Explore the vast range of titles available.

To investigate the relationship between viral load and secondary transmission in novel coronavirus disease 2019 (COVID-19). Epidemiological and clinical data were obtained from immunocompetent laboratory-confirmed patients with COVID-19 who were admitted to and/or from whom viral loads were measured at Toyama University Hospital. Using a case-control approach, index patients who transmitted the disease to at least one other patient were analysed as \"cases\" (index patients) compared with patients who were not the cause of secondary transmission (non-index patients, analysed as \"controls\"). The viral load time courses were assessed between the index and non-index symptomatic patients using non-linear regression employing a standard one-phase decay model. In total, 28 patients were included in the analysis. Median viral load at the initial sample collection was significantly higher in symptomatic than in asymptomatic patients and in adults than in children. Among symptomatic patients (n = 18), non-linear regression models showed that the estimated viral load at onset was higher in the index than in the non-index patients (median [95% confidence interval]: 6.6 [5.2-8.2] vs. 3.1 [1.5-4.8] log copies/μL, respectively). In adult (symptomatic and asymptomatic) patients (n = 21), median viral load at the initial sample collection was significantly higher in the index than in the non-index patients (p = 0.015, 3.3 vs. 1.8 log copies/μL, respectively). High nasopharyngeal viral loads around onset may contribute to secondary transmission of COVID-19. Viral load may help provide a better understanding of why transmission is observed in some instances, but not in others, especially among household contacts.

Background: Hyperuricemia is an adverse effect frequently observed during favipiravir treatment. The time course, from uric acid elevation to recovery, and quantitative relationship between drug exposure and changes in serum uric acid levels remain insufficiently characterized. We investigated the pharmacodynamic mechanism of uric acid elevation and described its time course by population pharmacokinetic and pharmacodynamic modelling. Methods: Patients who received favipiravir for coronavirus disease 2019 or severe fever with thrombocytopenia syndrome were retrospectively evaluated. The pharmacokinetics of favipiravir were described by a one-compartment model with first-order absorption and elimination. Metabolite concentrations were predicted based on previously reported values. Changes in serum uric acid levels were described by a turnover model with zero-order production and first-order elimination. The drug effect was implemented as inhibition of the uric acid elimination process. Simulations based on the final model were performed for 10 consecutive days after the clinical regimen, with a 21-day follow-up. Results: The final model supported the inhibition of uric acid elimination by favipiravir and its metabolite. Regarding simulations, serum uric acid levels reached a median peak of 6.93 mg/dL at 6.7 days after treatment initiation and returned to pre-treatment levels within 4.0 days after treatment discontinuation. Conclusions: This combined population pharmacokinetic and pharmacodynamic turnover model quantified favipiravir-associated increases in serum uric acid levels and showed a transient profile with rapid recovery after drug discontinuation. These findings underscore the need for monitoring serum uric acid levels during favipiravir treatment, particularly in patients at a higher risk of gout.

Adaptive immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) dynamics remain largely unknown. The neutralizing antibody (NAb) levels in patients with coronavirus disease 2019 (COVID-19) are helpful for understanding the pathology. Using SARS-CoV-2 pseudotyped virus, serum sample neutralization values in symptomatic COVID-19 patients were measured using the chemiluminescence reduction neutralization test (CRNT). At least two sequential serum samples collected during hospitalization were analyzed to assess NAbs neutralizing activity dynamics at different time points. Of the 11 patients, four (36.4%), six (54.5%), and one (9.1%) had moderate, severe, and critical disease, respectively. Fifty percent neutralization (N50%-CRNT) was observed upon admission in 90.9% (10/11); all patients acquired neutralizing activity 2–12 days after onset. In patients with moderate disease, neutralization was observed at earliest within two days after symptom onset. In patients with severe-to-critical disease, neutralization activity increased, plateauing 9–16 days after onset. Neutralization activity on admission was significantly higher in patients with moderate disease than in patients with severe-to-critical disease (relative % of infectivity, 6.4% vs. 41.1%; P  = .011). Neutralization activity on admission inversely correlated with disease severity. The rapid NAb response may play a crucial role in preventing the progression of COVID-19.

