UNASSIGNED: To describe characteristics and acute clinical outcomes for patients with COVID-19 treated with sotrovimab, nirmatrelvir/ritonavir or molnupiravir, or untreated patients at highest risk per National Health Service (NHS) criteria.
UNASSIGNED: Retrospective study of non-hospitalized patients between 1 December 2021 and 31 May 2022, using data from the Discover-NOW dataset (North-West London). Included patients were aged ≥12 years and treated with sotrovimab, nirmatrelvir/ritonavir or molnupiravir, or untreated but expected to be eligible for early treatment per NHS highest-risk criteria. COVID-19-related and all-cause hospitalizations were reported for 28 days from COVID-19 diagnosis (index). Subgroup analyses were conducted in patients with advanced renal disease, those aged 18-64 and ≥65 years, and by period of Omicron BA.1, BA.2 and BA.5 (post-hoc exploratory) predominance.
UNASSIGNED: Overall, 1503 treated and 4044 eligible high-risk untreated patients were included. A high proportion of patients on sotrovimab had advanced renal disease (29.3%), ≥3 high-risk comorbidities (47.6%) and were aged ≥65 years (36.9%). Five of 696 (0.7%) patients on sotrovimab, <5/337 (0.3-1.2%) on nirmatrelvir/ritonavir, 10/470 (2.1%) on molnupiravir and 114/4044 (2.8%) untreated patients were hospitalized with COVID-19. Similar results were observed across all subgroups. The proportion of patients dying within 28 days of the index period was similarly low across all cohorts (<2%).
UNASSIGNED: Patients receiving sotrovimab appeared to show evidence of multiple high-risk comorbidities. Low hospitalization rates were observed for all treated cohorts across subgroups and periods of predominant variants of concern. These results require confirmation with comparative effectiveness analyses adjusting for differences in underlying patient characteristics.

It is so far unclear how the COVID-19 winter waves started and what should be done to prevent possible future waves. In this study, we deciphered the dynamic course of a winter wave in 2021 in Saxony, a state in Eastern Germany neighbouring the Czech Republic and Poland. The study was carried out through the integration of multiple virus genomic epidemiology approaches to track transmission chains, identify emerging variants and investigate dynamic changes in transmission clusters. For identified local variants of interest, functional evaluations were performed. Multiple long-lasting community transmission clusters have been identified acting as driving force for the winter wave 2021. Analysis of the dynamic courses of two representative clusters indicated a similar transmission pattern. However, the transmission cluster caused by a locally occurring new Delta variant AY.36.1 showed a distinct transmission pattern, and functional analyses revealed a replication advantage of it. This study indicated that long-lasting community transmission clusters starting since early autumn caused by imported or locally occurring variants all contributed to the development of the 2021 winter wave. The information we achieved might help future pandemic prevention.

During the coronavirus disease 2019 (COVID-19) pandemic, known viral diseases declined in all ages. By using the current situation as a natural experiment, this study aimed to evaluate whether the change in the incidence of Kawasaki disease (KD) during the COVID-19 pandemic varies with age and whether a specific infectious disease mediates the occurrence of KD. Monthly number of KD patients were extracted from the nationwide inpatient database. Segmented regression analysis was conducted on the interrupted time series data. Additionally, causal mediation analysis was performed to examine the role of viral infections in the changes in the number of KD patients. After the first emergency declaration for COVID-19 in Japan, there was an immediate decrease in the number of KD patients per 100 000 population aged between 6 months and 4 years (immediate change = -2.66; 95% confidence interval [CI]: -5.16 to -0.16) and aged 5-15 years (immediate change = -0.26; 95% CI: -0.49 to -0.04). However, no immediate change was observed in patients under 6 months of age. In the causal mediation analysis for each viral infection, it was found that the decrease in the number of patients with KD was mediated by changes in the number of patients with pharyngoconjunctival fever and infectious gastroenteritis. The current results suggest that viral infections may be one of the etiological agents for KD, while they may not be the main cause in early infancy. Specifically, we found that adenovirus infection and gastroenteritis was closely related to the onset of KD in some areas of Japan.

