.

Influence of contrast medium on long-term renal function and outcomes in patients with septic acute kidney injury: A propensity-matched cohort study.

PURPOSE: To investigate the relationship between contrast medium administration and long-term mortality and renal function in patients with septic acute kidney injury (AKI). MATERIALS AND METHODS: We performed a retrospective, propensity-matched cohort study involving 1521 adult patients admitted with septic shock. Patients with septic AKI who underwent contrast or non-contrast CT scans were enrolled. The primary outcomes were the rates of 90-day mortality and dialysis within 90 days. The secondary outcomes included worsening of AKI, in-hospital mortality, and maintenance of dialysis after 90 days. RESULTS: During the study period, 609 patients with septic AKI were identified; 220 (36.1%) underwent contrast CT and 389 (63.9%) underwent non-contrast CT. After propensity score matching, 133 pairs were obtained. There were no significant differences between the contrast and non-contrast CT groups in 90-day mortality (54.9% vs. 58.6%, P = 0.579), dialysis within 90 days (6.8% vs. 8.3%, P = 0.655), worsening AKI (2.3% vs. 3.0%, P = 0.706), in-hospital mortality (10.6% vs. 14.4%, P = 0.369), or maintenance of dialysis after 90 days (0.0% vs. 0.8%, P > 0.99). CONCLUSIONS: The administration of intravenous contrast medium was not associated with long-term mortality, deterioration of renal function, or dialysis in patients with septic AKI.

Overcoming the age-dependent SARS-CoV-2 vaccine response through hybrid immunity: analysis of humoral and cellular immunity with mass cytometry profiling.

BACKGROUND: Age-dependent immune responses to coronavirus disease 2019 (COVID-19) vaccinations and breakthrough infections (BIs) in young and middle-aged individuals are unclear. METHODS: This nationwide multicenter prospective cohort study analyzed immune responses in participants of the ChAdOx1 (ChAd)-ChAd-mRNA vaccine group using cytometry by time-of-flight, anti-spike protein antibody (Sab) and anti-nucleocapsid antibody (Nab) titers, plaque reduction neutralization tests (PRNTs), and interferon-gamma (IFN-γ) release assays at various time points. RESULTS: We evaluated 347 participants with an average age of 38.9 ± 9.4 years (range: 21-63). There was a significant inverse correlation between age and Sab levels after the second dose (slope - 14.96, P = 0.032), and this was more pronounced after the third dose (slope - 208.9, P < 0.001). After BIs, older participants showed significantly higher Sab titers (slope 398.8, P = 0.001), reversing the age-related decline observed post-vaccination. This reversal was also observed in PRNTs against wild-type SARS-CoV-2 and the BA.1 and BA.5 variants. IFN-γ responses increased markedly after the third dose and Bis, but showed a weak positive correlation with age, without statistical significance. Immune cell profiling revealed an age-dependent decrease in the proportions of B-cell lineage cells. The proportions of naive CD4+ and CD8+ T cells were inversely correlated with age, whereas the proportions of mature T cell subsets with memory function, including memory CD4+ T, CD8+ TEM, CD8+ TEMRA, and TFH cells, increased with age. CONCLUSIONS: Age-dependent waning of the serologic response to COVID-19 vaccines occurred even in middle-aged individuals, but was reversed after BIs. IFN-γ responses were preserved, compensating for the decrease in naive T cell populations, with an increase in memory T cell populations.

Hepatitis B Reactivation and Vaccination Effectiveness after Solid Organ Transplantation: A Matched Case-Control Study.

Solid organ transplant (SOT) recipients are at significant risk of hepatitis B (HB) virus (HBV) reactivation (HBVr). Despite the clinical significance of HBVr after solid organ transplantation, data on the risk factors for HBVr and vaccine effectiveness in SOT recipients with resolved HBV infection are limited. This study evaluated the risk factors for HBVr and the seroconversion rates after HBV vaccination in SOT recipients. Patients who had undergone solid organ transplantation and those with a resolved HBV infection were identified. We matched patients who experienced post-transplantation HBVr with those who did not. We also explored the characteristics and seroconversion rates of HBV-vaccinated patients following transplantation. In total, 1299 SOT recipients were identified as having a resolved HBV infection at the time of transplantation. Thirty-nine patients experienced HBVr. Pre-transplant HB surface antibodies (anti-HBs) positivity and allograft rejection within 3 months after transplantation were independently associated with HBVr. Among the 17 HBV-vaccinated patients, 14 (82.4%) received three or fewer vaccine doses, and 13 (76.5%) had seroconversion with positive anti-HBs results. Pre-transplant anti-HBs(-) status and allograft rejection were risk factors for HBVr in SOT recipients with a resolved HBV infection, and HBV vaccination after transplantation resulted in a high rate of anti-HBs seroconversion. HBV vaccination after transplantation should be considered to reduce the HBVr risk.