Vancomycin (VCM) and daptomycin (DAP) are standard therapies for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia, despite concerns regarding clinical utility and growing resistance. Linezolid (LZD) affords superior tissue penetration to VCM or DAP and has been successfully used as salvage therapy for persistent MRSA bacteremia, indicating its utility as a first-choice drug against MRSA bacteremia. In a systematic review and meta-analysis, we compared the effectiveness and safety of LZD with VCM, teicoplanin (TEIC), or DAP in patients with MRSA bacteremia. We evaluated all-cause mortality as the primary effectiveness outcome, clinical and microbiological cure, hospital length of stay, recurrence, and 90-day readmission rates as secondary effectiveness outcomes, and drug-related adverse effects as primary safety outcomes. We identified 5328 patients across 2 randomized controlled trials (RCTs), 1 pooled analysis of 5 RCTs, 1 subgroup analysis (1 RCT), and 5 case-control and cohort studies (CSs). Primary and secondary effectiveness outcomes were comparable between patients treated with LZD versus VCM, TEIC, or DAP in RCT-based studies and CSs. There was no difference in adverse event incidence between LZD and comparators. These findings suggest that LZD could be a potential first-line drug against MRSA bacteremia as well as VCM or DAP.

In clinical practice, early recognition of bacteremia leads to prognostic improvement. Recently, cell population data (CPD) from the Sysmex XN-series hematology analyzer has attracted attention as a new method for the early diagnosis of bacteremia, but its usefulness in clinical practice remains unclear. We focused on the fluorescent light distribution of the neutrophil area (NE-WY) and used machine learning to determine whether predictions could be improved. Among adult patients with clinically suspected bacteremia at our hospital, 533 who did not meet the exclusion criteria were enrolled. Propensity score matching was performed for bacteremia (n = 106) and non-bacteremia (n = 427) cases. NE-WY showed the largest difference between the two groups (AUC, 0.768; sensitivity, 73.6%; specificity, 67.9%; cutoff value, 686.5(no unit)). In machine learning, the first branch of the decision tree was NE-WY, and the cutoff value was set at 689.5(no unit). Support vector machines were used to examine multiple variables, but there were no significant differences relative to NE-WY alone. This is the first report to demonstrate that NE-WY is useful for detecting bacteremia by analyzing CPD using machine learning. The combination of CPD and machine learning is expected to produce new results.

The level of neutralizing antibodies required to confer protection against COVID-19 breakthrough infections (BIs) is unclear, and the ability to know the immune status of individuals against the rapidly changing endemic variants is limited. We assessed longitudinal serum anti-RBD antibody levels and neutralizing activities (NTs) against Omicron BA.5 and XBB.1.5 in healthcare workers following the fourth monovalent and fifth bivalent BA.4–5 vaccines. The occurrence of BIs was also followed, and pre-infection antibody levels were compared between patients who developed BI and those who did not. In addition, we collected whole blood samples on the same day as the sera and stored them on filter papers (nos. 545, 590, and 424) for up to two months, then measured their NTs using dried blood spots (DBS) eluates, and compared them with the NTs in paired sera. Pre-infection levels of NTs were lower in patients who developed BI than those who did not, but the anti-RBD antibody levels were not different between them. The NTs below 50 % using 200-fold diluted sera might be one of the indicators of high risk for COVID-19 BI. However, the NTs against XBB.1.5 at 6 months after the fifth dose of bivalent BA.4–5 vaccine were lower than this threshold in almost half of infection-naïve participants. NTs measured using DBS eluates were strongly correlated with those measured using paired sera, but the time and temperature stability varied with the type of filter paper; no. 545 filter paper was found to most suitable for NT evaluation.

The role of type I interferons (IFNs) in the early phase of COVID-19 remains unclear. To evaluate the relationship between IFN-I levels in patients with COVID-19 and clinical presentation, SARS-CoV-2 viral load, and other major pro-inflammatory cytokines. This prospective observational study recruited patients hospitalized with COVID-19. The levels of interferon-alpha (IFN-α), interferon-beta (IFN-β), interleukin-6 (IL-6), and C-X-C motif chemokine ligand (CXCL10) within 5 days after symptom onset were measured using an ELISA, in serum from blood collected within 5 days after the onset of symptoms. The SARS-CoV-2 viral load was determined qPCR using nasal-swab specimens and serum. The study enrolled 50 patients with COVID-19. IFN-α levels were significantly higher in patients who presented with pneumonia or developed hypoxemic respiratory failure (p < 0.001). Furthermore, IFN-α levels were associated with viral load in nasal-swab specimens and RNAemia (p < 0.05). In contrast, there was no significant association between IFN-β levels and the presence of pneumonia or RNAemia, despite showing a stronger association with nasal-swab viral load (p < 0.001). Correlation analysis showed that the serum levels of IFN-α significantly correlated with those of IFN-β, IL-6, and CXCL10, while the levels of IFN-β did not correlate with those of IL-6 or CXCL10. Serum IFN-I levels in the early phase of SARS-CoV-2 infection were higher in patients who developed hypoxemic respiratory failure. The association between IFN-α, IL-6, and CXCL10 may reflect the systemic immune response against SARS-CoV-2 invasion into pulmonary circulation, which might be an early predictor of respiratory failure due to COVID-19.