BACKGROUND: Cytomegalovirus-specific T-cell-mediated immunity (CMV-CMI) protects from CMV infection in allogeneic hematopoietic cell transplantation (allo-HCT), but to date, there is no validated measure of CMV immunity for this population.
METHODS: In this prospective, observational, pilot study, CMV T-cell responses were evaluated monthly and at onset of graft-versus-host disease (GVHD) or CMV infection in CMV-seropositive allo-HCT recipients using a commercial flow cytometry assay, the CMV inSIGHT T-Cell Immunity Panel (CMV-TCIP). The primary endpoint was the time to first positive CMV-TCIP, defined as percentage of interferon-γ-producing CD4+ or CD8+ CMV-specific T cells >0.2%. Letermovir was prescribed from day +10 to ≥100.
RESULTS: Twenty-eight allo-HCT recipients were enrolled. The median time to first positive CMV-TCIP result was earlier for CD4+ (60 days [interquartile range, IQR 33‒148]) than for CD8+ T cells (96 days [IQR 33‒155]) and longer for haploidentical and mismatched transplant recipients (77 and 96 days, respectively) than for matched donors (45 and 33 days, respectively). CD4+ and CD8+ CMV-CMI recovery was sustained in 10/10 (100%) and 10/11 (91%) patients, respectively, without GVHD, whereas CD4+ and/or CD8+ CMV-CMI was lost in 4/6 and 2/6 patients, respectively, with GVHD requiring steroids. As a predictor of clinically significant CMV infection in patients with low-level CMV reactivation, the sensitivity and negative predictive value of CMV-TCIP were 90% and 87.5%, respectively, for CD4+ CMV-TCIP and 66.7% and 62.5%, respectively, for CD8+ CMV-TCIP.
CONCLUSIONS: There was significant variability in time to CMV-CMI recovery post-HCT, with slower recovery after haploidentical and mismatched HCT. CD4+ CMV-CMI may protect against CS-CMVi, but immunity may be lost with GVHD diagnosis and treatment.

BACKGROUND: We assessed the effectiveness of sotrovimab vs no early COVID-19 treatment in highest-risk COVID-19 patients during Omicron predominance.
METHODS: Retrospective cohort study using the Discover dataset in North West London. Included patients were non-hospitalised, aged ≥12 years and met ≥1 National Health Service highest-risk criterion for sotrovimab treatment. We used Cox proportional hazards models to compare HRs of 28-day COVID-19-related hospitalisation/death between highest-risk sotrovimab-treated and untreated patients. Age, renal disease and Omicron subvariant subgroup analyses were performed.
RESULTS: We included 599 sotrovimab-treated patients and 5191 untreated patients. Compared with untreated patients, the risk of COVID-19 hospitalisation/death (HR 0.50, 95% CI 0.24, 1.06; p=0.07) and the risk of COVID-19 hospitalisation (HR 0.43, 95% CI 0.18, 1.00; p=0.051) were both lower in the sotrovimab-treated group; however, statistical significance was not reached. In the ≥65 years and renal disease subgroups, sotrovimab was associated with a significantly reduced risk of COVID-19 hospitalisation, by 89% (HR 0.11, 95% CI 0.02, 0.82; p=0.03) and 82% (HR 0.18, 95% CI 0.05, 0.62; p=0.007), respectively.
CONCLUSIONS: Risk of COVID-19 hospitalisation in sotrovimab-treated patients aged ≥65 years and with renal disease was significantly lower compared with untreated patients. Overall, risk of hospitalisation was also lower for sotrovimab-treated patients, but statistical significance was not reached.