The prevalence and moderating factors of sleep disturbances in people living with HIV: a systematic review and meta-analysis.

This systematic review and meta-analysis aimed to investigate the prevalence of self-reported sleep disturbances in people living with HIV considering the effects of age, depression, anxiety, CD4 cell counts, time since HIV diagnosis, study region, and the instruments used to measure sleep disturbances. We searched PubMed, PsycINFO, and EMBASE to include eligible articles. In this meta-analysis of 43 studies, the pooled prevalence of self-reported sleep disturbances was 52.29% (95% confidence interval 47.69-56.87). The subgroup analyses revealed that variations in the sleep measurements and study region significantly contributed to the observed heterogeneity. In the meta-regression analyses, higher proportions of participants with depression or anxiety and longer times since HIV diagnosis were significantly associated with a higher prevalence of self-reported sleep disturbances after adjusting for mean age. Our findings emphasise the substantial burden of sleep disturbances in people living with HIV and identified comorbid depression and anxiety and the time since HIV diagnosis as significant moderators. These results underscore the importance of considering these factors when designing tailored screening programmes for high-risk patients and implementing early interventions to prevent and mitigate sleep disturbances in people living with HIV.

Clinical characteristics and risk factors for right-sided infective endocarditis in Korea: a 12-year retrospective cohort study.

Right-sided infective endocarditis (RSIE) is less common than left-sided infective endocarditis (LSIE) and exhibits distinct epidemiological, clinical, and microbiological characteristics. Previous studies have focused primarily on RSIE in patients with intravenous drug use. We investigated the characteristics and risk factors for RSIE in an area where intravenous drug use is uncommon. A retrospective cohort study was conducted at a tertiary hospital in South Korea. Patients diagnosed with infective endocarditis between November 2005 and August 2017 were categorized into LSIE and RSIE groups. Of the 406 patients, 365 (89.9%) had LSIE and 41 (10.1%) had RSIE. The mortality rates were 31.7% in the RSIE group and 31.5% in the LSIE group (P = 0.860). Patients with RSIE had a higher prevalence of infection with Staphylococcus aureus (29.3% vs. 13.7%, P = 0.016), coagulase-negative staphylococci (17.1% vs. 6.0%, P = 0.022), and gram-negative bacilli other than HACEK (12.2% vs. 2.2%, P = 0.003). Younger age (adjusted odds ratio [aOR] 0.97, 95% confidence interval [CI] 0.95-0.99, P = 0.006), implanted cardiac devices (aOR 37.75, 95% CI 11.63-141.64, P ≤ 0.001), and central venous catheterization  (aOR 4.25, 95%  CI 1.14-15.55, P = 0.029) were independent risk factors for RSIE. Treatment strategies that consider the epidemiologic and microbiologic characteristics of RSIE are warranted.

Correction: Increasing Fusobacterium infections with Fusobacterium varium, an emerging pathogen.

[This corrects the article DOI: 10.1371/journal.pone.0266610.].

Persistent differences in the immunogenicity of the two COVID-19 primary vaccines series, modulated by booster mRNA vaccination and breakthrough infection.