Acute immune responses to coronavirus disease 2019 (COVID-19) are influenced by variants, vaccination, and clinical severity. Thus, the outcome of these responses may differ between vaccinated and unvaccinated patients and those with and without COVID-19-related pneumonia. In this study, these differences during infection with the Omicron variant were investigated. A total of 67 patients (including 47 vaccinated and 20 unvaccinated patients) who were hospitalized within 5 days after COVID-19 symptom onset were enrolled in this prospective observational study. Serum neutralizing activity was evaluated using a pseudotyped virus assay and serum cytokines and chemokines were measured. Circulating follicular helper T cell (cTfh) frequencies were evaluated using flow cytometry. Twenty-five patients developed COVID-19 pneumonia on hospitalization. Although the neutralizing activities against wild-type and Delta variants were higher in the vaccinated group, those against the Omicron variant as well as the frequency of developing pneumonia were comparable between the vaccinated and unvaccinated groups. IL-6 and CXCL10 levels were higher in patients with pneumonia than in those without it, regardless of their vaccination status. Neutralizing activity against the Omicron variant were higher in vaccinated patients with pneumonia than in those without it. Moreover, a distinctive correlation between neutralizing activity against Omicron, IL-6 levels, and cTfh proportions was observed only in vaccinated patients. The present study demonstrates the existence of a characteristic relationship between neutralizing activity against Omicron, IL-6 levels, and cTfh proportions in Omicron breakthrough infection.

The effects of casirivimab and imdevimab (C/I) on the innate immune response against SARS-CoV-2 infection remain unclear. We evaluated the effect of C/I on type I interferon (IFN-I) and cytokines in patients with SARS-CoV-2 infection. This prospective observational study recruited consecutive patients hospitalized with SARS-CoV-2 infection. Blood levels of IFN-I and cytokines before and after C/I administration were assessed using enzyme-linked immunoassay. The study enrolled 29 patients in the C/I group. In addition, 11 patients who received remdesivir and dexamethasone (R/D group) during the early phase (≤5 days after the onset of symptoms) were included as a comparator group. After treatment, IFN-α and IFN-β levels decreased significantly in both the C/I group and R/D group, whilst the post-treatment neutrophil-to-lymphoid ratio increased in the early C/I group but not the R/D group. In the C/I group, temporal temperature elevation and hypoxemia were observed after treatment in 58.6% and 41.4% of the cohort, respectively. However, most patients recovered by 5 days after treatment. This study could demonstrate the high therapeutic effect of C/I with an antibody-dependent enhancement-like response and decreased IFN-I production, which was likely due to the immediate induction of an antibody-dependent immune response against SARS-CoV-2.

Ground-glass opacity (GGO) and organizing pneumonia (OP) are dominant pulmonary CT lesions associated with COVID-19. However, the role of different immune responses in these CT patterns remains unclear, particularly following the emergence of the Omicron variant. In this prospective observational study, we recruited patients hospitalized with COVID-19, before and after the emergence of Omicron variants. Semi-quantitative CT scores and dominant CT patterns were retrospectively determined for all patients within five days of symptom onset. Serum levels of IFN-α, IL-6, CXCL10, and VEGF were assessed using ELISA. Serum-neutralizing activity was measured using a pseudovirus assay. We enrolled 48 patients with Omicron variants and 137 with precedent variants. While the frequency of GGO patterns was similar between the two groups, the OP pattern was significantly more frequent in patients with precedent variants. In patients with precedent variants, IFN-α and CXCL10 levels were strongly correlated with GGO, whereas neutralizing activity and VEGF were correlated with OP. The correlation between IFN-α levels and CT scores was lower in patients with Omicron than in those with precedent variants. Compared to preceding variants, infection with the Omicron variant is characterized by a less frequent OP pattern and a weaker correlation between serum IFN-α and CT scores.