BACKGROUND: Pre-clinical data have revealed that viral infection, such as Hepatitis B virus (HBV), Hepatitis C virus (HCV), and Human Papilloma virus (HPV), may lead to the development of \"hot\" or \"immune-sensitive\" tumors, which may impact the efficacy of immune checkpoint inhibitor (ICIs). Therefore, This study aimed to investigate the impact of viral status on the efficacy of ICIs.
METHODS: Electronic databases were searched to identify relevant trials. The primary endpoints were overall survival (OS) and progression-free survival (PFS) measured by hazard ratio (HR). Stratified analyses were accomplished based on viral types, treatment regimens, and patient locations.
RESULTS: A total of 3255 participants were recruited, including 252 cases of gastric cancer, 156 cases of nasopharyngeal carcinoma, 1603 cases of hepatocellular carcinoma, and 1244 cases of head and neck squamous cell carcinoma. Pooled results demonstrated a significant association between viral infection and favorable outcomes in patients receiving ICIs, including improved OS [HR = 0.67, 95%CI (0.57-0.79), P < 0.0001], increased ORR [OR = 1.43, 95%CI (1.14-1.80), P = 0.0018], and a trend toward enhanced PFS [HR = 0.75, 95%CI (0.56-1.00), P = 0.05]. In subgroup analyses, patients treated with ICIs who were exposed to HBV/HCV or HPV infection exhibited an evidently superior OS without heterogeneity, compared to those without infection.
CONCLUSIONS: This study indicated that the presence of viral infection was evidently associated with improved outcomes in cancer patients undergoing ICIs, particularly in cases of HBV/HCV and HPV infections.

UNASSIGNED: Second to COVID-19 pandemic, other viral respiratory infections are still important causes of human diseases or co-infections. Hence, the present study was carried out to investigate the common respiratory viruses in patients with respiratory illness diagnosed negative for severe acute respiratory syndrome coronavirus-2 in primary screening.
UNASSIGNED: In a cross-sectional study, a real-time PCR was carried out using HiTeq. 17 Viro Respiratory pathogen One Step RT-PCR Kit (Genova, Bonda Faravar, Bioluence, Tehran, Iran).
UNASSIGNED: A total of 311 individuals (mean age ± SD: 48.2 ± 21.7 years, range: 1-97 years) underwent second PCR. Among these, 161 (51.7%) were female. In total, 55 (17.6%) cases (mean age ± SD: 45.7 ± 18.1 years) were found positive for respiratory viruses panel in the second PCR. The HCoV-OC43/HKU1 was in 5.4% (17/311), Flu A in 4.5% (14/311), HCoV-229E/NL63 in 2.8% (9/311), HMPV in 1.9% (6/311), HPiV 1, 2, 3 in 1.2% (4/311), HRSV in 0.9% (3/311), and HAdV in 0.6% (2/311) of the cases studies. Also, co-infection was detected in 4 samples (1.2%). In addition, sore throat (0.028), headache (p = 0.016), and body pain (p = 0.0001) were statistically the most significant symptoms in studied cases.
UNASSIGNED: According to the findings of our study, respiratory virus infections and co-infections were 17.6% and 1.2% frequent, respectively. Interestingly, nearly half of our positive cases (47.2%) were identified by coronaviruses (ОС43, Е229, NL63, and HKUI), followed by influenza A virus (25.4%). However, for more comprehensive results, we recommend using greater sample size.

The research presents data from a preclinical study on the anti-inflammatory effects of a sodium dichloroacetate and sodium valproate combination (DCA-VPA). The 2-week treatment with a DCA 100 mg/kg/day and VPA 150 mg/kg/day combination solution in drinking water\'s effects on the thymus weight, its cortex/medulla ratio, Hassall\'s corpuscles (HCs) number in the thymus medulla, and the expression of inflammatory and immune-response-related genes in thymocytes of male Balb/c mice were studied. Two groups of mice aged 6-7 weeks were investigated: a control (n = 12) and a DCA-VPA-treated group (n = 12). The treatment did not affect the body weight gain (p > 0.05), the thymus weight (p > 0.05), the cortical/medulla ratio (p > 0.05), or the number of HCs (p > 0.05). Treatment significantly increased the Slc5a8 gene expression by 2.1-fold (p < 0.05). Gene sequence analysis revealed a significant effect on the expression of inflammation-related genes in thymocytes by significantly altering the expression of several genes related to the cytokine activity pathway, the inflammatory response pathway, and the Il17 signaling pathway in thymocytes. Data suggest that DCA-VPA exerts an anti-inflammatory effect by inhibiting the inflammatory mechanisms in the mouse thymocytes.