INTRODUCTION: The long-term impact of initial immunogenicity induced by different primary COVID-19 vaccine series remains unclear. METHODS: A prospective cohort study was conducted at 10 tertiary hospitals in Korea from March 2021 to September 2022. Immunogenicity assessments included anti-spike protein antibody (Sab), SARS-CoV-2-specific interferon-gamma releasing assay (IGRA), and multiplex cytokine assays for spike protein-stimulated plasma. Spike proteins derived from wild-type SARS-CoV-2 and alpha variant (Spike1) and beta and gamma variant (Spike2) were utilized. RESULTS: A total of 235 healthcare workers who had received a two-dose primary vaccine series of either ChAdOx1 or BNT162b2, followed by a third booster dose of BNT162b2 (166 in the ChAdOx1/ChAdOx1/BNT162b2 (CCB) group and 69 in the BNT162b2/BNT162b2/BNT162b2 (BBB) group, based on the vaccine series) were included. Following the primary vaccine series, the BBB group exhibited significantly higher increases in Sab levels, IGRA responses, and multiple cytokines (CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1ß, interleukin (IL)-1ra, IFN-γ, IL-2, IL-4, and IL-10) compared to the CCB group (all P < 0.05). One month after the third BNT162b2 booster, the CCB group showed Sab levels comparable to those of the BBB group, and both groups exhibited lower levels after six months without breakthrough infections (BIs). However, among those who experienced BA.1/2 BIs after the third booster, Sab levels increased significantly more in the BBB group than in the CCB group (P < 0.001). IGRA responses to both Spike1 and Spike2 proteins were significantly stronger in the BBB group than the CCB group after the third booster, while only the Spike2 response were higher after BIs (P = 0.007). The BBB group exhibited stronger enhancement of T-cell cytokines (IL-2, IL-4, and IL-17A) after BIs than in the CCB group (P < 0.05). CONCLUSION: Differences in immunogenicity induced by the two primary vaccine series persisted, modulated by subsequent booster vaccinations and BIs.

Carbapenem-resistant Acinetobacter baumannii Outbreak in a COVID-19 Isolation Ward and Successful Outbreak Control with Infection Control Measures.

BACKGROUND: Even amid the coronavirus disease-19 (COVID-19) pandemic, the spread of multidrug-resistant bacteria and infection control are still important tasks. After recognizing the carbapenem-resistant Acinetobacter baumannii (CRAB) outbreak that occurred in the isolation room for COVID-19, we would like to introduce what infection control measures were implemented to eradicate it. MATERIALS AND METHODS: All COVID-19 patients with CRAB in any specimen admitted to the COVID-19 isolation ward of the tertiary hospital in Korea from October to November 2021 were analyzed. RESULTS: During the outbreak, 23 patients with COVID-19 and CRAB infections were identified. The index case was an 85-year-old female referred from a long-term care facility. CRAB was identified in sputum culture in most patients (91.3%). The CRAB outbreak occurred mainly in the rooms around the index case. Environmental cultures on the floor, air inlet, air outlet, and window frame of the rooms were performed. The antimicrobial resistance patterns of CRAB from patients and the environment were identical; whole-genome sequencing analyses revealed isolated clonality. Infection control measures with enhanced environmental cleaning using 1,000 ppm sodium hypochlorite and phenolic compounds, enhanced hand hygiene, additional education, and mandatory additional gowning and gloving of COVID-19 personal protective equipment (PPE) were applied on 29 October. No CRAB infection cases occurred from 2 November for two weeks. CONCLUSION: In addition to applying PPE and COVID-19 precautions in COVID-19 isolation wards, adhering to strict contact precautions along with environmental control can help prevent the spread of multidrug-resistant bacteria.

The obesity paradox in younger adult patients with sepsis: analysis of the MIMIC-IV database.

BACKGROUND: The obesity paradox suggests that individuals with obesity may have a survival advantage against specific critical illnesses, including sepsis. However, whether this paradox occurs at younger ages remains unclear. Therefore, we aimed to investigate whether obesity could improve survival in younger adult patients with sepsis. METHODS: We used clinical data sourced from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Patients with Sequential Organ Failure Assessment score ≥2 and suspected infection at the time of ICU admission were identified as having sepsis, following the Sepsis-3 definition. Individuals were classified into the obesity (BMI ≥30 kg/m²) and non-obesity (BMI <30 kg/m²) groups. Patients aged <50 and ≥50 years were categorized as younger adult patients and older patients, respectively. RESULTS: Of 73,181 patients in the MIMIC-IV ICU database, 18,120 satisfied the inclusion criteria: 2642 aged <50 years and 15,478 aged ≥50 years. The Kaplan-Meier curve showed that obesity was not associated with an improved mortality rate among younger adult patients with sepsis (log-rank test: P = 0.197), while obesity exhibited a survival benefit in older patients with sepsis (log-rank test: P < 0.001). After propensity score matching, in-hospital mortality did not differ significantly between the obesity and non-obesity groups (13.3% vs. 12.2%; P = 0.457) in the younger adult patients with sepsis. Multivariate logistic regression analysis revealed that BMI was not an independent risk factor for in-hospital mortality in younger adult patients with sepsis (underweight: adjusted odds ratio [aOR] 1.72, P = 0.076; overweight: aOR 0.88, P = 0.437; obesity: aOR 0.93, P = 0.677; and severe obesity: aOR 1.22, P = 0.580, with normal weight as the reference). CONCLUSION: Contrary to findings regarding older patients with sepsis, our findings suggest that the obesity paradox does not apply to younger adult patients with sepsis.

An Analysis of the Determinants of the Health-Related Quality of Life in Asian Patients With Cluster Headaches During Cluster Periods Using the Time Trade-Off Method.

BACKGROUND AND PURPOSE: Patients with cluster headache (CH) exhibit impaired health-related quality of life (HRQoL). However, there have been few studies related to the HRQoL of patients with CH from Asian backgrounds. This study aimed to determine the impact of CH on HRQoL and to identify the factors affecting HRQoL in patients with CH during cluster periods. METHODS: This prospective study enrolled patients with CH from 17 headache clinics in South Korea between September 2016 and February 2021. The study aimed to determine HRQoL in patients with CH using the EuroQol 5 Dimensions (EQ-5D) index and the time trade-off (TTO) method. Age- and sex-matched headache-free participants were recruited as a control group. RESULTS: The study included 423 patients with CH who experienced a cluster period at the time. EQ-5D scores were lower in patients with CH (0.88±0.43, mean±standard deviation) than in the controls (0.99±0.33, p<0.001). The TTO method indicated that 58 (13.6%) patients with CH exhibited moderate-to-severe HRQoL deterioration. The HRQoL states in patients with CH were associated with current smoking patterns, headache severity, frequency, and duration, and scores on the Generalized Anxiety Disorder 7-item scale (GAD-7), Patient Health Questionnaire 9-item scale (PHQ-9), 6-item Headache Impact Test, and 12-item Allodynia Symptom Checklist. Multivariable logistic regression analyses demonstrated that the HRQoL states in patients with CH were negatively correlated with the daily frequency of headaches, cluster period duration, and GAD-7 and PHQ-9 scores. CONCLUSIONS: Patients with CH experienced a worse quality of life during cluster periods compared with the headache-free controls, but the degree of HRQoL deterioration varied among them. The daily frequency of headaches, cluster period duration, anxiety, and depression were factors associated with HRQoL deterioration severity in patients with CH.

Pentraxin 3 as an Immune Recovery Marker in HIV Infection After Combination Antiretroviral Therapy.

Human immunodeficiency virus (HIV) infection causes chronic inflammation in affected individuals. Chronic inflammation may hinder immunological recovery. Treatment with combination antiretroviral therapy (cART) is insufficient to reduce inflammation. Pentraxin 3 (PTX3) is an inflammatory marker associated with cardiovascular disease, malignancy, and acute infection. This study evaluated the usefulness of serum PTX3 levels in measuring inflammation levels, which may be associated with the probability of immune recovery in people living with HIV (PLH). In this single-center prospective study, we measured serum PTX3 levels in PLH treated with cART. Clinical information on HIV status, type of cART administered, and CD4+ and CD8+ T cell counts at the initial diagnosis of HIV and at study enrollment was obtained from each participant. PLH were divided into good and poor responder groups according to their CD4+ T cell counts at enrollment. A total of 198 PLH were enrolled in this study. A total of 175 and 23 participants were assigned to the good and poor responder groups, respectively. The poor responder group exhibited higher PTX3 levels (0.53 ng/mL vs. 1.26 ng/mL, p = .032). Logistic regression analysis demonstrated that low body mass index [odds ratio (OR) = 0.8, p = .010], low initial CD4+ T cell counts at diagnosis (OR = 0.994, p = .001), and high PTX3 levels (OR = 1.545, p = .006) are clinical factors that were significantly associated with poor immune recovery in PLH. According to the Youden index, PTX3 levels >1.25 ng/mL are associated with poor immune recovery. PLH should be clinically, virologically, and immunologically evaluated. Serum PTX level is a useful inflammatory marker associated with immune recovery in PLH treated with cART.

DECIPHERING GUT MICROBIOTA IN PATIENTS WITH SEVERE SEPSIS AND SEPTIC SHOCK.