Asthma and its associated exacerbation are heterogeneous. Although severe asthma attacks are systematically prescribed corticosteroids and often antibiotics, little is known about the variability of response to these therapies. Blood eosinophils and fractional exhaled nitric oxide (FeNO) are type 2 inflammation biomarkers that have established mechanistic, prognostic and theragnostic values in chronic asthma, but their utility in acute asthma is unclear. We speculate that the clinical and biological response to those treatments varies according to inflammometry and microbiological test results.
An observational longitudinal pilot study with multimodal clinical and translational assessments will be performed on 50 physician-diagnosed ≥12-year-old asthmatics presenting with an asthma attack and 12 healthy controls, including blood eosinophil count (venous and point-of-care (POC) capillary blood), FeNO and testing for airway infection (sputum cultures and POC nasopharyngeal swabs). People with asthma will be assessed on day 0 and after a 7-day corticosteroid course, with home monitoring performed in between. The primary analysis will be the change in the forced expiratory volume in 1 s according to type 2 inflammatory status (blood eosinophils ≥0.15×109/L and/or FeNO ≥25 ppb) after treatment. Key secondary analyses will compare changes in symptom scores and the proportion of patients achieving a minimal clinically important difference. Exploratory analyses will assess the relationship between clinical, lung function, inflammatory and microbiome parameters; satisfaction plus reliability indices of POC tests; and sex-gender variability in treatment response. Ultimately, this pilot study will serve to plan a larger trial comparing the clinical and biological response to systemic corticosteroids according to inflammatory biomarkers, offering valuable guidance for more personalised therapeutic strategies in asthma attacks.
The protocol has been approved by the Research Ethics Committee of the CIUSSS de l\'Estrie-CHUS, Sherbrooke, Quebec, Canada (#2023-4687). Results will be communicated in an international meeting and submitted to a peer-reviewed journal.
ClinicalTrials.gov Registry (NCT05870215).

BACKGROUND: Delirium, an acute confusional state highlighted by inattention, has been reported to occur in 10% to 50% of patients with COVID-19. People hospitalized with COVID-19 have been noted to present with or develop delirium and neurocognitive disorders. Caring for patients with delirium is associated with more burden for nurses, clinicians, and caregivers. Using information in electronic health record data to recognize delirium and possibly COVID-19 could lead to earlier treatment of the underlying viral infection and improve outcomes in clinical and health care systems cost per patient. Clinical data repositories can further support rapid discovery through cohort identification tools, such as the Informatics for Integrating Biology and the Bedside tool.
OBJECTIVE: The specific aim of this research was to investigate delirium in hospitalized older adults as a possible presenting symptom in COVID-19 using a data repository to identify neurocognitive disorders with a novel group of International Classification of Diseases, Tenth Revision (ICD-10) codes.
METHODS: We analyzed data from 2 catchment areas with different demographics. The first catchment area (7 counties in the North-Central Florida) is predominantly rural while the second (1 county in North Florida) is predominantly urban. The Integrating Biology and the Bedside data repository was queried for patients with COVID-19 admitted to inpatient units via the emergency department (ED) within the health center from April 1, 2020, and April 1, 2022. Patients with COVID-19 were identified by having a positive COVID-19 laboratory test or a diagnosis code of U07.1. We identified neurocognitive disorders as delirium or encephalopathy, using ICD-10 codes.
RESULTS: Less than one-third (1437/4828, 29.8%) of patients with COVID-19 were diagnosed with a co-occurring neurocognitive disorder. A neurocognitive disorder was present on admission for 15.8% (762/4828) of all patients with COVID-19 admitted through the ED. Among patients with both COVID-19 and a neurocognitive disorder, 56.9% (817/1437) were aged ≥65 years, a significantly higher proportion than those with no neurocognitive disorder (P<.001). The proportion of patients aged <65 years was significantly higher among patients diagnosed with encephalopathy only than patients diagnosed with delirium only and both delirium and encephalopathy (P<.001). Most (1272/4828, 26.3%) patients with COVID-19 admitted through the ED during our study period were admitted during the Delta variant peak.
CONCLUSIONS: The data collected demonstrated that an increased number of older patients with neurocognitive disorder present on admission were infected with COVID-19. Knowing that delirium increases the staffing, nursing care needs, hospital resources used, and the length of stay as previously noted, identifying delirium early may benefit hospital administration when planning for newly anticipated COVID-19 surges. A robust and accessible data repository, such as the one used in this study, can provide invaluable support to clinicians and clinical administrators in such resource reallocation and clinical decision-making.