ABSTRACT: Introduction: Gut microbiota dysbiosis is associated with susceptibility to sepsis and poor outcomes. However, changes to the intestinal microbiota during sepsis and their value as biomarkers are unclear. In this study, we compared the intestinal microbiota of patients with sepsis and healthy controls. Methods: Stool was collected from patients with sepsis (subdivided according to mortality) and controls. Microbiome diversity and composition were analyzed by 16S rRNA gene pyrosequencing. The α-diversity of the intestinal microbiome was determined using operational taxonomic unit counts and the Chao1, Shannon, and ACE indices. Adjusted Cox regression analyses assessed 6-month mortality risk factors. Results: Fifty-nine patients (14 in-hospital deaths) and 29 healthy controls were enrolled. Operational taxonomic unit counts and Chao1 and ACE indices were lower in the nonsurvivor than in the other groups. The controls showed a higher Shannon and lower Simpson index than did the sepsis group. The genus Blautia was more abundant in controls than in the sepsis group, and Faecalibacterium less abundant in the nonsurvivor than in the other groups. Regression analysis associated low Shannon index with 6-month mortality. Conclusions: Survivors of sepsis, nonsurvivors, and healthy controls have different gut microbiomes, and a low Shannon index is a risk factor for 6-month mortality.

Frequency and Risk Factor Analysis for Metronidazole-Associated Neurologic Adverse Events.

BACKGROUND: Little is known about the risk factors and frequency of metronidazole-associated neurological adverse events. OBJECTIVE: To investigate the risk factors and frequency of metronidazole-associated neurological adverse events. DESIGN: This retrospective study contained two parts. First, we investigated metronidazole treatment-associated neurologic adverse events by performing a population-based cohort study using the Korea Adverse Event Reporting System (KAERS) database from January 2011 to December 2020. Second, we conducted a matched case-control study based on a retrospective cohort of patients treated with metronidazole between January 2006 and July 2021 at a tertiary hospital in South Korea. The data analysis was performed from August 2021 to April 2022. PARTICIPANTS: In the case-control study, case patients were defined as those diagnosed with metronidazole-associated encephalopathy or peripheral neuropathy during the study period with causal assessment based on the clinical diagnoses and findings from associated tests. In a ratio of 1:3, case patients were compared to a control group of patients prescribed metronidazole without neurologic adverse events matched for age and cumulative dose of metronidazole. MAIN MEASURES: Frequency and risk factors for metronidazole-associated neurological adverse events. KEY RESULTS: Overall, 2,309 cases of neurologic adverse events were reported to the KAERS from 2011 to 2020, and the number of reported neurological adverse events showed an increasing trend. Further, 92,838 patients were prescribed metronidazole during the study period at the Severance Hospital; 54 patients were diagnosed with metronidazole-associated encephalopathy or peripheral neuropathy, 40 with central and 28 with peripheral nervous system adverse events. Liver cirrhosis, chronic kidney disease, intravenous administration, and lower body weight were identified as risk factors for these adverse events. CONCLUSIONS: The number of reported metronidazole-associated neurological adverse events are increasing. Prolonged metronidazole treatment in patients with the aforementioned factors requires careful examination for neurological adverse events.

Clinical utility of quantitative immunoassays and surrogate virus neutralization tests for predicting neutralizing activity against the SARS-CoV-2 Omicron BA.1 and BA.5 variants.

Developing new antibody assays for emerging SARS-CoV-2 variants is challenging. SARS-CoV-2 surrogate virus neutralization tests (sVNT) targeting Omicron BA.1 and BA.5 have been devised, but their performance needs to be validated in comparison with quantitative immunoassays. First, using 1749 PRNT-positive sera, we noticed that log-transformed optical density (OD) ratio of wild-type (WT) sVNT exhibited better titer-correlation with plaque reduction neutralization test (PRNT) than % inhibition value. Second, we tried 798 dilutional titration tests with 103 sera, but nonlinear correlation between OD ratio and antibody concentration limited titration of sVNT. Third, the titer-correlations of two sVNT kits for BA.1 and two quantitative immunoassays for WT were evaluated with BA.1 and BA.5 PRNT. All tested kits exhibited a linear correlation with PRNT titers, but the sVNT kits exhibited high false-negative rates (cPass-BA.1 kit, 45.4% for BA.1 and 44.2% for BA.5; STANDARD F-BA.1 kit, 1.9% for BA.1 and 2.2% for BA.5), while quantitative immunoassays showed 100% sensitivity. Linear mixed-effects model suggested superior titer-correlation with PRNT for quantitative immunoassays compared to sVNT kits. Taken together, the use of quantitative immunoassays for WT, rather than rapid development of new kits, would be practical for predicting neutralizing activities against emerging new variants.